NMR experimental evidence of the differentiation of enantiotopic directions in C-s and C-2v molecules using partially oriented, chiral media

We report new and explicit experimental evidence of the differentiation of H-1-H-1, C-13-H-1, and C-13-H-2 enantiotopic directions in prochiral molecu les with C-s and C-2 nu symmetry dissolved in a chiral liquid-crystalline p hase using C-13 and H-2-{(1H)} NMR spectroscopy at the natural abundance le vel. The case of endo-bicyclo[2.2.2]oct-5-ene-2,3-dicarboxylic anhydride, b icyclo[2.2.1]hepta-2,5-diene, and ethyl alcohol oriented in organic solutio ns of poly-gamma -benzyl-L-glutamate (PBLG) or poly-epsilon -carbobenzyloxy -L-lysine (PCBLL) is investigated and discussed. Next, we describe the firs t NMR differentiation of enantiotopic directions in a C-2 nu, molecule with no prostereogenic carbon using malononitrile as a model. The various resul ts presented in this work experimentally validate our recent theoretical ar guments which predict that NMR spectra of nonplanar C-s and C-2 nu compound s embedded in a chiral oriented solvent should differ from those recorded i n nonchiral oriented media, because their effective molecular symmetry poin t group (interacting molecule) is different from their molecular point grou p (isolated molecule). In addition, the differentiation of enantiotopic dir ections in C-2 nu molecules exhibiting no prostereogenic tetrahedral center illustrates for the first time an old stereochemical hypothesis which spec ulates 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 achir al circumstances. However, the relationships between X and Y groups are not all equivalent. The four X-Y relationships may be ordered into two enantio topic sets of two equivalent relationships" (Mislow, K.; Raban, M. Top. Ste reochem. 1967, 1, 1) and validate the stereogenicity concepts proposed more recently by Fujita (Fujita, S. J. Am. Chem. Soc. 1990, 112, 3390).