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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 identified a new class of catalysts for the asymmetric reduction of prochiral ketones by borane. Key to the architecture of effective catalysts is an N–PO structural unit which may be part of a phosphinamide, phosphonamide or a related structure. Such catalysts are simple to prepare, are often crystalline solids and may be recovered from reduction reactions and reused. The catalysts act essentially as Lewis bases, serving to increase the reactivity of borane by electron donation. The incorporation of a hydroxy group into the catalyst provides an adjacent Lewis acid site upon reaction with borane and thus affords a superior catalyst capable of asymmetric inductions of up to 92% ee.

The effect of the configuration of the phosphorus atom in phosphinamide reduction catalysts has been studied through the preparation and use of a series of catalysts containing stereogenic phosphorus atoms of known configuration. The conclusion of this work is that a stereogenic centre at phosphorus can improve the selectivity of reductions using this catalyst, but is not sufficient in itself to generate the higher levels of selectivity which have been achieved with related catalysts. The X-ray crystallographic structure of a key compound is also featured.

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 novel class of recoverable and highly stable phosphinamide catalysts for the asymmetric reduction of ketones by borane is described. Enantiomeric excesses of up to 92% have been obtained using 10 mol% of the optimum catalyst.

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.

A novel class of recoverable and highly stable phosphinamide catalysts for the asymmetric reduction of ketones by borane is described. Enantiomeric excesses of up to 92% have been obtained using 10 mol% of the optimum catalyst.

The effect of the configuration of the phosphorus atom in phosphinamide reduction catalysts has been studied through the preparation and use of a series of catalysts containing stereogenic phosphorus atoms of known configuration. The conclusion of this work is that a stereogenic centre at phosphorus can improve the selectivity of reductions using this catalyst, but is not sufficient in itself to generate the higher levels of selectivity which have been achieved with related catalysts. The X-ray crystallographic structure of a key compound is also featured.

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 phosphinamide N-protecting group is demonstrated to be an effective directing group for diastereoselective reductions of proximal ketones. A range of methods for the preparation of the requisite α-amino ketones substrates are described.

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%.

A practical, general, and convergent route to epoxides with control of the relative and absolute stereochemistry has been achieved by generating the reactive intermediate (the diazo compound) in situ from tosylhydrazone salts (see scheme, PTC=phase-transfer catalyst, Ts=toluene-4-sulfonyl). High yields (58-82 %), high d.r. (88:12-98:2), and high ee values (87-94 %) have been obtained using a new class of stable chiral sulfides at low catalyst loading (5 mol %) and [Rh2 (OAc)4 ] (0.5 mol %).

A variety of metalated tosylhydrazone salts derived from benzaldehyde have been prepared and were reacted with benzaldehyde in the presence of tetrahydrothiophene (THT) (20 mol %) and Rh(2)(OAc)(4) (1 mol %) to give stilbene oxide. Of the lithium, sodium, and potassium salts tested, the sodium salt was found to give the highest yield and selectivity. This study was extended to a wide variety of aromatic, heteroaromatic, aliphatic, alpha,beta-unsaturated, and acetylenic aldehydes and to ketones. On the whole, high yields of epoxides with moderate to very high diastereoselectivities were observed. A broad range of tosylhydrazone salts derived from aromatic, heteroaromatic, and alpha,beta-unsaturated aldehydes was also examined using the same protocol in reactions with benzaldehyde, and again, good yields and high diastereoselectivities were observed in most cases. Thus, a general process for the in situ generation of diazo compounds from tosylhydrazone sodium salts has been established and applied in sulfur-ylide mediated epoxidation reactions. The chiral, camphor-derived, [2.2.1] bicyclic sulfide 7 was employed (at 5-20 mol % loading) to render the above processes asymmetric with a range of carbonyl compounds and tosylhydrazone sodium salts. Benzaldehyde tosylhydrazone sodium salt gave enantioselectivities of 91 +/- 3% ee and high levels of diastereoselectivity with a range of aldehydes. However, tosylhydrazone salts derived from a range of carbonyl compounds gave more variable selectivities. Although those salts derived from electron-rich or neutral aldehydes gave high enantioselectivities, those derived from electron-deficient or hindered aromatic aldehydes gave somewhat reduced enantioselectivities. Using alpha,beta-unsaturated hydrazones, chiral sulfide 7 gave epoxides with high diastereoselectivities, but only moderate yields were achieved (12-56%) with varying degrees of enantioselectivity. A study of solvent effects showed that, while the impact on enantioselectivity was small, the efficiency of diazo compound generation was influenced, and CH(3)CN and 1,4-dioxane emerged as the optimum solvents. A general rationalization of the factors that influence both relative and absolute stereochemistry for all of the different substrates is provided. Reversibility in formation of the betaine intermediate is an important issue in the control of diastereoselectivity. Hence, where low diastereocontrol was observed, the results have been rationalized in terms of the factors that contribute to the reduced reversion of the syn betaine back to the original starting materials. The enantioselectivity is governed by ylide conformation, facial selectivity in the ylide reaction, and, again, the degree of reversibility in betaine formation. From experimental evidence and calculations, it has been shown that sulfide 7 gives almost complete control of facial selectivity, and, hence, it is the ylide conformation and degree of reversibility that are responsible for the enantioselectivity observed. A simple test has been developed to ascertain whether the reduced enantioselectivity observed in particular cases is due to poor control in ylide conformation or due to partial reversibility in the formation of the betaine.

The addition of silyl enol ethers to cyclic enol ethers by zinc dibromide catalysed electrophilic addition of a phenylsulphenyl group has been shown to give exclusively the trans- diastereoisomer when the silyl enol ether of acetophenone is used. The same reaction was catalysed by a zinc(II) alkoxyamine complex, but the use of the chiral ligand (+)- cinchonine in this reaction did not result in any asymmetric induction.

A practical, general, and convergent route to epoxides with control of the relative and absolute stereochemistry has been achieved by generating the reactive intermediate (the diazo compound) in situ from tosylhydrazone salts (see scheme, PTC=phase-transfer catalyst, Ts=toluene-4-sulfonyl). High yields (58-82 %), high d.r. (88:12-98:2), and high ee values (87-94 %) have been obtained using a new class of stable chiral sulfides at low catalyst loading (5 mol %) and [Rh

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.

New catalysts for the asymmetric reduction of ketones to chiral alcohols are described. Together they represent an entirely novel class of catalysts which have in common an N-PO structural unit.

A practical, general, and convergent route to epoxides with control of the relative and absolute stereochemistry has been achieved by generating the reactive intermediate (the diazo compound) in situ from tosylhydrazone salts (see scheme, PTC=phase-transfer catalyst, Ts=toluene-4-sulfonyl). High yields (58-82 %), high d.r. (88:12-98:2), and high ee values (87-94 %) have been obtained using a new class of stable chiral sulfides at low catalyst loading (5 mol %) and [Rh2 (OAc)4 ] (0.5 mol %).