The cis/trans ratio of N-methylformamide (NMF), N-methylacetamide (NMA), and N-(2-endo-norbornyl)formamide (NNF) in dilute solutions in chloroform, methanol, and water have been experimentally measured by 1 H NMR. Unlike NMA and NMF, the cis/trans ratio of NNF is sensitive to the solvent environment. To understand the anomalous behavior of NNF, we have performed calculations of ∆G and other observables between the cis and trans isomers of NMA, NMF, and NNF both in gas phase and in solution using several ab initio and DFT methods and SCRF models. The strikingly predominance of the trans isomers of N-alkyl substituted formamides can be rationalized in terms of close contact interactions between the formyl group and the C-H bond of the N-alkyl group. The molecular geometries and dipole moments of the studied amides using the RHF and B3LYP theoretical levels and split valence sets are in good accordance with the experimental values. The rotational barriers (ca. 7.0 kcal/mol) around the C2-N bond of cis-and trans-NNF were determined with the RHF/3-21G and B3LYP/6-31G* methods. On the other hand, the PCM model of the SCRF theory offers a satisfactory explanation of the different solvent dependence of NMA and NNF but fails in the computation of the cis/trans ratio of NMF in polar solvents.

Valuable chiral sources of C(10)-substituted camphors and C(10)-substituted fenchones can be straightforwardly obtained by treatment of an appropriate, easily obtainable, camphor- or fenchone-derived 2-methylenenorbornan-1-ol with an electrophilic reagent. The process takes place via a tandem regioselective carbon-carbon double-bond addition/stereocontrolled Wagner-Meerwein rearrangement. A complete study of the enantiospecificity, scope, and limitations of this process, as well as about the role played by the hydroxyl group attached at the C(1) bridgehead position of the starting 2-methylenenorbornan-1-ols, has been realized. The feasibility of the described methodology has been exemplified by the highly efficient enantiospecific preparation of several interesting C(10)-halogen-, C(10)-O-, C(10)-S-, C(10)-Se-, or C(10)-C-substituted camphors and fenchones.