Zhao Pinjing, Lucht Brett L, Kenkre Sarita L, Collum David B
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, USA.
J Org Chem. 2004 Jan 23;69(2):242-9. doi: 10.1021/jo030221y.
Mechanistic studies of the enolization of 2-methylcyclohexanone mediated by lithium hexamethyldisilazide (LiHMDS; TMS(2)NLi) solvated by hindered dialkyl ethers (ROR') are described. Rate studies using in situ IR spectroscopy show that enolizations in the presence of i-Pr(2)O, 2,2,5,5-tetramethyltetrahydrofuran, and cineole proceed via dimer-based transition structures [(TMS(2)NLi)(2)(ROR')(ketone)]. Comparing the relative solvation energies and the corresponding solvent-dependent activation energies shows that the highly substituted ethers accelerate the enolizations by sterically destabilizing the reactants and stabilizing the transition structures. Comparisons of hindered dialkyl ethers with their isostructural dialkylamines reveal that the considerably higher rates elicited by the amines derive from an analogous relative destabilization of the reactants and relative stabilization of the transition structures.
描述了由受阻二烷基醚（ROR'）溶剂化的六甲基二硅基锂（LiHMDS；TMS(2)NLi）介导的2-甲基环己酮烯醇化的机理研究。使用原位红外光谱进行的速率研究表明，在异丙醚、2,2,5,5-四甲基四氢呋喃和桉叶油素存在下的烯醇化反应通过基于二聚体的过渡结构[(TMS(2)NLi)(2)(ROR')(酮)]进行。比较相对溶剂化能和相应的溶剂依赖性活化能表明，高度取代的醚通过空间上使反应物不稳定并稳定过渡结构来加速烯醇化反应。将受阻二烷基醚与其同结构的二烷基胺进行比较表明，胺引发的速率显著更高源于反应物类似的相对不稳定和过渡结构的相对稳定。
