Asymmetric Reduction of Ketones Under Mild Conditions Using NaBH₄ and TarB‐NO₂: An Efficient and Unusual Chiral Acyloxyborohydride Reducing System

Abstract

High enantioselectivities are obtained for the reduction of a series of ketones using the inexpensive and mild reducing agent NaBH4 with TarB‐NO2 (1). This easily prepared tartaric acid‐based reagent combines a Lewis acid with carboxylic acids in a single bifunctional reagent. When combined with NaBH4, the resulting chiral acyloxyborohydride mediates the reduction of aromatic ketones to provide the product alcohols in enantiomeric excesses of 93–98 %. Several aliphatic ketones were also reduced with moderate to excellent enantioselectivity. A unique mechanism is provided with supporting calculations for the proposed active species and transition state. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Synthesis of New Allocolchicinoids with Seven‐ and Eight‐Membered B‐Rings by Enyne Ring‐Closing Metathesis

“…This synthesis was based on the introduction of the stereogenic center at C7 by asymmetric reduction of the ketone 8 . In their synthesis of the natural (–)‐(7 S )‐allocolchicine ( 2a ), Wulff and co‐workers reported5a that the procedure developed by Singaram and co‐workers for the enantioselective reduction of ketones with (+)‐TarB‐NO 2 ( 29 )25 had been found to give the best yields of the (7 R )‐alcohol 26. When ketone 8 was treated with 2 equiv.…”

5‐Carboxymethyl‐2‐(4‐methylthiophenyl)‐1,3,2‐dioxaborolan‐4‐one: synthesis, characterization and application in enantioselective reduction of ketones

“…This fact influences strongly the kinetics of the formation of 3e . In two independent experiments 2a was reacted with 1a or with tartaric acid13, 14 and the rate of the hydrogen evolution was controlled. The experiments revealed that reaction with 1a is much slower than the reaction with tartaric acid (Scheme ).…”

Mild and Practical Reductions of Prochiral Ketones to Chiral Alcohols Using the Chiral Boronic Ester TarB-H

“…We concluded that this increase in induction was due to the fact that only the acyloxyborohydride, which is formed when sodium borohydride reacts with the carboxylic acid moiety of TarB-X, is soluble in tetrahydrofuran and thus direct reduction of the ketone in solution is minimized. 6,7 TarB-NO 2 proved adept in the reduction of various ketones at room temperature, but required a dry and inert atmosphere to maintain high enantioselectivities.…”

“…Computer modeling and 11 B NMR data supports our theory that reduction proceeds via a chiral acyloxyborohydride intermediate species, which is formed when the carboxylic acid group on TarB-X reacts with sodium borohydride (Scheme 3). 7 Most boron-derived reducing agents, including CBS and DIP-Cl, are extremely susceptible to hydrolysis and thus No are usually used under an inert atmosphere. 8,9 In order to make the TarB-X system more amenable to large-scale synthesis, we conducted various experiments to find a derivative that could give the same results as TarB-NO 2 without the need for a dry and inert atmosphere.…”