The first syntheses of optically active [trans-2,6-2H2]cyclohexanone (1) and [2-3H]cyclohexanone (2) are presented. These compounds are synthesized by use of the enzyme acetoacetate decarboxylase (AAD), and assignments of configurations based on chemical degradation and spectroscopy are described. Circular dichroism spectra for electronic transitions and fundamental vibrational transitions are reported for both enantiomers of 1 from 2000 to 40000 cm-'. The results of observation and calculation of vibrational circular dichroism (VCD) intensities of 1 and its a-monodeuterio analogue, 3, are presented in both the C-H and C-D stretching regions. Qualitative agreement is obtained between experiment and theory in the C-H region of 1, confirming the results of independent determinations of the absolute configurations. Measurable VCD in the C-H stretching region was not observed for dilute solutions of either enantiomer of 3 in cyclohexanone-CCl,, although strong VCD bands were observed in the C-D stretching regions of both enantiomers. Only minimal VCD is predicted in the C-D stretching regions of 1 and 3; however, large observed intensitias over a wide frequency range in this region indicate a pronounced and possibly obscuring contribution from overtone and combination bands. The utility of enzymic methods for synthesis of chirally deuterated molecules is described, along with the potential for assignment of absolute configuration by VCD compared with chemical degradation. In recent years, stereochemical investigations using isotopes as perturbers of molecular symmetry have received increased attention. Of particular significance are studies where the molecular chirality arises solely from an isotopic substitution. This particular aspect has been a focus of electronic optical activity (EOA) investigations, because in the Born-Oppenheimer approximation, isotopic substitution in a parent achiral molecule is not expected to support EOA. Nevertheless, it is now well understood that the observed EOA in such cases arises from vibronic interactions that differ for isotopically substituted and parent molecules. Several workers have now observed the EOA due solely to isotopic substitution,24 and some theoretical models have been developeds-' to include vibronic interactions in EOA predictions. In vibrational optical activity (VOA)* several reports of VOA due solely to isotopic substitution have a ~ p e a r e d . ~ I ~ More specifically, the vibrational circular dichroism (VCD) in the C-D stretching regions of (-)-[(1R)-2H]neopentyl ~ h l o r i d e , ~ (-)-[(lR)-'H]-lphenylpropane,I0 and, more recently, (-)-[( 1R)-2H]neopentyl bromide have been reported. Similarly, ( +)-(S)-[CY-~H] benzyl alcohol and (-)-( lS)-4,4-dideuterioadamantan-2-0ne~~ have been subjected to Raman optical activity (ROA) investigations. The presence of VOA in isotopically chiral molecules is easily con( 1 ) (a) Syracuse University. (b) Alfred P. Sloan Foundation Fellow. (c) Harvard University. (d) Brandeis University. Address correspondence to: Department of Chemistry, University of California, Riverside, Riverside, California 92521. (2) Djerassi, C.; Tursch, B. J. Am. Chem. SOC. 1961, 83, 4609-4612. (3) Simek, J. W.; Mattern, D. L.; Djerassi, C. Tetrahedron Lett. 1975, (4) Lightner, D. A.; Gawronski, J. K.; Bouman, T. D. J. Am. Chem. Soc. ( 5 ) Klingbiel, R. T.; Eyring, H. J. Phys. Chem. 1970, 74, 4543-4551. (6) Dezentse, R. F. R.; Dekkers, H. P. J. M. Chem. Phys. 1976, 18, (7) Bouman, T. D.; Lightner, D. A. J. Am. Chem. SOC. 1976, 98, (8) Nafie, L. A.; Diem, D. Ace. Chem. Res. 1979, 12, 296-302. (9) Holnvarth, G.; Hsu, E. C.; Mosher, H. S.; Faulkner, T. R.; Moscowitz, A. J. Am. Chem. SOC. 1974, 96, 251-252. (10) Stephens, P. J.; Clark, R. In Optical Activity and Chiral Discrimination, Mason, S. F., Ed.; D. Riedel Publishing Co.: Dordrecht, 1979. (11) Laux, L.; Abbate, S.; Paultz, V. N.; Havel, H. A.; Ferber, S. D.; Overend, J.; Moscowitz, A. Thirty-Fifth Symposium on Molecular 367 1-3674.