Heteroaromatic organolithium addition to a congested ketone: conformational isomerism in (N-alkylpyrrol-2-yl)di(1-adamantyl)methanols
Abstract
Tertiary alcohols have been prepared by reaction of 2-lithio-N-methylpyrrole and 2-lithio-N-ethylpyrrole with di(1-adamantyl)ketone. The conformations of the N-methyl derivatives have been determined by single crystal X-ray diffraction studies. The N-alkylpyrrol-2-yl derivatives are synthesized as the anti isomers which upon heating undergo rotation about the sp2–sp3 C–C bond to give the more stable, syn isomers with activation energies in benzene of 31.0 (Me) and 30.7 (Et) kcal mol–1. Semi-empirical (AM1) and ab initio (3-21G*//AM1) calculations indicate that the energy difference between the two rotamers is of the order of 5 kcal mol–1. Ionic hydrogenation of anti-(N-methylpyrrol-2-yl)diadamantylmethanol in dichloromethane–TFA–triethylsilane gives the anti isomer of (N-methylpyrrol-2-yl)diadamantylmethane, accompanied by substantial amounts of diadamantylketone. The barrier to anti→syn rotation in the deoxygenation product is about 4 kcal mol–1 higher than for the corresponding alcohol.