Development and Investigation of an Organocatalytic Enantioselective [10 + 2] Cycloaddition

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DOI

A stereoselective [10 + 2] cycloaddition for the reaction of homologated indenecarbaldehydes with α,β-unsaturated aldehydes, providing tetrahydrocyclopenta[a]indenes, has been developed and investigated mechanistically. The reaction proceeds via an aminocatalytic double Michael addition in high formal peri-, diastereo-, and enatioselectivity (up to 99% enantiomeric excess). Mechanistic investigations conclude that the reaction takes advantage of the in situ generation of a highly reactive amino isobenzofulvene intermediate via an aromative aminocatalytic strategy. A significant nonlinear effect is observed, consistent with a dual-activation model. Kinetic studies suggest a stepwise mechanism which is further supported by the identification and isolation of diastereomeric precyclization intermediates. These intermediates showed that in the presence of the aminocatalyst, they re-enter the catalytic cycle and afford the [10 + 2] cycloadduct with the same stereoselectivity observed in the prototypical reaction. Density functional theory calculations identified a Curtin-Hammett scenario where the stereoisomer of the [10 + 2] cycloadduct is determined by downstream species. These mechanistic investigations provide an understanding of the reaction pathway and stereoselectivity and continue to increase the knowledge of higher-order cycloadditions.

Original languageEnglish
JournalACS Catalysis
Volume10
Issue18
Pages (from-to)10784-10793
Number of pages10
ISSN2155-5435
DOIs
Publication statusPublished - Sep 2020

    Research areas

  • aminocatalysis, Curtin-Hammett principle, DFT, higher-order cycloadditions, isobenzofulvenes, nonlinear effect

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