Asymmetric Hydrocyanation of Hydrazones Catalyzed by in Situ Formed O-Silylated BINOL-Phosphate: A Convenient Access to Versatile α-Hydrazino Acids

Abstract

A first organocatalytic enantioselective route was developed for the conversion of readily prepared and air stable aliphatic hydrazones to synthetically valuable alpha-hydrazinonitriles. This BINOL-phosphate catalyzed Strecker-type reaction (see scheme, Ar = p-NO(2)-Ph) provides a new practical and direct route to alpha-hydrazino acids of synthetic and biological importance. The actually active catalyst is proposed to be an in situ formed O-silylated BINOL-phosphate, thus shifting the nature of catalysis from Brønsted acid to Lewis acid organocatalysis.

Hydrazones as Singular Reagents in Asymmetric Organocatalysis

“…In 2010, Tsogoeva andc o-workers reported an enantioselective organocatalytic hydrocyanation of aliphatic N-benzoyl hydrazones 69 employing trimethylsilyl cyanide (TMSCN) as the cyanide source and BINOL-phosphoric acid XVIa in combination with tBuOH as the catalytic system (Scheme 20). [40] As supported by 31 PNMR studies, the active catalytic speciesw as proposed to be an in situ generated O-silylated BINOL-phosphate XVIa',a cting as aL ewis acid. The interaction of hydrazones 69, presumably through the acyl group, with the silicon centeri n XVIa' wask ey to obtain a-hydrazinonitriles (R)-70 in good-tohigh yields and enantioselectivities.T hismethodology provides ad irect route to biologically relevant a-hydrazinoacids, such as (R)-71.…”

“…In 2010, Tsogoeva and co‐workers reported an enantioselective organocatalytic hydrocyanation of aliphatic N ‐benzoyl hydrazones 69 employing trimethylsilyl cyanide (TMSCN) as the cyanide source and BINOL‐phosphoric acid XVIa in combination with t BuOH as the catalytic system (Scheme ) . As supported by 31 P NMR studies, the active catalytic species was proposed to be an in situ generated O ‐silylated BINOL‐phosphate XVIa′ , acting as a Lewis acid.…”

Synthesis of (R)-Modafinil via Organocatalyzed and Non-Heme Iron-Catalyzed Sulfoxidation Using H2O2 as an Environmentally Benign Oxidant

“…A class of powerful organocatalysts is represented by Brønsted acid catalysts such as BINOLderived phosphoric acids, which have already been applied in numerous highly enantioselective transformations [40][41][42][43][44][45][46][47][48][49] since the pioneering studies by the groups of Akiyama et al [50] and Uraguchi and Terada [51].…”

A magnetically recyclable heterogeneous BINOL organocatalyst for the asymmetric aldol reaction

“…Due to the toxic nature of heavy metal-based catalysts, the development of organocatalyst has become an attractive research area [2]. Amongst various types of organocatalyst, 1,1'-bi-2-naphthol (BINOL) and its derivatives have been greatly used as organocatalysts for a wide range of asymmetric organic reactions [1, [3][4][5][6][7][8]. Based on literature review, most of the commercially available BINOL derivatives are expensive while many others are not commercially available.…”