Bis(tetrahydropyran-2-yl)methane 4 along with its racemate have been synthesized. MM3 calculations suggest that the conformer 4a should be populated to cu. 85% in the conformer equilibrium. Analysis of the 'H NMR coupling constants show that one conformer predominates by about 9: 1. That this is the conformer 4a is shown by various NMR techniques, as well as by comparison of calculated with measured CD spectroscopic data. The study is extended to the methyl-substituted bis(tetrahydropyrany1)methanes 2 1 and 23 which show, as predicted from MM3 calculations, essentially monoconformational behaviour.Conformation design aims at the recognition and synthesis of segments of molecular backbones, which are conformationally flexible, but populate predominantly (ie. >90?/~) a single conformation. The starting point for the considerations is a multi-conformational carbon chain. A mono-conformational structure should result if destabilizing interactions could be introduced by structural modification into all but one of the low energy conformations. For instance, pentane has five low energy conformations (Ere, < 3 kcal mol-It) a~ailable.~ Introduction of two methyl groups into the 2 and 4 position reduces the conformational diversity to a bi-conformational situation,' as 2,4-dimethylpentane (1) populates just two enantiomorphic 1 : l c"3*H3

The absolute configurations of both 1,5-diaza-c/s-decalin enantiomers were determined by com-parison of measured and calculated CD spectra. CD spectra for both enantiomers were recorded. Theoretical CD spectra for one of the isomers were calculated by means of the semiempirical CNDO/2S method. Eight local minima on the energy hypersurface of the title compound were used to describe the conformer equilibrium mixture. The geometries of these conformers were calculated employing one-determinant ab initio calculations using the split valence 6-31G* basis set. Boltzmann factors were then obtained using relative energies calculated with three different basis sets and including correlation(MP2)-and zero point vibrational energy. Comparing the sign of the observed and calculated longest wavelength Cotton effect, we assign an absolute configuration to the compound. This assignment was verified by means of X-ray structure determination of one of the enantiomers’ α-methoxy-α-trifluoromethylphenyl aceticacid (MTPA, Mosher’s reagent) derivative.

The absolute configuration of bis(tetrahydropyran-2-yl)methane (1) was determined by comparison of measured and calculated CD spectra. The theoretical CD spectra were obtained by means of the CNDO/2S method. The five presumably lowest local minima on the energy hypersurface of the title compound were used to describe the conformer equilibrium mixture. The geometries of these conformers were calculated employing the MM3 force field, the semiempirical AM1 method and one-determinant ab initio calculations employing the 6-31G* basis set. Boltzmann factors were then obtained using relative energies calculated with three different basis sets and including correlation- and zero point vibrational energy. Based on the sign of the observed and calculated longest wavelength Cotton effect we assign an absolute configuration to the compound which is in keeping with the chirality expected from the assumed reaction mechanism. The results of force field and ab initio calculations converge to the point that the conformer equilibrium is dominated (85 -96%) by one single conformer which is energetically separated from the other conformers by about 2-3 kcal/mol. This result agrees with previous experimental data.

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The absolute configuration of the conformationally flexible aldehyde ester methyl-2-formyl-2-(phe-nylsulfanyl)-3-(3,4,5-trimethoxyphenyl)-propanoate was determined by comparison of measured and calculated CD spectra. The spectra were calculated by means of the so-called matrix method assuming R configuration at the stereogenic center. Calculated and observed signs of the first three most intense CD bands agree. Therefore, it was concluded that the absolute configuration of the compound was also R, which is in perfect agreement with the results of an X-ray structure determination.