CBS-oxazaborolidine

Catalytic Enantioselective Reduction of Ketones. An even more efficient approach to enantioselective reduction is to use a chiral catalyst. One of the most developed is the oxazaborolidine 18, which is derived from the amino acid proline.148 The enantiomer is also available. These catalysts are called the CBS-oxazaborolidines. 

Scheme 5.6. Enantioselective Reduction of Ketones Using CBS-Oxazaborolidine... 

The CBS-catalyst [(S)-2-methyl-CBS-oxazaborolidine] (S)-5 (1.0 M in toluene) (The CBS catalyst is named after Corey, Bakshi, and Shibata) and the borane-THF complex (1.0 M in THF) were obtained from Aldrich Chemical Co., Inc. and used as received. THF was distilled from potassium directly before use. 

Triphenylphosphine Phosphine, triphenyl- (8,9) (603-35-0) (S)-2-Methyl-CBS-oxazaborolidine (CBS named after Corey, Bakshi, Shibata) ... 

For example, (S)-2-methyl-CBS-oxazaborolidine binds reversibly with diborane to form the reactive reducing species 1.64. Coordination of the ketone oxygen with the Lewis acidic boron orients and activates the carbonyl group for hydride transfer to its si face. The... 

Enantioselective reduction of ketones by boranes and an enantiomeric catalyst oxazaboro-lidine (the CBS catalyst) is known as the Corey, Bakshi and Shibata method . Both enantiomers of 2-methyl-CBS-oxazaborolidine (6.52 and 6.53) are used for the reduction of prochiral ketones, imines and oximes to produce chiral alcohols, amines and amino alcohols in excellent yields and enantiomeric excesses. 

We have also examined the use of chiral bi-2-naphthol to resolve some other racemic amino alcohols. The S-diphenylpyrrolidinemethanol S-10, synthesised from S-proline is useful in the preparation of the CBS oxazaborolidine catalyst,16 widely used in catalytic asymmetric reductions. Accordingly, the corresponding R-10 enantiomer is also a valuable chiral compound. 

In 2003, Molander et al. reported the synthesis of (+ )-isoschizandrin, a natural product displaying anti-ulcer activity in rats. The key step of the synthesis was the atropo-enantioselective reduction of a seven-membered lactone by using a chiral oxazaborolidine, (i )-2-methyl-CBS-oxazaborolidine, which provided the corresponding chiral lactone after recycling (Scheme 5.45). Similar conditions were also applied to the corresponding six-membered lactone, which led to the formation of the corresponding chiral diol in excellent yield and enantioselectivity, as shown in Scheme 5.45. 

S)-2-methyl-CBS-oxazaborolidine and BH3.THF, providing the corresponding lactone-opened product in an enantioselective manner (Scheme 5.46). 

Yet another route to the popular Blechert intermediate (—)-402, by Bates and Dewey, started with an unusual conversion of tetrahydrofuian into 4-azidobutan-l-ol (411), which was oxidized to the aldehyde and treated with lithiated trimethylsilylacetylene to give the racemic adduct ( )-412 (Scheme 57). Oxidation to the ketone and reduction with cat-echolborane and the Corey (S)-2-methyl-CBS-oxazaborolidine produced (R)-(- -)-412, but in an ee of only about 75%. A further two steps afforded... 

Nicolaou and coworkers completed the enantioselective synthesis of these two natural products molecules through a short and equally efficient route (12 steps from commercially available material with the 4% overall yield) involving a series of cascade reactions and novel skeletal rearrangements [107b]. This unique route commenced with a CBS asymmetric reduction of ketone 288 that is easily generated from the resveratrol monomer (Scheme 10.55). The chiral benzylic alcohol 289 was obtained in 85% yield and 95% ee in the presence of one equivalent of catecholborane and catalytic amount of (/ )-(+)-2-methyl-CBS-oxazaborolidine. This newly formed C8a center would be served as a chiral source by which other stereocenters within the architectnre... 

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