This study examines the intramolecular hydrogen bonding (H-bonding) that influences the semipinacol rearrangement of 1,2-dialkyl-2,3-epoxy cyclopentanol to form 2,2-dialkyl-1,3-ketol, which requires the epoxy group to be cis to the neighboring alcohol group. A conformational analysis of 11 different 1,2-dialkyl-2,3-epoxy cyclopentanol compounds was performed. Full geometry optimizations were carried out for each diastereomer with the M06-2X method and the cc-pVTZ correlation consistent triple-ζ basis set. Additionally, rotomers of the cis conformers that do and do not form a H-bond between the alcohol and epoxy groups were examined. Harmonic vibrational frequency computations on all 33 optimized structures (11 trans, 11 cis with H-bond, 11 cis without H-bond) indicate that each one is a minimum with no imaginary frequencies. Analysis of simple dimethyl fluoro and chloro analogues of these epoxy cyclopentanols reveals that (i) the M06-2X/cc-pVTZ energetics are within 0.1 kcal mol-1 of CCSD(T)/cc-pVTZ values, (ii) the trans configurations intrinsically have lower electronic energies than their cis counterparts and (iii) the intramolecular H-bond inverts this order, giving the H-bonded cis conformations lower energies than the corresponding trans structures. These trends regarding cis/trans relative energies did not change when reevaluated with continuum solvation models (PCM and SMD) of dichloromethane. M06-2X/cc-pVTZ computations on the series of 1,2-dialkyl-2,3-epoxy cyclopentanols show that the electronic energies of active cis diastereomers are lower than those of the corresponding trans diastereomers by an average of 0.9 kcal mol-1. Intramolecular hydrogen bonding stabilizes the cis substrate energy by 3.4 kcal mol-1, on average.

Conformational analysis of 1,2-dialkyl-2,3-epoxy cyclopentanol diastereomers

255th National Meeting (2018)

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