Enantioselective Intramolecular Friedel−Crafts-Type α-Arylation of Aldehydes

Abstract

Enantioselective organo-SOMO catalysis has, in the last two years, been the subject of considerable development and exploration. A number of new and unique transformations have been reported, such as alpha-allylation, alpha-oxyamination, alpha-enolation, and alpha-vinylation of aldehydes. Herein, we report a modification of this activation mode that involves the intramolecular Friedel-Crafts-type alpha-arylation of aldehydes carrying electron-donating groups on their aromatic nucleus and its application to the total synthesis of demethyl calamenene, a potent cytotoxic agent against human adenocarcinoma A 549.

Development of a potent 2-oxoamide inhibitor of secreted phospholipase A2 guided by molecular docking calculations and molecular dynamics simulations

“…Compounds 23b , 45 24b , 45 25a , 46 26a , 46 25b , 47 26b 48 have been described elsewhere and their analytical data are in accordance with literature.…”

Quantum Mechanical Investigations of Organocatalysis: Mechanisms, Reactivities, and Selectivities

“…Both the Nicolaou 83 and MacMillan 84 groups reported asymmetric intramolecular α-arylation reactions via SOMO-activation (Scheme 63). …”

Organocatalysis

“…18 In conjuction with MacMillan, Houk and co-workers have investigated the nature of the intermediates involved in organo-SOMO catalysis of α-arylation of aldehydes. 19 This was due to the fact that both the MacMillan group 20 and Nicolaou group 21 have reported the intramolecular α-arylation of aldehydes, where cyclization of a enamine radical was shown to react ortho to the methoxy group (as in Scheme 19), but 1,3,4-substituted aldehydes were shown to have a different reaction profile, preferring to cyclize to afford para arylated products. The selectivity of the α-arylation reactions was attributed to the activation energies and relative stabilities of the isomeric transition states.…”