Corey-Bakshi-Shibata Reduction
The Corey-Bakshi-Shibata (CBS) reduction, also known as the Corey-Itsuno reaction, is the enantioselective reduction of ketones using a catalytic oxazoborilidine.
General features:
1. When the oxazaborolidine has a rigid bicyclic structure, high enantiomeric excess can be achieved. 2. The CBS catalyst presents good air and moisture stability; however, the presence of water in the reaction mixture has been shown to have a significant effect on enantiomeric excesses. Hence, the reduction must be conducted under anhydrous conditions. 3. This reaction is an effective and powerful method to reduce a wide range of ketones in a stereoselective and chemoselective manner. 4. The driving force for the face-selective intramolecular hydride transfer has two main reasons. (1) the activation of the borane reagent by coordination to the Lewis basic nitrogen and (2) the enhancement of the Lewis acidity of the boron atom (of the catalyst) for coordination to the ketone.
Corey-Bakshi-Shibata Reduction
Reaction Mechanism
1. Coordination of BH3 (Lewis acid) to the tertiary nitrogen atom (Lewis base) of the CBS catalyst to enhance the Lewis acidity of the boron atom and to activate the BH3 to become a strong hydride donor. 2. The CBS catalyst-borane complex then binds to the ketone at the sterically more accessible lone pair, the lone pair closer to the smaller substituent. 3. Hydride transfer via a six-membered transition state delivers the alkoxyborane and regenerates the catalyst. 4. Final acidic workup yields the desired chiral alcohol.
Experimental Procedure
A solution of the cyclopentenone (56 mmol, 1.0 eq) in anhydrous toluene (110 mL) was cooled to -78 °C, (R)-2-methyl-CBS-oxazaborolidine (1.0 M in toluene, 0.2 eq) was added, and the reaction mixture stirred for 5 min at -78 °C. Then, catecholborane solution (1.0 M in THF, 1.8 eq) was added slowly, and the reaction mixture was stirred for 24 h at -78 °C before quenched by saturated sodium bicarbonate solution. The resulting mixture was extracted with ether, and the combined organic extracts washed sequentially with 2 M NaOH, and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel to give the desired alcohol (90% yield, 92% ee).
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The Chemists' Cookbook
The Chemists’ Cookbook will be your favorite study or lab companion. It features 201 named reactions with detailed reaction schemes and experimental procedures. It includes a list of reactions organized by categories, making it simple to find reactions that perform similar transformations or target specific functional groups. Available as an ebook or in paperback.
NEW RELEASE OUT NOW!
The Chemists' Cookbook
The Chemists’ Cookbook will be your favorite study or lab companion. It features 201 named reactions with detailed reaction schemes and experimental procedures. It includes a list of reactions organized by categories, making it simple to find reactions that perform similar transformations or target specific functional groups. Available as an ebook or in paperback.
