CBSreduction

CBSreduction refers to a chemical process used in organic synthesis to selectively reduce carbonyl compounds (aldehydes and ketones) to their corresponding alcohols without affecting other functional groups present in the molecule. The method is named after the reagents commonly employed: cyanoborohydride salts, such as sodium cyanoborohydride (NaBH₃CN) or ammonium acetate-buffered sodium cyanoborohydride. This reduction is particularly valuable in pharmaceutical and fine chemical synthesis due to its mild conditions and compatibility with sensitive functional groups like esters, amides, and nitriles.

The CBS reduction is a stereoselective reduction, meaning it can produce chiral alcohols with high enantiomeric excess (ee). The process relies on a chiral catalyst derived from borane and a ligand, often a phosphine or phosphinite, which directs the approach of the hydride to one face of the carbonyl group. The most widely used catalyst system is developed by Corey, Bakshi, and Shibata (CBS), which employs borane-tetrahydrofuran complexes in combination with a chiral ligand, such as (S)-2-methyl-CBS-oxazaborolidine or its enantiomer.

The mechanism involves the formation of a borane complex with the carbonyl compound, followed by hydride transfer from the borane to the carbonyl carbon. The chiral ligand controls the facial selectivity, leading to the formation of one enantiomer preferentially. The reaction typically proceeds under mild conditions, often at low temperatures, and can be carried out in non-protic solvents like toluene or dichloromethane. After the reduction, the intermediate borate ester is hydrolyzed to release the alcohol product.

CBSreduction is widely applied in the synthesis of complex natural products, chiral intermediates, and pharmaceuticals where stereochemical control is critical. Its compatibility with various functional groups and ability to deliver high enantioselectivity make it a cornerstone technique in asymmetric synthesis.