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

Abstract

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.

Copper(I)‐Catalyzed Asymmetric Allylation of Ketones with 2‐Aza‐1,4‐Dienes

“…However, the regioselective for γ-addition was not achieved. In light of our previous work on copper(I)-catalyzed asymmetric allylation with 1,4-dienes, [5,9] it was envisioned that 2-aza-1,4-dienes could be suitable substrates for catalytic asymmetric allylation of ketones (γ-carbon addition) under proton-transfer conditions. As shown in Scheme 1e, in the presence of a chiral copper(I) catalyst and a base, the deprotonation of N-allyl-1,1-diphenylmethanimine [10,11] (1 a) would occur smoothly to afford a chiral α-N-(diphenylmethylene) allyl copper(I) species.…”

Polyaromatic Hydrocarbon (PAH)-Based Aza-POPOPs: Synthesis, Photophysical Studies, and Nitroanalyte Sensing Abilities

“…Additionally, 1,3-dipolar cycloaddition of organic azides with alkynes as dipolarophiles is the most straightforward way to obtain useful 1,2,3-triazoles [ 5 ]. Applications of the Cu-catalyzed (cyclo)addition reactions have already contributed to many areas of modern chemistry, including asymmetric synthesis [ 20 , 21 , 22 , 23 , 24 ], and Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) is a convenient tool for bioconjugation reactions, peptidomimetic chemistry, polymer and materials sciences, and supramolecular chemistry [ 25 , 26 ]. The chemistry of 1,2,3-triazoles has gained much attention since its discovery, and various synthetic protocols have been developed for the synthesis of this moiety [ 27 , 28 ].…”

The cross-coupling reaction of organoalane reagents with 2-methylthiobenzo[d]thiazolesviaC–S bond cleavage catalyzed by nickel

“…Numerous effective methodologies of synthesis of 2-substituted benzo[ d ]thiazoles have been reported. 16 Typical synthetic protocols for 2-substituted benzo[ d ]thiazoles include: condensation cyclization of o -aminothiophenol derivatives (Fig. 2, route a ), 17 the cyclization of o -haloaniline with CS 2 and thiol/thiocyanate (Fig.…”