Enantioselective and Diastereoselective C–H Alkylation of Benzamides: Synergized Axial and Central Chirality via a Single Stereodetermining Step

Abstract

In this report, distally disposed axial and central chirality has been installed in a synergistic fashion via rhodium-catalyzed C–H alkylation of benzamides using N-arylmaleimide as the alkylating reagent, in which the enantio- and diastereo-determining steps are merged into a single one. The coupling system features mild reaction conditions, broad substrate scope, and excellent enantio- and diastereoselectivity. The chiral induction has been enabled by judicious choice of a chiral rhodium cyclopentadienyl catalyst that serves to control both the orientation of the olefin unit and the prochiral C–N bond.

Transition-metal-catalyzed C–H bond alkylation using olefins: recent advances and mechanistic aspects

“…78 Recently, Li and co-workers discovered Rh-catalyzed enantioselective hydroarylation of various bulky N -arylmaleimides 22h with diverse benzamides 22g (Scheme 22C). 79 Interestingly, they were able to synergistically install distally disposed axial and central chirality in the product. A single stereo-determining migratory insertion step established the axial and central chirality in the molecule, which is enabled by the chiral rhodium cyclopentadienyl catalyst.…”

Construction of Non-Biaryl Atropisomeric Amide Scaffolds Bearing a C–N Axis via Enantioselective Catalysis

“…More recently, Li and coworkers successfully created N -aryl succinimides 119 , containing an axially chiral axis and a central chirality via a single stereo-determining step, in which the rhodium-catalyzed C–H alkylation of benzamides 117 was utilized, with N -arylmaleimides 118 as the alkylating reagent ( Scheme 28 ) [ 90 ]. This transformation featured mild reaction conditions, broad functional group tolerance, and excellent enantio- and diastereo-selectivity.…”

Maleimides in Directing‐Group‐Controlled Transition‐Metal‐Catalyzed Selective C−H Alkylation

“…Then, a 6-membered rhodacycle C-2 could be formed through During the preparation of this paper, Li developed the first asymmetric CÀ H alkylation of benzamides with bulky Narylmaleimides enabled by a chiral rhodium cyclopentadienyl catalyst based on a CÀ H alkylation-desymmetrization process (Scheme 30). [35] Notably, both distally disposed axial and central chirality were established through a single "migratory insertion into the olefin" stereodetermining step. The asymmetric catalytic system featured mild reaction conditions, excellent enantio-and diastereoselectivity (> 19 : 1 dr, 81-99 % ee) and broad substrate scope (> 50 examples).…”