Palladium-Catalyzed Amide-Directed Enantioselective Carboboration of Unactivated Alkenes Using a Chiral Monodentate Oxazoline Ligand

Abstract

A Pd-catalyzed carboxamide-directed enantioselective 1,2-carboboration reaction of unactivated alkenes with C−H nucleophiles and B 2 Pin 2 has been developed using a second generation of chiral monodentate oxazoline (MOXca) ligand. The MOXca ligand featuring a modular design of a Nlinked carbazole side arm can be readily synthesized from serine and NH-carbazoles and provided further improved enantiocontrol of the AQ-directed nucleopalladation over MOXin ligand. The use of KTFA additive and TFE solvent was critical to obtain high reactivity in this difunctionalization reaction system. Preliminary study showed that 1,2-aminoboration of 3-butenamide with imide N-nucleophiles and B 2 Pin 2 under the same conditions proceeded in good yield and high enantioselectivity.

Anti-selective [3+2] (Hetero)annulation of non-conjugated alkenes via directed nucleopalladation

“…During the past 5 years, our laboratories have developed a variety of transition-metal-catalyzed, three-component directed alkene 1,2-difunctionalization reactions facilitated by the 8aminoquinoline (AQ) auxiliary, a strongly coordinating bidentate directing group. Using this strategy we and others have reported examples of hydrofunctionalization [21][22][23][24][25][26][27][28][29][30][31][32][33] , dicarbofunctionalization [34][35][36][37][38][39] , carboamination 40,41 , and carbo-/aminoboration [42][43][44][45] , among other transformations 46,47 (Fig. 1c).…”

Transition‐Metal‐Catalyzed 1,2‐Carboboration of Alkenes: Strategies, Mechanisms, and Stereocontrol

“…This phenomenon is caused by the rapid E / Z isomerization prior to nucleopalladation, as supported by stoichiometric experiments. Shortly after our report, the group of Peng, Chen, He and coworkers also described an asymmetric carboboration method with a structurally similar ligand L14 that offered higher levels of enantioselectivity . The origin of the effectiveness of this particular ligand was elucidated by DFT studies.…”

“…Shortly after our report, the group of Peng, Chen, He and coworkers also described an asymmetric carboboration method with a structurally similar ligand L14 that offered higher levels of enantioselectivity. [33] The origin of the effectiveness of this particular ligand was elucidated by DFT studies. Compared with L13, the larger aromatic system in L14 could provide enhanced shielding of one side of the alkene thereby enhancing facial differentiation during carbopalladation.…”

Metal‐Catalyzed Substrate‐Directed Enantioselective Functionalization of Unactivated Alkenes

“…This strategy was further employed for enantioselective difunctionalization of unactivated alkenes. The groups of Engle and Peng, Chen and He reported Pd‐catalyzed substrate‐directed enantioselective anti‐carboboration of alkenes independently. The MOXin ligand was used in Engle's system (Scheme ) while a newly developed MOXca ligand was employed in Peng, Chen and He's system (Scheme ).…”