Oxazaborolidines, hydroboration

Corey extended the utility of this catalytic hydroboration chemistry remarkably (38). Scheme 15 shows some examples of the highly en-antioselective asymmetric borane reduction of ketones. The well-designed chiral oxazaborolidines, which act as catalyst precursors, have... 

S -Methyl lactate gives a poor ee in hydroboration of acetophenone, but ZnCl2 raises it.322 A molecular orbital method has looked at the enantioselectivities associated with four oxazaborolidine catalysts acting on phenyl methyl ketone.323 0>... 

The pioneering studies by Itsuno [1] and Corey [2] on the development of the asymmetric hydroboration of ketones using oxazaborolidines have made it possible to easily obtain chiral secondary alcohols with excellent optical purity [3]. Scheme 1 shows examples of Corey s (Corey-Bakshi-Shibata) CBS reduction. When oxazaborolidines 1 were used as catalysts (usually 0.01-0.1 equiv), a wide variety of ketones were reduced by borane reagents with consistently high enan-tioselectivity [2]. The sense of enantioselection was predictable. Many important biologically active compounds and functional materials have been synthesized using this versatile reaction [2-4]. 

In reactions with polymer-bound catalysts, a mass-transfer limitation often results in slowing down the rate of the reaction. To avoid this disadvantage, homogenous organic-soluble polymers have been utilized as catalyst supports. Oxazaborolidine 5, supported on linear polystyrene, was used as a soluble immobilized catalyst for the hydroboration of aromatic ketones in THF to afford chiral alcohols with an ee of up to 99% [40]. The catalyst was separated from the products with a nanofiltration membrane and then was used repeatedly. The total turnover number of the catalyst reached as high as 560. An intramolecularly cross-linked polymer molecule (microgel) was also applicable as a soluble support [41]. 

D. The use of chiral oxazaborolidines as enantioselective catalysts for the reduction of prochiral ketones, imines, and oximes, the reduction of 2-pyranones to afford chiral biaryls, the addition of diethylzinc to aldehydes, the asymmetric hydroboration, the Diels-Alder reaction, and the aldol reaction has recently been reviewed.15b d The yield and enantioselectivity of reductions using stoichiometric or catalytic amounts of the oxazaborolidine-borane complex are equal to or greater than those obtained using the free oxazaborolidine.13 The above procedure demonstrates the catalytic use of the oxazaborolidine-borane complex for the enantioselective reduction of 1-indanone. The enantiomeric purity of the crude product is 97.8%. A... 

Other Applications. Chiral oxazaborolidines derived from ephedrine have also been used in asymmetric hydroborations, and as reagents to determine the enantiomeric purity of secondary alcohols. Chiral l,3,2-oxazaborolidin-5-ones derived from amino acids have been used as asymmetric catalysts for the Diels-Alder reaction,and the aldol reaction. ... 

Hydroboration of simple ketones eatalyzed by proline-derived oxazaborolidine 45 provides a practical method for the preparation of chiral secondary alcohols (Scheme 13). Under this protocol, a key intermediate in the synthesis of MK-0417 (44), a water-soluble carbonic anhydrase inhibitor, has been prepared... 

Chiral chromans are redueed stereoselectively by oxazaborolidine-catalyzed hydroboration to give the potent antiarrhythmia agent MK-0499, which acts as a potassium channel blocker [46]. 

Keywords Hydroboration, Ketone, Reduction, Oxazaborolidine, Oxazaphospholidine, Borane, Borohydride... 

Hydroboration of the C-C unsaturated bond may be a possible side reaction in the reduction of a,P-unsatuxated ketones. However, in many cases, some ox-azaborolidines successfully catalyze the selective reduction of ketone carbonyls (Scheme 6). The borane reduction of 2-methylnon-l-en-3-one with oxazaborolidine 45 showed a clean conversion to the allylic alcohol (98%, 92% ee S) [82]. The same catalyst [83] and 4b [84] were effective for the reduction of a,P-ynones [83]. 

Oxazaborolidines have also been used as catalysts in atrop enantioselective ring-opening (49), asymmetric addition of diethylzinc to aldehydes (50), asymmetric Diels-Alder reactions (57, 52), aldol reactions (55), Rh catalyzed hydroboration (54), etc. 

Brown, J. M. Lloyd-Jones, G. C. Catalytic Asymmetric Hydroboration with Oxazaborolidines. Tetrahedron Asymmetry 1990,1,869-872. 

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