摘要:

Annual Reports, Section Baims to provide an overview of the most important advances and achievements in organic chemistry and related fields, described in the literature of a calendar year.The chapters on synthetic aspects of organic chemistry this year include the regular reports on recent advances in synthetic methodology together with coverage of other important areas of research in organic synthesis. New chapters this year include oxidation and reduction methods and marine natural products; new authors include Gareth Rowlands, Alan Armstrong, Paul Clarke, and Bob Hill.The core chapters on synthetic methodology cover a very wide range of reaction type. Ian Fairlamb continues his thorough coverage of organometallic chemistry. Matthew Fletcher again writes about heteroatom methods. Gareth Rowlands succeeds Clive Penkett in discussing free radical methodology, and Paul Clarke takes over from Alan Spivey in reporting on protecting groups. Advances in the field of oxidation and reduction methodology are discussed for the first time by Alan Armstrong.Rob Stockman continues his contribution on heterocyclic chemistry, and Steve Allin’s commentary on highlights of natural product synthesis also appears in Annual Reports for the second time in this volume.The interface of the biological sciences with chemistry continues to provide new opportunities for research. In this field, Ben Davis writes again about enzyme methods, and Harri Lönnberg describes advances in the chemistry of natural polymers. The field of supramolecular chemistry continues to evolve rapidly; Phil Gale addresses some of the most interesting developments in his second year of contributing to Annual Reports.The chapters on physical aspects of organic chemistry contain a blend of authors continuing from last year and new contributors. There are three core chapters on organic reaction mechanisms. James Tanko has replaced Mark Workentin in preparing the chapter on “Radical and radical ion reactions”, and Kevin Dalby and Kathleen Morgan have continued their coverage of “Polar reactions” and “Pericyclic reactions”, respectively.Brian Yates has again contributed a chapter on “Computational organic chemistry” and Mary Boyd has continued to cover “Organic photochemistry”. Paul Wenthold has taken over from Richard O’Hair in covering “Organic gas-phase ion chemistry” and Nicholas Williams has replaced Bruce Armitage in contributing a chapter on “Bioinspired organic chemistry”.The Scientific Editors wish to express their appreciation to the work of this year’s reporters, without whom there would be no volume 99.

ISSN:0069-3030    

DOI:10.1039/b212019b

出版商:RSC    

年代:2003

数据来源: RSC

摘要:

This review highlights a number of synthetic advances made using radical reactions in the field of organic chemistry during 2002. The development of tin-free radical reactions continues to be the focus of considerable attention. Walton has developed 1-phenylcyclohexa-2,5-diene-1-carboxylates as pro-aromatic sources of clean free radicals.1Treatment of1with a peroxide radical initiator results in formation of the cyclohexadienyl radical2. β-Scission then forms the alkoxycarbonyl radical3and the innocuous biphenyl (Scheme 1). The former extrudes carbon dioxide to generate the desired alkyl radical4, which can be trapped by an internal alkene in good yield. Previous cyclohexadiene precursors have contained an alkyl substituent at the 1-position and have suffered from low yields due to competitive β-scission. This is not observed with1and its analogues as this would result in formation of the energetically unfavourable aryl radical. Good yields could be obtained for intramolecular 5-exocyclisations. Unfortunately, yields for intermolecular reactions were not as satisfactory. This, in conjunction with difficulty in preparing the precursors, limits the scope of this methodology at present.In related research, Studer has utilised a silylated cyclohexadiene to generate silicon-centred radicals that are able to undergo intramolecular hydrosilylation (Scheme 2).2The reaction works for a variety of alkenes but is sensitive to terminal substitution. Remarkably, the methodology allowed the first example of a 5-endo-digradical cyclisation to be achieved, furnishing5in an impressive 55% yield for two steps.Walton has developed an elegant method for the synthesis of lactams utilising the photosensitised decomposition of oxime oxalate amides as a source of clean radicals.3The radical precursors were readily prepared from an oxime and oxalyl chloride followed by treatment with a secondary amine. Cyclisation was achieved by photolysis of the radical precursors6in the presence of 4-methoxyacetophenone (MAP) as a photosensitiser (Scheme 3). Interestingly, if cyclisation resulted in a secondary radical7, hydroxylation was observed, resulting in alcohols8. Presumably the more stable radical has the opportunity to react with oxygen from the solvent.Kim has continued to develop a range of ingenious tin-free radical reactions utilising sulfones as radical reagents and precursors. Alkyl iodides9were found to undergo radical cyanation with toluenesulfonyl cyanide10in the presence of the initiator V-40 [azobis(cyclohexanecarbonitrile), a thermally more stable analogue of AIBN] and methyl allyl sulfone11(Scheme 4).4The methyl allyl sulfone11acts as a source of methyl radicals for the atom transfer process. The initially-formed toluenesulfonyl radical12interacts with11to give the methyl sulfonyl radical13. Whilst13could add to either11or14, neither process is detrimental; addition to11is degenerate whilst addition to the latter regenerates12. Thermal decomposition of13gives the methyl radical14, which undergoes atom transfer with9to give the desired alkyl radical15. Finally, this reacts with10to give product16and regenerate12. Whilst the reaction gave good results with tertiary and benzylic iodides, primary and secondary alkyl halides were far inferior due to the competing direct addition of the methyl radical to toluenesulfonyl cyanide over iodine atom transfer. This limitation could be overcome by employing alkyl tellurides, thus allowing more complex products17to be formed.The inefficiency of iodine atom transfer from primary halides has limited a number of tin-free radical methodologies. As a result other radical precursors have been developed. Kim has used alkyl allyl sulfones (e.g.18) as a source of primary radicals (Scheme 5).5The proposed pathway for the radical chain reaction is analogous to the previous cyanation process (vide supra) and has been used in cyanation, vinylation, allylation and tandem radical reactions (19to20) (Scheme 5).N-Ethylpiperidine hypophosphate (EPHP) has found considerable use as a cheap, clean and convenient alternative to organotin reagents in radical reactions.6,7Jang has developed an environmentally benign intermolecular addition of alkyl halides to electron-deficient alkenes that utilises EPHP in water (Scheme 6).8For hydrophobic substrates the use of a phase transfer reagent was shown greatly to enhance the reaction.Other metal reagents offer advantages over organotin compounds in terms of cost, stability, toxicity and ease of the work-up process. It is impossible to discuss all these studies in detail, and so just one example of each class of reagent is highlighted. Samarium diiodide continues to be a popular single electron transfer reagent.9The intramolecular coupling of aldehydes or ketones to various C&z.dbd;N bonds is a well known transformation. The analogous intermolecular cross coupling is far less successful due to competing homocoupling and simple reduction. Py and Vallée have overcome this limitation by employing nitrones21as the nitrogen component. Both aromatic and aliphatic nitrones reacted efficiently with a variety of aldehydes and ketones22in the presence of samarium diiodide to give products23(Scheme 7).10No side-products from reduction or homocoupling were observed. Surprisingly, evidence suggests that single electron transfer occurs to the nitrone first. When an α-cyclopropylketone was employed, no ring-opening was observed, indicating that the ketyl radical was not an intermediate.Indium shows great potential as a reagent in radical reactions.7,11Baba has shown that indium hydride (Cl2InH), generatedin situby the reduction of a catalytic quantity of indium chloride with sodium borohydride, acts as an efficient radical reagent.12Both intra-24and intermolecular25radical additions could be carried out efficiently (Scheme 8). The mechanism of initiation is unclear, however, the authors believe that homolytic cleavage of the indium hydride bond is responsible and have discounted the participation of an indium(0) species.Naito has utilised indium metal (In(0)) as a radical initiator in the addition of alkyl radicals to both electron-deficient C&z.dbd;N bonds26and alkenes in water.13The reaction proceeds at a slower rate than those initiated by triethylborane but is cleaner, resulting in less side-products, and requires fewer equivalents of the iodide to achieve good yields (Scheme 9). Water was found to be essential for reactivity. The presence of a radical trap stopped the reaction. It should be noted that this is not conclusive proof that the reaction proceeds through a radical addition and thus does not necessarily contradict the previous work (vide supra).Gansäuer has studied a number of common single electron transfer reagents in the reductive ring-opening of epoxides in order to elucidate the reasons that Nugent's titanocene reagent is superior to other reagents.14In a series of comparison experiments between titanocene(iii) chloride, samarium diiodide, chromium(ii) chloride and [V2Cl3(THF)6]2[Zn2Cl6] it became clear that only the titanocene reagent had the required properties of low Lewis acidity, to prevent epoxide opening through either SN2 or SN1 mechanisms, coupled with low reducing power towards the β-metal oxy radical. Intriguingly, CrCl2was the only other reagent that allowed carbon–carbon bond formation, but at present has too low a reactivity to be of any synthetic use. Clearly this is a deficiency that will soon be rectified.Gansäuer has exploited the activity of Nugent's reagent to synthesise bicyclic alkenes with excellent control of the alkene geometry through a tandem ring-opening–cyclisation–intermolecular radical addition process (Scheme 10).15Choice of solvent was critical for the success of the tandem reaction. It was necessary that the solvent had a lower hydrogen donor propensity than THF so that the reactive vinyl radical intermediate was not reduced prior to intermolecular addition. The solvent also had to enable fast reduction of the titanocene(iv) pre-catalyst in order to maintain the catalytic cycle. Ethyl acetate was found to be the optimum solvent. The control of the alkene geometry during the intermolecular addition is thought to arise by the titanium oxygen complex blocking approach of the enone from one face27.A number of examples of manganese(iii) acetate-mediated oxidative free radical reactions of 1,3-dicarbonyl compounds were reported during 2002.16One interesting example was the preparation of macrocycles28in good yields (Scheme 11).17Various diketones29containing a pendant allyl ether substituent could be cyclised with 5 equivalents of Mn(OAc)3in acetic acid at reflux to give the bicyclic compounds28. Surprisingly, the best yield was achieved for the cyclodecane (n= 4) system, which is the hardest ring-size to form by intramolecular cyclisation, whilst formation of cyclopentane derivative (n= 0), a favourable 5-exo-trigprocess, proved impossible.Most manganese(ii)-mediated radical reactions use an excess of the reagent, a property that is unattractive from a practical standpoint. A catalytic variant, employing Mn(OAc)2, Co(OAc)2and oxygen has been developed by Ishii (Scheme 12).18The Mn(ii) is continuously oxidised to the reactive Mn(iii) by the action of a Co(iii)–dioxygen complex; it can then oxidise the diketone to a radical species, which undergoes addition to the alkene. The system works well for a variety of diketones and alkenes. The major limitation is the need for a large excess of the diketone. An impressive example is outlined inScheme 12.An elegant radical cascade employing catalytic palladium(0) and light has been reported by Ryu and Komatsu.19The methodology is analogous to Pd(0) catalysed cascades, resulting in both carbonylation and cyclisation, but, due to its radical nature, functions with alkyl halides instead of aromatic or vinylic halides. Irradiation of a variety of 4-alkenyl iodides30in the presence of Pd(PPh3)4, triethylamine and DMAP under an atmosphere of carbon monoxide initially results in the formation of cyclopentanone31, which can then undergo a second carbonylation process (Scheme 13). The reaction is terminated by addition of an alcohol or a secondary amine to give a variety of esters or amides32. It is postulated that Pd(0) is oxidised to Pd(i) with concomitant formation of the alkyl radical33under the photolysis conditions. Radical carbonylation followed by 5-exo-trigcyclisation then occurs to give31. A second carbonylation generates an acyl radical34which oxidises the Pd(i) to an acylpalladium(ii) intermediate35. Finally reductive elimination in the presence of either