Shielding effects sulfoxides

The isolation of the isomeric axial and equatorial sulfoxides (94) and (95), from the preparation of a series of hexahydrothiopyrano[4,3-c]pyrazoles (93), prompted a study (79JOC2513) to determine what effect the introduction of an S—O bond had on the carbon shifts of the methylene carbons a to sulfur. When the oxygen atom is situated in an axial position as in isomer (94), it has a deshielding effect of +17 ppm on the / carbon atoms and a shielding effect on the carbons y (—10 ppm and — 9 ppm) and 5 (— 3 ppm) relative to the carbon atoms in the unsubstituted derivative (93). The trends are similar for the equatorial derivative (94). The magnitude and trends are comparable to reported data on monocyclic thiopyran derivatives. The chemical shifts of the carbon atoms of the sulfone derivative are comparable to the signals in both sulfoxides (94) and (95). 

The picture is less clear when free electron pairs on other heteroatoms (O, S, etc.) are involved. There is only one clear-cut case providing evidence concerning endocyclic sulfoxides The unusually large shieldings of carbon atoms in gauche position relative to an axial oxygen atom in thiane oxides 79, 80, 82, and 83 (p. 252) (200,201) have been partially ascribed to an upfield-shifting effect of the equatorial antiperiplanar lone pair (cf. Section III-C). 

Conversion of thiacycloalkanes into sulfoxides and sulfones deshield the a ring carbon nuclei due to the enhanced ( —) inductive effects of SO and S02 groups. Stronger deshieldings are induced by S02 in four- and six-membered rings, and by SO in three-and five-membered rings [412]. Carbon nuclei in a p and y position are shielded, particu-... 

The P-addition of alkyl radicals to 4-methyl-2-(arylsulfinyl)-2-cyclopentenone 117 has been shown to occur in a completely stereocontrolled manner. Of a mixture of (4/ )- and (45)-117, only (4R)-117 reacts with t-Bu and i-Pr radicals to give the trans adducts 119a and 119b in 99% yield, while (45)-117 remained entirely unreacted. The stereochemical outcome of the reaction shows that the alkyl radical approaches from the side opposite to the aryl moiety in an antiperiplanar orientation to the carbonyl and sulfoxide bond. The 2,4,6-triisopropylphenyl group on sulfur plays a critical role, as it effectively shields the olefin face at the P-position by one of the isopropyl groups. This was confirmed by the 1 1 diastereomeric mixture obtained in the reaction of 4-methyl-2-(p-tolylsulfmyl)-2-cyclopentanone with the tert-butyl radical. 

For syn substrates, in the equatorial sulfoxide conformation 17, the bulk of the dithiane ring effectively shields one face of the n-system, the other face being exposed unless a very large 2-alkyl group is present. 

In the alternative, equatorial, sulfoxide conformation 20, one face of the enolate is effectively shielded by the bulk of the dithiane ring, the other face being exposed unless a very large 2-alkyl substituent is present. Stereoselectivity is therefore expected to become poorer as the relative size of the (equatorial) 2-alkyl substituent is increased, an effect which can be observed in the results outlined in Table 4 on moving from R = Me to R = Ph. 

The stereochemistry at C-4 in 3-methylenecephams derived from these chemical reductions was determined from detailed NMR studies on their sulfoxides and computer calculations based on lanthanide-induced NMR shifts (Ochiai et ai, 1972d,e). Both procedures led to the conclusion that the proton at position 4 was in the p orientation. Methyl 7-phenoxyace-tamido-3-methylene-cepham-4-carboxylate (16) was oxidized with m-chloroperbenzoic acid to give the p-sulfoxide (17S), and with N,N-di-chlorourethane to give the a-sulfoxide (17R). The anisotropic effect of each sulfoxide on its respective C-4 proton was examined. The proton at C-4 was found to be shielded by 0.06 ppm in the a-sulfoxide (R) and deshielded by 0.09 ppm in the p-sulfoxide (5). Dreiding models of the two conformational possibilities (A) and (B) for both sulfoxides suggest... 

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