NMR experimental evidence of the differentiation of enantiotopic directions in C(s) and C(2v) molecules using...

We report new and explicit experimental evidence of the differentiation of (1)H-(1)H, (13)C-(1)H, and (13)C-(2)H enantiotopic directions in prochiral molecules with C(s) and C(2v)symmetry dissolved in a chiral liquid-crystalline phase using (13)C and (2)H-[(1)H] NMR spectroscopy at the natural abundance level. The case of endo-bicyclo[2.2.2]oct-5-ene-2,3-dicarboxylic anhydride, bicyclo[2.2.1]hepta-2,5-diene, and ethyl alcohol oriented in organic solutions of poly-gamma-benzyl-L-glutamate (PBLG) or poly-epsilon-carbobenzyloxy-L-lysine (PCBLL) is investigated and discussed. Next, we describe the first NMR differentiation of enantiotopic directions in a C(2v) molecule with no prostereogenic carbon using malononitrile as a model. The various results presented in this work experimentally validate our recent theoretical arguments which predict that NMR spectra of nonplanar C(s) and C(2v) compounds embedded in a chiral oriented solvent should differ from those recorded in nonchiral oriented media, because their effective molecular symmetry point group (interacting molecule) is different from their molecular point group (isolated molecule). In addition, the differentiation of enantiotopic directions in C(2v) molecules exhibiting no prostereogenic tetrahedral center illustrates for the first time an old stereochemical hypothesis which speculates that "for molecules of the type CXXYY. the two X groups as well as the Y groups are equivalent and cannot be distinguished in chiral or achiral circumstances. However, the relationships between X and Y groups are not all equivalent. The four X-Y relationships may be ordered into two enantiotopic sets of two equivalent relationships" (Mislow, K.; Raban, M. Top. Stereochem. 1967, 1, 1) and validate the stereogenicity concepts proposed more recently by Fujita (Fujita, S. J. Am. Chem. Soc. 1990, 112, 3390).