A Tandem Conjugate Addition/Cyclization Protocol for the Asymmetric Synthesis of 2-Aryl-4-aminotetrahydroquinoline-3-carboxylic Acid Derivatives

作者：Davies Stephen G^*; Mujtaba Nadeam; Roberts Paul M; Smith Andrew D; Thomson James E

来源：Organic Letters, 2009, 11(9): 1959-1962.

DOI：10.1021/ol9004118

Condensation of tert-butyl (E)-3-(2'-aminophenyl)propenoate with a range of aromatic and heteroaromatic aldehydes gives the corresponding imines as single diastereoisomers (>98% de). Addition of lithium (R)-N-benzyl-N-(alpha-methylbenzyl)amide initiates a tandem conjugate addition/cyclization reaction to generate 2-aryl-4-aminotetrahydroquinoline-3-carboxylic acid derivatives in >98% de, >98% ee and high isolated yield. Hydrogenolysis of an N(1)-Boc protected derivative allows selective cleavage of the N-benzyl-alpha-methylbenzyl protecting groups without compromise of the diastereo- or enantiopurity.

• 出版日期2009-5-7