John R. Studley

New catalysts containing an N-PO structural unit for the asymmetric reduction of ketones.

Abstract 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.

New chiral phosphinamide catalysts for highly enantioselective reduction of ketones

Abstract 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.

Novel catalysts for asymmetric reduction of carbonyl groups

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%.

Stereoelectronic requirements for a new class of asymmetric ketone reduction catalysts containing an NPO structural unit.

Abstract 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.

PHOSPHINAMIDES CATALYSTS CONTAINING A STEREOGENIC PHOSPHORUS ATOM FOR THE ASYMMETRIC REDUCTION OF KETONES BY BORANE

Abstract 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.

DESIGN, SYNTHESIS AND APPLICATIONS OF A KETONE REDUCTION CATALYST CONTAINING A PHOSPHINAMIDE COMBINED WITH A DIOXABOROLIDINE UNIT

Abstract 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 use of phosphinamide N-protecting groups in the diastereoselective reduction of ketones

Abstract 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.

Chiral phosphinamides: new catalysts for the asymmetric reduction of ketones by borane

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.

Studies of the zinc(II) catalysed addition of silyl enol ethers to cyclic enol ethers

Abstract 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.