摘要:

Protecting groupsAnother excellent and comprehensive annual ‘update’ review of the 2000 literature relating to protecting group (PG) strategies in organic synthesis has appeared this year.1The employment of PGs to direct ‘docking’ at oxidative enzyme active sites thereby controlling subsequent hydroxylation of unactivated carbon atoms has also been overviewed.2,3Moreover, a summary of the use of microwave (MW) heating for accelerating various PG manipulations (acylation, alkylation, silylation, acetalisation, deacylation, desilylation and deacetalisation) with particular reference to carbohydrate manipulations has appeared.4Two reviews focusing on orthogonal PG strategies for ribonucleic acid synthesis5and solid phase peptide synthesis6, respectively, have also appeared.

ISSN:0069-3030    

DOI:10.1039/b111463h

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

1.IntroductionOur literature search for this report resulted in around 1000 references. While demonstrating the continuing strength of the field, this gave us a difficult task, since a complete bibliography alone would fill these pages. Therefore, this report is not comprehensive. Instead, it gives a flavour of the subject area in 2006 and some pointers to further sources of information.Looking back over 20 years of organic chemistry of phosphorus, sulfur, selenium, tellurium and silicon we were interested to note changes in where this chemistry is practised.Fig. 1shows the geographical distribution of organic chemistry papers about phosphorus, sulfur and silicon for 2006 and 1986. We leave the reader to draw their own conclusions.Percentage of papers published on (a) organophosphorus, (b) organosulfur and (c) organosilicon chemistry by territory for the years 2006 and 1986. *Separate figures for Russia for 1986 were not available—USSR total is given; 1986 figures for People’s Republic of China include figures for Hong Kong.

ISSN:0069-3030    

DOI:10.1039/b617791n

出版商:RSC    

年代:2007

数据来源: RSC

摘要:

1.IntroductionSummarising the organic chemistry of the aforementioned heteroatoms from 2007 was no easy task and it was inevitable that some publications had to be omitted due to space constraints. We hope that this review provides an overall flavour of high-quality research taking place worldwide rather than attempt to provide a comprehensive account.The review is organised into sections by heteroatom. Each section discusses the advances made in the synthetic chemistry followed by intermediary or catalytic chemistry of organoheteroatom compounds.

ISSN:0069-3030    

DOI:10.1039/b717023h

出版商:RSC    

年代:2008

数据来源: RSC

摘要:

1IntroductionA snap-shot of this chemical literature is reviewed herein. Reactions involve a metal component either catalytically or stoichiometrically and the review is divided into general reaction types. The author has emphasised reactions of current interest in academic and industrial sectors in the fields of organic, organometallic and bioorganic chemistry. The style of the review is generally similar to previous review articles written by the author.1

ISSN:0069-3030    

DOI:10.1039/b515096p

出版商:RSC    

年代:2006

数据来源: RSC

摘要:

1IntroductionThis section of the work focuses on the organic chemistry of phosphorus, arsenic, sulfur, selenium, tellurium and silicon; the corresponding heterocyclic, free radical and transition metal chemistry is largely ignored as it is covered elsewhere. The review was compiled using a combination of on-line searching and selective reading of the literature.The journalHeteroatom Chemistrydedicated two special issues in “Tribute to Professor Naoki Inamoto in honour of his outstanding contributions to main group chemistry”. Numerous articles pertinent to this report are contained therein,1the first among which is an overview by Inamoto himself of his own group's work on organosulfur, organoselenium and organophosphorus compounds.2

ISSN:0069-3030    

DOI:10.1039/b111386k

出版商:RSC    

年代:2002

数据来源: RSC

摘要:

3Organoselenium and organotellurium chemistryThe commonly used method of synthesising organoselenium and organotellurium compounds by directed lithiation of aromatic compounds is the subject of a review by Mugesh and Singh.53The method is exemplified by Braga and co-workers' preparation of the chiral diselenide ligand61, by oxazoline directedortho-lithiation and subsequent reaction with elemental selenium; oxidation of the resulting lithium selenolate60yielded the diselenide61(Scheme 23).54Alternative classes of organochalcogens may be prepared from lithium chalcogenolates such as60by trapping with electrophiles, or from dichalcogenides such as61by chalcogen–chalcogen bond cleavage (e.g.with halogens).53(i) BuLi, Et2O, 0 °C, (b) Se, 0 °C, (c) NaHCO3(aq), (d) O2, 30%.The synthesis of selenocysteine derivatives and their applications in peptide and protein chemistry,i.e.chemoselective ligations, investigations of enzyme mechanism, structural studies and preparation of peptide conjugates, has been reviewed by van der Donk and co-workers.55Tellurium ylides may be used for the stereoselective formation of cyclopropanes and alkenes, and Tang and co-workers have reviewed their work in this area.56

ISSN:0069-3030    

DOI:10.1039/b212000n

出版商:RSC    

年代:2003

数据来源: RSC

摘要:

1.IntroductionThere have been many exciting advances using transition metals for organic synthesis published in 2007, and it is beyond the extent of this review to do justice to all these areas of interest. This review predominantly focuses on catalytic usage of metal species for organic synthesis. The author has chosen to give an overview of the progress made in fields of widespread and growing general interest to synthetic chemists; metathesis and noble-metal catalysis.

