Sodium Isopropyl(trimethylsilyl)amide: A Stable and Highly Soluble Lithium Diisopropylamide Mimic

The preparation, structure, physical properties, and reactivities of sodium isopropyl(trimethylsilyl)amide (NaPTA) are described. The solubilities at room temperature range from n-heptane (0.55 M), n-hexane (0.60 M), toluene (0.65 M), MTBE (1.7 M), Et₃N (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. ²⁹Si NMR spectroscopy shows exclusively a mixture of cis and trans stereoisomeric dimers in 0.10–12 M THF in hexane. Density functional theory (DFT) computations suggest that the pK_b 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 (k_NaPTA/LDA = 1–30). While the rates of arene metalation are high, the lower pK_b of NaPTA limits the substrates. Metalation of pseudoephedrate-based carboxamides to form disodiated Myers enolates solves several challenging technical problems.