Abstract
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 language | English |
|---|---|
| Journal | ACS Catalysis |
| Volume | 10 |
| Issue | 18 |
| Pages (from-to) | 10784-10793 |
| Number of pages | 10 |
| ISSN | 2155-5435 |
| DOIs | |
| Publication status | Published - Sept 2020 |
Keywords
- aminocatalysis
- Curtin-Hammett principle
- DFT
- higher-order cycloadditions
- isobenzofulvenes
- nonlinear effect
- TROPONE
- ASYMMETRIC-SYNTHESIS
- CONSTRUCTION
- TRICYCLOPENTANOIDS