Expeditious and practical synthesis of tertiary alcohols from esters enabled by highly polarized organometallic compounds under aerobic conditions in Deep Eutectic Solvents or bulk water

An efficient protocol was developed for the synthesis of tertiary alcohols via nucleophilic addition of organometallic compounds of s-block elements (Grignard and organolithium reagents) to esters performed in the biodegradable choline chloride/urea eutectic mixture or in water. This approach displays a broad substrate scope, with the addition reaction proceeding quickly (20 s reaction time) and cleanly, at ambient temperature and under air, straightforwardly furnishing the expected tertiary alcohols in yields of up to 98%. The practicability of the method is exemplified by the sustainable synthesis of some representative S-trityl-t-cysteine derivatives, which are a potent class of Eg5 inhibitors, also via telescoped one-pot processes. (C) 2020 Elsevier Ltd. All rights reserved.

Automated summary

An efficient protocol for synthesizing tertiary alcohols via nucleophilic addition has been developed, with high yields of up to 98%. The method demonstrates broad substrate scope and can be conducted under environmentally friendly conditions.