alcohol or amine furnishes the product32and regenerates the Pd(0) catalyst. The efficient formation of functionalised ring-systems by the construction of 4 new bonds under mild conditions is extremely attractive.Aminohydroxylation of alkenes offers an attractive route to a variety of biologically important motifs. Göttlich has achieved a catalytic radical aminohydroxylation through a group transfer reaction utilising a copper(i) catalyst in the presence of boron trifluoride etherate (Scheme 14).20Although the N–O bond is often considered to be weak it was found that a combination of Lewis acid and copper(i) species was essential for activity. The Lewis acid plays two roles, first activating the N–O bond in36, thus allowing the copper(i) to reduce it to an aminyl radical37. The radical can then undergo intramolecular addition to the alkene efficiently when it is activated by the Lewis acid. The resulting alkyl radical38is rapidly oxidised by a copper(ii) complex to give the product39and regenerate the catalyst.Zard has continued to investigate extensively tin-free radical synthesis utilising dithiocarbonyl derivatives and lauroyl peroxide (DLP) as radical initiator.21Analogously to Göttlich, pyrrolidinones40could be synthesised by a group transfer radical cyclisation (Scheme 15).22In an elegant extension of this work, use of stoichiometric DLP allowed a radical cascade onto an aromatic ring to be achieved, generating the tetracycle41in good yield (Scheme 15).Tin hydrides still hold a privileged position in radical chemistry and as a result methods to improve their utility in synthesis continue to be developed. Clive has developed stannane42(Fig. 1).23This reagent behaves analogously to tributyltin hydride but has the advantage that it can be readily removed by either mild acid or base hydrolysis followed by an aqueous NaHCO3wash, thus alleviating one of the disadvantages of conventional tin reagents. The polyaromatic hydrocarbon-supported tin hydride reagent43also allows for facile purification.24Again, the reagent mediates radical reactions well and can be removed simply by adsorption on to activated carbon. The greatest drawback of such reagents is their lengthy synthesis.Radical reactions continue to play a key role in organic synthesis due to their good functional group compatibility and ability to perform multi-step processes. Renaud has developed a three-component, one-pot coupling reaction that formally results in the carboazidation of alkenes (Scheme 16).25Hexabutyldistannane and di-tert-butyl hyponitrite (TBHN) are used to form an electrophilic enolate radical in the presence of an alkene and phenylsulfonyl azide. The radical adds exclusively to the alkene and not to the sulfonyl azide as this reagent is also electrophilic. The resulting alkyl radical then undergoes azidation, either directly or through an atom transfer process, to give44. The reaction can be coupled with a reduction step to give an amine that spontaneously cyclises allowing rapid entry to the bicyclic lactam45framework. A diastereoselective variant of this reaction has also been achieved.26An alternative means of forming C–N bonds has been reported with the first examples of radical-mediated vinyl amination.27The cyclisation of a vinyl radical onto an azomethine nitrogen allows the direct synthesis of enamines by a non-dehydrative method. Normally the resulting enamines were trapped as their benzoylated adduct in reasonable yields for the two steps. The vinyl radicals could either be formed directly from vinyl halides or by addition of heteroatom-centred radicals to an alkyne (Scheme 17). In all cases just one alkene geometry was observed.Bowman has developed an impressive cascade reaction for the formation of tetracyclic alkaloids46by radical addition to an aromatic ring (Scheme 18).28Good yields could be achieved if the vinyl iodide47was used as opposed to the bromide. The reaction had to be carried out with hexamethylditin to avoid reduction of the reactive intermediates48or49. It is believed that the reaction proceeds through a 5-exocyclisation of a vinylic radical48onto the nitrile followed by 6-endocyclisation. The driving force for this second cyclisation is thought to be delocalisation of the unpaired electron over nearly the entire compound. Finally hydrogen abstractionviaan unknown species gives the product46in an impressive 73%. It is possible that the reaction proceedsviaa spirocyclic intermediate, but the use of substituted aryl rings suggest this is not the case.Azadirachtin (Fig. 2) is a challenging synthetic target that has yet to succumb to total synthesis. Two groups have reported the use of radicals in model studies towards this demanding target. The main obstacle is the formation of the C8–C14 bond bridging the two halves of the molecule. Nicolaou has investigated a radical cyclisation approach to the formation of this bond (Scheme 19).29Linking the appropriate bromide to the decalin portionviaa temporary acetal tether allowed the C-7 hydroxyl group to control the stereochemistry of the new bond. The pentacycle50was found to undergo spontaneous hydrolysis to the desired product51. Although the route shows great potential, it is currently limited by the non-stereoselective formation of the radical precursor.In an alternative strategy, Ley forms the C8–C14 bond by a Claisen rearrangement and then utilises a radical cyclisation of the xanathate52on to an allene to generate analogue53(Scheme 20).30Intriguingly, the desiredendoalkene53and not the anticipatedexoalkene was formed exclusively. The authors suggested that the highly congested nature of the tertiary radical centre (at C-14) prevents protonation occurring at this point and only allows it to occur at the more accessible primary radical centre (C-18). The high yield demonstrates the utility of radicals and their high functional group tolerance.The [3+2]-cycloaddition of homoallylic methine radicals to simple alkenes is a well-known means of producing the cyclopentane skeleton. Surprisingly, prior to 2002 there had been only one example of the use of dienes in this reaction. Such systems would allow the formation of bicyclic systems through a radical cascade. Problems associated with the reaction include the limited reactivity of the homoallylic radicals and the necessity forcisstereoselectivity in the initial cyclisation. Taguchi has overcome these with the use of54as the homoallylic radical precursor in an iodine atom transfer reaction in the presence of Et3B and Yb(OTf)3.31The success is thought to arise due to the increased reactivity of the methine radical due to coordination of the malonate to the Lewis acid. A variety of dienes and enynes can be employed in good yields (Scheme 21).Stereoselectivity in radical chemistry remains an important area of study. In a fascinating study Curran has investigated stereocontrol at the steady state in radical cyclisations of acyclic dihalides55(Scheme 22).32In this reaction two radical precursors compete for one acceptor. Under these conditions, stereoselectivity is not due to two competing stereoisomeric transition states, as observed in the majority of stereoselective processes, but is instead the result of the two stereoisomeric intermediates56and57undergoing different chemical reactions. For brevity only the two pathways leading to the major diastereoisomers are illustrated (Scheme 22). For stereoselection to occur, the initially-formed radicals56and57must undergo either reduction or cyclisation at different rates. As long as56undergoes reduction faster and57undergoes cyclisation then the desired diastereoisomers58should be the major product. The results show that it is possible to achieve reasonable, predictable selectivities by extending the principles of the Beckwith–Houk model.Sulfoxides are attractive chiral auxiliaries but their use in diastereoselective radical reactions can be problematic. Toru has investigated the radical allylation of α-(arylsulfinyl)alkyl radicals generated by the addition oftert-butyl radicals to vinyl sulfoxides59to give products60and61(Scheme 23).33Interestingly, only the phenyl sulfoxide provided sufficient activation to allow radical addition to the alkene59. Unfortunately subsequent allylation occurred with no selectivity even in the presence of a Lewis acid. Use of electron-rich aromatic rings (Ar = Py) deactivated the alkene. When a Lewis acid was able to coordinate to both the sulfoxide and the heterocycle then not only was the alkene activated for the initial addition, but also good diastereoselectivity could be achieved. The best example used a 1-methylimidazol-2-yl ring with Zn(OTf)2.Guindon has utilised a diastereoselective radical hydrogen atom transfer process to access the challenging 2,3-anti-3,4-antipropionate motif.34The initial 3,4-antirelationship was set up by the Mukaiyama aldol reaction of a tetrasubstituted selenosilylketene acetal62(Scheme 24). Treatment of the resulting product63with tributyltin hydride in the presence of triethylborane, Hünig's base and a boron Lewis acid resulted in the formation of the desired 2,3-antiproduct64in excellent yield and selectivity (75%; ≫ 20 : 1). Remarkably, the reaction could be carried out in a one-pot procedure with excellent yields and selectivities.Sibi has continued to test the limits of diastereoselective radical additions to electron deficient alkenes. Having previously investigated stereocontrol at both the α- and β-centres, attention has turned to the γ-centre. This can be achieved by adding prochiral radicals to substituted alkenes.35Interestingly, the best diastereoselectivity between the β- and γ-centres was achieved with halogenated radicals, indicating that a subtle stereoelectronic effect could be involved. The use of lanthanide Lewis acids in the presence of achiral additives was also found to improve the selectivity. Combining all the information garnered, an elegant example utilising a chiral auxiliary was reported (Scheme 25). This promising result bodes well for the future.Garner has developed an effective chiral auxiliary for hydroxylalkyl radicals (Scheme 26).36A number of tetrahydropyran (THP) and sugar derivatives were investigated. The results indicated that the C-6 substituent was vital for good selectivity. The simple C-6-tert-butyl THP gave excellent diastereoselectivity but unfortunately resulted in only moderate isolated yields. This was overcome by forming a more robust sugar-derived auxiliary. Utilising this auxiliary allowed formation of the protected aldol product65with excellent diastereoselectivity (Scheme 26). The complementary nature of this reaction to more classical means of forming the aldol product suggests that it has great potential.Ultimately the development of enantioselective radical reactions is more attractive than that of the analogous diastereoselective processes. Sibi utilised a variety of Lewis acid-based systems to control the absolute stereochemistry in radical conjugate additions to enoates.37The best control of β-stereocentre was achieved utilising samarium triflate in the presence of the proline-derived ligand66(Scheme 27). The optimum conditions were found to be 30 mol% of the Lewis acid catalyst in the presence of the achiral additive67(95%, 84% ee). It is thought that this additive prevents the product from coordinating to the samarium and so producing a less selective complex.It is possible to control the absolute stereochemistry at the α-position by the addition of alkyl radicals to a α-methacrylate followed by enantioselective hydrogen atom transfer. In a comprehensive survey of conditions, Sibi varied the nature of the Lewis acid, the ligand and the achiral template on the methacrylate.38The optimum conditions utilised magnesium and bisoxazoline68as the Lewis acid. More interesting is the effect of the achiral template on the selectivity. The best results were obtained with 1,8-naphthosultam69(Scheme 28). It appears that the tetrahedral nature of the sulfone moiety is the key to the success of this template.Considering that one of the advantages of radical transformations is their ability to undergo tandem and cascade reactions, it is somewhat surprising that 2002 saw the first report of an enantioselective atom-transfer tandem radical cyclisation.39Although the best enantioselectivity was 84% ee, this was at the expense of chemical yield. The most promising result was the formation of 6,5-cis-70from the diene71in the presence of a stoichiometric amount of Yb(OTf)3and tridentate bisoxazoline72in 60% yield and 66% ee (Scheme 29). Impressively, two rings and four contiguous stereocentres are set up in one step. Such a reaction shows great potential for the future.Roberts has employed carbohydrate-derived thiols as catalysts for enantioselective radical-chain reactions.40Lactone73undergoes enantioselective hydrosilylation in the presence of triphenylsilane, an initiator and the appropriate thiol (Scheme 30). The thiol acts as a chiral source of hydrogen atoms and the chain-carrier. The enantiocontrol appears to be controlled by two factors: the orientation of the thiol in relation to the pyranose ring (β-glucose thiols are active whilst α-glucose thiols give no selectivity) and the orientation of the C-2 substituent (β-mannose is far more effective than β-glucose).

