The synthesis of chiral N-heterocyclic carbene–borane and –diorganoborane complexes and their use in the asymmetric reduction of ketones

Chiral N-heterocyclic carbene–borane complexes have been synthesised, and have been shown to reduce ketones with Lewis acid promotion. Chiral N-heterocyclic carbene–borane and –diorganoborane complexes can reduce ketones with enantioselectivities up to 75% and 85% ee, respectively.

Anthraquinone catalysis in the glucose-driven reduction of indigo to leuco-indigo

Anthraquinone immobilised onto the surface of indigo microcrystals enhances the reductive dissolution of indigo to leuco-indigo. Indigo reduction is driven by glucose in aqueous NaOH and a vibrating gold disc electrode is employed to monitor the increasing leuco-indigo concentration with time. Anthraquinone introduces a strong catalytic effect which is explained by invoking a molecular "wedge effect'' during co-intercalation of Na+ and anthraquinone into the layered indigo crystal structure. The glucose-driven indigo reduction, which is in effective in 0.1 M NaOH at 65 degrees C, becomes facile and goes to completion in the presence of anthraquinone catalyst. Electron microscopy of indigo crystals before and after reductive dissolution confirms a delamination mechanism initiated at the edges of the plate-like indigo crystals. Catalysis occurs when the anthraquinone-indigo mixture reaches a molar ratio of 1:400 (at 65 degrees C; corresponding to 3 mu M anthraquinone) with excess of anthraquinone having virtually no effect. A strong temperature effect ( with a composite E-A approximate to 120 kJ mol(-1)) is observed for the reductive dissolution in the presence of anthraquinone. The molar ratio and temperature effects are both consistent with the heterogeneous nature of the anthraquinone catalysis in the aqueous reaction mixture.

Experimental and theoretical evidence for homogeneous catalysis in the gas-phase reaction of SiH2 with H2O (and D2O): a combined kinetic and quantum chemical study

Time-resolved kinetic studies of the reaction of silylene, SiH2, with H2O and with D2O have been carried out in the gas phase at 297 K and at 345 K, using laser flash photolysis to generate and monitor SiH2. The reaction was studied independently as a function of H2O (or D2O) and SF6 (bath gas) pressures. At a fixed pressure of SF6 (5 Torr), [SiH2] decay constants, k(obs), showed a quadratic dependence on [H2O] or [D2O]. At a fixed pressure of H2O or D2O, k(obs) Values were strongly dependent on [SF6]. The combined rate expression is consistent with a mechanism involving the reversible formation of a vibrationally excited zwitterionic donor-acceptor complex, H2Si...OH2 (or H2Si...OD2). This complex can then either be stabilized by SF6 or it reacts with a further molecule of H2O (or D2O) in the rate-determining step. Isotope effects are in the range 1.0-1.5 and are broadly consistent with this mechanism. The mechanism is further supported by RRKM theory, which shows the association reaction to be close to its third-order region of pressure (SF6) dependence. Ab initio quantum calculations, carried out at the G3 level, support the existence of a hydrated zwitterion H2Si...(OH2)(2), which can rearrange to hydrated silanol, with an energy barrier below the reaction energy threshold. This is the first example of a gas-phase-catalyzed silylene reaction.

Total synthesis of (+/-) maculalactone A, maculalactone B and maculalactone C and the determination of the absolute configuration of natural (+) maculalactone A by asymmetric synthesis

Maculalactones A, B and C from the marine cyanobacterium Kyrtuthrix maculans are amongst the only compounds based on the tribenzylbutyrolactone skeleton known in nature and (+) maculalactone A from the natural source possesses significant biological activity against various marine herbivores and marine settlers. We now report a concise synthesis of racemic maculalactone A in five steps from inexpensive starting materials. Maculalactones B and C were synthesized by a minor modification to this procedure, and the synthetic design also permitted an asymmetric synthesis of maculalactone A to be achieved in around 85% ee. The (+) and (-) enantiomers of maculalactone A were assigned, respectively, to the S and R configurations on the basis of the chiral selectivity expected for catecholborane reduction of an unsymmetrical ketone in the presence of Corey's oxazoborolidine catalyst. Surprisingly, it appeared that natural (+) maculalactone A was biosynthesized in K. maculans in a partially racemic form, comprising ca. 90-95% of the (S) enantiomer and 5-10% of its (R) enantiomer. Coincidentally therefore, the percentage enantiomeric excess of the product obtained from asymmetric synthesis almost exactly matched that found in nature. (C) 2004 Elsevier Ltd. All rights reserved.

