Ethylthio sulfoxide

Slight variations of the structure of this acyl anion equivalent have led in fact to the discovery of particularly valuable alternative reagents. Among them, ethyl ethylthio sulfoxide can be both monoalkyl-ated or sequentially dialkylated (Scheme 74, entries c and d). f-Butyl methylthio sulfoxide and phenyl methylthio analogs have also been monoalkylated but not dialkylated (Scheme 79, entry c Scheme 80, entry a). 

Carbanions formed from methyl methylthiomethyl sulfoxide 94 and ethyl ethylthio-methyl sulfoxide 95 were shown to be alkylated in excellent yields126,127. Treatment of 94 with rc-BuLi or KH and subsequent reaction with 1, n-dihalo- or bis(tosyloxy)alkane gave 3-, 4-, 5- and 6-membered 1-methylsulfmyl-l-methylthiocycloalkanes128"130. Upon hydrolyses of these products, the corresponding aldehydes and ketones are obtained. 

Cyclization of a suitably substituted sulfoxide thiophene 398 in acidic conditions is the key reaction in the synthesis of 4-(ethylthio)-6-phenylthieno[2,3-c]furan 399 from 3-methylthiophene-2-carboxylic acid (Equation 10) <1996JOC6166>. 

The stronger inductive effect of the sulfoxide group results in preferential a-deprotonation of (Z)-l-(ethylsulfmyl)-2-(ethylthio)ethene which leads to 1-substituted -products 6 via lithiated intermediate 2. Additionally small amounts of 2-substituted products 7 are formed via intermediate 3 due to /1-dcprotonation. Temperature dependent experiments demonstrate that a-lithi-ated Z-intermediate 2 is configurationally labile and is in equilibrium with the corresponding -intermediate which leads to products 5. 

The anions of alkyl alkylthiomethyl sulfoxides have found broader application. Alkylation of the x-carbanion of methylsulfinyl(methylthio)methane with various haloalkanes and subsequent hydrolysis give aldehydes68. The use of ethylsulfinyl(ethylthio)methane leads to improved yields of alkylation products (>95%) 69. 

An interesting disulfide cleavage is performed with 7,7/-dithio-bis[l,3,6-trimethyllumazine] (276) in basic medium yielding the relatively stable silver 7-sulfenate (277) and thiol (278) (Scheme 44). The free 1,3-dimethyllumazine-7-sulfenic acid (279) has been prepared from 7-isopropylthio and 7-[2-(4-nitrophenyl)ethylthio]-l,3-dimethyllumazine first by oxidation to the corresponding sulfoxides (282, 283) then by a modified Cope elimination and dbu treatment, respectively (Scheme 44). 

Sulfoxid Ethyl-(1-ethyl-1-ethylthio-4-oxo-pentyl)- Ell, 798 (RS CHR-SO-R + En COOR)... 

Carbamoylpyrazine was methylated to 3-carbamoyl-l -methylpyrazinium iodide by methyl iodide in methanol at reflux (138) and by methyl iodide in dimethyl sulfoxide at room temperature (666) under the latter conditions the rate of methylation relative to pyrazine was 0.53 (666). 3-Carbamoyl-l-methylpyrazinium iodide reacted with liquid ammonia at — 40° to give 2-amino-5-carbamoyl-l-methyl-1,2-dihydropyrazine (46) (609). With nitromethide ions in liquid ammonia, none of the carbon addition reaction was found (721), but with ethanethiolate ion in liquid ammonia it gave 5-carbamoyl-2-ethylthio-l-methyl-1,2-dihydropyrazine (721). 2-(4 -Morpholino)carbonylpyrazine with methyl iodide gave 3-(4 -morpholino)-carbonyl-1-methylpyrazinium iodide (870). 

This methodology was employed for the synthesis of the reported structure of the alkaloid jamtine (02OL715, 02JOC929). The key sulfoxide intermediate 307 was heated with CSA to produce several tricyclic products (98% yield) as a mixture (5 2 1 1) of diastereomers in which 308 predominated (Scheme 57). The stereochemistry of 308 was secured by X-ray crystallographic analysis and is consistent with a Nazarov-type conrotatory 47i-electrocyclization followed by attack of the nucleophilically disposed aromatic ring from the least hindered side of the intermediate iminium ion. Reaction of a-ethylthio amide 308 with NaH effected an intramolecular alkylation to provide tetracycle 309. 

The use of different oxidizing agents for the conversion of the 26-dialkylamino-ethylthio derivatives of pristinamycin Ilg to the corresponding sulfoxides was investigated. The results of these investigations into the oxidation of 26-diethylaminoethyl thioether (94a=94, = R2 = Et) with m ta-chloroper-... 

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