A tandem conjugate addition/cyclization protocol for the asymmetric synthesis of 2-aryl-4-aminotetrahydroquinoline-3-carboxylic acid derivatives.
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-N-alpha-methylbenzyl protecting groups without compromise of the diastereo- or enantiopurity.
Davies
Stephen G
SG
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK. steve.davies@chem.ox.ac.uk
Mujtaba
Nadeam
N
Roberts
Paul M
PM
Smith
Andrew D
AD
Thomson
James E
JE
D000577:Amides / Q000737:chemistry; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D008094:Lithium / Q000737:chemistry; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000577:Amides; D002264:Carboxylic Acids; D009942:Organometallic Compounds; D011804:Quinolines; D008094:Lithium