Subtle Mitsunobu couplings under super-heating: the role of high-throughput continuous flow and microwave strategies

Abstract

Non-conventional heating techniques, high-throughput microwave-assisted synthesis and continuous flow penetrate almost every scientific field. Mitsunobu coupling is a ubiquitous choice for the dehydrative redox condensation of primary or secondary alcohols with (pro)nucleophiles. The aim of this review is to showcase the ease of subtle Mitsunobu coupling under super-heating. Surprisingly, this strategy is rather non-trivial; considering the sensitivity of reagents, Mitsunobu chemistry is typically performed at lower temperatures or under ambient conditions. In view of the absence of any previous work focusing on this topic, the current review considers the utility of super-heating in fragile Mitsunobu reactions. Therefore, we anticipate that this review will also bridge some of the apparent gaps in the extant literature by specifically describing the advances made by non-conventional heating assisted by microwave or continuous flow in one of the most powerful stereochemical transformations.