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 degrees C and 7 days at 70 degrees 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 pKb 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 (kNaPTA/LDA = 1-30). While the rates of arene metalation are high, the lower pKb of NaPTA limits the substrates. Metalation of pseudoephedrate-based carboxamides to form disodiated Myers enolates solves several challenging technical problems.

Automated summary

The preparation, structure, physical properties, and reactivities of sodium isopropyl(trimethylsilyl)amide (NaPTA) were investigated. NaPTA showed different solubilities in various solvents, with good stability in neat THF. Compared to LDA, NaPTA exhibited higher reactivities in metalations of different compounds. The study also explored the applications of NaPTA in THF and its metalation reactions with various substrates.