Carbene-catalyzed chemoselective reaction of unsymmetric enedials for access to Furo[2,3-b]pyrroles

A carbene-catalyzed chemoselective reaction of unsymmetric enedials is disclosed. The reaction provides a concise access to bicyclic furo[2,3-b]pyrroles derivatives in excellent selectivity. A main challenge in this reaction is chemoselective reaction of the two aldehyde moieties in the enedial substrates. Mechanistic studies via experiments suggest that our chemoselectivity controls are mostly achieved on the reducing properties of different sited Breslow intermediates. Several side reactions processes and the corresponding side adducts are also studied by high resolution mass spectroscopy analysis. Our method allows for efficient assembly of the furo[2,3-b]pyrrole structural moieties and their analogues widely found in natural products and pharmaceuticals.Ministry of Education (MOE)Nanyang Technological UniversityNational Research Foundation (NRF)Published versionThe authors acknowledge funding supports from the National Natural Science Foundation of China (21732002, 22061007, P.C.Z; and 22071036, Y.R.C); Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules, Department of Education, Guizhou Province [Qianjiaohe KY number (2020)004, Y.R.C]; The 10 Talent Plan (Shicengci) of Guizhou Province ([2016] 5649,Y.R.C); Science and Technology Department of Guizhou Province [Qiankehe-jichu-ZK[2022]zhongdian024, P.C.Z], ([2018]2802, [2019]1020, Y.R.C); Program of Introducing Talents of Discipline to Universities of China (111 Program, D20023, Y.R.C) at Guizhou University; Singapore National Research Foundation under its NRF Investigatorship (NRF-NRFI2016-06, Y.R.C.) and Competitive Research Program (NRF-CRP22-2019-0002, Y.R.C); Ministry of Education, Singapore, under its MOE AcRF Tier 1 Award (RG7/20, RG5/19, Y.R.C), MOE AcRF Tier 2 (MOE2019-T2-2-117, Y.R.C), and MOE AcRF Tier 3 Award (MOE2018-T3-1-003, Y.R.C); a Nanyang Research Award Grant; and a Chair Professorship Grant, Nanyang Technological University