Sodium Diisopropylamide-Mediated Dehydrohalogenations: Influence of Primary- and Secondary-Shell Solvation

Eliminations of alkyl halides by sodium diisopropylamide (NaDA) in tetrahydrofuran (THF)/hexane or THF/ N,N -dimethylethylamine (DMEA) solutions are facile and complementary to analogous reactions of lithium diisopropylamide in THF. Rate studies show a dominance of monomer-based metalations and prevalent secondary-shell solvation effects overlaid on primary-shell effects. 1-Halooctanes exclusively undergo elimination rather than substitution. Rate and isotopic labeling studies on 1-bromooctane reveal an E2-like elimination pathway via trisolvated NaDA monomer. By contrast, 1-chlorooctane is eliminated via disolvated monomer through a carbenoid mechanism. exo -2-Norbornyl chloride and bromide are also eliminated via disolvated monomer; a syn E2 mechanism is inferred for these substrates. The cis- and trans -4- tert -butylcyclohexyl bromides show a preference for the elimination of the cis isomer ( k cis/ax / k trans/eq = 10). Rate and isotopic labeling studies are consistent with a trans-diaxial E2 elimination via trisolvated monomer for the cis isomer and a carbenoid mechanism via disolvated monomer for the trans isomer. Vicinal haloethers show substrate-dependent reactivities, affording alkynes and enol ethers. trans -1-Bromo-2-methoxycyclohexane provides enol ether 1-methoxycyclohexene, while trans -1-bromo-2-methoxycyclooctane provides dimeric products consistent with fleeting cycloocta-1,2-diene (cyclic allene), which was fully characterized as two conformers.