Asymmetric remote C-H borylation of internal alkenes via alkene isomerization

Abstract

Recent years have witnessed the growing interest in the remote functionalization of alkenes for it offers a strategy to activate the challenging C-H bonds distant from the initiation point via alkene isomerization/functionalization. However, the catalytic enantioselective isomerization/functionalization with one single transition metal catalyst remains rare. Here we report a highly regio- and enantioselective cobalt-catalyzed remote C-H bond borylation of internal alkenes via sequential alkene isomerization/hydroboration. A chiral ligand featured twisted pincer, anionic, and non-rigid characters is designed and used for this transformation. This methodology, which is operationally simple using low catalyst loading without additional activator, shows excellent enantioselectivity and can be used to convert various internal alkenes with regio- and stereoisomers to valuable chiral secondary organoboronates with good functional group tolerance.

Fig. 1

Remote functionalization of alkenes via sequential alkene isomerization/functionalization. a Asymmetric hydrofunctionalization of alkenes. b The concept of asymmetric remote functionalization of alkenes via isomerization. c A general pathway for the remote functionalization of alkenes via isomerization

Fig. 2

Ligands screen for asymmetric isomerization/hydroboration. Reaction conditions: 1a (1 mmol), HBpin (1.2 mmol), Co(OAc)₂ (5.0 mol%), ligand (6.0 mol%), Et₂O (1 M), r.t., 20 h

Fig. 3

Applications. a Gram-scale reaction. b Synthesis of anti-breast-cancer agent 4

Fig. 4

Isotope labeling and control experiments. a Deuterium labeling experiment. b Utilization of a mixture of geometrical and positional alkene isomers. c The reaction of product 2b with HBpin using enantiomer of L7

Fig. 5

The time course study of 1b. Reaction conditions: 1b (0.5 mmol), HBpin (0.6 mmol), Co(OAc)₂ (2.5 mol%), L8 (3.0 mol%), Et₂O (1 M), r.t., 0–20 h