Asymmetric synthesis of (1R,2S,3R)-3-methylcispentacin and (1S,2S,3R)-3-methyltranspentacin by kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate

Conjugate addition of lithium dibenzylamide to tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate occurs with high levels of stereocontrol, with preferential addition of lithium dibenzylamide to the face of the cyclic alpha,beta-unsaturated acceptor anti- to the 3-methyl substituent. High levels of enantiorecognition are observed between tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate and an excess of lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide (10 eq.) (E > 140) in their mutual kinetic resolution, while the kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate with lithium (S)-N-benzyl-N-alpha-methylbenzylamide proceeds to give, at 51% conversion, tert-butyl (1R, 2S, 3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-c arboxylate consistent with E > 130, and in 39% yield and 99 +/- 0.5% de after purification. Subsequent deprotection by hydrogenolysis and ester hydrolysis gives (1R, 2S, 3R)-3-methylcispentacin in > 98% de and 98 +/- 1% ee. Selective epimerisation of tert-butyl (1R, 2S, 3R, alphaS)-3-methyl-2-N- benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate by treatment with (KOBu)-Bu-t in (BuOH)-Bu-t gives tert-butyl (1S, 2S, 3R, alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carb oxylate in quantitative yield and in > 98% de, with subsequent deprotection by hydrogenolysis and ester hydrolysis giving (1S, 2S, 3R)-3-methyltranspentacin hydrochloride in > 98% de and 97 +/- 1% ee.

Stereodivergent approach to the asymmetric synthesis of bacillariolides: A formal synthesis of ent-bacillariolide II

Asymmetric synthesis of densely functionalized bicyclic frameworks for entry into bacillariolides I/III and ent-bacillariolide II is reported. The key features are ring-closing metathesis of a pair of diastereomerically related dienes obtained through a stereodivergent route from a R-(+)-glyceraldehyde derivative, transformation of a nonstereoselective cyclopentene ester enolate alkylation process to a completely stereoselective one through alkylation of a bulky ester enolate with a bulky electrophile, and a remote silyloxymethyl group directed epoxidation.

Asymmetric synthesis of arylalanines via asymmetric aza-darzens (ADZ) reaction

(R)-3-Arylalanines may be prepared in high enantiomeric purity from N-dpp imines by a four-step reaction sequence involving asymmetric aza-Darzens reaction, dephosphinylation, hydrogenolysis and hydrolysis. The amino acids thus obtained were of >95% enantiomeric purity.

Convenient route to enantiopure aryl cyclopentanes via Diels-Alder reaction of asymmetric dienes. Total synthesis of (+)-herbertene and (+)-cuparene

A general route for the synthesis of highly substituted aryl cyclopentanes has been developed involving Diels-Alder reaction of asymmetric dienes prepared from (+)-camphoric acid followed by aromatization of the resulting cyclohexene derivatives. Employing this protocol enantiospecific synthesis of (+)-herbertene and (+)-cuparene has been accomplished. (C) 2003 Elsevier Science Ltd. All rights reserved.

Application of the asymmetric hetero Diels-Alder reaction for synthesising carbohydrate derivatives and glycosidase inhibitors

This review provides a discussion of recent developments in the asymmetric hetero Diels-Alder reaction (AHDAR), with particular emphasis on the synthesis of carbohydrates, their derivatives, and inhibitors of carbohydrate processing enzymes.

Asymmetric aziridine synthesis by aza-Darzens reaction of N-diphenylphosphinylimines with chiral enolates. Part 2: inversion of diastereoselectivity

The aza-Darzens ('ADZ') reactions of N-diphenylphosphinyl ('N-Dpp') imines with chiral enolates derived from N-bromoacetyl 2S-2,10-camphorsultam proceed in generally good yield to give N-diphenylphosphinyl aziridinoyl sultams. However, the stereoselectivity of the reaction is dependent upon the structure of the imine substituent: when the chiral enolate was reacted with arylimines substituted in the ortho-position, mixtures of cis- and trans-2'R,3'R-aziridines were obtained, often with a complete selectivity in favour of the trans-isomer. (c) 2006 Elsevier Ltd. All rights reserved.

Asymmetric aziridine synthesis by aza-Darzens reaction of N-diphenylphosphinylimines with chiral enolates. Part 1: formation of cis-aziridines

Theaza-Darzens ('ADZ') reactions off-diphenylphosphinyl (W-Dpp') imines with chiral enolates derived from oxazolidinones and camphorsultam have been Studied. Whilst oxazolidinone enolates reacted poorly in terms of aziridination, the use of the chiral enolate derived from both antipodes of N-bromoacetyl 2, 10-camphorsultam, 2R-(5) and 2S-(5), with N-diphehenylphosphinyl aryl and tert-butylimines proceeded in generally good yield to give, respectively, (2'R,3'R)- or (2'S,3'S)-cis-N-diphenylphosphinyl aziridinoyl sultams of high de. (c) 2006 Elsevier Ltd. All rights reserved.

Asymmetric ammonium ylid rearrangements: the effect of nitrogen asymmetry

[2,3]-Sigmatropic rearrangements of allylic ammonium ylids derived from glycinoylcamphorsultams are highly selective in terms of relative and absolute stereocontrol only when acyclic alkenes are present. When chiral esters of ylids derived from N-methyltetrahydro-pyridine ('NMTP') undergo rearrangement, the reactions show exclusive cis-stereoselectivity but the products are obtained with virtually no absolute stereocontrol. These observations support the notion that sigmatropic rearrangements of N-chiral ammonium ylids are controlled by nitrogen stereogenicity. (c) 2006 Elsevier Ltd. All rights reserved.