Search

The use of (i) enantiomerically pure phosphinamides coupled to borane and (ii) an enantiomerically pure amino alcohol coupled to a transfer hydrogenation process, in the asymmetric catalysis of the reduction of ketones to alcohols, is described. The former process is particularly suited to the reduction of alpha-chlorinated substrates, affording e.e.s of up to 94%, whilst the latter process is optimal for unfunctionalised ketones, affording e.e.s of up to 98%.

We have designed and prepared a catalyst for the asymmetric reduction of ketones which combines a phosphinamide and a boron-containing heterocyclic ring. The former group acts to direct and activated the borane, whilst the latter provides a well defined position for location of the ketone. The resulting reduction therefore takes place in a well-defined stereochemical environment. Enantiomeric excesses of up to 59%, in a predictable absolute sense, were achieved. Evidence that O- co-ordination of borane is important in the reduction mechanism is also presented

A number of new catalysts for the asymmetric reductions of ketones by borane are described. The highest accelerations are achieved by catalysts in which the phosphinamide (R 2 NPO) unit can adopt a planar geometry. This observation has provided an insight into the mechanism of catalysis.

We have designed and prepared a catalyst for the asymmetric reduction of ketones which combines a phosphinamide and a boron-containing heterocyclic ring. The former group acts to direct and activated the borane, whilst the latter provides a well defined position for location of the ketone. The resulting reduction therefore takes place in a well-defined stereochemical environment. Enantiomeric excesses of up to 59%, in a predictable absolute sense, were achieved. Evidence that O- co-ordination of borane is important in the reduction mechanism is also presented

The development of catalytic methods for the synthesis of non-racemic epoxides has been a long standing goal in asymmetric synthesis. For epoxide synthesis, attention has largely focused on the asymmetric oxidation of alkenes and good enantioselectivities are now beginning to emerge for an increasing range of substrates.1-3 Alkenes are themselves commonly obtained by Wittig reaction from the corresponding aldehyde or ketone and so epoxidation is usually a two step process from carbonyl compounds. However, in terms of efficiency and atom economy this overall process is poor compared to direct epoxidation of carbonyl compounds using sulfur ylides. However, in terms of catalysis and asymmetric induction, oxidation of alkenes is still superior as epoxidation of carbonyl compounds using sulfur ylides usually requires stoichiometric amounts of sulfides/sulfur ylides and only gives moderate enantioselectivities.4 We have described a catalytic process for epoxidation involving sulfur ylides which now overcomes this limitation (Scheme 1).5 Whilst only low levels of enantioselectivity were originally achieved we now report significant improvements and describe chiral sulfides which provide high levels of asymmetric induction.6

The development of catalytic methods for the synthesis of non-racemic epoxides has been a long standing goal in asymmetric synthesis. For epoxide synthesis, attention has largely focused on the asymmetric oxidation of alkenes and good enantioselectivities are now beginning to emerge for an increasing range of substrates.1-3 Alkenes are themselves commonly obtained by Wittig reaction from the corresponding aldehyde or ketone and so epoxidation is usually a two step process from carbonyl compounds. However, in terms of efficiency and atom economy this overall process is poor compared to direct epoxidation of carbonyl compounds using sulfur ylides. However, in terms of catalysis and asymmetric induction, oxidation of alkenes is still superior as epoxidation of carbonyl compounds using sulfur ylides usually requires stoichiometric amounts of sulfides/sulfur ylides and only gives moderate enantioselectivities.4 We have described a catalytic process for epoxidation involving sulfur ylides which now overcomes this limitation (Scheme 1).5 Whilst only low levels of enantioselectivity were originally achieved we now report significant improvements and describe chiral sulfides which provide high levels of asymmetric induction.6

Triphenylarsine catalyses the formation of epoxides from carbonyl compounds and tosylhydrazone salts. This convergent synthesis gives complete trans selectivity for all aldehyde and tosylhydrazone salt coupling partners.