ISSN:0069-3030    

DOI:10.1039/b716606k

出版商:RSC    

年代:2008

数据来源: RSC

摘要:

1Catalytic coupling reactions (C–C and C–X coupling)It is somewhat difficult to find an issue of any journal that does not contain some aspect of Pd catalysis. Interest in the diverse and extremely powerful transformations that are mediated by this metal continue to gather pace. The following sub-sections are thus dominated by this valuable transition metal. It is fairly clear that mechanistic insights are key to understanding and exploiting this area—we need to know more than just what works and what does not work. This is of particular importance in the pharmaceutical sector, where Pd-mediated processes are routinely carried out on heterocyclic substrates, often as part of large libraries. Being able to understand theblack-boxin Pd chemistry is essential for a more in-depth understanding of the field in general. That not only encompasses substrate scope, but also is associated with Pd source, ligand, additives, solvents, concentration and temperature (thermal, microwaves and use of ultra sound). It is universally accepted that these individual parameters, usually, but not always, require some optimisation. It is intriguing to link the structural identity and associated reactivity of the substrate with these changing reaction parameters, which ultimately, when Pd coupling chemistry is fully understood, could derive from the interaction of the substrates with higher order Pd species. In this respect, Pd colloids/clusters continue to attract attention, particularly since the revelation that lower Pd catalyst loadings lead to more active catalysts (an inverse correlation). These aspects are discussed in this section. Other transition metal-mediated coupling processes are highlighted with appropriate examples.1.1Heck coupling reactionsThere were 409 papers reporting use of the Heck reaction in some form in 2004. Generally, both activated and non-activated aryl bromides undergo smooth Heck alkenylation reactions with activated alkenese.g.acrylates, styrenesetc. In stark contrast to what was previously thought,ligandlessHeck reactions are as effective as those mediated in the presence of donor ligandse.g.phosphines. In a twist to this story, this is only the case provided that low concentrations of Pd salts such as Pd(OAc)2are used (ideally 0.01–0.1 mol%, no comment was passed about global Pd concentration—a more informative indicator). Higher loadings lead to lower catalytic activity. Reetz and de Vries recently surmised that Pd nanoparticles (colloids/clusters) are formed readily at higher catalyst loadings, which are either inactive catalyst species or precipitate from the reaction mixture.1It also remains a possibility that the first step in catalysis (oxidative addition) takes place at the outer rim of the Pd cluster. It is not clear when and if the key Pd species then becomes detached from the Pd cluster. Further studies on polynuclear Pd species are required to understand their interaction with individual substrates. One can envisage that acrylates, for example, could stabilise such species, either through alkene binding or carbonyl coordination through bridged intermediates.The mechanism of the Heck reaction using palladium complexes with large phosphoramidite ligands has been studied by Rothenberget al. It was shown that the catalyst precursor is an inactivedimericspecies that equilibrates with an activemonomericspecies.2FT-NIR spectroscopy was used to determine the concentration profiles for the reactions, and these compared with a series of simple kinetic models (based on classically assumed intermediates). The differential equations fit when the simplified mechanism is considered at low conversions, but deviates significantly at higher conversions with increasing deactivation. By factoring in the formation of Pd clusters and production of Pd black, the situation is clearer, in that the deactivation processes appear to be represented by a single first-order process. Formation of palladium clusters and palladium black is then included, with the simplification that all the deactivation processes are represented by a single first-order process. A five-step mechanism shows the importance of dimer-monomer equilibrium, a Pd(ii)/Pd(0) catalytic cycle, and then a catalyst deactivation process.Development of new catalystsMore efficient catalysts are continually being developed for the Heck reaction. Moreno-Manas and co-workers have recently reported the preparation of 15-membered macrocycles, which may be compared with the stable Pd(0) precursor Pd2dba3·solvent (solvent = CHCl3, CH2Cl2, benzeneetc.).3,4Macrocycle1coordinates to palladium(0), platinum(0), and silver(i) (Scheme 1). The first class provide useful and reusable catalysts for the Heck reaction (2+3→4), as well as Suzuki cross-couplings, butadiene telomerisations, and the hydroarylation of alkynes.Reagents and conditions:i,1(cat., Ar1= ferrocenyl-; Ar2= 4-CH3C6H4-), KOAc, Bu4NBr, DMF, 60 °C.In the presence of donor ligands such as PPh3, the macrocycle releases Pd(0) and produces Pd(PPh3)n. In the presence of O2, oxidation of the phosphine occurs and the macrocycle is able to sequester and free Pd(0) in solution. A simple mechanism is presented inFig. 