Divergent asymmetric synthesis of 3,5-disubstituted piperidines.
A divergent synthesis of various 3,5-dioxygenated piperidines with interesting pharmacological properties is described. A mixture of the achiral cis- and racemic trans-3,5-piperidine diol could be efficiently obtained from N-benzylglycinate in five steps by the use of chemoenzymatic methods. In the subsequent enzyme- and Ru-catalyzed reaction, the rac/meso diol mixture was efficiently transformed to the cis-(3R,5S)-diacetate with excellent diastereoselectivity and in high yield. Further transformations of the cis-diacetate selectively delivered the cis-piperidine diol and the cis-(3R,5S)-hydroxy acetate. Alternatively, the DYKAT could be stopped at the monoacetate stage to give the trans-(3R,5R)-hydroxy acetate.
Olofsson
Berit
B
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
Bogár
Krisztián
K
Fransson
Ann-Britt L
AB
Bäckvall
Jan-E
JE
D000085:Acetates; D000438:Alcohols; D002384:Catalysis; D004798:Enzymes; D006880:Hydroxy Acids; D010100:Oxygen / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis*; D012428:Ruthenium
D000085:Acetates; D000438:Alcohols; D004798:Enzymes; D006880:Hydroxy Acids; D010880:Piperidines; D012428:Ruthenium; D010100:Oxygen