Catalytic Asymmetric Cyanation Research Articles

Non-enzymatic catalytic asymmetric cyanation of acylsilanes

The asymmetric cyanation of acylsilanes affords densely functionalized tetrasubstituted chiral carbon centers bearing silyl, cyano, and hydroxy groups, which are of particular interest in synthetic and medicinal chemistry. However, this method has been limited to a few enzymatic approaches, which employ only one substrate because of substrate specificity. Here we show the non-enzymatic catalytic asymmetric cyanation of acylsilanes using a chiral Lewis base as an enantioselective catalyst, trimethylsilyl cyanide as a cyanating reagent, and isopropyl alcohol as an additive to drive catalyst turnover. High enantio- and site-selectivities are achieved in a catalytic manner, and a variety of functional groups are installed in optically active acylsilane cyanohydrins, thus overcoming the limitations imposed by substrate specificity in conventional enzymatic methods. A handle for the synthetic application of the products is also established through the development of a catalyst for protecting acylsilane cyanohydrins, which are unstable and difficult to protect alcohols.

Catalytic Asymmetric Cyanation Reactions of Aldehydes and Ketones in Total Synthesis

AbstractCatalytic asymmetric cyanation reactions of aldehydes and ketones provide efficient routes for the synthesis of optically active cyanohydrins, which are versatile synthons for the preparation of natural products and chemical pharmaceuticals. This review aims to provide a summary of recent achievements concerning catalytic enantioselective cyanation reactions of aldehydes and ketones employed in the total syntheses of various natural products, drugs, and pharmaceutically active compounds.magnified image

Asymmetric counteranion-directed Lewis acid organocatalysis for the scalable cyanosilylation of aldehydes.

Due to the high versatility of chiral cyanohydrins, the catalytic asymmetric cyanation reaction of carbonyl compounds has attracted widespread interest. However, efficient protocols that function at a preparative scale with low catalyst loading are still rare. Here, asymmetric counteranion-directed Lewis acid organocatalysis proves to be remarkably successful in addressing this problem and enabled a molar-scale cyanosilylation in quantitative yield and with excellent enantioselectivity. Also, the catalyst loading could be lowered to a part-per-million level (50 ppm: 0.005 mol%). A readily accessible chiral disulfonimide was used, which in combination with trimethylsilyl cyanide, turned into the active silylium Lewis acid organocatalyst. The nature of a peculiar phenomenon referred to as a “dormant period”, which is mainly induced by water, was systematically investigated by means of in situ Fourier transform infrared analysis.

Catalytic Asymmetric Cyanation Reactions

Catalytic asymmetric cyanations of prochiral unsaturated compounds affording the corresponding nitrile products in high enantiomeric excess (≥90% in general) are summarized in this review. The nucleophilic cyanide addition onto aldehydes, ketones, and imines is promoted by chiral metal complexes and organocatalysts. Recent progress in asymmetric conjugate cyanation of α,β-unsaturated carbonyl compounds is also discussed. The asymmetric cyanation of unactivated alkenes is catalyzed by chiral transition-metal complexes. Current topics of intramolecular carbocyanation and aminocyanation in addition to the traditional hydrocyanation are reviewed.

Catalytic Asymmetric Cyanation of Alkylideneindolenines Generated from Sulfonylalkylindoles

Abstract The catalytic asymmetric phase-transfer cyanation of alkylideneindolenines, generated in situ from sulfonylalkylindoles, was developed. In the presence of sodium cyanide and a catalytic amount of chiral 1,2,3-triazolium salt, a series of sulfonylalkylindoles can be transformed into the corresponding chiral 3-sec-alkylindoles with good-to-high levels of efficiency and enantioselectivity.

Organocatalytic asymmetric cyanation of isatin derived N-Boc ketoimines

We report the first catalytic asymmetric cyanation of N-Boc ketoimines, which enables highly enantioselective synthesis of oxindole based α-amino nitriles. An unprecedented tandem aza-Wittig/Strecker reaction is also developed, emerging as a promising strategy for the catalytic asymmetric cyanation of ketoimines formed in situ from achiral ketones.

Toward a Rational Design of the Assembly Structure of Polymetallic Asymmetric Catalysts: Design, Synthesis, and Evaluation of New Chiral Ligands for Catalytic Asymmetric Cyanation Reactions.

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Toward a rational design of the assembly structure of polymetallic asymmetric catalysts: design, synthesis, and evaluation of new chiral ligands for catalytic asymmetric cyanation reactions

New chiral ligands ( 4 and 5) for polymetallic asymmetric catalysts were designed based on the hypothesis that the assembled structure should be stable when made from a stable module 8. A metal–ligand=5:6+μ-oxo+OH complex was generated from Gd(O i Pr) 3 and 4 or 5, and this complex was an improved asymmetric catalyst for the desymmetrization of meso-aziridines with TMSCN and conjugate addition of TMSCN to α,β-unsaturated N-acylpyrroles, compared to the previously reported catalysts derived from 1– 3. These two groups of catalysts produced opposing enantioselectivity even though the ligands had the same chirality. The functional difference in the asymmetric catalysts is derived from differences in the higher-order structure of the polymetallic catalysts.

Recent Developments in the Catalytic Asymmetric Cyanation of Ketimines

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Recent developments in the catalytic asymmetric cyanation of ketimines.

Recent developments in the catalytic asymmetric cyanation of ketimines.

Efficient Two‐Step Conversion of α,β‐Unsaturated Aldehydes to Optically Active γ‐Oxy‐α,β‐unsaturated Nitriles and Its Application to the Total Synthesis of (+)‐Patulolide C.

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