1.Reaction of donor ligands with a Pd(0) macrocycle1.The partial decomplexation of Pd(0) from1in the Heck reaction led the investigators to test aryl diazonium salts as substrates, since a superior activity of the nucleofuge (formation of N2) is seen over bromide and iodide. The process requires shorter reaction times, milder conditions and the addition of base is not mandatory. Pd(0) macrocycle1efficiently catalysed the arylation of acrylates and styrene with aryl diazonium tetrafluoroborates in ethanol at room temperature. The recovery of the Pd(0) macrocycle was quantitative. Electrospray-mass spectrometric studies provided evidence for the accumulation of the oxidative addition product species ([1/C6H4X]+) formed in the catalytic cycle immediately before the alkene insertion step. This study indicates the potential for alkene tuning—an exploitable property for higher reactivity and selectivity.Theoretical studiesThe potential broad application of Ni as a catalyst for the Heck reaction has long been sought after as an alternative cheaper replacement for Pd. There are a number of reasons why Pd is a superior metal, but Ni still represents an exploitable system. Using density functional methods, Linet al.have probed the potential use of Ni in Heck reactions.5It was found that Ni- and Pd-mediated Heck reactions are quite similar. Oxidative addition and alkene insertion occur with lower energy barriers with Ni. β-Hydride elimination is more efficient for Pd systems, whereas Ni systems result in poor vinylation selectivity—where Michael addition is the viable alternative. Another problem is that catalyst regeneration, through HX removal, is considerably more difficult to achieve with the Ni system, indicating a requirement for a strong base. Alternatively, a reductive pathway should be factored into catalyst design to remove HX from the Ni(ii) species. In stark contrast to the Pd system, oxidative addition of an alkenyl or aryl chloride is not much harder than oxidative addition of an alkenyl or aryl iodide in the Ni system. The Ni-catalysed Heck reaction may well be applied to alkenyl or aryl chloride in a straightforward manner. The slow β-hydride elimination is a potentially exploitable step, in that alkyl halides may be used. It was proposed that phosphine and pyridine ligands can reasonably reduce the free energy in the HX removal step. All the above observations are derived from considering a neutral M(0)/M(ii) cycle. However, neither cationic or anionic pathways alter the general trends and differences in reactivity seen between Ni and Pd.1.2Stille coupling reactionsThe reaction of organohalides and organostannanes, the union of two carbon components to give rise to a new carbon–carbon bond, is Stille coupling. The mechanism of Stille coupling is continually being debated. Espinet and Echavarren have comprehensively reviewed the literature for this reaction, which puts into context the various arguments for the operation of neutral/anionic Pd(0)/Pd(ii) and Pd(ii)/Pd(iv) cycles.6The intricacies of oxidative addition, transmetallation and reductive elimination are discussed in detail. The importance of halides has been put into context by Jutand, relating to support for an anionic Pd(0)/Pd(ii) cycle.7Development of new catalystsThe biggest breakthrough in recent years has been the ability to perform Stille coupling on strong carbon–halogen bondse.g.C–Cl bonds. A number of highly active catalysts has been developed for Stille coupling—Fu'st-Bu3P/Pd catalyst system is arguably the benchmark to surpass. One limitation to thet-Bu3P ligand is its air sensitivity. Less sensitive, but equally reactive, ligands are continually sought after. Verkade and co-workers continue to apply their proazaphosphatrane ligand5, (P(i-BuNCH2CH2)3N. N → P Activation makes the phosphorus atom in5electron-rich, in the σ-donating sense, making it a useful commercially available ligand. In combination with Pd2dba3it provides a highly effective catalyst for cross-coupling of aryl chlorides with organotin compounds.8Other proazaphosphatranes, similar to5, possessing benzyl substituents also generate very active catalysts. A wide array of aryl chlorides can be coupled to various aryl, vinyl and allyl tin reagents (the latter without allylic transposition).Effect of additivesArguably one of the most significant discoveries for this process in 2004 was that made by Baldwin and co-workers on the synergic effects of Cu(i) salts and fluoride ion (from CsF).9In some of the most difficult Stille couplings known, excellent yields and low reaction times with a standard Pd(0) catalyst, namely Pd(PPh3)4, were attained. The origin of the cooperativity presumably derives from transmetallation of the organostannane with Cu(i) to give a more reactive organocuprate, and the reaction of CsF with soluble XSnBu3, which accumulates throughout the course of the reaction, to give insoluble FSnBu3(polymeric) (Scheme 2). Although not proposed by the authors, one would assume that in the presence of excess CsF, that F2SnBu3−Cs+would be formed and is the most stable by-product.Cooperative effects in simultaneous use of Cu(i) and fluoride in Stille coupling.1.3Suzuki coupling reactionsNew catalystsScrivanti and co-workers have reported that an iminophosphine–palladium(0) complex6is a highly active catalyst for Suzuki coupling. It was pleasing to see that the new catalysts have been applied in a synthesis to the undecaaryl substituted corroles.10High turnover numbers (∼200,000) were observed against a variety of aryl halides and arylboronic acids. 2,3,7,8,12,13,17,18-Octabromo-5,10,15-triphenylcorroleCu(iii) was reacted with 4-chlorophenylboronic acid in toluene at 90 °C in presence of6, with a corrole/catalyst ratio of 40,000 ∶ 1 (a N2atmosphere was essential). Compound6was able to catalyse the complete substitution of the eight peripheral bromine atoms to give the fully undecasubstituted corrole in 55% after only 2 hours—no products of partial substitution were observed (Scheme 3).Reagents and conditions: i,6(5 mol%), 4-ClC6H4B(OH)2, K2CO3.It is often the case that tuning of Pd catalysts for cross-coupling reactions is done through alteration of the ligands for the metal. Sometimes, the halide and pseudohalide play a role in catalysis, as do other additives,vide supra. A comparison of the type of Pd precursor catalyst is also important—it is common to find Pd(OAc)2compared against Pd2dba3(dba =E,E-dibenzylideneactone) and (MeCN)2PdCl2. The odd complex here is Pd2dba3, as it is well established that dba plays a non-innocent role in cross-coupling reactions. The main problem is dba ligation to Pd, which essentially removes the active Pd(0) species from the catalytic cycle—one could argue that it stabilises this species, serving as a reservoir of Pd(0) to enter into the catalytic cycle. In a recent study, it was shown that by alteration of the aryl groups on dba, through addition of various electron-releasing and withdrawing substituents, that it was possible to control the concentration of Pd catalyst in the catalytic cycle in Suzuki