Asymmetric three- and [2 + 1]-component conjugate addition reactions for the stereoselective synthesis of polysubstituted piperidinones.
The efficiency and stereoselectivity of the conjugate addition of lithium (Z)- or (E)-beta-amino ester enolates, generated by lithium amide conjugate addition to an alpha,beta-unsaturated ester or deprotonation of a beta-amino ester, respectively, to a range of alpha,beta-unsaturated acceptors has been investigated. Deprotonation of a beta-amino ester with LDA, followed by conjugate addition to a chiral alpha,beta-unsaturated oxazolidinone gives high 2,3-anti selectivity ( approximately 90% d.e.), with hydrogenolysis and purification to homogeneity generating stereodefined trisubstituted piperidinones as single stereoisomers. Asymmetric three-component couplings of alpha,beta-unsaturated esters and alkylidene malonates initiated by lithium amide conjugate addition proceeds with high levels of 2,3-anti stereoselectivity, with hydrogenolysis giving tetrasubstituted piperidinones.
Davies
Stephen G
SG
Department of Organic Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK. steve.davies@chem.ox.ac.uk
Roberts
Paul M
PM
Smith
Andrew D
AD
D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry; D008094:Lithium / Q000737:chemistry; D023303:Oxazolidinones / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature
D004952:Esters; D023303:Oxazolidinones; D010880:Piperidines; D010881:Piperidones; D008094:Lithium