Yoshimura Tomoyuki
Institute for Chemical Research, Kyoto University, Kyoto, Japan.
Yakugaku Zasshi. 2012;132(11):1287-95. doi: 10.1248/yakushi.12-00217.
The synthesis of β-lactams with contiguous tetra- and trisubstituted carbon centers has been accomplished via the 4-exo-trig intramolecular conjugate addition of C-N axially chiral enolates generated from α-amino acid derivatives. Use of a metal carbonate in a protic solvent (i.e., Cs(2)CO(3) in EtOH) was found to be critical for the success of the reaction. Under optimized reaction conditions, axially chiral enolates were generated in very low concentration, thereby favoring intramolecular conjugate addition while minimizing intermolecular side reactions. The highly strained β-lactam enolates formed through this reversible intramolecular conjugate addition were rapidly protonated by EtOH in the reaction media to afford β-lactams in up to 97% ee.
通过由α-氨基酸衍生物生成的C-N轴手性烯醇盐的4-外式-三原子环化分子内共轭加成反应，实现了具有相邻四取代和三取代碳中心的β-内酰胺的合成。发现在质子性溶剂（即乙醇中的碳酸铯）中使用金属碳酸盐对于反应的成功至关重要。在优化的反应条件下，轴手性烯醇盐以非常低的浓度生成，从而有利于分子内共轭加成，同时使分子间副反应最小化。通过这种可逆的分子内共轭加成形成的高度张力的β-内酰胺烯醇盐在反应介质中被乙醇快速质子化，以高达97%的对映体过量得到β-内酰胺。