coupling from precursor Pd(0) complexes12a–c, where aN-heterocyclic carbene (NHC,11) was used as the activating ligand for aryl chloride cross-coupling (9→10,Scheme 4).11Such minor changes have a large affect on the overall rates of reaction, showing that one can exploit Pd-η2–alkene interactions.Reagents and conditions: i,11(3 mol%), Pd complexes12a–c(based on Pd, 3 mol%),n-Bu4NBr (10 mol%), KOMe (3 equiv. in MeOH), toluene, 40 °C.Beller, Zapf12Generally, phosphine-based catalysts (containing BuPAd2,o-biph-PCy2or P(t-Bu)3) appear to be more efficient for amination and Suzuki reactions of aryl chlorides. On the other hand, the carbene-based (containing ligand11) Pd-catalysts work well in Kumada couplings with various aryl chlorides. Several mono-carbene ligated Pd-alkene complexes (13a–e) have been developed by the same group. Indeed, in this report, the specific type of alkene is shown to play a non-innocent role in Suzuki coupling of 4-bromoanisole14and phenylboronic acid15to give16(Scheme 5), depending on the effective backdonation (synergic effects) of the Pd(0) dπ-electrons to the π*-orbital of the alkene, which is proposed to decrease the activity for oxidative addition into the C–X bond. One may argue that the π-donor properties of the alkene should promote oxidative addition, thus it appears likely that the alkene blocks needed coordination sites on the Pd(0) centre, increasing the concentration of “Ln-Pd(0)-η2-alkene”. Thus the addition of excess alkenee.g.napthaquinone (NQ, entry 3) or divinyldisiloxane (dvds, entry 6) results in loss of catalytic activity (Table 1). Thein situaddition of IMesHCl to Pd(dvds), which is expected to generate13a, clearly does not in this reaction (entry 7)—the result indicates that precatalyt mixing was ineffective under the conditions used.Reagents and conditions: i, [Pd]13a–e(3 mol% Pd), ligand (3 mol%), Cs2CO3, dioxane, 80 °C, 2 h.Suzuki coupling of 4-bromoanisole14and phenylboronic acid15with various catalystsEntryCatalystConversion(%)Yield(%)Reaction conditions as forScheme 5.Solution of Pd(0) in dvds (ca. 8% wt.% Pd).1IMesPd(dvds)13a92652IPrPd(dvds)13b90713IPrPd(dvds)13b/NQ28114[IMesPd(NQ)]213d81765[IPrPd(NQ)]213e77636[IPrPd(NQ)]213e/dvds4027Pd(dvds)/IMesHCl5<18Pd(dvds)8<1A simple and efficient hemilabile-type phosphine ligand17for Suzuki coupling of aryl chlorides has been reported (Scheme 6).13TheP,O-type ligand is a strong σ-donor ligand, comparable to P(t-Bu)3, which can be prepared in two steps from benzoic acid. Low Pd-catalyst loading (0.05%) may be used. The ligand compares favourably against Buchwald's ligand (o-biphenyl)P(t-Bu)2) in Suzuki coupling of 2,6-dimethylchlorobenzene with phenylboronic acid. Selected examples are given inScheme 6. The unprotected chloroindole18coupled with tolylboronic acid19to give20in excellent yield. The highly substituted 4,6-di-tert-butyl-2-methoxybromobenzene21and phenylboronic acid22gave23also in excellent yield.Reagents and conditions: i, Ar′B(OH)2(1.5 equiv.), K3PO4·H2O (3.0 equiv.), stock solution of Pd-catalyst (Pd ∶17= 1 ∶ 2, 0.01 to 0.05 mol%), toluene, 100 °C, 14–24 h;ii, as fori, using 0.05 mol% Pd, 18 h;iii, as fori, but at 60 °C, 16 h, using 0.05 mol% Pd.Solid supported systemsNHCs generally have become universal ligands in organometallic and organic synthesis. They exhibit strong σ-donor and weak π-accepting properties, and can be compared with some phosphines. One of the major problems in the employment of these ligand systems, in the presence of Pd, is separation and recycling of the catalysts and contamination of the ligand residue in the final product. To overcome these problems, several types of heterogeneous methods which anchor the Pd catalyst to various solid-supports have been developed, such as PS-PEG, Wang resin, PS-DVB and Merrifield resin. These types of solid supports possess catalytic active sites in all the regions of the resin, including the interior—Lee and co-workers suggest that this is sometimes a problem for reagent diffusion into the interior, the result being a reduction in reaction rate, stating that it would be better if catalytic active sites were located at the resin surface.14Thus they have used a poly(imidazoliummethyl styrene)-surface grafted-polystyrene resin24(prepared by suspension polymerization), acting as the polymer-supported carbene precursor for ligation to Pd-complex25(Scheme 7). The best Pd-loadings on the resin were found when a 4-fold excess of Pd(OAc)2was employed (0.11 mmol Pd g−1). This supported system efficiently catalysed the Suzuki coupling of aryl iodides with phenylboronic acid (TON ∼ 10,000). It should be noted that PEG systems, containing palladacycles, have been developed, which exhibit catalytic activity that exceeds that reported for theN-heterocyclic carbene Pd/polystyrene system.15Reagents and conditions: i, Pd(OAc)2(4 equiv.), Cs2CO3(5 equiv.), water/DMF (1 ∶ 1, v/v), 50 °C, 2 h.Substrate scopeThe preparation and reactivity of a 2-pyridylboronate stabilised by aN-phenyldiethanolamine28tether has been reported (Scheme 8).16These studies were prompted by the sparse reports on use of 2-pyridyl borate species. The main problem is associated with the stability of such compounds. It was determined that theN-phenyldiethanolamine was the most stabilising (it is well known that diols and thiols stabilise boronic acids). One would expect thatN→Belectron-donation would stabilise the boron centre, but would also serve to promote transmetallation in Suzuki coupling. Compound28can be prepared by reaction of 2-lithiopyridine, formed by reaction ofn-butyllithium and 2-bromopyridine26, with triisopropyl borate to give27.In situreaction of27withN-phenyldiethanolamine afforded28in 75% yield (on a 4 molar scale).Reagents and conditions: i, (i-PrO)3B,n-BuLi, THF, −75 °C, then warm to 25 °C, 16 h;ii,N-phenyldiethanolamine, IPA, reflux, 4 h.Suzuki coupling of this boronate is generally efficient for a range of aryl halide substrates. However, in some cases significant aryl–aryl exchange from the phosphine ligand was observed (no comment was passed about the high concentration (20 mol%) of PAr3and CuI (40 mol%)—presumably the latter acts as