Mechanochemical Mitsunobu Reactions

Author:

Williams Matthew T. J.1,Adarve Cardona Laura12,Bolm Carsten1ORCID

Affiliation:

1. Institute of Organic Chemistry RWTH Aachen University Landoltweg 1 52074 Aachen Germany

2. Laboratory of Organic Synthesis Bio- and Organocatalysis Chemistry Department of Chemistry Universidad de Los Andes Cra. 1 No 18A-12 Bogota 111711 Colombia

Abstract

AbstractA Mitsunobu process performed under neat grinding conditions, using a mixer mill, is reported. It proceeds in the absence of reaction solvent and in short reactions times (10–20 min). A broad substrate scope encompassing primary and secondary alcohols, as well as oxygen, nitrogen, sulfur, and carbon‐centered nucleophiles is demonstrated. Application to the functionalization of a selection of APIs is shown, also. The developed process is amenable to scale up on a planetary ball‐mill, yielding over 2 grams of product. Finally, a representative alcohol is inverted with excellent stereoselectivity.

Funder

RWTH Aachen University

Publisher

Wiley

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