ISSN:0069-3030    

DOI:10.1039/b212009g

出版商:RSC    

年代:2003

数据来源: RSC

摘要:

The volumes ofAnnual Reports, Section Boffer a selective overview of advances in some aspects of organic chemistry, taken from the primary literature published over the previous year or two, with chapters written by experts in each field.This year, a number of recurring themes are evident in the various chapters, including organocatalysis and catalysis by gold. Indeed, both of these topics appear in Karl Hemming’s first contribution on heterocyclic chemistry, where other highlights include advances in new methods for the asymmetric epoxidation of α,β-unsaturated carbonyl species. Catalysis by noble metals also appears in Paul Davies’ Report on transition metals in organic synthesis, where another focus is on C–H activation and functionalization. Organocatalysis again this year has a chapter all to itself, by Ben Buckley, who comments on the enormous growth in this area over the last 10 years, and is also highlighted by Gareth Rowlands in his discussion of free-radical reactions, with a fascinating combination of photoredox chemistry with enamine catalysis.Other advances in synthetic methodology include new organic chemistry of silicon, phosphorus, sulfur, selenium, and tellurium, where Paul Taylor describes, among many other processes, the uses of organophosphorus and organosulfur species as coupling agents. Oxidation and reduction methods are covered for the first time by Simon Lewis, who has identified a number of significant new processes, for example site-selective epoxidation of polyprenols, bis(hydroxamic acid) ligands for vanadium(v)-catalysed enantioselective epoxidation, direct catalytic aziridination of styrenes with ammonia, adaptive supramolecular ‘METAMORPhos’ ligands for asymmetric alkene hydrogenation, and the use of ‘frustrated Lewis pairs’ to effect H2bond scission for imine and nitrile reduction. Steven Nolan and co-authors provide a further overview of the ever-growing interest in the use ofN-heterocyclic carbenes (NHCs), focusing on transition metal-mediated transformations.Biological catalysis in synthetic organic chemistry is again ably addressed by Gideon Grogan, who points to notable achievements including a carboxylesterase with specificity for tertiary alcohols that has been engineered for inverted enantioselectivity, a ketoreductase that has been used in combination with palladium catalysis to perform a two-step Suzuki-coupling/carbonyl reduction, and a coupling ofin silicoenzyme design with directed evolution techniques to deliver an enzyme which catalyses a reaction not known in Nature, the Kemp elimination, with far-reaching implications for the possible design of enzymatic catalysts in the future.Highlights of total syntheses of complex natural products are discussed by Yvette Jackson and Nadale Downer-Riley; their Report is organised according to the class of the natural products, and concentrates on the key strategic steps of each synthesis. Bob Hill focuses on marine natural products with unusual structures or interesting biological activities, and his chapter is organised by biogenetic origin, from polyketides, terpenoids, alkaloids and peptides; Scott Dalgarno, in his first contribution for Annual Reports, provides a commentary on significant developments in supramolecular chemistry under three headings covering molecular recognition, structure and assembly, and functional systems.Bioinspired organic chemistry is considered for the first time by Salvador Tomas, who describes in four sections a selection of contributions from researchers who, using organic chemistry tools and inspiration from biomolecular systems, have developed new techniques, approaches and applications. The first three sections deal with progress in organic chemistry inspired by the major classes of biomolecules. The fourth section focuses on recent developments in organic chemistry inspired by the complexity of biomolecular systems, and notes that ‘more than a decade after the first artificial self-replicators were described, a discipline that deals with complexity in artificial chemical systems is beginning to take shape, under the name of Systems Chemistry.’Stereochemistry and has long been integral to organic synthesis. But, the burgeoning number, and increasing complexity, of enantioselective processes has seen enantioselectivity develop into a research area of its own, particularly where catalysis is involved. Fundamental to understanding the often complex and esoteric influences in these reactions is the study of mechanism. We welcome a new author, Ai-Lan Lee, who reviews in detail some recent highlights. Her review concentrates on asymmetric Heck couplings, alkene metathesis and interlocked architectures. The subtle influences involved in Heck couplings are shown by a reaction where presence of an additional ‘spectator’ achiral ligand actually improves it by preventing catalyst precipitation. As for interlocked architectures a fascinating report of the ‘freezing’ of a dynamically racemising chiral rotaxane into uneven amounts ofRandSenantiomers is described.The mantle of covering reactivity in organised assemblies has been taken up by Niklaas Buurma and Lavinia Onel. They report papers covering “chameleon-type” behaviour of zwitterionic micelles, enzyme kinetics at the micellar interface, “DNA-based approaches to reactivity”, and a kinetic method for assessing antioxidant distribution between the various regions of an emulsion. Nanoparticle catalysis is also covered, including a report of a non-linear Arrhenius plot for hydrogenation by palladium nanoparticles within “hairy” silica.Developments in the field of computational organic chemistry continue apace. Steven Bachrach again provides a perceptive report, in which, for example, caution is urged in the use of composite methods. As last year, he has presented some intriguing papers. In one, the classic SN2 reaction is revealed in new complexity, while in another, a ‘tortuous’ inverted adamantane is presented!In NMR spectroscopy, Mark Edgar has written a report that helps the organic chemist make sense of this field in the face of the ever-rising tide of acronyms. Concentrating on the topics of speed and sensitivity, the solid-state, simulation and calculation, Mark shows how organic NMR spectroscopy has progressed far beyond the simple proton spectrum; an example is the ability of solid-state NMR to probe a35Cl counterion and to differentiate different polymorphs.Douglas Neckers has provided a comprehensive report ranging from ‘traditional’ photophysics, photochemistry and spectroscopy, through photochemistry related to DNA, to solar cells. Among the many articles reported is one describing a molecular folding screen that folds into a zigzag by photocycloaddition, and opens thermally. Another outlines the use of stilbene photoisomerisation to power a molecular muscle.The traditional three explicit mechanisms are again represented this year. In covering pericyclic reaction mechanisms, Dean Tantillo and Jeehiun Lee present many examples from the 2008 literature including retrocycloadditions of pyrollidinofullerenes, multidimensional tunnelling in 1,5-H shifts, and the lithium-catalysed Claisen rearrangement, to name but a few. Further examples are reported of bispericyclic reactions, these are reactions where the path bifurcates to alternative products after a single transition state. Polar mechanisms are reported by AnneMarie O’Donoghue and Chukwuemeka Isanbor. A phosphine-catalysed (3 + 2) cycloaddition of allene to alkeneviaa 1,3-dipole, but with several polar steps, and a study of the effect of metal ions on the hydrolysis of phosphate esters, are a couple of examples from many. Jim Tanko provides, as usual, an excellent report on radical mechanisms. The latest developments in substitution and atom transfer, addition/cyclisation, fragmentation and cascading rearrangement processes are considered. His report concludes with remarkable evidence that a flavin-tryptophane radical pair may provide the basis for a “chemical compass” used by birds for navigation.

