Catalytic Asymmetric Cyanoalkylation of Electron-Deficient Olefins with Potassium Cyanide and Alkyl Halides

Abstract

The stereoselective cyanoalkylation of electron-deficient olefins with potassium cyanide and alkyl halides was developed based on the utilization of modular chiral 1,2,3-triazolium salts featuring a hydrogen bond-donor ability as catalysts. The reaction involving multiple carbon−carbon bond formations proceeds via the enantioselective conjugate addition of a cyanide ion and the consecutive catalyst-controlled diastereoselective alkylation of intermediary chiral triazolium enolates. Control experiments revealed that the use of a properly tuned chiral triazolium ion as a catalyst and the presence of the cyano functionality in the intermediary enolate are of crucial importance for achieving high levels of acyclic absolute and relative stereocontrol. Article pubs.acs.org/JACS

Catalytic Asymmetric Strecker Reaction of Ketoimines with Potassium Cyanide

“…However, harnessing an alkali metal cyanide for asymmetric reactions is a nontrivial pursuit because of its low solubility in organic solvents and high reactivity of the cyanide ion to be tamed by a catalyst. Therefore, efforts to realize catalytic asymmetric cyanation with alkali metal cyanides have met with limited success [4–8] . For instance, while a number of reliable protocols have been developed for the asymmetric Strecker reaction of ketoimines, [2h,i,9,10] catalytic systems that operate with alkali metal cyanides remain underdeveloped.…”

“…Therefore, efforts to realize catalytic asymmetric cyanation with alkali metal cyanides have met with limited success. [4][5][6][7][8] For instance, while a number of reliable protocols have been developed for the asymmetric Strecker reaction of ketoimines, [2h,i,9,10] catalytic systems that operate with alkali metal cyanides remain underdeveloped.…”

“…During the course of our research to expand the potential of asymmetric catalysis with chiral 1,2,3-triazolium ions, [11] we have demonstrated that these cations act as effective catalysts for the asymmetric conjugate addition of cyanide ion to α,βunsaturated carbonyl compounds in the presence of KCN. [6,7] The preeminent anion-binding ability of the triazolium ions allows efficient solid-liquid or liquid-liquid extraction of cyanide ion and ensuing delivery to the β-carbon of the unsaturated carbonyl acceptors while precisely discriminating their prochiral faces. We envisioned that this salient phase-transfer catalysis of triazolium ions would serve as a powerful means to address the issue associated with the use of KCN as a practically advantageous cyanide-ion source for the asymmetric Strecker reaction of ketoimines.…”

“…Thus, we decided to re-optimize the reaction conditions using a Brønsted acid as an additive so that the intermediary triazolium and potassium amidates could be effectively protonated (Table 3). [7,8] Cyanation of 2a was attempted with aqueous KCN in toluene under the influence of 1g (1 mol%) and acetic acid (3 equiv.) at 0 °C for various durations.…”

Highly Efficient and Diastereoselective Construction of Substituted Pyrrolidines Bearing A Quaternary Carbon Center via 1,3-Dipolar [3 + 2] Cycloaddition

“…The dearomative cycloadditions between non-stabilized azomethine ylides and 3-cyanoindoles or benzofuran also had been develop to afford the corresponding cyano-group compounds bearing a quaternary carbon centre at the ring junction (scheme 1b) [28]. on the other hand, the cyano [29][30][31][32] and sulfonyl group [33][34][35][36] is a valuable functional group in organic synthesis and has shown interesting application potential in drug design and synthesis. Inspired by these previous studies, we developed that a general approach to access functionalized pyrrolidines from ,β-unsaturated ,-disubstituted aryl cyanosulfones [37,38] with non-stabilized azomethine ylides via [3 + 2] dipolar cycloaddition (scheme 1c).…”