Construction of Quaternary Stereocenters by Nickel‐Catalyzed Heck Cyclization Reactions

Abstract

A nickel-catalyzed Heck cyclization for the construction of quaternary stereocenters is reported. This transformation is demonstrated in the synthesis of 3,3-disubstituted oxindoles, which are prevalent motifs seen in numerous biologically active molecules. The method shows broad scope, proceeds in synthetically useful yields, and provides a rare means to construct stereochemically complex frameworks by nonprecious-metal catalysis.

Ni-catalysed regioselective 1,2-diarylation of unactivated olefins by stabilizing Heck intermediates as pyridylsilyl-coordinated transient metallacycles

“…We performed the reaction of phenylvinylsilane 47 with 4-bromobenzotrifluoride and PhZnI under the standard conditions. Despite Ni being a good catalyst for the Heck reaction, 14 , 21 phenylvinylsilane 47 did not afford any Heck or the dicarbofunctionalized product. Only the direct cross-coupling product was formed in 81% yield.…”

Nickel‐Catalyzed Enantioselective Conjunctive Cross‐Coupling of 9‐BBN Borates

“…After a survey of other chiral ligands provided only modest improvement in selectivity we considered the efficacy of Ni catalysts. While Ni complexes are less prolific than their Pd counterparts in terms of alkene π-activation, important precedents in the arena of Heck reactions [9] , olefin polymerization [10] and oligomerization [11] , suggested that Ni(II) complexes might be effective for conjunctive coupling.…”

Enantioselective Nickel-Catalyzed Mizoroki–Heck Cyclizations To Generate Quaternary Stereocenters

“…To accomplish this goal, we initiated our studies from our recently published work that allows the construction of quaternary carbon centers, albeit without control of absolute stereochemistry. 14 We had discovered that the combination of an unhindered electron-rich phosphine with manganese 15 gave rise to Mizoroki-Heck cyclization to form oxindoles with high functional group tolerance. From control experiments, we propose a Ni(0)/Ni(II) catalytic cycle instead of a radical-induced cyclization.…”

“…After extensive screening of ligands, encouraging hits were obtained with phosphine ligands such as CatASium Ktb 14 and Duanphos 17 (Table 1, entry 2). However, use of the P -chiral bisphosphine QuinoxP* 18 led to the highest enantioselectivity with ee values up to 96% (entry 1).…”

“…14 We initially focused our attention on the migratory insertion step of the Z -alkene. Detailed analysis of the energetics of the transformation revealed that the insertion step proceeds with only low selectivity (Scheme 3, selectivity of insertion, theory=15% ee).…”