ISSN:0069-3030    

DOI:10.1039/b914362a

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

A number of reviews have been published on various aspects of radical reactions in organic synthesis, most are referenced at the appropriate section in the Report, with the exception of a review on radical conjugate additions1and one on the formation of five- and six-membered heterocycles,2which do not fit elsewhere.

ISSN:0069-3030    

DOI:10.1039/b515104j

出版商:RSC    

年代:2006

数据来源: RSC

摘要:

HighlightsThis report is intended to offer an illustrative overview of the current state of free-radical reactions in organic synthesis. The author has emphasised reactions that are of interest to the practising synthetic chemist. The layout of the review is in keeping with the style of previous reviews by the author.1,2The highlights this year include the successful addition of nucleophilic radicals to carboxylic acid derivatives,3–7the use of organic chiral additives to induce enantioselectivity8–11and, most significantly, the development of transition metal catalysts for the generation of alkyl radicals from simple halides.12–19The latter research is likely to have a dramatic impact on radical chemistry in coming years.

ISSN:0069-3030    

DOI:10.1039/b614415m

出版商:RSC    

年代:2007

数据来源: RSC

摘要:

IntroductionThe use of radicals in organic synthesis continues to grow due to the myriad of advantages they offer over ‘traditional’ ionic reagents. This report collates a number of pertinent examples that highlight the synthetic potential of radical chemistry and is not a comprehensive overview. The report is organised in keeping with previous reviews by the author.1–4The popularity of radical chemistry is highlighted by the publication of an issue ofTetrahedrondedicated to radicals,5and a number of specialist reviews on the use of organocatalysis in enantioselective radical chemistry,6the applications of TEMPO in synthesis,7samarium(ii) iodide in asymmetric synthesis,8the effect of additives on samarium(ii) iodide,9the use of tris(trimethylsilyl)silane10and the chemistry ofN-,11P-12andS-centred radicals.13

ISSN:0069-3030    

DOI:10.1039/b822047f

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

1Oxidation reactionsMany of the transformations covered here involve oxidation of alkenes. A recent review assesses and compares several methods for enantioselective alkene oxidation, including epoxidation, dihydroxylation and aminohydroxylation.81.1Alkene epoxidationMethyl (trioxo)rhenium (MTO) has been studied extensively in recent years as a catalyst for alkene epoxidation by various oxidants, including hydrogen peroxide,9which is attractive since the by-product is water.10Use of hexafluoroisopropanol as solvent has been reported to allow efficient alkene epoxidation with 30% H2O2in the presence of low MTO loadings (0.1 mol%).11Polymer-supported variants of the MTO catalyst (poly-4-vinylpyridine/polystyrene) as recyclable epoxidation catalysts have been described.12In a non-metal mediated alternative, the fluoroketone1(1–5 mol%) is reported to effect alkene epoxidation using Oxone®when hexafluoroisopropanol (HFIP) is used as solvent.13H2O2in HFIP–CH3CN can also be used as co-oxidant, but the reaction is less efficient. Urea- H2O2adduct in HFIP has also been studied, and reactive alkenes are epoxidised without the need for a ketone catalyst.14Catalytic asymmetric epoxidation of alkenes continues to be intensively studied. In the landmark Sharpless asymmetric epoxidation of allylic alcohols mediated by Ti(OPr)4–diethyl tartrate, the use of a tertiary furyl hydroperoxide as co-oxidant which can be recycled has been reported.15Williams has studied the extension of his interesting concept of “catalytic electronic activation” to Sharpless epoxidation.16The idea was that reversible hydrocyanation of an enal would lead to an allylic cyanohydrin which would undergo Sharpless kinetic resolution, followed by regeneration of the aldehyde (Scheme 1). The process would therefore effect indirect asymmetric epoxidation of α,β-unsaturated aldehydes. In the event, the authors were able to demonstrate the first Sharpless kinetic resolution of allylic cyanohydrins as well as conditions for the reversible hydrocyanation of enals. However, the higher temperatures needed for the hydrocyanation resulted in disappointing selectivities for the kinetic resolution. The complete catalytic cycle (i.e.in situregeneration of the aldehyde) remains to be accomplished.For so-called “unfunctionalised” alkenes, chiral Mn(salen) complexes as pioneered by Jacobsen and Katsuki are the best known reagents, and interest in these systems is unabated.17,18Several groups have reported attachment of salen ligands to solid supports.19–24Novel chiral Mn(iii)salen catalysts with built-in phase-transfer capabilities have been described.25Of particular interest are studies on the mechanism of the Mn(salen) catalysed epoxidation, and two substantial contributions have appeared. The fact that the stereospecificity of the epoxidation ofcis-stilbenes (i.e. ratios ofcis/transepoxide that are obtained) varies with the co-oxidant and counterion has led Roschmann and co-workers to put forward an explanation based on a bifurcation step in the catalytic cycle.26In this model, reaction of the Mn(iii) catalyst with the oxygen donor leads to formation of an adduct Mn(iii)OLG (LG = leaving group) as well as the established Mn(v)(oxo) intermediate. The latter epoxidises olefins through a stepwise, non-stereospecific process, while the former acts as a Lewis-acid activated epoxidant, effecting concerted, stereospecific epoxidation. Based on the observedcis/transepoxide ratios, the authors suggest that PhIO, C6F5IO, Bu4NIO4and O3afford predominantly the Mn(v)(oxo) species, leading to extensive loss of stereospecificity; while Bu4NHSO5, NaOCl and dimethyl dioxirane result largely in concerted epoxidationviaMn(iii)OLG. A Hammett study by Linde and co-workers also supports the operation of two separate reaction pathways.27Cr(salen) complexes can give complementary substrate scope to their Mn counterparts—for example, they afford good selectivity forE-alkenes, which generally give poor ee with Mn(salen) catalysts. Additionally, and, again in contrast to the Mn(oxo) species, the Cr(v)&z.dbd;O oxidants can be isolated and employed in stoichiometric epoxidations, thus allowing issues of catalysis and enantioselectivity to be separated. Gilheany and co-workers have reported the effect of added phosphoryl ligands on this process.28Triarylphosphine additives were most effective in increasing enantioselectivity, with a ceiling effect being observed in that the effect of additive was least significant with the more enantioselective salen ligands. Up to 93% ee was obtained for epoxidation ofE-β-methylstyrene.Highly promising results continue to emerge from the study of chiral ketones as epoxidation catalysts,viadioxirane intermediates, usually with Oxone®as the stoichiometric oxidant. Competing Baeyer–Villiger reaction of the ketone generally means that high catalyst loadings are required. Armstrong has reported further details of the use of the fluorotropinone2as catalyst; this compound is stable and so can be used in relatively low loadings.29Up to 83% ee is obtained at room temperature for epoxidation ofE-1,2-disubstituted and trisubstituted aromatic alkenes. Roberts has reported the preparation and testing of some 2-substituted-2,4-dimethyloxabicyclo[3.2.1]octanones, including the fluoroketone3.30The methyl substituents generally lower the catalyst reactivity. Denmark has reported full details of the use of the fluorotropinone4, as well as the biaryl difluoroketone5.31This ketone gives very good enantioselectivity for the epoxidation of some substrates (94% ee forE-stilbene), but its synthesis is more lengthy. Behar screened several fluorinated biaryl ketones, with the best being6(up to 86% ee for epoxidation of β-methylstyrene, but at −15 °C).32Shing described a series ofd-glucose-derived ulose catalysts, with the best being7, which affordedtrans-stilbene oxide of up to 71% ee.33Tomioka has developed the novel chiral ketone8and itsC2-symmetric analogue9, which epoxidisesE-stilbene with up to 64% ee, and gives 82% ee for epoxidation of 1-phenylcyclohexene.34In general, the aforementioned ketone catalysts work best fortrans- and disubstituted alkenes. Asymmetric epoxidation of terminal alkenes is still generally an unsolved problem. In continuation of his outstanding results with chiral ketone catalysis, Shi has recently described the novel ketone10which affords very promising results (Scheme 2).1This catalyst, which is prepared in 9 steps fromd-glucose, also gives good results for somecis-alkenes. Shi has also reported another new ketone catalyst, diacetate11, which effects highly enantioselective epoxidation of α,β-unsaturated esters (Scheme 3).35Good enantioselectivities have also been reported for the epoxidation of cinnamic acid derivatives with dioxiranes derived from keto bile acids.36A related non-metal mediated epoxidation system employs iminium salts as catalysts, which are convertedin situby Oxone®to oxaziridinium salts. Page has described two novel chiral dibenzazepinium catalysts12and13.37Relative to the six-membered ring iminium salt14previously reported by Page, these compounds show greater reactivity. Iminium salt12gives lower ee than the other catalysts. The best ee obtained for13(60% ee with 1-phenylcyclohexene) is similar to that with14(59% with phenylstilbene), but the selectivity pattern is different. In this iminium-catalysed Oxone®epoxidation system, Lacour has reported that the use of the interesting TRISPHAT counteranion15he has developed, in the presence of 18-crown-6, allows the use of a two-phase CH2Cl2–H2O solvent system which can afford higher enantioselectivities than the usual homogeneous CH3CN–H2O conditions.38In the best case, using Page's iminium cation13with counteranion15, epoxidation of 1-phenyldihydronaphthalene increased from 41 to 76% ee using the new solvent system.Asymmetric variants of nucleophilic epoxidation reactions are also making excellent progress. Roberts has reviewed the use of (polyamino)acids for the epoxidation of α,β-unsaturated ketones.39This approach has been used for the epoxidation of chalcone in a continuously operated membrane reactor.40Asymmetric phase transfer catalysis is another important method.41In an interesting variant of this, Lygo has described a double oxidation process in which conversion of an allylic alcohol substrate to an enone is combined with asymmetric epoxidation using the modified cinchona alkaloid phase transfer catalysts he has developed (Scheme 4).42Since the starting enones are often preparedviathe allylic alcohols, this procedure saves one synthetic step.1.2Alkene dihydroxylationAlkene dihydroxylation (AD) mediated by osmium tetroxide is one of the most reliable and general organic transformations. The reaction is given added importance by the success and generality of the Sharpless asymmetric variant. Certain substrates,e.g. electron-poor or hindered alkenes, sometimes exhibit poor turnover and/or enantioselectivities in catalytic dihydroxylations. By employing a high-throughput screening protocol, Sharpless has evaluated over 500 additives in Os-catalysed dihydroxylation withN-methylmorpholine-N-oxide (NMO) and has discovered that electron-poor alkenes react much more efficiently in acidic media.43Citric acid is the additive of choice, leading to simple practical procedure where mixing of reagents intBuOH–H2O is often followed simply by filtration of the reaction product (Scheme 5). A mechanistic rationale is presented in terms of the “two-cycle” catalytic mechanism (Scheme 6).44Generally, the second cycle is considered deleterious to enantioselectivity in the AD since the chiral ligand is not involved. Indeed, the conventional ferricyanidetBuOH–H2O co-oxidant system was developed to remove this second cycle. Lower ee is often obtained using the UpjohnN-methylmorpholine-N-oxide co-oxidant since the second cycle operates in a homogeneous acetone–water solvent system. Recently, however, Sharpless has started to explore the possibility of exploiting the second cycle for asymmetric catalysis by employing chiral ligands that take the place of one of the diol ligands in the intermediate16and remain attached to the osmium species throughout the process, thus rendering the second cycle enantioselective. Promising results have been obtained withN-tosyl-1,2-amino alcohol ligands (Scheme 7).45Recent trends over the last few years in studies of the Sharpless AD have included the investigation of more environmentally friendly co-oxidant systems, including molecular oxygen. From an industrial viewpoint, the high cost of the osmium catalyst and chiral ligand as well as the toxicity and volatility of OsO4are obstacles to large-scale application. Several approaches are currently under investigation to allow easier recycling of osmium and/or ligand. Zhang has reported a novel modified ligand17which is soluble in thetBuOH–H2O solvent system usually used for the Sharpless AD reaction, but which can be recovered by extraction with CH2Cl2followed by precipitation with ether.46This ligand can be employed in lower loadings than polymer-supported variants reported previously. Immobilisation of osmium is also an important goal. A detailed study of recoverable catalysts based on OsO42−on ion exchange resins has been reported.47The current interest in the use of ionic liquids as reaction solvents is reflected by reports from several groups of their use in osmium-catalysed dihydroxylation reactions. The diol products can be extracted with an immiscible organic solvent, leaving the osmium reagent in the ionic liquid layer, which can be re-used. Two groups reported this concept for non-asymmetric dihydroxylation using the Upjohn co-oxidant system (N-methylmorpholine-N-oxide, NMO).48,49Interestingly, Yao observed that the presence of DMAP was needed to ensure “anchoring” of the OsO4in the ionic liquid [[bmim]PF6] (bmim = 1-butyl-3-methylimidazolium).49A further two reports have successfully accomplished Sharpless asymmetric dihydroxylation in ionic liquids. Afonso employed K2OsO2(OH)4and ferricyanide co-oxidant in [bmim]PF6and water, with or withouttBuOH.50Song also used [bmim][PF6], but studied the Upjohn NMO process and found that leaching of the catalyst system out of the ionic layer could be avoided by using 1,4-bis(9-O-quininyl)phthalazine [(QN)2PHAL] as ligands rather than the usual dihydroquininyl (DQN) series.51Presumably the alkenes in the (QN)-ligands undergo initial dihydroxylation.Donohoe's work on directed dihydroxylationsyn-to hydroxyl groups using OsO4with diamine ligands [N,N,N′,N′-tetramethylethylenediamine (TMEDA)] has solved a long-standing problem, allowing complementary stereocontrol to that usually observed (Scheme 8). An account of the development of this work has recently appeared,52along with a full paper on the directed dihydroxylation of cyclic allylic alcohols and trichloroacetamides.53While osmium catalysis is by far the most widely studied, there are several interesting recent reports of alternative metals for alkene dihydroxylation. Que has continued his studies on non-heme iron oxidation catalysts.54Hage and Feringa have observed diol formation (in competition with epoxidation) in a Mn-based system with H2O2as co-oxidant.55Brown has reported an alternative to the Sharpless AD reaction which uses stoichiometric permanganate in the presence of a chiral phase-transfer reagent (18).56Good enantioselectivities were obtained for dihydroxylation of enones (Scheme 9).1.3Alkene aminohydroxylationcis-Aminohydroxylation of alkenes, involving osmium catalysis in the presence of a nitrogen source, is a powerful approach to amino alcohol synthesis. It is fair to say, however, that this process has yet to reach the practicality of the closely related dihydroxylation reaction, due to problems with regiocontrol and competing diol formation. The Sharpless asymmetric aminohydroxylation has been thoroughly reviewed very recently.57Sharpless has studied the use of ligands that promote “second cycle” reaction, as discussed above for dihydroxylation, in the aminohydroxylation process.45Ojima has studied the regiochemistry of aminohydroxylation of several protected 4-hydroxy-2-butenoates and has put forward a model based on the interaction of the substrate with the chiral ligand's binding pocket.58,59In an interesting approach to regiocontrol, Donohoe has developed an intramolecular aminohydroxylation of allylic carbamates and has now applied this to cyclic allylic carbamates (Scheme 10).60The reaction works for five membered rings (as long as the alkene is exocyclic), as well as seven- and eight-membered.1.4Alcohol oxidationAs one of the most widely employed reactions in synthesis, there is currently tremendous interest in “clean” alcohol oxidation using environmentally friendly reagents and reaction media.61The Swern reaction employing DMSO activated by oxalyl chloride is one of the most popular oxidation methods, particularly for complex substrates, and an odourless version using dodecyl methyl sulfoxide has been described.62Another oxidant that has proved its worth in complex molecular environments is TPAP (tetra-N-propylammonium perruthenate), which can be employed catalytically with, for example, NMO as co-oxidant. The groups of Ley63and Welton64have independently described catalyst recovery by use of tetralkylammonium salts or room-temperature ionic liquids. Sheldon has reported a two-phase [methyltert-butyl ether (MTBE)–H2O], buffered (pH 8.5) catalytic co-oxidant system for TPAP with NaOCl, from which the catalyst is recoverable.65A buffered Ru–NaOCl system also effects α-oxidation of ethers to esters.66Molecular oxygen is a particularly attractive oxidant from an environmental viewpoint.61In 2001, Sigman67and Stoltz68independently reported a Pd-catalysed asymmetric aerobic oxidation of secondary alcohols in the presence of sparteine, allowing kinetic resolution. Further mechanistic studies have appeared, indicating that sparteine plays the roles both of ligand on Pd and base.69Replacement of sparteine with triethylamine allows (non-asymmetric) alcohol oxidation to take place at room temperature with 3 mol% Pd(OAc)2and oxygen.70Cinnamyl alcohol does not work well; this is believed to be because the product α,β-unsaturated carbonyl compound undergoes coordination to Pd. In contrast, another interesting aerobic oxidation system that has appeared recently offers an alternative to manganese dioxide, the standard reagent for selective allylic oxidation (Scheme 11). This chemistry involves an Os–Cu–co-catalyst system.71Despite the cost of Os, the catalytic nature means that it is competitive with the use of stoichiometric MnO2. From a practical viewpoint, the fact that the reactions work at ambient temperatures and atmospheric pressure is highly attractive. Air can be used in place of oxygen as long as it is bubbled through the reaction mixture. Sulfide and acetal functional groups are tolerated.IBX19, the synthetic precursor to the popular Dess–Martin reagent, is receiving increasing attention for alcohol oxidation. One perceived limitation has been the need to use DMSO as reaction solvent in order to dissolve the IBX. Finney has developed a practical protocol for the use of IBX in EtOAc or dichloroethane as solvent.72The trick is to heat the reaction mixture to 80 °C, at which temperature the reagent dissolves. On cooling, the reduced form of IBX precipitates out and can be removed by filtration. The reaction works for conversion of a range of primary and secondary alcohols to aldehydes and ketones respectively; exceptions noted are benzyl alcohol, which is converted to benzoic acid, and Fmoc-phenylglycinol. These are isolated problem substrates, however, since oxidations of other benzylic alcohols stopped at the aldehyde stage, and Fmoc-aminoethanol was oxidised cleanly (Scheme 12).1.5Dehydrogenation of carbonyl compoundsFollowing the discovery of novel reactivity modes during total synthesis programmes, Nicolaou and co-workers have extensively exploited IBX19as a reagent in organic synthesis. One important application is the dehydrogenation of carbonyl compounds, and a comprehensive full paper on this chemistry has appeared, containing a wealth of synthetic and mechanistic detail.2These reactions are believed to proceedviaSET mechanisms. Selected examples are shown inSchemes 13–15. Cycloheptanone20can be converted to either the mono- (21) or bisenone (22) depending on the number of equivalents of IBX employed and the reaction temperature (Scheme 13). Indeed, cycloheptanol may be used as starting material instead, since IBX will oxidise it to the ketone. The reaction tolerates a wide range of functional groups, including acetates, methoxy groups and primary nitriles. Other notable examples include the successful dehydrogenation of23, with an alkene five carbon atoms away (Scheme 14), and the amino acid derivative24(Scheme 15).Nicolaou has discovered some interesting ligand acceleration effects in this reaction. In particular, complexation of IBX with 4-methoxypyridine-N-oxide (MPO) results in the new reagent25(Scheme 16) which is sufficiently reactive to effect dehydrogenation of carbonyl compounds at room temperature.73Other oxidation processes such as benzylic oxidation (vide infra) do not compete at this temperature, and reactive or volatile aldehydes can now be employed. As a further example of the increased substrate scope, the first example of a substrate containing an alkylamine was achieved (Scheme 17). In a complementary study, the same workers have also shown that IBX and IBX·MPO will also effect dehydrogenation of silyl enol ethers to enones.74Nicolaou has begun to explore less expensive variants of IBX,i.e. reagents lacking the aromatic backbone. The iodine complexes26and27derived from DMSO and iodic acid or iodine pentoxide, respectively (Scheme 18), were found to be mild and effective oxidants for dehydrogenation of aldehydes and ketones, with the former generally preferred due to its lower cost. Cyclohexene was added as co-solvent in order to scavenge any iodine by-product. The scope of the reaction was found to be similar to the IBX reaction, with the indanone28performing better with the new reagent (Scheme 19). Additionally, alcohols are inert to26and27, so carbonyl dehydrogenation may be performed in their presence.1.6Benzylic and allylic oxidationAs a further aspect of the SET-chemistry mediated by IBX, introduced above, full details have appeared of the use of this reagent for benzylic oxidation (Scheme 20).2In contrast to conventional oxidants, the presence of alkenes,N-heterocycles, amides and aldehydes does not interfere. The reaction does not proceed with electron-poor substrates such asp-cyano- andp-acetyltoluene, however.The asymmetric variant of the Kharasch–Sosnovsky allylic oxidation reaction, involving the use of Cu-catalysis, chiral bisoxazoline ligands and peroxy esters, was reported simultaneously by several groups in the early 1990s. The area has been reviewed recently by Andrus and Lashley.75The Andrus group has also reported that higher enantioselectivities can be obtained iftert-butylp-nitrobenzoate is used. Screening of a panel of bisoxazolines allowed highly enantioselective allylic oxidation of cyclopentene, cyclohexene, cycloheptene and cyclooctadiene to be accomplished. High ee (94–99%) was obtained, but reaction times are still long (often several days), and yields are often low.76