an phosphine scavenger in THF), with some combinations of ligand and substrates. The amount of the exchange by-product can be minimised by appropriate choice of phosphine ligand (Table 2). The best ligand appears to be P(o-tolyl)3—theortho-methyl substituent in this ligand presumably hinders aryl–phenyl exchange in the intermediate Pd(ii) complex and subsequent coupling with the 2-pyridyl boronate.Reagents and conditions: Pd(OAc)2(5 mol%), PAr3(20 mol%),CuI (40 mol%), K2CO3(2 equiv.), reflux, THFRatio of the 2-arylpyridine30/by-product31ArIPPh3P(o-tolyl)3P(p-tolyl)3P(p-anisole)3Ratio of30∶31determined by HPLC.N/A: Product and by-product are identical.R = 4-CH382/1899.9/0.1N/A92/8R = 4-OMe77/23>99.9/<0.172/28N/A1.4Sonogashira coupling reactionsMechanistic studiesAlkynes may be activated through Pd-mediated Sonogashira coupling (Scheme 9, eqn 1) and multi-component coupling processes (Scheme 9, eqn 2). Although the mechanism for Sonogashira coupling is not fully understood, the terminal alkyne is believed to be involved in the second step of the catalytic cycle,i.e., in atransmetallationstep with a arylpalladium(ii) complex (generated in theoxidative additionof the aryl halide to a Pd(0) complex (Scheme 9, eqn 3)), with an alkynylcuprate intermediate (generatedin situfrom reaction of the terminal acetylene, base and CuX,Scheme 9, eqn 4). In multicomponent reactions, the alkyne again reacts in the second step of the catalytic cycle,i.e.in acarbopalladationstep with a arylpalladium(ii) complex (Scheme 9, eqn 5). It is now well established that certain types of alkenese.g.acrylates and styrenes, in the Heck reaction slow down the reaction rate of oxidative addition, a result that derives from partial coordination of the alkene to Pd(0), which gives an unreactive Pd(0) complex. It would not be unexpected to assume, based on this finding, that alkynes behave similarly. Indeed, in a comprehensive study, Amatore and Jutand have shown that the oxidative addition of PhI to Pd(PPh3)4in DMF is slower when performed in the presence of terminal alkynes.17The key problem is that the alkyne ligates Pd(0) in an η2-fashion, ultimately stabilising the Pd(0) centre, but reducing the overall concentration of reactive Pd(0)(PPh3)2complex for the oxidative addition reaction (Scheme 9, eqns 6 and 7). Although not correlated, a comparison with 4-methoxy- and 4-trifluoromethylphenylacetylene with phenylacetylene should lead to the observation that the electron-rich acetylene should favour shifting the equilibrium (K2) to the left-hand-side and increasing the concentration of Pd(0)(PPh3)2(Scheme 9, eqn 7). In contrast, the electron-poor acetylene would favour shifting the equilibrium to the right-hand-side, decreasing the concentration of Pd(0)(PPh3)2and reducing the overall rate of reaction. The observation goes someway to explaining the reactivity differences often seen when electron-rich terminal alkynes and electron-poor terminal alkynes are employed. Overall, terminal alkynes appear to play an unexpected role in Sonogashira and multi-component coupling processes, since they influence the rate of the oxidative addition before their implication in the transmetallation or carbopalladation steps. Ultimately, this may not be a hindrance, as decreasing the rate of the rapid oxidative addition with reactive organohalides such as aryl iodides, may favour the efficiency of the catalytic cycle by means of bringing its rate closer to that of the slower transmetallation or carbopalladation steps. Generally, the dual roles of nucleophiles in Sonogashira, as well as in Heck and Stille coupling, has been reviewed by Jutand.18Steps in Sonogashira and multi-component coupling reactions.Optimised conditionsSonogashira coupling has been achieved in pure water without any additives or phase transfer catalysts. The reactions proceed well using lower Pd-catalyst loadings (Pd(PPh3)4, 0.5 mol%) and are very fast (30 min at 70 °C), producing high yields of the arylalkyne cross-coupled products.19Interestingly, a transition-metal-free Sonogashira-type coupling reaction has been found to occur in water under microwave heating.20A protocol that avoids use of a Cu(i) co-catalyst and amine as base has been developed for the Sonogashira reaction. Here, aminophosphines were employed as ligands.21A typical example is shown inTable 3, where various bases were compared.A comparison of bases for a Sonogashira reaction in the presence of ligand32EntryBaseYield(%)Reagents and conditions: i, PhCCH (1.2 equiv.), Pd(OAc)2(2.5 mol%),32(7.5 mol%), base (3 equiv.), THF, 65 °C, 8 h.1Et3N212Morpholine243K2CO3974Na2CO3255NaHCO3236K3PO4·3H2O907KF7The best base in this reaction was K2CO3(entry 3), although K3PO4·3H2O shows similar activity. Other bases investigated, including Et3N, were poor bases for this reaction. Ligand32is easily prepared by reaction of LDA with Ph2PCl.Doucet and Santelli continue to report on the use of tedicyp33as an activating ligand for Sonogashira coupling (Scheme 10).22In combination with the pre-catalyst, [Pd(η3-C3H5)Cl]2, a very efficient catalyst evolves for the alkynylation ofortho-substituted aryl bromides34to give36. A variety of substituents such as phenyl, trifluoromethyl, acetyl, formyl or nitrile, are tolerated. High turnover numbers can be obtained with most of these aryl bromides. The coupling of the sterically very congested aryl bromides such as 9-bromoanthracene or 2,4,6-triisopropylbromobenzene, also proceeds in good yields.Reagents and conditions: i, terminal acetylene (1.1 equiv.), [Pd(η3-C3H5)Cl]2,33, CuI, K2CO3, DMF.Ma and co-workers have reported that CuI/N,N-dimethylglycine-catalysed effectively mediates the coupling reaction of aryl halides with terminal alkynes, providing the reaction is carried out in DMF at 100 °C, to furnish the corresponding coupled products in good to excellent yields.23Under the developed conditions, homocoupling of the terminal acetylene was minimal. Copper nanoclusters, in the absence of palladium and ligand, have also been shown to catalyse the cross-coupling of alkynes and aryl halides to give the corresponding disubstituted alkynes.24Sakai and co-workers have reported the use