Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, United States.
J Org Chem. 2022 Nov 4;87(21):14223-14229. doi: 10.1021/acs.joc.2c01745. Epub 2022 Oct 25.
The preparation, structure, physical properties, and reactivities of sodium isopropyl(trimethylsilyl)amide (NaPTA) are described. The solubilities at room temperature range from -heptane (0.55 M), -hexane (0.60 M), toluene (0.65 M), MTBE (1.7 M), EtN (3.2 M), and THF (>6.0 M). The half-life to destruction in neat THF is >1 year at 25 °C and 7 days at 70 °C, which compares favorably to 2.5 months and 1.5 days, respectively, for LDA in neat THF. This study focuses on NaPTA in THF. Si NMR spectroscopy shows exclusively a mixture of and stereoisomeric dimers in 0.10-12 M THF in hexane. Density functional theory (DFT) computations suggest that the p is intermediate between dimeric sodium diisopropylamide (NaDA) and dimeric sodium hexamethyldisilazide (NaHMDS). Metalations of arenes, epoxides, ketones, hydrazones, alkenes, and alkyl halides show higher reactivities than LDA ( = 1-30). While the rates of arene metalation are high, the lower p of NaPTA limits the substrates. Metalation of pseudoephedrate-based carboxamides to form disodiated Myers enolates solves several challenging technical problems.
本文描述了异丙基（三甲基硅基）酰胺钠（NaPTA）的制备、结构、物理性质和反应活性。在室温下的溶解度范围从庚烷（0.55 M）、己烷（0.60 M）、甲苯（0.65 M）、MTBE（1.7 M）、EtN（3.2 M）和 THF（>6.0 M）。在 25°C 下，纯 THF 中的半衰期至破坏>1 年，而在 70°C 下为 7 天，这与 LDA 在纯 THF 中的半衰期分别为 2.5 个月和 1.5 天相比具有优势。本研究重点关注 THF 中的 NaPTA。Si NMR 光谱显示在 0.10-12 M THF 中在己烷中仅存在和异构体二聚体的混合物。密度泛函理论（DFT）计算表明 p 介于二异丙基酰胺钠（NaDA）和六甲基二硅氮烷钠（NaHMDS）之间。芳族化合物、环氧化物、酮、腙、烯烃和烷基卤化物的金属化反应活性高于 LDA（=1-30）。虽然芳族化合物的金属化反应速率很高，但 NaPTA 的 p 较低限制了底物的范围。基于伪麻黄碱的酰胺的金属化形成双钠盐 Myers 烯醇化物解决了几个具有挑战性的技术问题。
