Structural Study‐Guided Development of Versatile Phase‐Transfer Catalysts for Asymmetric Conjugate Additions of Cyanide

Abstract

New phase transfer catalysts are reported for the first example of an organocatalytic asymmetric conjugate addition of cyanide with acetone cyanohydrin. Utilizing an accessible cupreidinium salt and a cyanation reagent suitable for industrial scale, this reaction holds significant promise for practical asymmetric synthesis. Additionally, the reported catalysts were developed as a result of gaining key structural insights via X-ray analysis of a series of catalysts of varying efficiencies and asymmetric induction.

Enantioselective Addition of Cyanide to CF3‐Substituted Alkylidenemalonates: Construction of Trifluoromethylated All‐Carbon Quaternary Stereocenters

“…In our quest to develop simple and effective catalytic systems, we have previously reported several cost‐effective and recyclable chiral catalysts for asymmetric organic transformations . Recently, cinchona alkaloids derived catalyst design received much attention and emerged as an effective catalyst for enantioselective nucleophilic addition reactions ,–,,,,. This provoked us to develop a simple catalytic system based on cinchonine for constructing highly valuable all‐carbon quaternary stereocenter from sterically hindered substrates.…”

Enantioselective Catalytic Reactions with N-Acyliden Penta-atomic Aza-heterocycles. Heterocycles as Masked Bricks To Build Chiral Scaffolds

“…With these reagents (S,R,R)-X and (R,S,R)-XI, with Cs 2 CO 3 instead of Rb 2 CO 3 , the same enantioselection is induced, and the opposite enantiomers are obtained again with excellent enantioselectivities. 35 As suggested by the authors, these bifunctional phase-transfer catalysts bearing a hydrogen-bond-donor moiety could interact by hydrogen bonding with either the CN donor species (e.g., 53 in Scheme 17) and/or the CN-accepting substrate 1. These interactions, which could have a strong influence on the structure of the reacting intermediates, will be discussed in a forthcoming section.…”

“…The pseudoenantiomeric catalysts establish a facile access to both enantiomers of 48: (S,R,R)-X gives (S)-48, while (R,S,R)-XI affords the opposite enantiomer (R)-48 (Scheme 17). 35 The excellent results are reported in Table 6 (entries 2, 3, 5, 6, 16− 23), and it is interesting to compare the results of 1al with three catalysts ( Table 6, entries 1−3) and those of 1h with four catalysts ( Table 6, entries 4−6 and Table 5, entry 6).…”

“…The Michael cyanation of 3-alkyl-substituted 1-(1H-pyrrol-1-yl)-prop-2-en-1-ones (1) and chalcones 10, performed with acetone cyanohydrin 53 and cupreidinium (S,R,R)-X or cupreinium (R,S,R)-XI salts as phase-transfer catalysts, allows one to discuss this approach. 35 These pseudoenantiomeric organocatalysts establish facile access to both enantiomers of 48 and 50, because (S,R,R)-X gives (S)-48 and (S)-50, while (R,S,R)-XI produces the opposite enantiomers (R)-48 and (R)-50 (Scheme 17). The crystal X-ray structures of cupreidinium (S,R,R)-X′ and cupreinium (R,S,R)-XI′ salts have been reported in the literature, 35 and these structures are very similar to those of X and XI.…”

“…35 These pseudoenantiomeric organocatalysts establish facile access to both enantiomers of 48 and 50, because (S,R,R)-X gives (S)-48 and (S)-50, while (R,S,R)-XI produces the opposite enantiomers (R)-48 and (R)-50 (Scheme 17). The crystal X-ray structures of cupreidinium (S,R,R)-X′ and cupreinium (R,S,R)-XI′ salts have been reported in the literature, 35 and these structures are very similar to those of X and XI.…”