Conformational analysis. 47. Stereochemistry of organic sulfur compounds. 21. Conformation of oxanes with sulfur substituents (original) (raw)

1987, The Journal of Organic Chemistry

The energy difference between equatorial and axial sulfur functions at C(3) in oxane has been determined in various solvents by low-temperature 13C NMR spectroscopy. The values in CDBClz are as follows: MeS,-1.21 f 0.11 kcal/mol; SOMe, more polar isomer, 4. 1 0 f 0.05 kcal/mol, less polar isomer, 4-4 3 f 0.13 kcal/mol; SOZMe, ca.-1.45 kcal/mol; Me2S+, 0.55 kcal/mol; HS,-1.1 f 0.1 kcal/mol (negative values meaning preference for the equatorial conformer). The configurations of the two sulfoxides were determined by a combination of X-ray crystallography and proton and 13C NMR spectroscopy. In the case of MeS,-AGO is close to the average of the corresponding conformational free energy differences in cyclohexane and dioxane (at C-5). For MeSO the same is true for the mean-AGO of the two sulfoxides but not for the individual values. In the case of MeS02, the experimental value of-AGO is much larger than the above average, supporting an earlier hypothesis that in 1,3-dioxan-5-yl methyl sulfone the methyl group is turned into the ring. In the methyl 3-tetrahydropyranyl sulfone, this would produce serious steric compression with the axial hydrogen a t C(5). In previous publications we have discussed conformational equilibria of oxanes substituted with nonpolar (methyl) group^,^ of thianes and their sulfoxides, and sulfones substituted with hydroxy, alkoxy, and acetoxy groups,la as well as conformational properties of acyclic compounds with vicinal oxygen and sulfur function^.^ The present work deals with oxanes substituted in position 3 with sulfide, sulfoxide, sulfone, and sulfonium functions and serves as a check for the magnitudes of pertinent sulfur/oxygen gauche interactions; it also points to some characteristic differences in conformational equilibria of sulfur-substituted cyclohexanes and corresponding 1,3dioxanes (substituent in 5) on one hand and 3-substituted oxanes on the other. In contrast to the conformational energies of nonpolar substituents in ~x a n e s ,~ the AGO values for polar substituents are not necessarily midway between those in cyclohexanes and those in 1,3-dioxanes. Synthesis and Configurational Assignment. Compounds in the 3-substituted oxane series were synthesized as shown in Scheme 1, R = H. Free radical catalyzed addition of thiolacetic acid to dihydropyran followed by saponification to mercaptide and methylation gave the methylthio ether 1, which was oxidized with 1 equiv of sodium periodate to a diastereomer mixture of sulfoxides 2 and 3, which were separated by chromatography. Oxidation of 1 with excess periodate gave the sulfone 4; sulfonium salt 5 was prepared from 1 and methyl ptoluenesulfonate. Acidification of the solution of mercaptide (vide supra) gave thiol 6. We also prepared the corresponding cis-and trans-6methyl compounds (Scheme I, R = CH3) by starting from 6-methyldihydr~pyran~ in place of dihydropyran. The diastereomeric 2-methyl-5-(methylthio)oxanes (7) were separated by chromatography and the cis isomer was (1) (a) Part 4 6