Davies Stephen G, Roberts Paul M, Smith Andrew D
Department of Organic Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.
Org Biomol Chem. 2007 May 7;5(9):1405-15. doi: 10.1039/b701226h. Epub 2007 Mar 23.
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.
分别通过酰胺锂对α,β-不饱和酯的共轭加成或β-氨基酯的去质子化反应生成的锂（Z）-或（E）-β-氨基酯烯醇盐，与一系列α,β-不饱和受体进行共轭加成反应的效率和立体选择性已得到研究。用LDA使β-氨基酯去质子化，然后与手性α,β-不饱和恶唑烷酮进行共轭加成反应，可得到高的2,3-反式选择性（约90%的对映体过量），经氢解和纯化至均一性后，可生成立体构型明确的三取代哌啶酮作为单一立体异构体。由酰胺锂共轭加成引发的α,β-不饱和酯与亚烷基丙二酸酯的不对称三组分偶联反应以高水平的2,3-反式立体选择性进行，经氢解可得到四取代哌啶酮。