ISSN:0069-3030    

DOI:10.1039/b212010k

出版商:RSC    

年代:2003

数据来源: RSC

摘要:

1Oxidation reactions1.1Alkene epoxidationDevelopment of “clean” methods for alkene epoxidation using hydrogen peroxide as co-oxidant continues to be a highly active area. Several metal-catalysed methods1–5as well as a kinetic study of activation of hydrogen peroxide in 1,1,1,3,3,3-hexafluoro-2-propanol6have appeared. Stack has studied the influence of ligand and pH on Mn-mediated epoxidation of terminal alkenes with peracetic acid.7For metal-catalysed oxygen transfer reactions, crucial insights into reactivity have emerged from computational studies and recent results on epoxidation by inorganic peroxides have been summarised by Deubel.8Amongst methods for the key asymmetric alkene epoxidation process, Jacobsen/Katsuki Mn(salen) chemistry is synthetically well established, and here again the precise mechanistic details are being further illuminated by theoretical studies.9Biocatalysis is another potentially efficient approach and the use of a cell-free flavin- and NADH-dependent bacterial monooxygenase for the highly enantioselective epoxidation of styrenes in a dodecene/water emulsion has been described.10Exceptional progress continues to be registered in the development of metal-free methods for catalytic asymmetric epoxidation of unfunctionalized alkenes. Activation of Oxone (active constituent KHSO5) has provided the best results to date, and Armstrong has provided an overview of the field.11Chiral ketones (viadioxirane intermediates) continue to receive considerable attention.12Two of the most prevalent workers in the area, Shi13and Yang,14have presented summaries of their achievements. In an application of Yang's binaphthyl-based chiral ketone catalysts, Seki has provided a detailed study of the synthesis of glycidic acids by asymmetric epoxidation of cinnamic acid derivatives.15In continuing detailed structure/selectivity studies to allow rational catalyst improvement, Shi has compared the ketone1to its carbocyclic analogue2.16Carbocycle2gives higher enantioselectivities than1in the asymmetric epoxidation of styrenes (up to 93% ee). Shi suggests that the electron withdrawing oxygen in1lowers the energy of the dioxirane oxygen lone pairs, reducing their overlap with the substrate alkene's π*-orbital in the epoxidation transition state and thus reducing the preference for a spiro-TS relative to a planar one. This is important since it is suggested that the planar and spiro-arrangements lead to opposite product enantiomers. The lengthy synthesis of the more selective catalyst2(13 steps from quinic acid) is a practical disadvantage, however. Shi has also reported a study of the asymmetric epoxidation of severalcis-β-methylstyrenes catalysed byN-aryloxazolidinones3.17In the non-asymmetric dioxirane area, Toy has developed a poly(ethylene glycol)-supported trifluoroacetophenone epoxidation catalyst,18and further computational studies on the dioxirane epoxidation reaction have been performed.19Iminium salts will also promote epoxidation by Oxone,viaoxaziridinium intermediates. As well as a new non-aqueous reaction system (using the tetraphenylphosphonium salt of Oxone),20Page has reported significantly improved levels of asymmetric induction compared to earlier attempts. Catalyst4afforded 95% ee for the asymmetric epoxidation of phenylnaphthalene (Scheme 1).21The dihydroisoquinolinium core has been a commonly studied iminium motif, and Bohé has shown that its catalytic efficiency in achiral epoxidations may be improved by incorporating 7-nitro- and 3,3-dimethyl-substitution.22The aforementioned epoxidation methods are generally electrophilic in nature, and the complementary array of nucleophilic reagent systems provides the methods of choice for electron-poor alkenes (e.g.enones). Catalysis by polyleucine is a fascinating area and saw renewed interest in 2004. The original reaction system was triphasic (inorganic base and H2O2in water; substrate in organic phase; insoluble polyleucine). Geller and co-workers found that the addition of a phase-transfer catalyst (Bu4NBr) allows much faster reactions without the induction period otherwise needed for catalyst activation, and far lower quantities of base and H2O2are required.23They also investigated the effect of the method used for the preparation of polyleucine, and found that material made by high-temperature polymerization gave best results. Importantly, much lower loadings of polyleucine can now be used (0.5 mol% for chalcone epoxidation). These workers have carried out the process on 100 g scale. Roberts and co-workers built upon the finding of the beneficial effect of a phase-transfer catalyst by showing that stirring NaOH, H2O2, Bu4NHSO4and polyleucine in water/toluene followed by removal of the aqueous phase provides a biphasic gel in toluene in which the polyleucine has sequestered the peroxide. This active gel is particularly useful for base-sensitive substrates and was used to prepare epoxides5and6in good yields and excellent enantioselectivities.24Vinyl sulfones are now also viable substrates (e.g. formation of7). Further mechanistic work on the system has been performed.25This includes an interesting discussion of asymmetric amplification: studies using polyleucine derived from non-enantiopure amino acid show highly amplified epoxide enantiomeric excess and fit a mathematical model requiring the active catalyst to have five terminal homochiral residues,26as rationalized by molecular modeling studies.27Asymmetric phase-transfer catalysis is another valuable approach for enone epoxidation. The novel “dual function” catalyst8from Maruoka's group has hydroxyl groups which were incorporated to allow hydrogen bonding to the enolate intermediate, and catalyses enone epoxidation with 89–99% ee.28Interestingly, and unlike some other systems, alkyl substitution in the β-position is tolerated (Scheme 2). Lanthanum–BINOL catalysts also represent an important reagent class, and tris(trifluorophenyl)phosphine oxide has been shown to be an effective additive, allowing enone epoxidation with up to 99% ee.291.2Alkene dihydroxylationOsmium-mediated alkene dihydroxylation is an exceptionally powerful synthetic method, but the reagent's cost and toxicity are often cited as a problem. Thus there is much ongoing interest in systems that allow easy reagent separation and recycling.30The use of fluorous-phase diol ligands for osmium31is one recent example. A quaternary solvent mixture (tBuOH/MeCN/hexane/H2O) has been reported which allows homogeneous dihydroxylation, but becomes binary on addition of extra water. In the presence of dendritic ligands, osmium then partitions into the organic phase, but the diol product resides in the aqueous one, allowing separation.32A reusable “biomimetic” system has been reported consisting of a flavin andN-methylmorpholine-N-oxide immobilized in an ionic liquid that can be employed with aqueous H2O2.33Ionic liquids have also been used34to help facilitate purification and recycling in the Sharpless asymmetric dihydroxylation (AD) reaction, one of the best known and most successful methods for asymmetric synthesis. The development of modified co-oxidant systems for this process also continues, with NaClO2being a recent example.35The most commonly used ligands in Sharpless AD chemistry consist of two cinchona alkaloid units linked by a phthalazine (PHAL) spacer. Bradley has developed a new, readily accessed ligand class centred on a triazine core, which when compared to Sharpless ligands gives similar ee values fortrans-alkenes (although lower for other substitution patterns).36New synthetic applications of the Sharpless AD continue to emerge: for example, 1-silyloxy-1,3-dienes can be converted into furanose derivatives through regioselective dihydroxylation, which surprisingly occurs on the alkene furthest from the silyloxy group.37AD of arylallenes proceeds regioselectively and provides an interesting approach to α-hydroxyketones (Scheme 3).38Substrates with electron-rich aryl groups give best results. Finally, in achiral osmium-mediated dihydroxylationen routeto conformationally-locked difluorosugar analogues, Percy and co-workers noted an unexpected relative stereochemical outcome which was attributed to a possible directing effect by coordination to a ketone carbonyl.39Given the aforementioned cost and toxicity disadvantages of osmium tetroxide, the search for efficient alternative dihydroxylation reagents is an important one. Ruthenium tetroxide is one possibility, but this reagent is more usually associated with alkene cleavage. A recent computational study provides insights into why this is the case.40Last year's Report outlined studies by Plietker and co-workers on the development of modified conditions to allow RuO4-mediated dihydroxylation. The alkene cleavage products usually formed from use of this reagent were suggested to arise directly from the intermediate cyclic ruthenate ester rather thanviathe diol product, and the addition of sub-stoichiometric sulfuric acid to promote hydrolysis of the intermediate was indeed found to allow diol formation to predominate. A detailed account of the optimization, scope and limitations of this chemistry has now appeared.41Interestingly, Plietker has also shown that an added co-oxidant (Oxone) can intercept the ruthenate ester intermediate, leading to direct formation of α-hydroxyketones from alkenes (Scheme 4).42The reaction conditions have been optimized, and a non-aqueous work-up procedure developed which allows recovery of the Ru-catalyst by centrifugation or filtration. The process tolerates several common functional groups including chloride, acetate and even acetals. As shown inScheme 4, good levels of regiocontrol can be observed for non-symmetrical substrates, especially when one of the substituents is an electron withdrawing group. For cyclic alkenes, cleavage competes, but can be minimized by performing the reaction at lower temperatures. While there is not yet an asymmetric version of this ketohydroxylation, it can be used to process enantiomerically pure diols obtained from Sharpless asymmetric dihydroxylation, thus yielding enantiomerically pure α-hydroxyketones (Scheme 5).431.3Alkene aminohydroxylationAlkene aminohydroxylation is closely related to dihydroxylation, and potentially as useful. Muniz has provided an account of the chemistry of the imidoosmium(viii) compounds involved.44As with dihydroxylation, procedures to aid catalyst/ligand recovery are attracting attention, with the use of a polyethyleneglycol-bound cinchona alkaloid ligand providing a recent example.45One complication with aminohydroxylation (which is not an issue with dihydroxylation) is control of regiochemistry. Donohoe has previously demonstrated one strategy for surmounting this by developing intramolecular, “tethered” aminohydroxylation, and has advanced these studies by looking at acyclic stereocontrol in chiral allylic carbamates.46High levels ofsyn-stereoselectivity were observed, even for 1,1-disubstituted substrates where A1,2and A1,3-strain effects are often in competition (Scheme 6). Taylor has provided an application of the tethered aminohydroxylation in an approach to simplified analogues of the natural product scyphostatin.471.4Alcohol oxidationAs one of the most widely employed oxidation reactions in synthesis, conversion of alcohols to carbonyl compounds continues to attract interest, particularly in the quest for cleaner and more selective methods. The 2004 literature contains reviews on biocatalytic alcohol oxidation.48Oxidation using molecular oxygen is especially environmentally attractive, and progress in the field has also recently been reviewed.49,50Marko has further refined his copper-catalysed aerobic oxidation of primary alcohols to aldehydes mediated by dialkyl azodicarboxylates.51A catalytic aerobic system using V2O5has been described which allows selective oxidation of secondary alcohols in the presence of primary ones.52The most spectacular examples of aerobic metal-catalysed alcohol oxidation reactions in recent years have come from the independent studies of Stoltz and Sigman on Pd-catalysed kinetic resolution of secondary alcohols in the presence of sparteine. These workers have provided accounts of their work to date53,54and their most recent contributions include the use of ambient air as the stoichiometric oxidant55as well as further mechanistic studies,56models to rationalize the enantioselectivity,57,58and applications of the methodology to the synthesis of pharmaceutical building blocks.59The 2,2,6,6-tetramethylpiperidinyloxy radical (TEMPO) is by now a well established catalyst for alcohol oxidation,60particularly for selective alcohol oxidation in carbohydrates,61and an aerobic, metal free catalytic system has now been reported (Scheme 7),62as well as a further example of a polymer-supported variant of TEMPO.63Hypervalent iodine reagents are another important class of oxidant for alcohols.64IBX9is one such reagent, the chemistry of which has been extensively developed in recent years. Its uses in ionic liquids65and under solvent-free conditions66have been described. Recent alcohol oxidations to be reported using9include oxidations of lactols to lactones,67and Iwabuchi has shown that it will effect oxidative rearrangement of cyclic (5- and 6-membered ring) tertiary allylic alcohols, providing an alternative to classical chromium reagents for this enone transposition tactic.68The strategy of one-pot alcohol oxidation and subsequentin situfunctionalization of the generated carbonyl compound continues to be explored in Taylor's laboratories, with recent examples including MnO2oxidation/trapping with 1,2-diamines to give quinoxalines or dihydropyrazines,69conversion of alcohols to 1,1-dibromoalkenes70and tandem oxidation/cyclopropanation.711.5Other oxidationsWacker oxidation of alkenes is a well established transformation, and normally converts terminal alkenes to ketones. In an interesting application of Ru-chemistry, Che has described direct conversion of styrenes and aromatic 1,3-dienes to aldehydes (Scheme 8).72The process proceeds by initial epoxidation followed by rearrangement. Since the Ru-catalyst will also promote formation of ylides from diazo compounds, the oxidation can be combined with an olefination step in a one-pot procedure (Scheme 9).IBX9will effect other useful oxidations besides conversion of alcohols to carbonyl compounds. For example, it can effect aromatization through dehydrogenation,73and Nicolaou has provided a detailed account of its use for oxidation of amines and dithianes (leading to deprotection in the case of the latter functionality).74IBX will also effect α-oxidation of acetophenones.75For this type of transformation, however, the most exciting recent findings have been the use of proline as catalyst along with nitrosobenzene as oxidant, effecting α-oxidation of carbonyl compounds.76Reported earlier for aldehydes, 2004 saw this chemistry extended to ketones (Scheme 10),77,78affording products which are highly versatile synthetically. The reaction is mechanistically intriguing,79since Blackmond has shown that the reaction rate rises with time, and that there is a positive non-linear effect in ee of product relative to that of proline catalyst.80Formation of an enamine intermediate between proline and the substrate, along with hydrogen bonding between product and proline, are now believed to be involved.81Synthetic developments have included modified proline catalysts82andin situfunctionalization of the α-oxygenated aldehyde products by olefination83and allylation.84Cordova has also reported that molecular oxygen can be used in place of nitrosobenzene in these proline-catalysed α-oxidations of aldehydes, but the enantioselectivities are currently moderate.85