of both PdCl2(PPh2)2–InBr2to catalyse cross-coupling reactions of a variety of aryl iodides with several terminal alkynes to give functional alkyne products in good to excellent yields (Scheme 11, eqn 1).25Moreover, a catalytic amount of InBr3effectively catalyses the intramolecular cycloaddition of 2-phenylethynylaniline38, produced byin situalkynylation of37, to form an indole skeleton39in high yield (Scheme 11, eqn 2).Reagents and conditions: i, InBr3(0.05 equiv.), piperidine, rt, 2.5 h;ii, ArI, PdCl2(PPh3)2(0.05 equiv.), piperidine, rt.Unusual observationsImportant consequences for analysis of Sonogashira coupling reactions of activated substrates have been reported.26Continued reaction was observed in samples quenched by treatment on silica alone (by elution with dichloromethane). Both soluble Pd and Cu species promote further reaction in dilute samples used in GC analysis (the structural identity of these species remains unknown). Improved quenching methods that utilise 1,2-diphenylphosphinoethane were reported.Application in target-directed synthesisThe first and concise total synthesis of murisolin40utilised Sonogashira coupling as one of the key steps.27Thus, alkynylation of42, from41, was achieved under standard conditions to give the enediyne43in 72% yield (Scheme 12). Subsequent hydrogenation using Wilkinson's catalyst afforded alcohol44in 47% yield, with standard silyl deprotection providing40in 91% yield. Generally, it is noted that researchers in this applied field of Sonogashira coupling still chose the standard precatalyst (PdCl2(PPh3)2/co-catalyst (CuI) system, using Et3N as the base for this transformation, rather than using more active catalyst systems developed over the last five or so years.Reagents and conditions: i, PdCl2(PPh3)2, CuI, Et3N, rt;iii, H2, Rh(PPh3)3Cl, MeOH–benzene, rt;iii, HF (aq.), MeCN–THF, rt.1.5Reactions involving C–X bond forming processes (X = O, S or N)Carbon–heteroatom bond-forming reactions continue to expand in terms of catalyst development and in application in target-directed synthesis. Buchwald and Hartwig have been instrumental in developing these synthetic tools, however other research groups have begun to shed light on the mechanism(s) of these processes, create new methods, and also optimise the pioneering studies in the area.C–N bond forming reactionsBuchwald and co-workers have developed a method using copper as the catalyst for theN-arylation of π-rich nitrogen heterocycles. The coupling of either aryl iodides or aryl bromides (45) with common nitrogen heterocycles such as pyrroles (46,Scheme 13, eqn 1), pyrazoles48,Scheme 13, eqn 2), indazoles (49,Scheme 13, eqn 3) provides theN-arylated products (47,49and51, respectively) in good yields, using catalysts derived from diamine ligand53and CuI. Imidazoles and triazoles may also be coupled equally well. The conditions were found to be tolerant to a variety of functional groups such as aldehydes, ketones, alcohols, primary amines, and nitriles on the aryl halide or heterocycle.28Reagents and conditions: i, CuI (5 mol%), ligand53(20 mol%), K2CO3(2.1 equiv.), 24 h, 100 °C, toluene;ii, CuI (10 moL%), ligand59(20 mol%), NaI, 24 h, 100 °C, toluene;iii, K3PO4, treat with57.In the case of the indazoles (Scheme 13, eqn 3), a dramatic lowering of regioselectivity was observed when using aryl bromides rather than iodides as substrates. The change in regioselectivity is proposed to be due to the fact that oxidative addition with aryl bromides is expected to be much slower than that of aryl iodides. Thus, the indazole first reacts to form a kinetic (N,N)Cu(indazole) intermediate,54a(Scheme 13, eqn 4). This intermediate is expected to be in equilibrium with54b. When oxidative addition is fast,e.g.as in the aryl iodide case, oxidative addition to54aoccurs faster than the54a/54bequilibration, accounting for the predominant formation of the N-1 substituted product51after reductive elimination. For reactions with aryl bromides, the rate of the54a/54bequilibration competes with the rate of oxidative addition, thus a mixture of products results (51and52). A two-step one-pot process using a Cu-catalysed halide exchange process, enables aryl bromides to be used. For example, 4-bromotoluene reacts with 2-acetylpyrroleviathe aryl iodide to giveN-arylated product58in good yield (Scheme 13, eqn 5).N-Trialkylsilylimines61have been employed as coupling partners in Pd-catalysed C–N bond-forming reactions with aryl bromides60to furnish theN-arylated imines62(Scheme 14). The one-step method allows easy access to imines and azadienes from aryl and alkenyl bromides, respectively.29Reagents and conditions: i,60(1 equiv.),61(1.2 equiv.), NaOt-Bu (1.4 equiv.), [Pd2dba3] (4 mol%), BINAP (8 mol%), toluene, 90 °C.The mechanism for this process is expected to involve an initial oxidative addition reaction of LnPd(0) with the aryl halide, followed by reaction of the Pd(ii) halide speciesIwith an imine anion, generatedin situby reaction of an appropriate nucleophile with61, to give the Pd(ii) amido speciesII. Reductive elimination releases theN-arylated product62, regenerating the Pd(0) catalyst.C–O bond forming reactionsChiral chromans or the closely related chromenes are a class of compounds possessing significant biological properties. Trost and co-workers have reported that Pd-catalysed asymmetric allylic alkylation (AAA) of phenol allyl carbonates such as63, using theC2-symmetric modular ligand65, serves as an efficient way to construct the allylic C–O bond, facilitating access to chiral chromans such as64, in up to 98% ee (Scheme 15).30The methodology was used to explore an enantioselective route to the vitamin E core, the first enantioselective total synthesis of (+)-clusifoliol and (−)-siccanin, and the synthesis of an advanced intermediate toward (+)-rhododaurichromanic acid.Reagents and conditions: i, Trost modular ligand64(6 mol%), Pd2dba3·CHCl3(2 mol%), HOAc (1 equiv.), CH2Cl2, rt.C–S bond forming reactionsJoyce and co-workers have shown that intramolecular C–S bond formation is possible when aryl halides containing a thiourea66are treated with either a Cu/1,10-Phen or Pd catalyst system, allowing access