Synthesis of [3a,7a]-Dihydroindoles by a Tandem Arene Cyclopropanation/3,5-Sigmatropic Rearrangement Reaction

• Type of Material: Article
• Authors: Sidney M. Wilkerson-Hill, Emory University; Brandon E. Haines, Emory University; Djamaladdin G. Musaev, Emory University; Huw M.L. Davies, Emory University
• Language: English
• Date: 2018-06-25
• Publisher: American Chemical Society
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 American Chemical Society
• Final Published Version (URL): https://doi.org/10.1021/acs.joc.8b00812
• Title of Journal or Parent Work: The Journal of Organic Chemistry
• Volume: 83
• Issue: 15
• Start Page: 7939
• End Page: 7949
• Grant/Funding Agency: UNCF-Merck; NIH; NSF
• Grant/Funding Information: We are grateful to the NIH for financial support (Project No. 2R01GM099142-05). S.M.W.H is grateful for a UNCF-Merck postdoctoral fellowship. We thank Dr. John Bacsa, Emory X-ray Crystallography Facility, for the X-ray structural analysis of compounds 4a, 7a, 8a, and 7b. D.G.M. acknowledges NSF MRI-R2 grant (CHE-0958205) and the use of the resources of the Cherry Emerson Center for Scientific Computation. Funds to purchase the NMR and X-ray spectrometers used in these studies were supported by NSF (CHE 1531620 and CHE 1626172).
• Keywords: Tandem Arene Cyclopropanation; [3a,7a]-Dihydroindoles; donor/acceptor carbene
• Subject - Topics: Computational chemistry; Chemistry, Organic; Organic compounds--Synthesis

Abstract

Donor/acceptor carbenes provide a powerful platform for building molecular complexity, but the majority of their reactions have been limited to aryl and vinyl donor groups. We found that a N-containing donor/acceptor carbene precursor, 4-phthalimido-N-methanesulfonyl-1,2,3-triazole, reacts with unactivated arenes resulting in a mixture of [3+2]-cycloadducts, [3a,7a]-dihydroindoles, and formal C–H functionalization products in up to 82% yield upon heating. We also demonstrate that the formal C–H functionalization products arise from ring-opening of the [3+2]-cycloadducts. Computational studies suggest that the formal cycloaddition process takes places through a tandem arene cyclopropanation/6π electrocyclization/6π electrocyclic ring opening/3,5-sigmatropic rearrangement reaction, which also accounts for the distinctive regioselectivity of the formal cycloaddition reaction.