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

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.

Approaching sub-ppm-level asymmetric organocatalysis of a highly challenging and scalable carbon–carbon bond forming reaction

“…4a). 35,36 The absorption peak of the carbonyl group of ketone 1a at 1688 cm -1 was monitored during the reaction in the presence of 0.1 mol% of IDPi catalyst C-6 at 20 °C (step A). After 7 min, silyl ketene acetal 2a (1656 cm -1 ) was added to the reaction mixture (step B).…”

Synthesis of 1,1′‐Spirobiindane‐7,7′‐Disulfonic Acid and Disulfonimide: Application for Catalytic Asymmetric Aminalization

“…Among a variety of catalysts reported to date, chiral 1,1′‐binaphthyl‐2,2′‐disulfonic acids (BINSAs) and their disulfonimide derivatives (Figure , top) are attractive in terms of their stronger Brønsted acidity compared with chiral phosphoric acids and carboxylic acids . In addition to working as a Brønsted acid, these catalysts can be used as ligands for a metal center and chiral anions to control enantioselectivity ,,,. Their versatility and efficient catalytic activity have prompted chemists to pursue the steric and electronic tuning of these catalysts ,,,.…”

Die katalytische, asymmetrische Mukaiyama‐Michael‐Reaktion von Silylketenacetalen mit α,β‐ungesättigten Methylestern

“…Die größere sterische Hinderung für Silylketenacetal D und eine dadurch niedrigere Reaktivität könnten ausschlaggebend für diese Beobachtung sein. Im Allgemeinen korrelierten die isolierten Ausbeuten gut mit der Menge an eingesetzten SKA (siehe Hintergrundinformationen für weitere Details), und die Selbstheilungseigenschaften der Silylium‐Lewis‐Säurekatalyse ermöglichten es uns darüber hinaus, die Reaktion auch in nicht getrocknetem Lösungsmittel unter Verzicht auf Inertgas durchzuführen. Das Produkt 3 a wurde mit identischer Ausbeute und Enantioselektivität unter diesen Bedingungen erzeugt.…”