Abstract
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.
Highlights
Due to the high versatility of chiral cyanohydrins, the catalytic asymmetric cyanation reaction of carbonyl compounds has attracted widespread interest
We commenced our study by carrying out the asymmetric cyanosilylation of 2-naphthaldehyde (2a) with TMSCN (3) as a model reaction to afford chiral cyanohydrin 4a
The resulting species 1-TMS is immediately hydrolysed back to the pre-catalyst 1, while water and silanol 9 are being converted to silanol 9 and hexamethyldisiloxane 10, respectively
Summary
Due to the high versatility of chiral cyanohydrins, the catalytic asymmetric cyanation reaction of carbonyl compounds has attracted widespread interest. Our research group has recently developed chiral disulfonimides as efficient Brønsted acid organocatalysts[10,11], which can conveniently be utilized as precursors for silylium-mediated Lewis acid organocatalysts, when combined with silicon containing organic nucleophiles[11,12,13] This catalytic system afforded remarkably high enantioselection, by pairing a silylium ion equivalent with a chiral enantiopure counteranion, exploiting the concept of asymmetric counteranion-directed catalysis[14]. We observed an interesting phenomenon referred to as dormant period, during which the catalyst is completely inactive and which is reversibly induced by water This phenomenon was systematically investigated by means of in situ Fourier transform infrared (FT-IR) analysis, providing important mechanistic insight into the pre-catalytic cycle
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