Copper(I)-Catalyzed Asymmetric Conjugate Addition of 1,4-Dienes to β‑Substituted Alkenyl Azaarenes

Chiral azaarene compounds are extremely important due to their prevalence in pharmaceutical ingredients. Herein, an array of chiral molecules bearing azaaryl groups is synthesized in moderate-to-excellent yields with moderate-to-excellent Z/E ratios, high dr, and excellent enantioselectivity by a copper­(I)-catalyzed asymmetric conjugate addition of 1,4-dienes to (E)-β-substituted alkenyl azaarenes. The reaction is carried out under mild proton-transfer conditions, which enjoys very high atom economy. Moreover, the reaction features a broad substrate scope on (E)-α,β-unsaturated azaarenes as various azaarenes are well tolerated, such as benzothiazole, thiazole, N-methyl-benzimidazole, benzoxazole, quinoline, isoquinoline, pyrimidine, pyrazine, and triazine. Interestingly, the reaction with (Z)-α,β-unsaturated azaarenes affords the same products in excellent results but with a reversed absolute configuration. DFT calculations indicate that the C–C bond-forming nucleophilic addition is a Z-/E- and enantio-selectivities-determining step and provides a rationale for the origin of selectivities. At last, the synthetic utilities of the product are showcased by several transformations, including olefin metathesis, [4 + 2] cyclization, [2 + 1] cyclization, and cleavage of the benzothiazole ring.