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