Catalytic Asymmetric Allylic Substitution with Copper(I) Homoenolates Generated from Cyclopropanols

Abstract

By using copper(I) homoenolates as nucleophiles, which are generated through the ring‐opening of 1‐substituted cyclopropane‐1‐ols, a catalytic asymmetric allylic substitution with allyl phosphates is achieved in high to excellent yields with high enantioselectivity. Both 1‐substituted cyclopropane‐1‐ols and allylic phosphates enjoy broad substrate scopes. Remarkably, various functional groups, such as ether, ester, tosylate, imide, alcohol, nitro, and carbamate are well tolerated. Moreover, the present method is nicely extended to the asymmetric construction of quaternary carbon centers. Some control experiments argue against a radical‐based reaction mechanism and a catalytic cycle based on a two‐electron process is proposed. Finally, the synthetic utilities of the product are showcased by means of the transformations of the terminal olefin group and the ketone group.

Insights into the Mechanism of Enantioselective Copper‐Catalyzed Ring‐Opening Allylic Alkylation of Cyclopropanols

“…Apart from this, our experience with enantioselective copper catalysis with phenol‐NHC chiral ligands [10] led to the discovery that the reaction between 1‐alkylcyclopropanols and γ‐substituted allylic phosphates was promoted with high enantioselectivity (up to 89% ee) by copper catalysts obtained from our phenol‐NHC ligand library. During our investigation, however, an almost identical reaction based on the phenol‐NHC/copper catalysis was reported by Yin and co‐workers (Scheme 1c) [11] . They introduced a new sophisticated variant of the phenol‐NHC chiral ligand, and achieved excellent enantioselectivity (up to 99% ee) with a broad substrate scope including those constructing stereogenic quaternary carbon centers.…”

“…During our investigation, however, an almost identical reaction based on the phenol-NHC/copper catalysis was reported by Yin and co-workers (Scheme 1c). [11] They introduced a new sophisticated variant of the phenol-NHC chiral ligand, and achieved excellent enantioselectivity (up to 99% ee) with a broad substrate scope including those constructing stereogenic quaternary carbon centers. Soon after the Yin's report, Trost and co-workers reported the same reaction using their original ProPhenol/ZnÀ Cu catalysis.…”

Recent Advances in Non-Precious Metal Catalysis

“…In this vein, the chiral copper(I)−NHC complex was shown to promote ring-opening of 1-cyclopropanols, leading to nucleophilic Cu(I)-homoenolate. 47 The resulting alkylcopper then underwent S N 2′substitution with a variety of allylic phosphates to furnish chiral γ-vinyl ketones (Scheme 35). Of note, this methodology could be readily applied to the construction of chiral quaternary centers with 3,3′-disubstituted allylic phosphates with similarly high levels of enantioselectivity.…”

“…Recent efforts in Cu-catalyzed allylic substitution have been directed toward the formation of nucleophilic copper­(I) species in situ intermediates. In this vein, the chiral copper­(I)–NHC complex was shown to promote ring-opening of 1-cyclopropanols, leading to nucleophilic Cu­(I)-homoenolate . The resulting alkylcopper then underwent S N 2′-substitution with a variety of allylic phosphates to furnish chiral γ-vinyl ketones (Scheme ).…”

Asymmetric β-arylation of cyclopropanols enabled by photoredox and nickel dual catalysis

“…2 In the presence of transition metal (TM) catalysis or single electron transfer (SET) catalysis, they have been widely applied in the synthesis of β-functionalized ketones by involving intermediates of homoenolates or β-keto radicals generated via ring-opening pathways, albeit mostly in racemic forms (Scheme 1A). 3,4 Despite recent advances, 5 the development of catalytic asymmetric strategies to access various enantioenriched β-functionalized ketones through ring-opening of cyclopropanols has proven to be quite challenging yet highly desirable.…”