Consecutive and Selective Double Methylene Insertion of Lithium Carbenoids to Isothiocyanates: A Direct Assembly of Four-Membered Sulfur-Containing Cycles

Raffaele Senatore; Monika Malik; Thierry Langer; Wolfgang Holzer; Vittorio Pace

doi:10.1002/anie.202110641

Consecutive and Selective Double Methylene Insertion of Lithium Carbenoids to Isothiocyanates: A Direct Assembly of Four-Membered Sulfur-Containing Cycles

Angew Chem Int Ed Engl. 2021 Nov 15;60(47):24854-24858. doi: 10.1002/anie.202110641. Epub 2021 Oct 13.

Authors

Raffaele Senatore¹, Monika Malik¹, Thierry Langer¹, Wolfgang Holzer¹, Vittorio Pace^{1

2}

Affiliations

¹ University of Vienna, Department of Pharmaceutical Sciences, Althanstrasse, 14, A-1090, Vienna, Austria.
² University of Turin, Department of Chemistry, Via P. Giuria 7, 10125, Turin, Italy.

Abstract

A formal CH₂ -CH₂ homologation conducted with C1 carbenoids on a carbon electrophile for the obtainment of a four-membered cycle is reported. The logic proposes the consecutive delivery of two single nucleophilic CH₂ units to an isothiocyanate-as competent electrophilic partner-resulting in the assembling of a rare imino-thietane cluster. The single synthetic operation procedure documents genuine chemocontrol, as indicated by the tolerance to various reactive elements decorating the starting materials. Significantly, the double homologation protocol is accomplished directly on a carbon electrophile, thus not requiring the installation of heteroatom-centered manifolds (e.g. boron).

Keywords: carbenoids; chemoselectivity; homologation; isothiocyanates; thietanes.