26910-40-7

Phosphines were previously unusable as Pummerer-type nucleophiles due to competing redox chemistry with sulfoxides. Here we circumvent this problem to achieve a formal phosphine Pummerer reaction that offers thioalkyl phosphonium salts that, in turn, give rise to diverse vinyl sulfides via Wittig olefinations. Thirty vinyl sulfides are thus prepared from (alkylthioalkyl)triphenyl phosphonium salts and aldehydes. The hydrolysis of these vinyl sulfides offers an efficient and versatile two-step one-carbon homologation of aldehydes to ketones.

The homologation of carbon dioxide with stable, (enantiopure) magnesium carbenoids constitutes a valuable method for preparing α-halo acid derivatives. The tactic features a high level of chemocontrol, thus enabling the synthesis of variously functionalized analogues. The flexibility to generate magnesium carbenoids through sulfoxide-, halogen- or proton- Mg exchange accounts for the wide scope of the reaction. (Figure presented.).

A study on the mechanism of the thermal decomposition of α- and β-heteroatoms substituted ethyl phenyl sulfoxides was carried out using 1-chloroethyl phenyl sulfoxide (1); two diastereomeric 1-acetoxyethyl (substituted phenyl) sulfoxides (2a) and (2b); and 2-chloroethyl phenyl, 2-bromoethyl phenyl, and 2-methoxyethyl phenyl sulfoxides (3, 4, 5). The rate of pyrolysis of 1 was 4.8 times faster at 160°C than that of ethyl phenyl sulfoxide used as a reference, while those of 2a and 2b were 107 and 155 times faster, respectively. The results indicate that the lone pair of electrons on the α-heteroatoms has a larger rate acceleration effect than the electronegativity of them. The substituent effects of the phenyl group of 2a and 2b gave positive Hammett ρ-values (ρa= 0.76 and ρb= 0.80 vs. σ). Activation parameters for 2a and 2b are as follows: 2a, ΔH?= 112 kJmol-1, ΔS?= -20 JK-1mol-1; 2b, ΔH?= 107 kJmol-1, ΔS?= -29 JK-1mol-1. Large deuterium kinetic isotope effects for 1-acetoxyethyl-2,2,2-d3 phenyl sulfoxides (2ad and 2bd) were observed (kH/kD= 3.5 ～ 4.1). These results suggest that the pyrolysis of -heteroatom substituted ethyl phenyl sulfoxides proceeds via a five-membered transition state deviated to E1-like in character. On the other hand, from the results of kinetics for the pyrolysis of 3, 4, and 5, no effect by the β-halogen atoms or some deceleration effect by the β-methoxy group was observed. Thus the reaction seems to proceed via an E1-like mechanism. Copyright Taylor & Francis Group.

To better understand the skin sensitization mechanism of 15-hydroperoxyabietic acid-like compounds, 2-(1'-hydroperoxy-1'-methylethyl)-4a-methyl-3,4,4a,5,6,7-hexahydronaphthalene 7 was synthesized. The allergenic activity of this compound was tested on mice using the local lymph node assay, and further evaluated on guinea pigs using the Freund's complete adjuvant test. Using these methods, hydroperoxide 7 was found to be a strong sensitizer. Radical-trapping experiments were carried out on this compound in the presence of the spin-trapping agent, 1,1,3,3-tetramethylisoindolin-2-yloxyl 17, using light to induce radicals. The formation of carbon-centered radicals derived from compound 7 by intramolecular cyclization of an oxygen-centered radical was observed. The reaction of these intermediates with 17 gave various adducts in a very low yield, but a 1/1 mixture of diastereomers 18a and 18b (0.1% yield) was isolated and characterized, together with compound 19 (0.03% yield). The results suggest that carbon-centered reactive radicals are formed from allylic hydroperoxides and that this could be the possible mechanism involved in allergic contact dermatitis to abietic acid.

Various sulfides 1 reacted with sulfuryl chloride in the presence of metal nitrates in acetonitrile under mild conditions to give the corresponding α-chloro sulfoxides 2 in good yields.

Alkyl aryl sulfoxides are readily halogenated by silica-gel supported N-halosuccinimides.The conversion of optically active alkyl 4-methylphenyl sulfoxides into 1-haloalkyl 4-methylphenyl sulfoxides is accompanied by inversion of configuration at the S-atom.The stereoselectivity of the solid-phase halogenation of alkyl aryl sulfoxides is much higher than that observrd for the halogenation in solution.