Mechanochemical Mitsunobu Reactions

Advanced Synthesis & Catalysis, vol. 366, pp. 2220–2225

Abstract

Abstract A 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.

Authors 3

1. Matthew T. J. Williams Aachen Institute of Organic Chemistry

   RWTH Aachen University

   Affiliation as printed

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

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

2. Laura Adarve-Cardona Aachen Institute of Organic Chemistry

   RWTH Aachen University · Universidad de Los Andes

   Affiliation as printed

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

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

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

3. Carsten Bolm corresponding Aachen Institute of Organic Chemistry

   RWTH Aachen University

   Affiliation as printed

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

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