Asymmetric Acyl-Strecker Reaction Promoted by Novel Thiourea Organocatalyst

Asymmetric acyl-Strecker reaction using novel thiourea organocatalyst is described.Screening experiments of the catalysts revealed that a bifunctional organocatalyst afforded an enantio-enriched product via an unique mechanism.That is, dihydroisoquinoline derivatives were converted to a corresponding 1-cyano-1,2,3,4-tetrahydroisoquinolines using the bifunctional thiourea catalyst derived from Betti base in moderate yield and enantioselectivity. 5Recently, thiourea organocatalysts have been widely used in asymmetric reaction 6 owing to their strong activation of imino, carbonyl or nitro groups through efficient hydrogen bonding interactions. 7We previously reported an asymmetric Strecker reaction using the Jacobsen's catalyst for the synthesis of tetrahydroisoquinoline alkaloids. 8The Strecker reaction of 6,7-dimethoxy-3,4-dihydroisoquinoline was succeeded in high yield and high enantiomeric excess, and a 1-cyano-1,2,3,4-tetrahydroisoquinoline derivative thus obtained could be readily converted to a variety of alkaloids.One of the drawbacks of the reaction was that the Jacobsen catalyst was expensive because synthesis of the compound proceeded in multi-steps using rare L-t-leucine as a chiral source.Therefore, it was thought that more readily prepared catalyst was necessary for the present asymmetric reaction.In addition, List's recent works described an asymmetric acyl-Strecker reaction using less toxic acetyl cyanide as a cyanide source catalyzed by thiourea catalysts.9