Configurational and Conformational Analysis of Chiral Molecules Using IR and VCD Spectroscopies: Spiropentylcarboxylic Acid Methyl Ester and Spiropentyl Acetate F. J. Devlin, † P. J. Stephens,* ,† C. O ¨ sterle, ‡ K. B. Wiberg, ‡ J. R. Cheeseman, § and M. J. Frisch § Department of Chemistry, University of Southern California, Los Angeles, California 90089-0482, Department of Chemistry, Yale University, New Haven, Connecticut 06511, and Gaussian Inc., 140 Washington Avenue, North Haven, Connecticut 06473 stephens_pj@hotmail.com; pstephen@usc.edu Received April 2, 2002 The chiral monosubstituted derivatives of spiropentane, spiropentylcarboxylic acid methyl ester, 1, and spiropentyl acetate, 2, have been synthesized in optically active form. Configurational and conformational analysis of 1 and 2 has been carried out using infrared (IR) and vibrational circular dichroism (VCD) spectroscopies. Analysis of the experimental IR and VCD spectra has been carried out using ab initio density functional theory (DFT). For both 1 and 2, DFT predicts two populated conformations. Comparison to experiment of the conformationally averaged IR and VCD spectra of 1 and 2, predicted using DFT, provides unequivocal evidence of the predicted conformations and yields the absolute configurations R(-)/S(+) for 1 and R(+)/S(-) for 2. These absolute configurations are consistent with the R(-)/S(+) absolute configuration of spiropentylcarboxylic acid, assigned previously via X-ray crystallography of its R-phenylethylammonium salt. Introduction We report the configurational and conformational analysis of two chiral derivatives of spiropentane, spiro- pentyl carboxylic acid methyl ester, 1, and spiropentyl acetate, 2, using vibrational unpolarized absorption (infrared (IR)) and vibrational circular dichroism (VCD) spectroscopies. The stereochemistry and mechanism of the nitrous acid deamination of spiropentylamine in acetic acid was recently studied. 1 Optically active spiropentylamine, 3, and spiropentyl acetate, 2, of known relative configura- tions were prepared from optically active spiropentyl- carboxylic acid, 4, using reactions of known stereochem- istry (Scheme 1), and the specific rotations of 2 and 3 established. Measurement of the specific rotation of 2 obtained by deamination of optically active 3 then led to the conclusion that deamination occurs with essentially complete inversion of configuration, consistent with S N 2 displacement at a spiropentyldiazonium ion intermediate. Simultaneously, the absolute configuration (AC) of 4 was determined via X-ray crystallography of its salt with (S)- (-)-R-phenylethylamine to be R(-)/S(+). 1 This in turn allowed the ACs of 2 and 3 to be inferred: 2, R(+)/S(-); 3, R(-)/S(+). The determination of the AC of 4 from the X-ray structure of its R-phenylethylammonium salt re- quires the discrimination of the isoelectronic CH 3 and NH 3 + groups of the R-phenylethylammonium ion. One of these groups is adjacent to the COO - group of a spiro- * To whom correspondence should be addressed. Fax: (213) 740- 3792. † University of Southern California. ‡ Yale University. § Gaussian Inc. (1) Wiberg, K. B.; O ¨ sterle, C. J. Org. Chem. 1999, 64, 7763. SCHEME 1 a a Reagents and conditions: (a) Curtius reaction; (b) MeLi, urea/ H2O2 and (CF3CO)2O; (c) HNO2 in CH3COOH; (d) CH2N2. 8090 J. Org. Chem. 2002, 67, 8090-8096 10.1021/jo020225n CCC: $22.00 © 2002 American Chemical Society Published on Web 10/23/2002