Controllable, Sequential, and Stereoselective C–H Allylic Alkylation of Alkenes

Abstract

The direct conversion of C-H bonds into new CC bonds represents a powerful approach to generate complex molecules from simple starting materials. However, a general and controllable method for the sequential conversion of a methyl group into a fully substituted carbon center remains a challenge. We report a new method for the selective and sequential replacement of three C-H bonds at the allylic position of propylene and other simple terminal alkenes with different carbon groups derived from Grignard reagents. A copper catalyst and electron-rich biaryl phosphine ligand facilitate the formation of allylic alkylation products in high branch selectivity. We also present conditions for the generation of enantioenriched allylic alkylation products in the presence of catalytic copper and a chiral phosphine ligand. With this approach, diverse and complex products with substituted carbon centers can be generated from simple and abundant feedstock chemicals.

Installing the “magic methyl” – C–H methylation in synthesis

“…In 2019, Tambar exploited the allylic ene reaction, to perform copper-catalysed allylic C-H alkylation (Scheme 74). 187 In this work, sulfur diimide was used both as an electrophilic oxidant and as a leaving group in the subsequent copper-catalysed alkylation step, where regioselectivity was controlled by a sterically demanding phosphine ligand. The proposed reaction mechanism begins with an ene reaction between the sulphur diimide oxidant and the terminal allyl group, generating adduct (I), which is then activated by a Grignard reagent to furnish sulfimine (II).…”

Enantioselective Formation of Quaternary Centers by Allylic Alkylation with First-Row Transition-Metal Catalysts

“…In 2019, an attractive strategy incorporating unactivated olefins as substrates was described by Tambar and co-workers . On the basis of their previous work involving a selective C–H allylic functionalization with sulfur diimide reagent [(PhSO 2 N) 2 S] and a subsequent copper-catalyzed alkylation, the authors developed a sequential and controllable conversion of a methyl group into a fully substituted allylic carbon center (Scheme ).…”

Redox-Neutral Propargylic C–H Functionalization by Using Iron Catalysis

“…As early as 1939, Riley oxidation conditions using stoichiometric selenium dioxide were applied to the allylic hydroxylation of olefins, a process that was later rendered catalytic in selenium by Umbreit and Sharpless. 7 Recently, Tambar and co-workers developed mechanistically related chemistry to permit the allylic amination, 8 alkylation, 9 or sulfimidation of terminal or internal alkenes. 10 Systems that use transition-metal catalysis for -functionalization also have a long history.…”