ISSN:0069-3030    

DOI:10.1039/b418910h

出版商:RSC    

年代:2005

数据来源: RSC

摘要:

1.Oxidation reactionsGeneral reviews on metal-catalysed aerobic oxidation1and on ruthenium-catalysed oxidations2have appeared.1.1Alkene epoxidationDevelopment of more efficient methods for alkene epoxidation, particularly using “clean” oxidation systems such as air3or H2O24continues to be a very active area. New methods for enantioselective epoxidation are a particularly interesting challenge, and a review of progress so far appeared in 2005.5The Sharpless Ti/tartrate epoxidation of allylic alcohols is an historical landmark in the field, and one of its most attractive features is the high level of confidence with which the epoxide product’s absolute configuration can be predicted. Intriguingly, Janda and co-workers have confirmed that when the tartrate is attached to poly(ethyleneglycol) monomethyl ether (MPEG), the sense of enantioselectivity can be reversed for a particular tartrate enantiomer. Remarkably, the reversal is dependent on the molecular weight of the polymer, and occurs within a relatively small molecular weight range. Thus, epoxidation ofE-2-hexenol in the presence ofl-tartrate-MPEG350gives the expected (2S, 3S)-enantiomer, butl-tartrate-MPEG750gives the (2R, 3R)-epoxide (Scheme 1). It is suggested that the predominant species in the Ti/MPEG mixture is a 2∶1 Ti∶ligand complex, as opposed to the 2∶2 Ti∶ligand complex of traditional Sharpless epoxidations.6Walsh has developed a one-pot procedure in which a vinyl zinc reagent, preparedin situfrom an alkyne, undergoes enantioselective addition to an aldehyde in the presence of a chiral ligand, leading to an allylic zinc alkoxide which is then epoxidised upon addition of Ti(OiPr)4and molecular oxygen (Scheme 2).7Products are obtained in excellent enantioselectivity and moderate diastereoselectivity. As an alternative to Ti-based systems for allylic alcohol epoxidation, Yamamoto has recently focused on V-catalysis using hydroxamic ligands. This chemistry has seen a notable advance with the use of complexes2bearing aC2-symmetrical ligand (Scheme 3).8Yamamoto points out several advantages over the Sharpless epoxidation including low catalyst loading (down to 0.2 mol%) and the possibility of using aqueoustBuOOH rather than an anhydrous solution. High enantioselectivities were observed for epoxidation of trisubstituted- andtrans-1,2-disubstituted alkenes as well as—notably—forcis-1,2-disubstituted substrates.For enantioselective epoxidation of “unfunctionalised” alkenes, the chiral Mn(salen) complexes associated with Jacobsen and Katsuki are the best known catalysts. The chemistry of Mn(salen) complexes—as well as their Cr-counterparts, which can display usefully different selectivities9—is the subject of an excellent review.10Modified11and polymer-supported12salen ligands continue to attract attention. Studies of rate and selectivity in the Mn(salen)-catalysed epoxidation of methyl-substituted styrenes have allowed analysis of several competing modes of approach of the alkene to the intermediate Mn(oxo) species,13while computational and1H NMR studies have related observed epoxide enantioselectivities to the conformation of the salen catalysts.14Katsuki has reported some interesting di-μ-oxotitanium catalysts for alkene epoxidation using hydrogen peroxide. Reaction of the corresponding salen ligand with Ti(OiPr)4leads to reduction of one of the imines through a Meerwein-Pondorff-Verley type process to give3, and the addition of water leads to assembly of4. Interestingly, the homochiral isomer (with regard to the configuration at Ti), as depicted schematically inScheme 4, is formed selectively in this case. This catalyst then effects alkene epoxidation in high ee (Scheme 4); styrene was epoxidised in 93% ee under these conditions.15Other catalysts studied recently for enantioselective alkene epoxidation using H2O2include Ru-based systems16and methyltrioxorhenium (VII) (MTO)17in the presence of chiral pyridines.18The use of chiral metalloporphyrin catalysts has been reviewed.19Amongst metal-free alternatives for asymmetric epoxidation, systems involving Oxone as co-oxidant continue to be prevalent. Shing has reported some novel arabinose-derived ketone catalysts such as5, containing a tuneable butanediacetal motif, which effect alkene epoxidation with up to 90% ee.20Shi reported catalyst6in 2002 which is resistant to Baeyer–Villiger reaction and can be used for the enantioselective epoxidation of α,β-unsaturated esters.21An efficient synthesis of6has been described (4 steps from fructose).22Shi has reported further studies of a range of ketones bearing a spirocyclic oxazolidinone in the α-position with the aim of probing the structure-enantioselectivity effects in alkene epoxidation.23The results suggest that an attractive interaction between alkene π-substituents and the oxazolidinone ring in ketones such as7is responsible for the high enantioselectivities observed in the epoxidation of conjugatedcis-alkenes. Further information regarding the reaction transition state has come from a study of kinetic resolution of trisubstituted cyclic alkenes.24Singleton has shown that experimental and calculated kinetic isotope effects for epoxidation by dioxiranes derived from chiral ketones are in good agreement, lending validity to the computational methods and providing new insights into the mode of asymmetric induction.25In particular, this study suggests that asynchronicity with regard to the formation of the two epoxide C–O bonds is a major consideration when developing transition state models.The related epoxidation system in which Oxone is activated by an iminium salt continues to show promise. A paper by Lacour summarises earlier attempts at using chiral iminium salts and provides a detailed account of some diphenylazepinium catalysts such as8with an exocyclic chiral substituent on the nitrogen.26These salts, employed with the TRISPHAT [tris(tetrachlorobenzenediolato)phosphate(v)] counterion, afford up to 80% ee for epoxidation of 1-phenylnaphthalene. Interestingly,1H NMR and CD studies suggested no obvious correlation between the ability of the exocyclic chiral substituent to control the catalyst’s chiral biaryl axis, and product epoxide ee. Having previously developed a non-aqueous oxidation system employing tetraphenylphosphonium monoperoxysulfate as co-oxidant,27Page applied these conditions along with catalyst9to effect highly asymmetric epoxidation of alkene10, allowing enantioselective synthesis of the antihypertensive agent levcromakalim12(Scheme 5).28The non-aqueous reaction conditions have also made it possible to investigate the reaction by1H NMR spectroscopy, with evidence being obtained for the proposed oxaziridinium intermediate.29In a further mechanistic contribution, Biscoe and Breslow have shown that hydrophobic effects are important in oxaziridinum epoxidations, since more hydrophobic alkenes are epoxidised faster in competition experiments in aqueous solvents.30Amines can also catalyse alkene epoxidation by Oxone. Yang has reported a detailed study using fluorinated amines which supports a dual role of the amine as Oxone activator and phase transfer catalyst, with ee’s of up to 61% being obtained.31A mechanistically distinct type of amine catalysis is demonstrated in the work of Jorgensen, who has discovered an impressive system for the asymmetric epoxidation of α-β-unsaturated aldehydes.32Here, the proline-derived catalyst13activates the enal substrate towards conjugate addition of hydrogen peroxide with formation of an intermediate iminium ion. This explains the regioselective epoxidation shown inScheme 6. Excellent enantioselectivities and high diastereoselectivities are observed fortrans-aliphatic and aromatic enals, with a slightly lower ee for a β,β-disubstituted example. Aqueous alcohol solvent mixtures can also be employed.33Amongst methods for the nucleophilic epoxidation of enones, the use of polyleucine as catalyst is one of the most mechanistically intriguing. Recent kinetic studies support the idea that the reaction proceeds by reversible addition of the chalcone substrate to a polyleucine-bound hydroperoxide.34Amongst other developments,35polyleucine has been grafted onto silica to facilitate catalyst recovery.36Another prominent method for enone epoxidation involves asymmetric phase transfer catalysis. Jew and co-workers have screened dimeric cinchona alkaloid-derived chiral quaternary ammonium salts and found that highly enantioselective epoxidation of chalcones can be achieved in the presence of surfactants, with Span 20 (sorbitan monolaurate) proving optimal.37Shibasaki has extended the utility of his Sm(BINOL)/Ph3AsO-catalysed asymmetric epoxidation of α,β-unsaturated amides by demonstratingin situopening of the epoxide product with nucleophiles (e.g.azide, phenylthiolate, cyanide).38Dynamic ligand exchange with the initial catalyst and the added nucleophile is believed to form a new catalystin situto promote the ring opening step. The scope of the epoxidation has been extended to α,β-unsaturated esters, for which an yttrium catalyst and a novel ligand14was employed (Scheme 7).39Alkyl substituents are also tolerated in the β-position, although higher catalyst loadings are required and enantioselectivities are slightly lower. A supported La(BINOL) catalyst for enone epoxidation has been developed.401.2Alkene dihydroxylationOsmium tetroxide-mediated alkene dihydroxylation and the Sharpless asymmetric variant are well established synthetic methods. The development of recyclable ligands41and osmium sources42and study of new reaction media43continue to attract much attention from the viewpoint of reducing cost and quantities of the toxic reagent. For the Sharpless AD, a computational study of the effect of chain length on enantioselectivity in the dihydroxylation of terminal alkenes has been reported, with the calculations matching the observed trends.44Muniz has shown that the presence of phenylboronic acid in the AD reaction leads to formation of the cyclic boronate ester product; this is shown to arise by electrophilic cleavage of the intermediate osmate ester rather than from functionalisation of an initially formed diol, and the process sometimes gives higher ee than the standard AD.45The development of alternative metal catalysts for alkene dihydroxylation is an important goal. Feringa has previously shown that the complex [MnIVO2(tmtacn)2]2+(tmtacn =N,N′,N″-trimethyl-1,4,7-triazacyclononane) acts as a catalyst for alkene oxidation with hydrogen peroxide, giving mixtures of diol and epoxide product. The same group has now shown that carboxylic acid additives can give improved efficiencies and selectivities, believed to be due to formation of carboxylate-bridged dimeric Mn complexes.46Interestingly, use of 2,6-dichlorobenzoic acid leads to higher selectivity for diol formation, while epoxide is the major product when salicylic acid is employed. Que’s work on Fe-catalysed systems has been another highlight in recent years. DFT calculations have provided insight into the factors balancing alkene dihydroxylationversusepoxidation by the intermediate oxidant, HO–FeV&z.dbd;O.47A new bio-inspired ligand15has been reported that allows the most efficient Fe-mediated alkene dihydroxylations to date, with hydrogen peroxide as co-oxidant.48Ruthenium chemistry, traditionally associated with alkene cleavage, continues to see further interest for controlled alkene functionalisation.49Che and co-workers have reported synthetic and kinetic studies using acis-dioxoruthenium(vi) complex that effects alkene dihydroxylation intBuOH, but cleavage when acetonitrile is used as solvent.50Plietker has reported a dihydroxylation system that is effective for relatively unreactive, electron poor alkenes, employing catalytic ruthenium trichloride and cerium trichloride along with sodium periodate.51Over the last few years, Plietker has also developed the direct conversion of alkenes to α-hydroxyketones using RuCl3as catalyst along with Oxone.52Studies on the diastereoselectivity of the process when an allylic oxygen substituent is present and on the relative rate of reactivity of various alkenes have now been described.53Finally, progress in some metal-free, indirect methods for alkene dihydroxylation has been reported. The Prevost oxidation (iodine/silver benzoate) and its Woodward modification (with addition of water) are classic methods for theanti- andsyn-1,2-dihydroxylation of alkenes, respectively. Catalytic versions have recently been described (Scheme 8) mediated by bromide ion in the presence of an oxidant.54Use of sodium periodate leads predominantly tosyn-1,2-dihydroxylation, because water is formedin situfrom acetic acid and periodate, whilst PhI(OAc)2affords largely theanti-1,2-diol. Davies has shown that epoxidation ofN,N-dibenzylcyclohex-2-ene with mCPBA in the presence of trichloroacetic acid gives thesyn-epoxyamine, presumably due to hydrogen bonding of the intermediate ammonium salt to the incoming peracid.55The resulting epoxide can then be manipulated to give either thesyn- oranti-1,2-diol.1.3Alkene aminohydroxylation and diaminationOsmium-catalysed alkene aminohydroxylation, closely related to Sharpless dihydroxylation, is potentially useful provided that the regioselectivity of the process can be controlled. Strategies such as rendering the process intramolecular by having the precursor to the nitrogen source (e.g.a sulfamate ester or sulfonamide)56in the homoallylic position have been adopted. A study of but-3-en-1-ol derivatives has shown that the 4-nitrophenyl ether can be converted selectively into either amino alcohol regioisomer by choice of spacer in the dimeric dihydroquinidine-derived ligand.57Acrylamides are poor substrates for Sharpless asymmetric aminohydroxylation in the presence of cinchona alkaloid ligands, but Muniz has shown that terminal acrylamides bearing anN-α-methylbenzyl substituent undergo aminohydroxylation using K2[OsO2(OH)4] and Chloramine-T (TsNClNa) with high regioselectivity for formation of the β-amino isomer, with a high level of diastereoselectivity.58In the asymmetric aminohydroxylation, the amino alcohol product can potentially act as a ligand for osmium, leading to the possibility of self-replication of chirality. However, a study by Muniz suggests that this is not a feasible process.59In further studies from the same group, it has been shown that carrying out aminohydroxylation under typical Sharpless conditions but with the omission of the chiral ligand can lead to the α-ketoamine, rather than the aminoalcohol, being the major reaction product (Scheme 9).60Enantiomerically enriched aminoalcohols can be converted to enantiomerically enriched α-aminoketones using similar conditions. A related observation comes from Zhu’s attempts to optimise the aminohydroxylation of cinnamate esters, in which the α,α-diaminoarylketone was observed as a by-product,61presumably arising by a second aminohydroxylation reaction on the enol form of the α-aminoketone, itself formed from the initial aminoalcohol by analogy to Muniz’s studies. Muniz has also described the first catalytic enantioselective diamination of alkenes (up to 90% ee) by using a chiral Ti(TADDOL)-based Lewis acid in conjunction with a stoichiometric osmium bisimidocomplex.62Johnston has accomplished a stereochemical outcome which is complementary to osmium-catalysed aminohydroxylation by demonstrating that treatment of unsaturated carbamates such as16with azides in the presence of triflic acid provides the anti-aminoalcohol (Scheme 10).631.4Alcohol oxidationDevelopment of aerobic alcohol oxidations continues to be of great interest. Contributions in 2005 include further studies on palladium catalysis64and the use of copper(ii) catalysis for oxidation of primary alcohols to aldehydes in ionic liquids.65Toste has described the synthesis of α-hydroxyesters of high enantiomeric purity by vanadium-catalysed oxidative kinetic resolution.66o-Iodoxybenzoic acid (IBX) has proved to be a popular oxidant in recent years, and its use in sub-stoichiometric quantities along with Oxone as co-oxidant is a notable recent advance.67A functional ionic liquid bearing a hypervalent iodine reagent for alcohol oxidation has also been reported.68In situfunctionalisation can be a valuable tactic for aldehydes that are unstable or difficult to isolate, and Taylor has provided a summary of his work on tandem MnO2alcohol oxidation/aldehyde transformations.691.5Other oxidationsNicolaou has described some interesting oxidative transformations of amine derivatives mediated by the Dess–Martin periodinane (DMP).70Thus, secondary amides are converted to imides (Scheme 11), with carbamates and benzylic positions being inert to the reaction conditions, while vinylogous amides and carbamates can be prepared by dehydrogenation (Scheme 12). DMP will also convert benzylic amines to nitriles.Higuchi has shown thatN-acyl cyclic amines are converted toN-acylaminoacids by oxidation with a ruthenium porphyrin complex and 2,6-dichloropyridine-N-oxide.71Secondary positions are oxidized selectively (Scheme 13), and the chemistry can be used for conversion ofN-benzoylproline to the corresponding glutamate derivative. Selective C–H oxidation continues to be a highly active area and an intriguing recent addition to the reagents that can effect this is osmium tetroxide.72An aerobic, organocatalytic Baeyer–Villiger reaction of cyclobutanones, mediated by a flavin derivative, has been reported.73Reviews have appeared on the oxidation of sulfides to sulfoxides74and the combination of asymmetric sulfoxidation and subsequent kinetic resolution has allowed highly enantioselective, vanadium-catalysed synthesis of aryl alkyl sulfoxides.75

ISSN:0069-3030    

DOI:10.1039/b515094a

出版商:RSC    

年代:2006

数据来源: RSC

摘要:

1Oxidation reactions1.1Alkene epoxidation2008 has seen the publication of reviews on aspects of epoxidation chemistry from Shi1(ketone and iminium organocatalysts), Linic2(heterogeneous catalysis), Katsuki3(Ti(salan) complexes) and Walsh4(tandem one-pot synthesis of epoxy alcohols). Oyama has also edited a book on epoxidation mechanisms.5Corey and Gnanadesikan have reported a strategy for the site-selective epoxidation of polyprenols that utilises silyl ether-linked aryl peracids to effect intramolecular epoxidation.6The method uses specific aryl motifs that may be varied to effect epoxidation of differing polyprenol double bonds (Scheme 1).The reactions are run at high dilution (0.5 mM) to minimise intermolecular oxygen transfer with respect to the desired intramolecular process. Corey and Gnanadesikan report achieving 92% selectivity for the Δ14olefin in a pentaprenol, or 89% selectivity for the Δ18olefin in a hexaprenol when employing a biaryl peracid.2008 has seen several advances in organocatalytic asymmetric alkene epoxidation. Deng and co-workers have reported a catalytic asymmetric epoxidation of α,β-unsaturated ketones, employing a cinchona alkaloid-derived catalyst forin situiminium formation.7Significantly, reaction conditions have been optimised such that a simple change in reaction temperature is sufficient to alter the course of the reaction from epoxidation to peroxidation; in both instances up to 97% e.e. was achievable. (Scheme 2). The List group independently and simultaneously developed an extremely similar catalytic system.8The List research group has disclosed two significant developments in the area. The first employs “asymmetric counterion-directed catalysis” (ACDC) to effect highly enantioselective epoxidations of α,β-unsaturated aldehydes.9A transient α,β-unsaturated iminium species is formed, with an axially chiral biaryl counteranion, which then undergoes nucleophilic epoxidation. Both aryl- and alkyl-substituted α,β-unsaturated aldehydes are viable substrates, with the former giving superior stereoinduction – up to 96% e.e. (Scheme 3). The second report discloses related methodology for the catalytic asymmetric epoxidation of cyclic enones,10although in this case the catalyst that is employed contains a homochiral cation in addition to the same biaryl anion. Once again, good enantioselectivity is observed, up to 99% e.e.The Lacour group have also investigated axially chiral biaryl asymmetric epoxidation catalysts and have undertaken a detailed study to identify biaryl azepinium salts that are effective catalysts, the active species being an oxaziridinium ion generatedin situwith oxone.11They have demonstrated a relationship between the biaryl dihedral angles and the extent of asymmetric transfer. The classes of structures investigated are shown inScheme 4; up to 92% e.e. has been achieved for certain trisubstituted aryl alkenes.Page and co-workers have also studied biaryl azepinium salts and have reported a new application of a catalyst with anN-substituent possessing both an α- and a β-stereocentre12(Scheme 5). Specifically, this system is able to utilise dry hydrogen peroxide (which is superior to oxone in terms of stability and solubility) for generation of the active oxaziridinium species. Optimised reaction conditions are reported for the epoxidation of phenylcyclohexene, with e.e. values up to 56% being obtained. Interestingly, the reaction is believed to involve an unusual double catalytic cycle.A joint publication from Page and Lacour examines biaryl azepines (as opposed to azepinium salts) with anN-substituent containing a hydroxyl group.13In conjunction with oxone, these act as catalysts for epoxidation of di- and tri-substituted olefins. Stereoselectivities of up to 81% e.e. are reported. Spectroscopic evidence is reported that is suggestive of the presence of iminium ions in the reaction mixture. The authors thus postulate that oxone effects oxidation of the amine catalyst to the corresponding iminium ion (viatheN-oxide) and that the catalytically active species is therefore actually an oxaziridinium ion, as per the two preceding examples (Scheme 6).Miller and co-workers have shown previously14that aspartate-containing oligopeptides can act as highly enantioselective catalysts for electrophilic alkene epoxidation (by intermediacy of the corresponding peracid). In 2008 they reported a comprehensive functional analysis of such systems, in which each amide motif was substituted in turn with an isosteric alkene in order to delineate the relative importance of H-bonding for each peptidic linkage (both intra- and intermolecular). In so doing they were able to identify the region most crucial for catalyst-substrate interaction (Scheme 7).Three reports have appeared in 2008 on the use of amino alcohols as organocatalysts to effect asymmetric epoxidation of α,β-unsaturated ketones by means of iminium formation. Zhu, Zhao and co-workers have reported the use of fluorine-containing prolinol derivatives to effect epoxidation of chalcones in up to 92% e.e. (Scheme 8).15In a similar vein, Loh and co-workers reported the use of a 2-azanorbornyl-3-methanol derivative for epoxidation of chalcones, achieving up to 88% e.e. (Scheme 8).16Finally, Lattanzi has disclosed a comparative study of numerous amino alcohols, both cyclic and acyclic, as potential catalysts for asymmetric epoxidation of chalcones; e.e. values up to 52% were obtained.17Two Japanese groups have reported uses of guanidines as asymmetric epoxidation catalysts. The Nagasawa group have reported a bifunctional hydroxylguanidine which is an effective organocatalyst for epoxidation of chalcones (Scheme 9).18Stereoselectivity up to 73% e.e. is reported. Similarly, the Terada group have reported an axially chiral biaryl guanidine for epoxidation of chalcones (Scheme 9also).19In this instance e.e. values up to 65% have been reported, with hydrogen peroxide being employed as oxidant, as opposed totert-butyl hydroperoxide in the previous case.Baceiredo and Kato have reported the use ofN-phosphonio imines as novel organocatalysts for alkene epoxidation (Scheme 10).20The catalytic activity of theN-phosphonio imine can be tuned easily by variation of theP-substituents or the imine component and they can be formedviaa facile two-step process fromN-silyl imines. 99% conversion was observed for the epoxidation of phenylcyclohexene and the authors state that development of an asymmetric variant of the reaction is underway. The approach is related to that reported by Jennings and Sepulveda-Arques, which employsN-phosphinoyloxaziridines.21Several advances have been reported in the field of dioxirane-mediated asymmetric alkene epoxidation. Shi has disclosed22a catalyst comprising a glucose-derived lactam-containing ketone, which undergoes dioxirane formationin situ. In contrast to earlier carbohydrate-derived ketone catalysts, this lactam system is able to effect the epoxidation of 1,1-disubstituted olefins with good enantioselectivity. The authors propose that for such substrates the reaction proceedsviaa planar transition state (Scheme 11).The Vidal-Ferran group have reported another carbohydrate-derived catalyst as a dioxirane precursor, in this instance a ketonehydrate; its selectivity in the epoxidation of aryl alkenes has been studied.23The group has also reported a mechanistic study of epoxidation with Shi-type catalysts.24Isotopic labelling with18O was employed to probe the origins of the stereoselectivity and it was determined that the catalyst mediates the transfer of the pro-Soxygen of the transient dioxirane species to the alkene in a doubly stereoselective manner. Also published in 2008 were two theoretical studies of dioxirane-mediated alkene epoxidation. Curci, Gandolfi and co-workers undertook a study contrasting dimethyldioxirane (DMDO) with methyl(trifluoromethyl)dioxirane (TFDO).25Epoxidations mediated by these two species were modelled by DFT. Rate data, from which Hammett ρ-values were estimated, confirm the electrophilic nature of the oxidant; the enhanced electrophilicity of TFDO with respect to DMDO paralleled the cathode reduction potentials for the two dioxiranes, as measured by cyclic voltammetry. A complementary report, from Werz, examines not the effect of dioxirane substituents but that of alkene substituents26– numerous alkenes, ranging from electron-rich to electron poor, were modelled by DFT and in all cases a net charge transfer from the alkene to the dioxirane was observed, again confirming the electrophilic character of DMDO.Substrate-induced stereoselectivity in alkene epoxidation with an achiral dioxirane (DMDO) has been examined by Peczuh for two specific substrate classes. It was found that epoxidation of carbohydrate fused [13]-macrodilactones was highly diastereoselective, with good stereoinductionfrom a remote stereocentre, the carbohydrate C4 position27(Scheme 12). Also, in collaboration with Hadad, carbohydrate-based oxepine glycals have been examined.28A combination of DFT modelling and experimental results have enabled the formulation of empirical rules for predicting the favoured face of epoxidation for highly substituted cyclic enol ethers. Glycals have also been examined as substrates for stereoselective epoxidation by Gammon and Sels, who have disclosed the tandem epoxidation-hydrolysis or epoxidation-alcoholysis of numerous glycals of varying configuration.29The field of metal-catalysed alkene epoxidation has been equally active in 2008. There have been numerous reports of the use of salen ligands in conjunction with various metals. Li and co-workers have reported nonsymmetric salen ligands wherein an azacrown ether is appended to one of the Schiff base motifs, and have shown that these effect epoxidation when chelated to Mn or Co; dioxygen affinities of the complexes have also been studied.30The Liese group has reported salen ligands conjugated to poly(ethyleneglycol) fragments, which they have employed (chelated to Mn or Co) for both alkene epoxidation (achieving up to 95% e.e. for a chromene substrate) and hydrolytic kinetic resolution.31Tomaselli and co-workers have employed Jacobsen’s Mn(iii)salen catalyst with NaOCl as oxidant in aqueous media, employing a surfactant (diethyltetradecylamineN-oxide) to enable epoxidation of β-alkyl styrenes in up to 91% e.e.; the surfactant loading is low with respect to substrate.32Sun and co-workers have adopted the approach of immobilising a bis(sulfonato)(salen)Mn(iii) catalyst on silica, which they then employed in ionic liquids, with NaOCl as oxidant for the epoxidation of styrene and α-methyl styrene, claiming e.e. values up to 100%.33Immobilisation of a (salen)Mn(iii) catalyst in silica was also reported by Amarasekara and co-workers, who employed a sol-gel process.34Stereoselectivity up to 86% e.e. was observed for epoxidation of aryl alkenes, and the authors note that such enantioselectivity was superior to that observed with the non-immobilised analogue.Also in the salen area, Noceraet al.have reported further examples of “Hangman” salen complexes, in which an acid-base group is “hung” over the redox platform of the salen complex. The Nocera group have synthesised salen complexes with various dibenzofuran and dibenzopyran appendages to probe the effects of altering the spatial arrangement of the hanging group and the metal. Both groups “hung” from the salicylyl ring and from the diamine ring have been examined35(Scheme 13). The authors examined the hangman complexes’ ability to effect alkene epoxidation and H2O2disproportionation. In a separate publication, Nocera and Yang report appending a single “hanging” group to modified salen-type ligands, comprising an amide and an imine linkage36(Scheme 14). Although these complexes are derived from a homochiral diamine, when employed in the epoxidation of 1,2-dihydronaphthalene, only racemic product was isolated.Progress has also been reported in the area of reduced salen ligands. The Berkessel group have published a detailed study of a (salalen)Ti complex37(Scheme 15). Partly reduced “salalen” ligands comprise an imine and an amine linkage. The complex is able to effect epoxidation of electron-rich olefins and the authors describe their investigations into the oxidative degradation of the complex, by mass spectrometric and isotopic labelling experiments; the authors note that the analogous more highly oxidised (salen)Ti complex is catalytically inactive.Two significant reports from Katsuki concern fully-reduced “salan” ligands (comprising two amine linkages). Katsuki’s group has reported the first asymmetric epoxidation of allylic alcohols employing H2O2as oxidant.38The oxidations are effected by a dimeric Nb(salan) complex, where the ligand contains stereochemical information not only in the 1,2-diamine salan backbone but also in two axially-chiral biaryl moieties (Scheme 16). Stereoselectivity of up to 83% e.e. has been achieved for both tri- andcis,transand 1,1-disubstituted allylic alcohols.A second report from Katsuki concerns the mechanism of a previously reported asymmetric epoxidation effected with a (salan)Ti complex.39They have isolated an unusual μ-oxo-μ-η2:η2-peroxo titanium complex, which they propose acts as a reservoir of catalytically active species for the asymmetric epoxidation.Numerous reports of epoxidation effected by metal complexes with non-salen ligands also emerged in 2008. The Yamamoto group has reported a vanadium-catalysed enantioselective desymmetrisation ofmesosecondary allylic and homoallylic alcohols that employsC2-symmetric bis(hydroxamic acid) ligands in conjunction with vanadium(v) (Scheme 17).40Notably, good e.e.s are obtained even withcis-disubstituted olefins, in contrast to Sharpless Ti-tartrate systems.Brückner has also examined such desymmetrisations, employing both Ti(iv)-tartrate (Sharpless) and Zr(iv)-tartrate catalytic systems.41Sharpless conditions furnishedanti-configured monoepoxides, but when zirconium was employed, the stereocomplementarysyn-configured monoepoxides were formed instead, potentially a transformation of great synthetic utility. The authors have also studied the relationship between e.e. and reaction time and present evidence to support a scenario of e.e. enhancement with time as a result of preferential overoxidation of the minor enantiomer.Other complexes reported in 2008 for metal catalysed epoxidation include Mn(poyrphyrinato) systems disclosed by Mohajer42and Rayati,43as well as a tripodalN-capped tris(oxo)amino Fe(iii) system disclosed by Dilworth and Pascu.44Saladino and Crucianelli have used adducts derived from MeReO3and homochiral amines to effect epoxidation with urea-hydrogen peroxide as primary oxidant; e.e. values were modest, but were observed to improve when the catalysts were microencapsulated in polystyrene.45Similarly, Yamazaki employed MeReO3with 3-methylpyrazole for organic solvent-free epoxidation.46Two reports have appeared on pyridyl iron complexes. The Kwong group have employed a homochiral sexipyridine ligand to prepare a diiron complex that catalysed the hydrogen peroxide-mediated epoxidation of aryl alkenes with e.e. values up to 43% (Scheme 18).47The approach of Che and co-workers was to employ a (non-stereogenic) bis(terpyridine)iron system wherein the ligands were fused to PEG fragments to aid catalyst recovery and reuse.48The catalyst was able to epoxidise a wide variety of alkenes including both electron-rich and electron-poor systems with varying substitution patterns, enones and dienes; yields were consistently high (Scheme 19).Two reports from Beller also concern iron-based catalysts. In one, an iron catalyst system is generatedin situfrom FeCl3·6H2O, pyridine-2,6-dicarboxylic acid and substituted benzylamines.49When employed in conjunction with hydrogen peroxide, a wide variety of aliphatic and aromatic alkenes may be epoxidised in good yield; it proved possible to vary the benzylamine substituents to optimise the yield for each substrate. In the second, related report, the catalytic system is generated from FeCl3·6H2O, pyridine-2,6-dicarboxylic acid and a homochiral aminosulfonamide.50This biomimetic catalytic system, in conjunction with hydrogen peroxide, effected the epoxidation of aryl alkenes in up to 71% e.e. Mechanistic studies are detailed and a small non-linear effect is described, implying the participation of several chiral iron complexes in catalysing the reaction.A significant disclosure from Shibasaki concerns the development of a system for the catalytic epoxidation of a specific, unusual substrate class, namely α,β-unsaturated phosphine oxides.51The optimal catalyst is derived from Y(OiPr)3and an axially chiral biaryl diol, and e.e. values up to 98% have been obtained (Scheme 20).Several reports in 2008 concern ligand-free metal-catalysed alkene epoxidation. Linic has demonstrated that a silver nanowire can catalyse ethylene epoxidation by O2and has demonstrated that the Ag(100) surface facet is most effective for minimising competing C–C bond cleavage in this transformation.52Silver was also employed by Chen and co-workers for the production of a magnetically-recyclable nanocomposite effective at catalysing thetert-butyl hydroperoxide-mediated epoxidation of styrene.53Wong reports the use of Mn(ClO4)2with peracetic acid for terminal aliphatic alkene substrates54and Bhattacharyya reports the use of oxo-diperoxo-Mo(vi) complexes with hydrogen peroxide.55Some progress in the field of electrochemically-mediated epoxidation has been made in 2008. Page and Marken report the use of iminium catalysts (including that shown inScheme 5), in conjunction with electrochemically-generated oxidants, to effect asymmetric alkene epoxidation.56Their approach employs the recently developed boron-doped diamond electrode for the direct generation of peroxo intermediates from water. Electrochemically-generated persulfate affords comparable e.e. values to those obtained with commercially available persulfate as oxidant. Percarbonate also proved to be a successful electrochemically-generated oxidant; its use with iminium salts to effect alkene epoxidation has not previously been reported. Another report, from Bouet, concerns the electrochemical generation of high-valent salen-Mn-oxo intermediates for stilbene epoxidation.57Other miscellaneous, noteworthy disclosures include Chmielewski’s report of glycosyl hydroperoxides as stereoselective stoichiometric oxidants for epoxidation of enones and quinones, for which e.e. values up to 95% are observed.58Similarly, Oh has employed homochiral tertiary amineN-oxides (strychnineN-oxide, brucineN-oxide and 17-oxosparteineN-oxide) as stereoselective stoichiometric oxidants for epoxidation of chalcones, achieving e.e. values up to 82%.59Bakó has reported an asymmetric phase-transfer epoxidation of chalcone catalysed by homochiral crown ethers derived from monosaccharides, which proceeds with up to 94% e.e.60Finally, the Rablen group have reported a comprehensive DFT study of the origins of stereoselectivity in the epoxidation of carene by performic acid.611.2Alkene dihydroxylationSeveral reviews have appeared in 2008 concerning various aspects of alkene dihydroxylation, from Christie62(contrasting Os and Pd for dihydroxylation and aminohydroxylation), Haudrechy63(osmylation regioselectivity), Pitts64(Os encapsulation, microwave acceleration) and Salvador65(dihydroxylation of steroids).Osmium-mediated asymmetric dihydroxylation remains an active area of research. Branco, Crespo, Afonso and co-workers have reported an attempt to render the Sharpless AD reaction more