Regio- and Stereoselective (SN2) N-, O-, C- and S-Alkylation using Trialkyl Phosphates

Abstract

Bimolecular nucleophilic substitution (S N 2) is one of the most known fundamental reactions in organic chemistry to generate new molecules from two molecules. In principle, a nucleophile attacks from the back side of an alkylating agent having a suitable leaving group, most commonly using a halide. However, alkyl halides are expensive, very harmful, toxic and not so stable which makes them problematic for laboratory use. In contrast, trialkyl phosphates are cheap, readily accessible, stable at room temperature, under air, and are easy to handle but rarely used as alkylating agents in organic synthesis. Here, we describe a mild, straightforward and powerful method for nucleophilic alkylation of various nucleophiles such as N-, O-, C- and S- using readily available trialkyl phosphate. The reaction proceeds smoothly with excellent yield and quantitative yield in many cases and covers a wide range of substrates. Further, the rare stereoselective transfer of secondary alkyl groups has been achieved with inversion of configuration of chiral centers (up to >99% ee).