Organocatalytic, enantioselective intramolecular [6 + 2] cycloaddition reaction for the formation of tricyclopentanoids and insight on its mechanism from a computational study

Yujiro Hayashi, Hiroaki Gotoh, Masakazu Honma, Kuppusamy Sankar, Indresh Kumar, Hayato Ishikawa, Kohzo Konno, Hiroharu Yui, Seiji Tsuzuki, Tadafumi Uchimaru

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Diphenylprolinol silyl ether was found to be an effective organocatalyst for promoting the asymmetric, catalytic, intramolecular [6 + 2] cycloaddition reactions of fulvenes substituted at the exocyclic 6-position with a δ-formylalkyl group to afford synthetically useful linear triquinane derivatives in good yields and excellent enantioselectivities. The cis-fused triquinane derivatives were obtained exclusively; the trans-fused isomers were not detected among the reaction products. The intramolecular [6 + 2] cycloaddition occurs between the fulvene functionality (6π) and the enamine double bond (2π) generated from the formyl group in the substrates and the diphenylprolinol silyl ether. The absolute configuration of the reaction products was determined by vibrational circular dichroism. The reaction mechanism was investigated using molecular orbital calculations, B3LYP and MP2 geometry optimizations, and subsequent single-point energy evaluations on model reaction sequences. These calculations revealed the following: (i) The intermolecular [6 + 2] cycloaddition of a fulvene and an enamine double bond proceeds in a stepwise mechanism via a zwitterionic intermediate. (ii) On the other hand, the intramolecular [6 + 2] cycloaddition leading to the cis-fused triquinane skeleton proceeds in a concerted mechanism via a highly asynchronous transition state. (iii) The fulvene functionality and the enamine double bond adopt the gauche-syn conformation during the C-C bond formation processes in the [6 + 2] cycloaddition. (iv) The energy profiles calculated for the intramolecular reaction explain the observed exclusive formation of the cis-fused triquinane derivatives in the [6 + 2] cycloaddition reactions. The reasons for the enantioselectivity seen in these [6 + 2] cycloaddition reactions are also discussed.

Original languageEnglish
Pages (from-to)20175-20185
Number of pages11
JournalJournal of the American Chemical Society
Volume133
Issue number50
DOIs
Publication statusPublished - 2011 Dec 21
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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