Epoxide opening reactions occur through two known mechanisms: base catalyzed, in which nucleophilic attack opens the ring, followed by a proton transfer to produce the substituted alcohol, and acid catalyzed, in which the oxirane oxygen is protonated via proton transfer, followed by nucleophilic attack to produce the substituted alcohol.  There is little debate about base catalyzed reactions involving the least substituted carbon in the epoxide due to the lack to steric hindrance to nucleophilic attack.  Two leading textbook authors, however, disagree about the regioselectivity involving acid catalyzed epoxide opening reaction when the carbons are primary and secondary.  Joel Karty asserts that the more substituted carbon is attacked in the acid catalyzed mechanism and offers bond length data to augment his argument.  David Klein, on the other hand, suggests that the less substituted carbon is attacked when the competing electrophiles are primary versus secondary due to “the steric effect predominating over the electronic effect.”  To investigate these dissenting opinions, we consider a series of asymmetric derivatives of oxirane.  Specifically, the optimized equilibrium geometries of 2-methyloxirane, 2,2-dimethyloxirane, 2,2,3-trimethyloxirane, 2-ethyloxirane, 2,2-diethyloxirane, 2,2,3-triethyloxirane, 2-tert-butyloxirane, and 2,2-di-tert-butyl-oxirane are computed using SCF theory, second-order perturbation theory, and density functional theory.  The DFT functionals employed are Becke’s three-parameter hybrid functional using the LYP correlation functional, the M06-2X high nonlocality hybrid functional from Thular and Zhao, and the ωB97XD functional from Head-Gordan and coworkers which includes empirical dispersion.  The basis sets employed are Dunning and coworkers’ correlation consistent basis sets, cc-pVDZ and cc-pVTZ.   Bond lengths should be indicative of bond strength; thus, the different C-O bonds are compared in each optimized structure and each protonated optimized structure.

Regioselectivity of acid-catalyzed epoxide ring-opening reactions

2019 Spring National Meeting

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