MAGNETIC RESONANCE IN CHEMISTRY Magn. Reson. Chem. 2004; 42: 524-533 Published online 16 March 2004 in Wiley Interscience (www.interscience.wiley.com). DOI: 10.1002/mrc.1376 Assignment of the relative configuration of spiro[4.5]decanes by 13c, 1 5 ~ and "0 NMR Jorge Antonio Guerrero-Alvarez, Antonio Moncayo-Bautista and Armando Ariza-Castolo* Departamento de Quimica, Centro de lnvestigacion y de Estudios Avanzados del IPN, Apartado Postal, 14-740, 07000 Mexico DF, Mexico Received 1 October 2003; Revised 19 December 2003; Accepted 16 January 2004 The relative configuration of 11 1,4-diazaspiro[4.5]decanes (la - lj and lm), 15 1,4-oxazaspiro[4.5]decanes (2a-20) and 10 1,4-dioxaspiro[4.5ldecanes (3a-3n) substituted at the 2-, 6-, 7- or 8-position by a methyl group or using the tert-butyl group as a model for the ananchomeric structure is reported. The relative stereochemistry was analyzed by 'H, 13C, 15N and ''0 NMR and all isomers present were characterized spectroscopically. Compounds with a methyl group in the six-membered ring show a chair conformation preference with the methyl group in the equatorial position. Compounds with one or two nitrogens exhibit a tautomeric equilibrium between the imine- diazolidine forms, as demonstrated by IR and 13C NMR. Copyright O 2004 John Wiley & Sons, Ltd. KEYWORDS: NMR; 13C NMR; 15N NMR; 170 NMR; relative configuration; substituent effects; spiro[4,5]decanes INTRODUCTION One of the most important aspects of structural elucida- tion is the assignment of configuration, not only owing to its relevance for compounds with biological activity, but also because it determines the stereoselectivity of the reac- tions. As a consequence, there is great interest in finding methods that permit the identification of stereogenic cen- ters, such as: circular dichroism,' high-performance liquid chromatography? electrophoresis,3 mass spectrometry; X- ray spectrometry 5 and NMR~ of different nuclei such as 'H, 13C 1 9 ~ 29s. 31p 77Se and , , 1 , , '95Pt by means of chiral solvents 7 or chiral reagentss In particular, oxazolidines? diazolidines"' and dioxolanes" have been recognized as chiral derivatizing agents for carbonyl compounds. 170 NMR spectroscopy has been shown to provide a useful tool for establishing the configurational preferences characteristic of alicyclic ethers and alcohols." Several investigations have dealt with stereochemical dependences of I7O chemical shift values of six-membered ring systems derived from alcohols and their corresponding ethers.13 170 NMR spectroscopy is an alternative to NOE measurements, which might cause problems during data interpretation because of the small or even vanishing effects on medium- sized molecules. Despite the experimental problems related to 170 measurements, they have been shown to provide valuable information for the solution of sophisticated stereochemical question^.'^ I5N NMR data also show additive substituent chemical shift (SCS) effects.15 In cyclohexane derivatives, the shifts induced by substituents at the B-position are valuable for 'Correspondence to: Armando Ariza-Castolo, Departamento de Quimica, Centro de hvestigacion y de Estudios Avanzados del IPN, Apartado Postal, 14-740, 07000 Mexico DF, Mexico. E-mail: aariza@mail.cinvestav.mx determining the configuration of a molecule based on the known chemical shift difference of at least 7 ppm between equatorial and axial positions.16 In this paper, 'H, 'v, '" and 170 NMR data were used to assign the relative configuration in 1,4- diazaspiro[4.5]decanes, 1,4-oxazaspiro[4.5]decanes and 1,4- dioxaspiro[4.5]decanes; some of these compounds were analyzed as mixtures. These compounds have from zero to three stereogenic centers (Scheme 1) and their relative configuration was elucidated based on SCS, aromatic solvent- induced shift (ASIS),17 and lanthanide-induced chemical shift (LIS)" effects and a combination of 2D spectra ('H,'H- COSY, '3C,'H-COSY and '3C,1H-COLOC). Many of these compounds had not been reported previously. RESULTS The 1,4-diheterospiro[4.5]decanes were prepared by the standard method.19 Compounds la - ld, lg, lj, lm, 2a-2c, 3a-3d, 3g, 3j and 3m yielded a single isomer whereas the remaining derivatives gave an equilibrium mixture of all expected stereoisomers in approximately the same ratio because the racemic mixture was used. Only the derivatives with two geminal methyl groups (If, li, 2f, 2i, 21 and 20) showed a 3 : 2 preference for the equatorial position; this observation confirmed the assignment. 13C NMR spectra were assigned using the C-%substituted fert-butyl derivatives as a model and the determination of the carbon type was obtained from APT or INEPT spectra. In order to assign the carbon signals, it was necessary to determine the 'H NMR spectrum in C6Dh using europium tris[3-trifluoromethy1hydroxymethylene)- (+)-camphorate] as shift reagent. The connectivity was established by 1D (APT, INEPT) and 2D (H,H-COSY, C,H- COSY, C,H-COLOC) spectra. In all cases, the hydrogens of Copyright Q 2004 John Wiley &Sons, Ltd.