environmentally benign by employing a water-surfactant medium.66They report comparable yields and enantioselectivities for a variety of substrates when compared to water–tert-butanol solvent systems and have demonstrated effective recovery and reuse of the active catalyst by nanofiltration. Use of environmentally benign hydrogen peroxide as terminal oxidant is also desirable and a recent development in this area is due to Richardson, who has reported oxidation ofN-methylmorpholine to theN-oxide (which in turn reoxidises the Os(vi)) by hydrogen peroxide, catalysed by carbon dioxide.67Perisamy has reported a mechanistic study relating the electronic character oftrans-stilbenes to the observed e.e. values for their dihydroxylation.68An interesting example of indole dihydroxylation in total synthesis has been disclosed by Cook, who presents a detailed mechanistic study on a substrate-controlled osmylation in the context of the total synthesis of (+)-alstonisine (Scheme 21).69Evidence is described that supports intramolecular delivery of OsO4byNb-precomplexation.Two reports concern cinchona AD ligand immobilisation. The Fenniri group have employed TentaGel-supported (DHQ)2PHAL ligands.70This permitted easy recycling and e.e. values were comparable with solution phase for some (but not all) substrates. In contrast, the Cha group have pursued copolymerisation of derivatised AD ligands with various monomers; in one instance a polymethylmethacrylate copolymer afforded good e.e. values, but activity varied for different substrates.71Two disclosures on Os-mediated dihydroxylation do not concern asymmetric induction. Lee and Lee have reported dihydroxylation catalysed by a polystyrene-imidazolium resin-supported Os complex72and Fache has reported an unexpected and potentially synthetically useful simultaneous Os-mediated dihydroxylation/tosyl group removal.73In addition to osmium-based systems, numerous reports on iron-based systems continue to appear, due to its vastly lower cost and toxicity. A significant disclosure from Que and co-workers concerns their recent attempts to develop biomimetic iron complexes for asymmetric alkene dihydroxylation.74They report three tetracoordinateC2-symmetric ligands (Scheme 22), which when complexed to Fe(ii) are able to catalyse the hydrogen peroxide-mediated dihydroxylation of alkenes with up to 97% e.e., although stereoselectivity is highly substrate-dependent, withcis-disubstituted and aryl alkenes giving markedly lower e.e. values.Three other reports also concern catalytic iron complexes inspired by non-heme Rieske dioxygenases. Gebbink has developed a bis(methylimidazolyl)propionate ligand,75Costas has employed a pyridyltriazacyclononane ligand76and Ruteledge has described a peptidomimetic pyridylcarboxylate ligand. The corresponding Fe(ii) complexes are shown inScheme 23. All are able to effect dihydroxylation of alkene substrates with varying activity and selectivity, although asymmetric induction has not yet been investigated. A DFT theoretical study of non-heme iron catalysis of alkene dihydroxylation has also been reported by Comba.77As regards other metals, Feringa has, in two reports, detailed dinuclear manganese complexes that effect alkene dihydroxylation (Scheme 24). The first concerns the mechanism of the reaction and the role played by additives.78The second concerns the use of homochiralN-protected amino acids as bridging ligands in such complexes and reports the first successful manganese-based system for catalytic asymmetric alkene dihydroxylation, albeit with modest e.e. values.79Other reports of metal-mediated alkene dihydroxylation include the use of a molybdenum acetylide by Umbarkar,80a ruthenium triazacyclononane system by Che81and methodology reported by Plietker that utilises ruthenium tetroxide as oxidant, employing a camphorsultam chiral auxiliary for substrate control of alkene dihydroxylation, proceeding in up to 99% e.e.82In the area of metal-free alkene dihydroxylation, a noteworthy disclosure from the Davies group, in the form of two reports published simultaneously, concerns the dihydroxylation of 3-aminocyclohexene andN-substituted analogues thereof.83They report a protocol that employs a peracid under strongly acidic conditions to furnish the 1,2-anti-2,3-synproduct with high diastereoselectivity. Protonation of the amino functionality is believed not only to suppressN-oxide formation, but also to ensure hydrogen bonding with the oxidant and epoxidation with high facial selectivity;trans-diaxial epoxide opening then ensues (Scheme 25).Selenium-catalysed dihydroxylation has been the subject of two reports by Santi, who details a catalytic system based on diphenyldiselenide in conjunction with stoichiometric hydrogen peroxide.84Both aryl and alkyl olefins are dihydroxylated in good yield, although bothsynandantidiols are formed, the ratio being dependent on the substrate. Interestingly, a preliminary attempt at asymmetric induction is also described, employing a diphenyldiselenide possessing anortho-substituent with an α-stereocentre (Scheme 26). An e.e. of 92% was obtained for dihydroxylation of 1-phenylcyclohexene, but both d.r. and overall yield were modest.1.3Alkene aminohydroxylationAn important disclosure in 2008 came from the Yoon group, who gave a full report on their development of a widely-applicable copper-catalysed aminohydroxylation reaction (Scheme 27).85The reaction employsN-sulfonyloxaziridines, more commonly associated with epoxidation and other oxygen transfer reactions; a mechanistic rationale is given for the catalyst-induced alternative reaction pathway observed in this instance. The conditions have been optimised for styrenes and 1,3-dienes, with excellent regioselectivity being observed for many dienes. The oxazolidine product may be ring-opened to the corresponding amino alcohol under acidic conditions and several useful further transformations are demonstrated. In a separate disclosure, the Yoon group have shown that a different transition metal catalyst can afford the isomeric isoxazolidine products.86The McLeod group have reported their studies on the regioselectivity of Sharpless asymmetric aminohydroxylation of various functionalised pent-2-enoic esters, which are precursors to various aminosugars.87They offer a rationale for the inversion of regiochemistry seen for these substrates upon switching from phthalazine (PHAL) to anthraquinone (AQN) ligands. The Davies group have previously developed methodology for the synthesis ofanti-α-hydroxy-β-amino esters by a two-step aminohydroxylation of the corresponding acrylates. In 2008 they used this methodology in the total syntheses of xestoaminol C, sphinganine and sphingosine.881.4Alkene diaminationSigman has recently reviewed palladium-catalysed alkene difunctionalisation, including alkene diamination.89Both the Shi and Muñiz groups have been very active in this area in 2008. The Shi group have continued to develop their methodology employing di-tert-butyldiaziridinone and have reported the catalytic asymmetric allylic and homoallylic diamination of terminal olefins (Scheme 28).90Cleavage of the imidazolidinone ring in the products may be effected under strongly acidic conditions, affording the corresponding vicinal diamines. Stereoinduction is good, with e.e. values generally >90% and in one instance 99% e.e. was obtained for a bifunctional substrate. In related work, the group have effected the diamination of dienes, employing both a Pd(0) catalyst91(up to 91% e.e.) and a Cu(i) catalyst92(up to 74% e.e.). The two catalytic systems enjoy a nice degree of complementarity in terms of regioselectivity, with the copper catalyst favouring diamination of the less substituted alkene and the palladium catalyst favouring the more substituted alkene (Scheme 29). Cycloguanidation by this methodology has also been reported.93The Shi group have also published a preliminary communication concerning diamination withN,N-di-tert-butylthiadiaziridine-1,1-dioxide which, proceedsviaa distinct mechanism to that which operates for di-tert-butyldiaziridinone; the regiochemical outcome is also different (Scheme 30).94The mechanism is discussed and the authors state that an asymmetric variant of this transformation is currently under investigation.The Muñiz group have reported several advances in their development of methodology for intramolecular diamination with tetheredN-sulfonylureas. The key transformation is outlined inScheme 31, and Muñiz has published an in-depth study95with PhI(OAc)2as oxidant, employing NMR titration, kinetic and competition experiments and isotopic labelling for mechanistic elucidation; evidence for Pd(iv) intermediates is presented.In a separate publication, Muñiz and Barluenga examine the importance of halogenated intermediates in the case of other stoichiometric oxidant(s), namely copper(ii) bromide. Also, the transformation may be effected with a source of electrophilic iodine; in this (palladium-free) case, a distinct mechanism involving an iodonium intermediate is operative.96Also in 2008, Muñiz has expanded the scope of the transformation to include diamination of acrylate esters97and also to effect cycloguanidation98(Scheme 32).Several other reports merit attention: Pan and Li have reported an unusual catalytic diamination of chalcones usingN,N-dibromo-p-toluenesulfonamide as electrophile and nitriles as nucleophiles.99The reaction employs copper(i)iodide and triphenylphosphine as catalyst, and acetonitrile as both solvent and nucleophile (Scheme 33).Lloyd-Jones and Booker-Milburn have reported previously on palladium(ii)-catalysed alkene diamination, and in 2008 have extended this methodology to encompass oxidative alkene carboamination as well.100Finally, M. Li and co-workers have reported a DFT theoretical study on the palladium(ii)-catalysed intermolecular 1,2-diamination of conjugated dienes.1011.5Alkene aziridination2008 has seen the publication of a review on the aziridination of α,β-unsaturated enones.102A significant development in this specific area was also communicated by Melchiorre and co-workers, who have described an organocatalytic asymmetric aziridination of α,β-unsaturated enones that has wide applicability and gives good stereoselectivity.103The transformation employs an unusual primary ammonium salt catalyst possessing stereocentres in both the cation and anion (Scheme 34). Good to excellent e.e. values (up to 99%) are achieved, although selectivity can drop with an aryl substituent on the enone β position.Minakata has also addressed the asymmetric aziridination of electron-deficient olefins, namely α,β-unsaturated esters, sulfones andN-acyloxazolidinones.104In this instance a cinchona-derived ammonium salt with an achiral anion was employed; e.e. values up to 87% were observed (Scheme 35). Zhang has employed cobalt porphyrins to effect alkene aziridination and in 2008 published both an initial communication on a non-asymmetric system105and a full article on an asymmetric variant.106As shown inScheme 36, various nitrene sources have been employed and a cyclopropyl stereocentre is used to induce asymmetry. Yields are high for the non-asymmetric variant; moderate to good e.e. values (up to 71%) have been obtained with the homochiral porphyrin, but at the expense of yield. Cenini has also reported studies on cobalt porphyrin-catalysed aziridination.107Elsewhere, two reports concern induction of asymmetry by means of chiral auxiliaries. Chen has used various camphor-derived auxiliaries to effect aziridination of α,β-unsaturated esters and hydrazides, withN-aminophthalimide and lead tetraacetate as oxidant.108Diastereomeric ratios >95:5 are reported, and cleavage of the auxiliary may be effected under basic conditions (Scheme 37).Dabbagh has taken the approach of attaching a chiral auxiliary to a nitrene source and has reported an intriguing BINOL-based imidoyl azide for this purpose.109No notable stereoinduction was observed in aziridination, but this conceptually distinct approach may yet be useful with further optimisation. O’Brien has explored substrate control in the diastereoselective aziridination of cyclic allylic alcohols with various chloramine salts.110Cis-hydroxyaziridines predominated, withcis/transratios influenced by choice of chloramine salt. In one specific instance (1-substituted cyclopent-2-en-1-ols), epoxy sulfonamide products were formed as opposed to aziridines. Substrate control also underlies the work of the Liu group, who have communicated their work on the intramolecular aziridination of glycals.111Tethered sulfonamides have been employed, undergoing rhodium-catalysed oxidation by hypervalent iodine reagents, with the nitrenes so generated effecting aziridination in a stereodefined manner; subsequent nucleophilic ring-opening allows access to aminoglycosides. DFT theoretical studies are also outlined.In the field of non-asymmetric alkene aziridination, a major disclosure has come from De Vos and Sels, who describe the first direct catalytic aziridination of styrenes with ammonia, obviating the need for protecting groups.112The reaction employs sodium chlorate as oxidant and iodide ions as catalyst in a micellar system achieving yields of 30–92% (Scheme 38). The use of a cheap oxidant, atom efficient nitrogen source, environmentally benign aqueous medium and mild conditions (ambient temperature) render this transformation likely to be widely adopted; the authors are currently determining the substrate scope of this reaction.Several other reports on metal-free alkene aziridination appeared in 2008. Butkevitch employed a bicyclicN-aminoimide as nitrene source,113and Fan and Wang have reported mild conditions for hypervalent iodine-mediated aziridination withp-toluenesulfonamide.114Fu and Guo have reported a triflic acid-promoted aziridination of electron-deficient olefins by aliphatic azides, and have undertaken a DFT theoretical study to permit elucidation of mechanism and to rationalise a correlation between olefin basicity and reaction yield.115Morita has employed an unusual method of nitrene generation, namely photolysis of sulfilimines.116In situtrapping with alkenes leads to the corresponding aziridines as shown inScheme 39.Amongst reports on metal-catalysed non-asymmetric aziridination, copper dominates. Appella has reported hypervalent iodine-induced aziridination of terminal aliphatic alkenes with sulfonamides, catalysed by a copperN-heterocyclic carbene complex.117Kühn has reported a catalytic copper complex with an unusual perfluoroalkoxyaluminate counteranion,118and Comba has disclosed an experimental and theoretical study of the catalytic activity of various copper(bispidine) complexes.119Pyridyl ligands have been employed by both Hirotsu120(who reports a copper thiacalix[3]pyridine complex) and Kim and Chang121(who report use of a chelating 2-pyridylsulfonyl ligand).Group 8 metals have also been employed – Gallo describes a heterogenised ruthenium porphyrin catalyst122and Che’s iron bis(terpyridine) complex, described in Section 1.1 (Scheme 19) for epoxidation, is also reported to effect aziridination.48Finally, Bolm has reported the catalytic activity of iron(ii) triflate in the iminoiodinane-mediated aziridination of styrenes123and silyl enol ethers,124which hydrolyse upon workup to give α-amino ketones. In the former instance, the accelerating effect of ionic liquid additives is described.1.6Alcohol oxidation2008 has seen continued activity in the field of aerobic alcohol oxidation, such is the desirability of systems that utilise molecular oxygen as terminal oxidant. A highly noteworthy advance in this area is that due to Liang,125who has reported a metal-free aerobic oxidation of primary and secondary alcohols (aryl and alkyl) to the corresponding carbonyl compounds. The reaction employs a catalytic mixture of TEMPO, NaNO2and HCl. The oxidation proceeds at ambient temperature and, crucially, at atmospheric pressure of O2, in contrast to previously reported work. The authors note the low cost of the constituents of the catalytic system and point out that the absence of metal catalysts removes concerns over metal contaminants in the products.Concerning metal-catalysed aerobic oxidations, the Ison group have communicated their investigations into the mechanism of an Ir(iii)-catalysed aerobic oxidation of primary and secondary alcohols.126The proposed mechanism is one in which iridium remains in the +3 oxidation state throughout the catalytic cycle. An advantage of this iridium-based system is that it does not exhibit any tendency to precipitate bulk metal due to catalyst decomposition, a problem that plagues certain analogous palladium-mediated aerobic oxidations.Palladium-mediated aerobic alcohol oxidation continues to develop, with Sun reporting a new class of sulfonated α-diimine ligands for this transformation127and Shimazu reporting palladium alkylamine complexes that exhibit good catalytic efficiency.128Aerobic palladium oxidation has been employed for specific synthetic purposes by Gozzi and Fache who report tandem one-pot allyl alcohol oxidation–Heck reactions,129and by Stoltz, who reports the use of palladium-mediated oxidative kinetic resolution methodology, developed previously, in the context of alkaloid total synthesis.130Other metals have also been employed for catalysis of aerobic alcohol oxidation in 2008, such as gallium–aluminium mixed-oxide-supported gold nanoparticles reported by Cao,131and copper nanocomposites reported by Pal.1321.7Other oxidationsChe and co-workers have described a ruthenium porphyrin-catalysed oxidation of terminal aryl alkenes to aldehydes.133This transformation is of particular note, since it employs air as the sole terminal oxidant. Under comparable aerobic conditions, the Pd(ii)- or Cu(ii)-mediated Wacker oxidation typically furnishes methyl ketones, thus Che’s method represents a useful reversal of regioselectivity. The reaction proceeds by epoxidation and subsequentin siturearrangement (Scheme 40).Other significant advances in oxidation methodology in 2008 include Kita’s report of a chiral hypervalent iodine reagent for the enantioselective dearomatisation of phenols,134Liu’s report of a palladium-catalysed intermolecular aerobic oxidative amination of terminal alkenes135and Katsuki’s reports on asymmetric sulfide oxidation catalysed by aluminium(salalen)136and iron(salan).137Also of importance are Donohoe’s report on the use of pyridine-N-oxide as an alternative re-oxidant for osmium-catalysed oxidative cyclisation,138and several reports from the Williams group further developing their “borrowing hydrogen” methodology, employing one pot tandem dehydrogenation/hydrogenation sequences to effect diverse functional group interconversions.139Barrett has disclosed mechanistic studies on benzylic oxidations catalysed by Bi(iii) salts.140Mention should also be made of continued progress in the field of biooxidation. Boyd has continued to publish extensively on enzymatic arene dihydroxylation, with specific highlights in 2008 including use of substrates such as 2-naphthyl (in conjunction with Gawronski),141mono- and tricyclic azaarene,1422,2′-bipyridyl,143and 4,4′bipyridyl144(in conjunction with James) and methyl benzoates.145Finally, Que and Tolman have published a concise review on biologically inspired oxidation catalysts,146Rossi has reviewed selective gold-catalysed oxidation,147Murahashi has reviewed ruthenium-catalysed biomimetic oxidation,148and Punniyamurthy has reviewed copper-catalysed oxidation.149

ISSN:0069-3030    

DOI:10.1039/b822050f

出版商:RSC    

年代:2009

数据来源: RSC