Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, USA.
J Org Chem. 2011 Sep 2;76(17):7065-75. doi: 10.1021/jo200991q. Epub 2011 Aug 1.
Chiral silylated pyrrolidine catalysts are obtained in high yield and enantioselectivity by sparteine-mediated lithiation of N-Boc-pyrrolidine and addition to silyl fluoride electrophiles. The activity and enantioselectivity of a new tert-butyldiphenylsilylpyrrolidine catalyst has been demonstrated for various asymmetric Michael reactions at 5 mol % catalyst loading and affords up to 99% ee for asymmetric Michael reactions with aldehydes and nitro-olefins. Acetaldehyde donors proceed with yields up to 77% and enantioselectivities up to 96% ee, avoiding common side reactions that often lower yields. Insight into the mechanism of pyrrolidine-based catalysts is provided by demonstrating ESI mass spectrometry evidence for activation of a nitro acceptor by formation of a hydrogen-bonding adduct with the catalyst amine. Analysis of reaction intermediates using mass spectrometry provides evidence that the pyrrolidine catalyst also plays a role in activating nitro-olefins through hydrogen-bonding.
手性硅基化吡咯烷催化剂可通过 Boc-保护的吡咯烷的 sparteine 介导的锂化和与硅氟化物亲电试剂的加成反应高产率和高对映选择性地获得。一种新的叔丁基二苯基硅基吡咯烷催化剂的活性和对映选择性已在各种不对称迈克尔反应中得到证明，在 5 mol%催化剂负载下，对于与醛和硝基烯烃的不对称迈克尔反应，可获得高达 99%的对映选择性。对于醛供体，产率高达 77%，对映选择性高达 96%ee，避免了通常会降低产率的常见副反应。通过证明 ESI 质谱证据表明通过与催化剂伯胺形成氢键加合物来活化硝基受体，提供了关于基于吡咯烷的催化剂的机制的见解。使用质谱分析反应中间体提供了证据，表明吡咯烷催化剂也通过氢键作用在活化硝基烯烃方面发挥作用。
