Catalytic Asymmetric Synthesis of Bicycloprolines by a 1,3-Dipolar Cycloaddition/Intramolecular Alkylation Strategy

This document is the Accepted Manuscript version of a Published Work that appeared in final form inJournal of Organic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.joc.6b01100 to Published Work, see http://pubs.acs.org/page/policy/articlesonrequest/index.htmlThe diastereoselective one-pot synthesis of hexahydrocyclopenta [b] pyrrole derivatives (bicycloprolines) has been achieved by base-mediated reactions of (E)-tert-butyl 6-bromo-2-hexenoate with α-imino esters. The catalytic asymmetric version of this process has been efficiently achieved using the CuI/(R)-DTBM-Segphos complex as a catalyst following a two-step 1,3-dipolar cycloaddition/intramolecular alkylation sequence.Financial support of this work by the Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (MINECO CTQ2012-35790 and MINECO/FEDER CTQ2015-66954-P) are gratefully acknowledged. M.G.-E. and A.P.-E. thank the MICINN for predoctoral fellowship