to 2-aminobenzothiazoles67(Scheme 16).31Interestingly, the Cu-catalysed method is generally superior and more cost effective than the Pd-catalysed protocol.Reagents and conditions: i, CuI (5 mol%), 1,10-Phen (10 mol%), Cs2CO3(2 equiv.), DMF, 80 °C, 16–24 h;ii, as fori, but using Pd(PPh3)4alone (no CuI and ligand).Buchwald and co-workers have developed a general method for the cross-coupling of thiols69with aryl halides (68, chlorides and bromides), using Pd(OAc)2as the catalyst and 1,1′-bis(diisopropylphosphino)ferrocene as the activating ligand (Scheme 17).32The catalyst system also facilitates coupling of secondary phosphines to aryl halides.Reagents and conditions: i, Pd(OAc)2(2 mol%), ligand71(2.4 mol%), NaOt-Bu (1.2 equiv.), dioxane, 100 °C, 18 h.Optimised proceduresRapid Buchwald–Hartwig amination of electron-neutral and rich aryl chlorides and bromides have been achieved using temperature-controlled microwave heating. Primary and secondary aliphatic amines can be coupled with these substrates in good yields, in reaction times ofca.10 min.33More elaborated structures, in the form of substituted aryl aminobenzophenone p38 MAP kinase inhibitors, were synthesised in good to excellent yields using microwave assisted Pd-catalysed aryl amination.34Purification has been made easier through use of a novel fluoroalkyl benzophenone imine reagent, which serves as a convenient ammonia surrogate for the Pd-catalysed Buchwald–Hartwig amination of aryl halides.35The highly fluorinated imine moiety acts as a handle for rapid purification by fluorous chromatographic techniques. The fluorous alkyl chain can be easily removed by acid hydrolysis to provide the corresponding primary anilines in good yields.1.6C–H Activation processesThe development of transition metal-catalysed processes for the regio- and chemoselective oxidative functionalisation of alkane, alkene and aryl carbon–hydrogen bonds remains a significant challenge to the field of organic and organometallic chemistry. A comprehensive literature search reveals that such transformations are generally rare. Moreover, the application of such methods to complex organic structures is limited, mainly due to the harsh reaction conditions that are often required, the problem of low turnover numbers and frequencies, and poor functional group tolerance. Studies by Sanford and co-workers have recently provided a highly selective catalytic method for the oxidative functionalisation of C–H bonds.36Initial experiments were focused on the Pd(ii)-mediated oxidation of benzo[h]quinoline72, which contains a single bond for directed C–H activation to give73—the C–H10position undergoes facile cyclopalladation under relatively mild conditions (Scheme 18).C–H Activation and oxidation.The reaction of the Pd(ii) palladacycle73with an oxidant was expected to give the oxidation product74. The oxidant employed was iodobenzenediacetate (PhI(OAc)2). In combination with this reagent (2 equiv.), compound72(1 equiv.) was converted into74(where X = OAc) by a catalytic reaction mediated by 2 mol% Pd(OAc)2in CH3CN at 75 °C for 12 hours. The reaction produces74and the analogous phenol in an 11 ∶ 1 ratio and 86% yield (after purification). The cyclopalladated complex73, when used as the catalyst, also gives product74under the same conditions, but in this case only oxidation at C10is observed. The nature of X may be altered by judicious choice of solvent. For example, in EtOH, MeOH,i-PrOH/AcOH and CF3CH2OH, X = EtO, MeO,i-PrO and CF3CH2O, respectively. Other compounds may be functionalised, such as 8-methylquinoline (75→76), azobenzene (77→78), pyrazole (79→80) and pyridine (81→82or83) (Scheme 19).Reagents and conditions: i, substrate (1 equiv.), AcOH or CH3CN, PhI(OAc)2(1.1–1.6 equiv.), Pd(OAc)2(1–6 mol%), 100 °C, 12–20 h;ii, substrate (1 equiv.), CH3CN, PhI(OAc)2(2.3–2.5 equiv.), Pd(OAc)2(6–8 mol%), 100 °C, 12 h.A mechanism for this transformation has been proposed, which involves chelate directed C–H activation (mandatory requirement for a chelating atom) to give the cyclopalladated intermediateII(Scheme 20). The subsequent step is proposed to involve oxidation of Pd(ii) to Pd(iv) to give intermediateIII. The final step involves reductive elimination to give the carbon–heteroatom product and to regenerate the catalystI. It is proposed, based on the literature precedent, that reductive elimination could proceed by an intramolecular C–X pathway, or by an attack from an external nucleophile (SN2-like). The authors concede that the Pd(0)/Pd(ii) is a possible catalytic cycle. Although not mentioned in the report, it is well known that nitrogen (a hard atom) stabilises the hard Pd(iv) centre, adding further support to the Pd(ii)/Pd(iv) cycle.Proposed catalytic cycle for oxidative functionalisation of C–H bonds.Very recently, unactivated sp3C–H bonds in both oxime and pyridine substrates have been shown to undergo highly regio- and chemoselective Pd(ii) catalysed oxygenation with PdI(OAc)2as the stoichiometric oxidant.37The process is again chelate-directed oxidation (Scheme 21). TheO-methyl oxime84reacts with catalytic Pd(OAc)2to give palladacycle85, which reacts in oxidative fashion with PhI(OAc)2to afford the mono-β-oxygenated product86(Scheme 21, eqn 1). The oxime of 2-methyl-4-tert-butyl cyclohexanone87is a good substrate for the β-oxygenation process to give88(Scheme 21, eqn 2). This reaction was rapid (5 min). The origin of the reactivity stems from thetert-butyl substituent locking the 2-methyl substituent into coplanarity with the oxime. A similar substrate without atert-butyl groupe.g.one possessing more flexibility, was much slower (1.5 h). Use of a structurally rigidtrans-decaloneO-methyl oxime89enabled functionalisation of an unactivated 2° sp3C–H bond to give90, which was formed as one diastereoisomer, with the OAc substituent positioned equatorially (Scheme 21, eqn 3).Reagents and conditions: i, substrate (1 equiv.), PhI(OAc)2(1.1–3.2 equiv.), Pd(OAc)2(5 mol%), AcOH, AcOH/50% Ac2O or CH2Cl2, 80–100 °C, 5 min–12 h.A related C–H activation process, involving the formation of a benzonaphthazepine where an amine acts as the chelate-director, has been reported.38

