Enantioselective Reductive Divinylation of Unactivated Alkenes by Nickel-Catalyzed Cyclization Coupling Reaction

Abstract

Catalytic asymmetric dicarbofunctionalization of tethered alkenes has emerged as a promising tool for producing chiral cyclic molecules; however, it typically relies on aryl-tethered alkenes to form benzene-fused compounds. Herein, we report an enantioselective cross-electrophile divinylation reaction of nonaromatic substrates, 2-bromo-1,6-dienes. The approach thus offers a route to new chiral cyclic architectures, which are key structural motifs found in various biologically active compounds. The reaction proceeds under mild conditions, and the use of chiral t-Bu-pmrox and 3,5-difluoro-pyrox ligands resulted in the formation of divinylated products with high chemo-, regio-, and enantioselectivity. The method is applicable for the incorporation of chiral hetero-and carbocycles into complex molecules.

Nickel‐Catalyzed Enantioselective Reductive Alkyl‐Carbamoylation of Internal Alkenes

“…This strategy enables the expedient synthesis of a range of valuable (hetero)cyclic structures that are frequently found in bioactive compounds. [4][5][6][7] Developed methods are mainly restricted to the use of terminal alkenes tethered to an electrophile, in which a chiral ligand enables the enantiodetermining migratory insertion of an organonickel intermediate to foster a single stereogenic center (Scheme 1a). In sharp contrast, the use of internal alkenes presents an inherent challenge for nickel-catalyzed reductive difunctionalization, which could be attributed to several factors.…”

“…In particular, Ni‐catalyzed enantioselective reductive dicarbofunctionalization of alkenes is currently undergoing rapid development to stereoselectively construct new carbon‐carbon bonds across an alkene, [3] which circumvents the use of prefunctionalized organometallic reagents. This strategy enables the expedient synthesis of a range of valuable (hetero)cyclic structures that are frequently found in bioactive compounds [4–7] . Developed methods are mainly restricted to the use of terminal alkenes tethered to an electrophile, in which a chiral ligand enables the enantiodetermining migratory insertion of an organonickel intermediate to foster a single stereogenic center (Scheme 1a).…”

Recent Advances in Non-Precious Metal Catalysis

“…To extend the synthetic application of the Ni-catalyzed cross-electrophile asymmetric divinylation of aryl-substituted alkenes to form benzene-fused compounds, Shu and co-workers explored the synthetic application of this chemistry to nonaromatic alkenes of the general structure of 2-bromo-1,6-diene systems to access a new class of carbo- and heterocyclic divinyl products. The reaction proceeded under mild conditions using NiBr 2 in DMAc in the presence of a chiral ligand at −5 to −18 °C.…”

Ni-catalyzed carbamoylation of unactivated alkenes for stereoselective construction of six-membered lactams

“…Herein, we report the unprecedented 6-exo-trig cyclized carbamoylation by the utilization of the nickel-catalyzed asymmetric reductive difunctionalization of alkenes strategy. It should be noted this also represents the only example for the construction of six-membered nitrogen-containing heterocycles in asymmetric reductive cross-coupling reactions 64 . The utilization of newly modified 8-Quinox ligand enables the synthesis of α-alkylated six-membered lactam with satisfied yields and enantioselectivities.…”