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.