A Photochemical Strategy towards Michael Addition Reactions of Cyclopropenes

Angewandte Chemie, vol. 137

Abstract

Abstract The development of Michael addition reactions to conjugated cyclopropenes is a challenge in organic synthesis due to the fleeting and reactive nature of such strained Michael acceptor systems. Herein, the development of a photochemical approach towards such conjugated cyclopropenes is reported that serves as a strategic entry point to densely functionalized cyclopropanes in a diastereoselective fashion. The process involves the light‐mediated generation of transient cyclopropenyl α,β‐unsaturated esters from vinyl diazo esters, followed by an organic base catalyzed nucleophilic addition of N‐heterocycles to directly access β‐N‐heterocyclic cyclopropanoic esters. With this synergistic approach, various trisubstituted cyclopropanes bearing N‐heteroaryl and N‐heterocyclic rings such as indole, pyrrole, benzimidazole, isatin, pyridinone, and quinolinone were accessed efficiently in good yield and decent to good diastereoselectivities. Further, β‐indolyl cyclopropanoic acids have been synthesized and were successfully evaluated as FABP‐4 inhibitors. Theoretical calculations have been performed to elucidate the mechanism, which was further supported by experimental findings.

Authors 11

1. Yaseen Hussain

   Indian Institute of Technology Jammu

   Affiliation as printed

   Department of Chemistry Indian Institute of Technology Jammu Jagti, NH-44 Nagrota Bypass Jammu J&K 181221 India

   Indian Institute of Technology Jammu, Department of Chemistry, INDIA

2. Ramanathan Prasanna

   Indian Institute of Technology Jammu

   Affiliation as printed

   Department of Chemistry Indian Institute of Technology Jammu Jagti, NH-44 Nagrota Bypass Jammu J&K 181221 India

   Indian Institute of Technology Jammu, Department of Chemistry, INDIA

3. Claire Empel Aachen Institute of Organic Chemistry

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen University Institute of Organic Chemistry Landoltweg 1 52074 Aachen

   RWTH Aachen University, Institute of Organic Chemistry, INDIA

4. Deepak Sharma

   Indian Institute of Technology Jammu

   Affiliation as printed

   Department of Chemistry Indian Institute of Technology Jammu Jagti, NH-44 Nagrota Bypass Jammu J&K 181221 India

   Indian Institute of Technology Jammu, Department of Chemistry, INDIA

5. Lennard Kloene Aachen Institute of Organic Chemistry

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen University Institute of Organic Chemistry Landoltweg 1 52074 Aachen

   RWTH Aachen University, Institute of Organic Chemistry, GERMANY

6. Wenyong Zhu

   Goethe University Frankfurt

   Affiliation as printed

   Goethe University Institute of Pharmaceutical Chemistry Max-von-Laue Str. 9 60438 Frankfurt am Main

   Goethe University Frankfurt, Institute of Pharmaceutical Chemistry, GERMANY

7. Astrid Kaiser

   Goethe University Frankfurt

   Affiliation as printed

   Goethe University Institute of Pharmaceutical Chemistry Max-von-Laue Str. 9 60438 Frankfurt am Main

   Goethe University Frankfurt, Institute of Pharmaceutical Chemistry, GERMANY

8. Lilia Weizel

   Goethe University Frankfurt

   Affiliation as printed

   Goethe University Institute of Pharmaceutical Chemistry Max-von-Laue Str. 9 60438 Frankfurt am Main

   Goethe University Frankfurt, Institute of Pharmaceutical Chemistry, GERMANY

9. Ewgenij Proschak

   Goethe University Frankfurt · Fraunhofer Institute for Translational Medicine and Pharmacology

   Affiliation as printed

   Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP) Theodor-Stern-Kai 7 60596 Frankfurt am Main Germany

   Goethe University Institute of Pharmaceutical Chemistry Max-von-Laue Str. 9 60438 Frankfurt am Main

   Goethe University Frankfurt, Institute of Pharmaceutical Chemistry, GERMANY

10. René M. Koenigs corresponding Aachen Institute of Organic Chemistry

    RWTH Aachen University

    Affiliation as printed

    RWTH Aachen University Institute of Organic Chemistry Landoltweg 1 52074 Aachen

    RWTH Aachen University, Institute of Organic Chemistry, Landoltweg 1, 52074 Aachen, GERMANY

11. Pankaj Chauhan

    Indian Institute of Technology Jammu

    Affiliation as printed

    Department of Chemistry Indian Institute of Technology Jammu Jagti, NH-44 Nagrota Bypass Jammu J&K 181221 India

    Indian Institute of Technology Jammu, Department of Chemistry, INDIA