ISSN:0069-3030    

DOI:10.1039/b418975m

出版商:RSC    

年代:2005

数据来源: RSC

摘要:

1.IntroductionThis article covers only a sample of the diverse contributions to the field from 2008 and the author apologises to those whose work has not been included. Particular advances that have caught the author’s eye in 2008 involve “coupling” type reactions. Organophosphorus and organosulfur compounds have been developed as coupling partners for carbon–carbon bond formation and, very interestingly, carbon–silicon bond formation through coupling reactions is an expanding theme. Pleasingly, there are some rigorous mechanistic studies providing a sound basis for future work.Some of the reviews in the field are listed below, followed by sections on organosilicon, organophosphorus, organosulfur and organoselenium and organotellurium chemistry.1.1Reviews‘Silylmetalation of Alkenes’.1‘Synthesis and Reactivity of Silylformylation Products Derived from Alkynes’.2‘Stereoselective reactions involving hypervalent silicate complexes’.3‘Functionalised fluoroalkyl and alkenyl silanes: Preparations, reactions, and synthetic applications’.4‘Kinetic Resolution and Desymmetrization by Stereoselective Silylation of Alcohols’.5‘Recent Developments in the Addition of Phosphinylidene-Containing Compounds to Unactivated Unsaturated Hydrocarbons: Phosphorus–Carbon’.6Bond Formation by Hydrophosphinylation and Related Processes‘Phosphate Esters as “tunable” reagents in organic synthesis’.7‘Synthesis and application of chiral monodentate phosphines in asymmetric hydrogenation’.8‘Recent advances in chiral phosphine-silver(i) complex-catalysed asymmetric reactions’.9‘Libraries of Bidentate Phosphorus Ligands; Synthesis Strategies and Application in Catalysis’.10‘Catalytic Asymmetric Synthesis of Chiral Phosphanes’.11‘Functionalised organolithium compounds by sulfur–lithium exchange’.12‘Transition metal catalyzed asymmetric oxidation of sulfides’.13‘Zinc Homologation–Elimination Reaction of α-Sulfinyl Carbanions as a New Route to Olefins’.14‘Catalytic and highly enantioselective reactions of α -sulfonyl carbanions with chiral bis(oxazoline)s’.15Enantioselective C–C bond formation to sulfonylimines through use of the 2-pyridinesulfonyl group as a novel stereocontroller.16

ISSN:0069-3030    

DOI:10.1039/b822046h

出版商:RSC    

年代:2009

数据来源: RSC

摘要:

IntroductionThis chapter attempts to bring to the readers’ attention some of the highlights of heterocyclic chemistry from the literature of 2005. The review focuses on the synthesis of heterocycles, rather than their reactivity. Solid support and combinatorial based reports are not included.

ISSN:0069-3030    

DOI:10.1039/b609196m

出版商:RSC    

年代:2006

数据来源: RSC