Ketone Enolization with Sodium Hexamethyldisilazide: Solvent- and Substrate-Dependent E-Z Selectivity and Affiliated Mechanisms.
Ketone Enolization with Sodium Hexamethyldisilazide: Solvent- and Substrate-Dependent E-Z Selectivity and Affiliated Mechanisms.
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DOI：
10.1021/jacs.1c06529
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发表时间：
2021-10
影响因子：
15
通讯作者：
Ryan A Woltornist;D. Collum
中科院分区：
文献类型：
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作者：
Ryan A Woltornist;D. Collum
六甲基二硅氮钠（NaHMDS）的酮烯醇化反应显示出显着的溶剂和底物依赖性。2-甲基-3-戊酮的烯醇化显示了在Et 3 N/甲苯（20：1）、甲基叔丁基醚（MTBE，10：1）、N，N，N '，N“，N”-五甲基二亚乙基三胺（PMDTA）/甲苯（8：1）、TMEDA/甲苯（4：1）、二甘醇二甲醚（1：1）、DME（1：22）和四氢呋喃（THF）（1：90）中的E-Z选择性。对照实验表明，在除THF以外的所有溶剂中缓慢或不存在立体化学平衡。用Me 3SiCl/Et 3 N捕集烯醇化物需要升温至-40 °C，而Me 3SiOTf在数秒内反应。在-78 °C下使用预形成的NaHMDS/Me 3SiCl混合物的原位烯醇化物捕集在Et 3 N/甲苯中是有效的，但在THF中通过形成（Me 3Si）3 N而失效。速率研究表明，烯醇化通过单和溶解的二聚体在Et 3 N/甲苯中，溶解的二聚体在TMEDA中，三溶剂化的单体在THF/甲苯中，和游离离子与PMDTA。密度泛函理论计算通过基于E和Z的过渡结构探索选择性。失败的理论实验相关的离子碎片是相当大的，即使等键比较可以取消电子相关误差。将2-甲基-3-戊酮与紧密的电子等排体2-甲基环己酮交换，导致在THF中基于三溶剂化单体的烯醇化机理的根本变化。
Ketone enolization by sodium hexamethyldisilazide (NaHMDS) shows a marked solvent and substrate dependence. Enolization of 2-methyl-3-pentanone reveals E-Z selectivities in Et3N/toluene (20:1), methyl-t-butyl ether (MTBE, 10:1), N,N,N',N″,N″-pentamethyldiethylenetriamine (PMDTA)/toluene (8:1), TMEDA/toluene (4:1), diglyme (1:1), DME (1:22), and tetrahydrofuran (THF) (1:90). Control experiments show slow or nonexistent stereochemical equilibration in all solvents except THF. Enolate trapping with Me3SiCl/Et3N requires warming to -40 °C whereas Me3SiOTf reacts within seconds. In situ enolate trapping at -78 °C using preformed NaHMDS/Me3SiCl mixtures is effective in Et3N/toluene yet fails in THF by forming (Me3Si)3N. Rate studies show enolization via mono- and disolvated dimers in Et3N/toluene, disolvated dimers in TMEDA, trisolvated monomers in THF/toluene, and free ions with PMDTA. Density functional theory computations explore the selectivities via the E- and Z-based transition structures. Failures of theory-experiment correlations of ionic fragments were considerable even when isodesmic comparisons could have canceled electron correlation errors. Swapping 2-methyl-3-pentanone with a close isostere, 2-methylcyclohexanone, causes a fundamental change in the mechanism to a trisolvated-monomer-based enolization in THF.