Wittig Reaction in Deep Eutectic Solvents: Expanding the DES Toolbox in Synthesis

Abstract

Wittig reaction between substituted phosphonium salts and (hetero)aromatic and alkyl carbonyl compounds in Deep Eutectic Solvents has been developed under a scalable and friendly protocol. Highly efficient reactions were successfully run with a wide range of bases including organic (DBU, LiTMP, t-BuOK) and inorganic (NaOH, K2CO3) ones in ChCl/Gly 1 : 2 (mol/mol) as solvent under mild conditions, at room temperature and under air. The proposed protocol was applied to a wide range of substrates, including (hetero)aromatic aldehydes with substituents as halogens (I, Br, Cl), EDG (alkoxy, methyl), EWG (NO2, CF3) or reactive groups as CN, esters, and ketones. Vinylic, alkynyl and cycloalkyl, alicyclic and α,β-unsaturated aldehydes can also be used. Highly electrophilic ketones gave good yields. The diastereoselectivity of the reaction is in complete agreement with the E/Z ratio predictable under traditional conditions. We demonstrated that the protocol is scalable to 2 g (5 mmol) of phosphonium salt, furthermore the proposed workup protocol allows to remove TPPO without need of additional chromatographic purification.