Stereochemistry of [2+2]Cycloaddition of Chlorosulfonyl Isocyanate to Olefins

Bartlomiej      Furman; Katarzyna      Borsuk; Zbigniew      Kaluza; Robert      Lysek; Marek      Chmielewski

doi:10.2174/1385272043485792

Abstract

The inexpensive and commercially available chlorosulfonyl isocyanate reacts readily with the variety of nucleophilic olefins to provide unstable [2+2]cycloadducts. The reaction proceeds via concerted mechanism rather than a stepwise process. The electron-donating substituent in the olefin component controls the regiochemistry of the reaction. The cycloaddition is stereospecific, leading from (Z)-olefin to the cis-adduct and from (E)-olefin to the trans-adduct. Increase of the reaction time or the presence of an acid contamination may result either in the epimerization at C(4) of the azetidin-2-one ring or in the rearrangement leading to the opening of the fourmembered ring. The N-deprotection of the [2+2]cycloadducts by reduction of the chlorosulfonyl group results in the formation of stable azetidin-2-ones, useful synthons in the synthesis of β-lactam antibiotics. The discussed reactions are sterically controlled and in many cases take place with a high asymmetric induction. Due to the observed exothermic nature of the cycloaddition, the conformation of the olefin in the transition state resembles, with a high probability, the low-energy ground-state conformation.

Keywords: cycloaddition, chlorosulfonyl isocyanate, nucleophilic olefins, n-deprotection, b-lactam antibiotics