Mn(III) salen complexes-catalyzed enantioselective addition of trimethyl silylcyanide to N-benzylimines in the presence of 4-phenyl pyridine-N-oxide as an additive

Chiral monomeric and dimeric Mn(III) salen complexes viz., [(S,S)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminato manganese(III) chloride and 5,5-methylene di-[(S,S)-{N-(3-tert-butyl salicylidine)-N′-(3′,5′-di-tert-butyl salicylidene)}-1,2-cyclohexanediaminato manganese(III) chloride were used as catalysts for the highly enantioselective Strecker reaction of various imines (derived by the condensation of aldehydes and amine) with TMSCN as a source of cyanide in toluene. Excellent yield (95%) of α-amino nitrile with ee >99% was achieved when N-(2-methoxybenzylidine)-1-phenylmethanamine was used as a substrate and 4-phenyl pyridine-N-oxide (4-PPNO) as an additive at −55 °C in 28 h. The dimeric catalyst was found to be more reactive and enantioselective than the monomeric catalyst. The chiral dimeric catalyst used in the present study was recoverable and recyclable several times with retention of its performance.

Graphical abstractIn asymmetric Strecker reaction the enantioselective α-aminonitriles were obtained by using various N-benzylimines with TMSCN as a source of cyanide at −55 °C with chiral monomeric and dimeric Mn(III) salen complexes in toluene. The dimeric catalyst 2 worked better than the catalyst 1 in terms of reactivity and enantioselectivity in the case of 2-MeO imine (9) for the synthesis of α-aminonitrile in high enantiomeric excess (>99%) with the added advantage of catalyst recyclability.Figure optionsDownload full-size imageDownload as PowerPoint slide

N-Benzyl (R)-2-amino-phenylacetonitrileC15H14N2[α]D25=+71.0 (c 1, CHCl3)Source of chirality: (1S,2S)-cyclohexanediamineAbsolute configuration: (R)

N-Benzyl (R)-2-amino-(4-methylphenyl)acetonitrileC16H16N2[α]D25=+34 (c 1, CHCl3)Source of chirality: (1S,2S)-cyclohexanediamineAbsolute configuration: (R)

N-Benzyl (R)-2-amino-(3-methylphenyl)acetonitrileC16H16N2[α]D25=+63.4 (c 1, CHCl3)Source of chirality: (1S,2S)-cyclohexanediamineAbsolute configuration: (R)

N-Benzyl (R)-2-amino-(2-methylphenyl)acetonitrileC16H16N2[α]D25=+74.6 (c 1, CHCl3)Source of chirality: (1S,2S)-cyclohexanediamineAbsolute configuration: (R)

N-Benzyl (R)-2-amino-(4-methoxyphenyl)acetonitrileC16H16N2O[α]D25=+25.0 (c 0.5, CHCl3)Source of chirality: (1S,2S)-cyclohexanediamineAbsolute configuration: (R)

N-Benzyl (R)-2-amino-(3-methoxyphenyl)acetonitrileC16H16N2O[α]D25=+29.1 (c 1, CHCl3)Source of chirality: (1S,2S)-cyclohexanediamineAbsolute configuration: (R)

N-Benzyl (R)-2-amino-(4-chlorophenyl)acetonitrileC15H13N2Cl[α]D25=+28.0 (c 0.8, CHCl3)Source of chirality: (1S,2S)-cyclohexanediamineAbsolute configuration: (R)

N-Benzyl (R)-2-amino-(1-naphthyl)acetonitrileC19H16N2[α]D25=+152.4 (c 0.45, CHCl3)Source of chirality: (1S,2S)-cyclohexanediamineAbsolute configuration: (R)

N-Benzyl (R)-2-amino-3,3-dimethyl butanonitrileC13H18N2[α]D25=+53.0 (c 1, CHCl3)Source of chirality: (1S,2S)-cyclohexanediamineAbsolute configuration: (R)