Sulfoxides from ketones

C-(w-propyl)-N-phenylnitrone to N-phenylmaleimide, 46, 96 semicarbazide hydrochloride to ami-noacetone hydrochloride, 45,1 tetraphenylcyclopentadienone to diphenyl acetylene, 46, 44 Alcohols, synthesis of equatorial, 47, 19 Aldehydes, aromatic, synthesis of, 47,1 /8-chloro-og3-unsaturated, from ketones and dimethylformamide-phosphorus oxychloride, 46, 20 from alkyl halides, 47, 97 from oxidation of alcohols with dimethyl sulfoxide, dicyclohexyl carbodiimide, and pyridinium trifluoroacetate, 47, 27 Alkylation, of 2-carbomethoxycyclo-pentanone with benzyl chloride, 45, 7... 

Optically active 3-keto sulfoxides are readily available from esters and methyl p-tolyl sulfoxide. The ketone function can be reduced with metal hydrides (DIBAL and ZnCl2/DIBAL) giving, with very high diastereoselectivity, opposite configurations in the resulting 3-hydroxy sulfoxides (Scheme 58). ... 

Epoxides from ketones Dimethyl sulfoxide-derived reagent (a)... 

Sulfides react faster with hydrogen peroxide and alkyl hydroperoxides than do alkenes. For this reason, transition metal catalysts are rarely necessary, but these reactions are acid catalyzed and first order in both sulfide and peroxide. The acid (HX) can be as weak as alcohol or water but the "effectiveness (of the oxidation) is determined by the pXa of the acid. Sulfides also react faster with peroxides than do ketones (see the Baeyer-Villiger reaction, sec. 3.6). Formation of the sulfone in these reactions is straightforward, but requires more vigorous reaction conditions. It is usually easy to isolate the sulfoxide from oxidation of a sulfide. Direct conversion of a sulfide to a sulfone requires excess peroxide and vigorous reaction conditions (heating, long reaction times, more concentrated peroxide). 

C-Methylation. Methyl iodide is an active alkylating agent employed in the C-methylation of carbanions derived from ketones, esters, carboxylic acids, amides, nitriles, nitroalkanes, sulfones, sulfoxides, imines, and hydrazones. The quantity of methyl iodide utilized in methylations varies from a slight (1.1 equiv) to a large excess (used as solvent). 

Zirconium tetrachloride is instantly hydrolyzed in water to zirconium oxide dichloride octahydrate [13520-92-8]. Zirconium tetrachloride exchanges chlorine for 0x0 bonds in the reaction with hydroxylic ligands, forming alkoxides from alcohols (see Alkoxides, METAl). Zirconium tetrachloride combines with many Lewis bases such as dimethyl sulfoxide, phosphoms oxychloride and amines including ammonia, ethers, and ketones. The zirconium organometalLic compounds ate all derived from zirconium tetrachloride. 

This ester is converted in high yield to the y -ketosulfoxide by means of the dimethyl sulfoxide anion. Heating in acetic acid then produces a hemi-mercaptal acetate, which on treatment with Raney nickel gives the desired 21-acetoxy-20-ketone in a 50-70% overall yield from the -ketosulfoxide. A 17a-hydroxyl may also be present during the sequence. 

Asymmetric induction by sulfoxide is a very attractive feature. Enantiomerically pure cyclic a-sulfonimidoyl carbanions have been prepared (98S919) through base-catalyzed cyclization of the corresponding tosyloxyalkylsulfoximine 87 to 88 followed by deprotonation with BuLi. The alkylation with Mel or BuBr affords the diastereomerically pure sulfoximine 89, showing that the attack of the electrophile at the anionic C-atom occurs, preferentially, from the side of the sulfoximine O-atom independently from the substituent at Ca-carbon. The reaction of cuprates 90 with cyclic a,p-unsaturated ketones 91 was studied but very low asymmetric induction was observed in 92. 

Methyl phenyl sulfide, see Thioanisole Methyl phenyl sulfoxide, 46, 78 from methylsulfinyl chloride and benzene with anhydrous alumi num chloride, 46, 80 Methyl vinyl ketone, reaction with 1-morpholino 1 cyclohexene, 45,... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

In this chapter the addition of carbon nucleophiles to simple a,j8-unsaturated sulfoxides, a-sulfinyl-a,/ -unsaturated ketones and a-sulfmyl-a,/ -unsaturated lactones will be discussed separately, in most cases the asymmetric induction arises from the chirality at sulfur. 

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. 

Other carbanionic groups, such as acetylide ions, and ions derived from a-methylpyridines have also been used as nucleophiles. A particularly useful nucleophile is the methylsulfinyl carbanion (CH3SOCHJ), the conjugate base of DMSO, since the P-keto sulfoxide produced can easily be reduced to a methyl ketone (p. 549). The methylsulfonyl carbanion (CH3SO2CH2 ), the conjugate base of dimethyl sulfone, behaves similarly, and the product can be similarly reduced. Certain carboxylic esters, acyl halides, and DMF acylate 1,3-dithianes (see 10-10. )2008 Qxj(jatjye hydrolysis with NBS or NCS, a-keto aldehydes or a-... 

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