Facile, green, and functional group-tolerant reductions of carboxylic acids…in water

Abstract

Facile reductions of carboxylic acids to aldehydes or alcohols can be effected under mild conditions upon initial conversion to their corresponding S-2-pyridyl thioesters. Upon treatment with a commercially available and air-stable nickel pre-catalyst and silane as a stoichiometric reductant, aldehydes are formed in moderate to good yields. Alternatively, the 1-pot conversion of acids to their thioester derivatives can be followed by reduction to the alcohol upon treatment with sodium borohydride. A variety of starting materials ranging from highly functionalized acids to educts from the Merck Informer Library can be transformed using these green reaction media.

Facile, green, and functional group-tolerant reductions of carboxylic acids…in, or with, water

“…Probenecid, a drug used to treat gouty arthritis, and Repaglinide, a drug used to treat diabetes, were both reduced in excellent yields ( products 43 and 51, respectively). Lastly, the fibrates, which are a class of lipid lowering drugs including gemfibrozil (44), ciprofibrate (45), and bezafibrate (46) were all reduced to the corresponding alcohols in excellent yields. It is interesting to note that the gem-dichlorocyclopropane moiety in ciprofibrate derivative 45 remains intact under these mild and green reducing conditions.…”

“…Reduction of ibuprofen (47) and the Merck informer libraryderived alcohol 49, are both illustrative of the higher efficiency of this methodology as compared to current literature methods. 46 Scheme 8 Reduction of late-stage functionalized carboxylic acids to alcohols.…”