Organocatalytic stereoselective cyanosilylation of small ketones

Abstract

Enzymatic stereoselectivity has typically been unrivalled by most chemical catalysts, especially in the conversion of small substrates. According to the ‘lock-and-key theory’1,2, enzymes have confined active sites to accommodate their specific reacting substrates, a feature that is typically absent from chemical catalysts. An interesting case in this context is the formation of cyanohydrins from ketones and HCN, as this reaction can be catalysed by various classes of catalysts, including biological, inorganic and organic ones3–7. We now report the development of broadly applicable confined organocatalysts for the highly enantioselective cyanosilylation of aromatic and aliphatic ketones, including the challenging 2-butanone. The selectivity (98:2 enantiomeric ratio (e.r.)) obtained towards its pharmaceutically relevant product is unmatched by any other catalyst class, including engineered biocatalysts. Our results indicate that confined chemical catalysts can be designed that are as selective as enzymes in converting small, unbiased substrates, while still providing a broad scope.

Imidodiphosphorimidates (IDPis): Catalyst Motifs with Unprecedented Reactivity and Selectivity

“…The high potency of enzymatic catalysis is usually unmatched by chemical catalysts but a recent breakthrough was contributed by IDPi catalysts where a derivative C13 could promote cyanosilylation of 2‐butanone in 98 : 2 er ( 53a ) compared to 93.5 : 6.5 er accomplished in enzymatic hydrocyanation (Scheme 8). [ 55‐56 ] A remarkable achievement in enantiofacial differentiation between methyl and ethyl groups with similar steric size (A values of 1.74 and 1.75) was displayed. This highly stereoselective process is not limited to this specific substrate: the conversion of alkyl aliphatic, functionalized aliphatic, aryl‐substituted aliphatic and (hetero)aromatic ketones that were represented by over 40 examples could be optimally performed by one of the developed catalysts ( C13 , C42 — C44 ) in good yields.…”

Role of Noncovalent Interactions in Inducing High Enantioselectivity in an Alcohol Reductive Deoxygenation Reaction Involving a Planar Carbocationic Intermediate

“…The recognized difficulty in facially controlling carbocations in enantioselective reactions has led to the implementation of numerous clever strategies (Figure ). For instance, chiral ion-pair formation has been demonstrated as valuable in enantioselective reactions involving tertiary carbocations . Another stride in this direction was reported by Carreira and co-workers concerning an Ir-catalyzed enantioselective reductive deoxygenation of racemic tertiary allenyl alcohol (Scheme ).…”

Sequentially Regulating the Structural Transformation of Copper Metal–Organic Frameworks (Cu-MOFs) for Controlling Site-Selective Reaction

“…The achievement of site-selective reactions of complex molecules has enabled attractive reconstruction with the advantages of atom economy, efficiency, and substrate diversity in the engineering and diversification of value-added complex scaffolds in synthetic chemistry. − Due to the multiple identical reaction sites with the same bonds and atoms, site selectivity was much more difficult to control because the same categories of functional groups possessed similar chemical properties and activation energies, which tend to promote the same transformation reaction. ,− Current strategies to achieve precise site selectivity rely primarily on substrate control, wherein reaction substrates with existing functional groups act as anchors to direct the catalysts or enabled one site-selective reaction that was constitutionally more reactive. − ,− The former site-selective processes required extra preparation steps to guide the orientation of functional groups, and both systems prominently blocked the varieties of substrates to allow oriented control of the site selectivity. ,,,− One dramatic and flexible pathway was to utilize a molecular recognition and self-assembly process to precisely construct a modular catalytic platform, which could be regulated to achieve different site-selective reactions.…”