Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
J Org Chem. 2010 Dec 17;75(24):8578-84. doi: 10.1021/jo1019877. Epub 2010 Nov 11.
Density functional theory calculations and experiment reveal the origin of stereoselectivity in the deprotonation-alkylation of chiral N-amino cyclic carbamate (ACC) hydrazones. When the ACC is a rigid, camphor-derived carbamate, the two conformations of the azaenolate intermediate differ in energy due to conformational effects within the oxazolidinone ring and steric interactions between the ACC and the azaenolate. An electrophile adds selectively to the less-hindered π-face of the azaenolate. Although it was earlier reported that use of ACC auxiliaries led to α-alkylated ketones with er values of 82:18 to 98:2, B3LYP calculations predict higher stereoselectivity. Direct measurement of the dr of an alkylated hydrazone prior to removal of the auxiliary confirms this prediction; the removal of the auxiliary under the reported conditions can compromise the overall stereoselectivity of the process.
密度泛函理论计算和实验揭示了手性 N-氨基环氨基甲酸酯（ACC）腙去质子化-烷基化立体选择性的起源。当 ACC 是刚性的莰衍生的氨基甲酸酯时，由于恶唑烷酮环内的构象效应和 ACC 与氮烯盐之间的空间相互作用，氮烯盐中间体的两种构象在能量上有所不同。亲电试剂选择性地添加到氮烯盐的非位阻较大的π-面上。尽管早期有报道称使用 ACC 助剂可得到 er 值为 82:18 至 98:2 的α-烷基化酮，但 B3LYP 计算预测了更高的立体选择性。在去除助剂之前直接测量烷基化腙的 dr 值证实了这一预测；在报道的条件下去除助剂可能会影响该过程的整体立体选择性。
