Of keto sulfoxides

In the latter cases, the stereoselective formation of keto sulfoxides 153 and 154 has been observed instead of the expected dicarbonyl compounds 151 (as found for 3-methyl-2-phenyl-5,6-dihydro-1,4-oxathiin (116), Sch. 67), only in the presence of an electron withdrawing group at the double... 

Stereoselective reduction of -keto sulfoxides. The reduction of the P-keto sulfoxide 1 with NaBH, in CH,OH/aq. NH, (9 1) proceeds with efficient 1,3-asymmetric induction and epimerization at C, (equation 1). Only slight stereoselectivity obtains in a neutral medium. The chirality of the sulfinyl group has no effect. 

Deoxygenation of sulfoxides. Tris(phenylseleno)borane is an effective reagent for the reduction of sulfoxides under mild conditions. Although this reagent converts ketones to selenoketals, selective deoxygenation of keto sulfoxides is possible. Deoxygenation of vinyl sulfoxides also proceeds smoothly. 

The intermediate a-sulfenyl carbonyl compounds may be alkylated prior to oxidative elimination. Phe-nylsulfenylation of the cw-fused butyrolactone (61), followed by methylation and oxidative elimination, gave the a-methylenebutyroiactone (62) because endocyclic elimination is stericaliy inhibited (Scheme 6). For the tran -fused butyrolactone (63), the alkylation was carried out first to ensure exocyclic elimination (Scheme 1). The intermediate a-sulfinylcarbonyl compounds may also be modified before elimination, the alkylation of keto sulfoxides (64) providing a useful synthesis of a,p-unsaturated -y-keto esters (65 Scheme In some cases the use of an excess of strong base provides a dimetaliated... 

Corey and Chaykovsky described the reduction of carboxylic esters to ketones by way of / -keto sulfoxides. The ester is treated in tetrahydrofuran with a solution of methylsulfinyl carbanions in a mixture of dimethyl sulfoxide and tetrahydrofuran at 0°. This yields a j8-keto sulfoxide which is reduced with aluminum amalgam in 90% aqueous tetrahydrofuran.527 The methylsulfinyl carbanions are formed by the action of sodium hydride on dimethyl sulfoxide under nitrogen at 65-70°. 

Many variants of this procedure exist. Thus, Kano and coworkers have carried out the condensation of /3-keto sulfoxides with diaminomaleonitrile (Scheme 36) (78S372). This reaction probably yields an intermediate dihydropyrazine which is oxidized under the reaction conditions, and it seems likely that the condensation of the carbonyl group and the amine is the first step. 

A new, versatile and selective synthesis of 6- and 7-substituted pteridines was reported by Rosowsky (73JOC2073). /3-Keto sulfoxides, which can be viewed as latent a keto aldehydes, react with (251) to give 6-substituted pterins, and the use of a-keto aldehyde hemithioacetals leads in a regiospecific synthesis to the isomeric 7-substituted pterins (equation 85). 

The reachons of -keto acid derivatives with tnfluoromethylsulfenyl chlonde give the a-tnfluoromethanesulfenyl substitution products [4 The products can be treated with a dunethyl sulfoxide-water soluhon to form tnfluoromethylthioke-tones or with potassium hydroxide solution to give tnfluoromethylthroacetic acid (equahon 3) (Table 2)... 

C. Reduction of )3-Keto Sulfoxides with Aluminum Amalgam (//)... 

Enantiomerically pure /J-keto sulfoxides are prepared easily via condensation of a-lithiosulfinyl carbanions with esters. Reduction of the carbonyl group in such /J-keto sulfoxides leads to diastereomeric /J-hydroxysulfoxides. The major recent advance in this area has been the discovery that non-chelating hydride donors (e.g., diisobutylaluminium hydride, DIBAL) tend to form one /J-hydroxysulfoxide while chelating hydride donors [e.g., lithium aluminium hydride (LAH), or DIBAL in the presence of divalent zinc ions] tend to produce the diastereomeric /J-hydroxysulfoxide. The level of diastereoselectivity is often very high. For example, enantiomerically pure /J-ketosulfoxide 32 is reduced by LAH in diethyl ether to give mainly the (RR)-diastereomer whereas DIBAL produces exclusively the (.S R)-diastereomer (equation 30)53-69. A second example is shown in... 

Another way of preparing ketones involves alkylationof 3-keto sulfoxides or... 

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-... 

For a review of the synthetic uses of 3-keto sulfoxides, sulfones, and sulfides, see Trost, B.M. Chem. Rev., 1978, 78, 363. For a review of asymmetric synthesis with chiral sulfoxides, see Solladie, G. Synthesis, 1981, 185. 

The mild character of the reaction conditions is exemplified effectively here by the preparation of 2-acetyl-2-cyclohexen-l-one from 2-acetyIcyclohexanone. The crude product is initially isolated entirely in the less stable enedione form which is partially converted to the more stable enol form, 2-ace tyl-1,3-cyclohexadien-l-ol, during distillation at 45-55°. A series of a,(3-unsaturated j3-keto esters, -diketones, and a p-keto sulfoxide have also been prepared in the unenolized form by this... 

IV. ADDITION OF NUCLEOPHILES TO P-UNSATURATED SULFOXIDES A. /J-Keto sulfoxides... 

The (3-keto sulfoxides can be alkylated via their anions. Inclusion of an alkylation step prior to the reduction provides a route to ketones with longer chains. 

Furthermore, as described by Mori and coworkers, the domino aldol/cyclization reaction of the 3-keto sulfoxide 2-422 with succindialdehyde (2-423) in the presence of piperidine at r.t. afforded the chromone 2-424 which, on heating to 140 °C, underwent a thermal syn-elimination of methanesulfenic acid to provide 2-426 in 22 % overall yield (Scheme 2.100) [227]. This approach was then used for the synthesis of the natural products coniochaetones A (2-425) and B (2-427) [228]. 

Figure 32.22 shows the diastereoselective hydrogenation of (R)-/ -keto sulfoxides with Meo-BIPHEP-Ru catalysts [72]. The R chiral center of the substrate matches with the S catalyst, giving the S,R alcohols in >99 1 selectivity, whereas reactions with the R catalyst affords a 6 94 to 10 90 mixture of the S,R and R,R diastereomeric alcohols. The diastereoselection is controlled mainly by the configuration of the catalyst. 

Pentitol synthesis An asymmetric synthesis of L-arabinitol involves condensation of the (E)-a,fJ-unsaturated ester (2) with the anion of methyl (R)-p-tolyl sulfoxide (1). The resulting p-keto sulfoxide (3) is reduced stereoselectively by ZnCl2/DIBAH (13, 115-116) to 4. Osmylation of 4 with (CH,)3NO and a catalytic amount of 0s04 (13, 224-225) yields essentially a single triol (5). Finally, a Pum-merer rearrangement of the sulfoxide followed by reduction of an intermediate... 

In the presence of carp, molinate was rapidly transformed into more polar metabolites. Twenty-four hours after treatment, conversion of molinate to organosoluble metabolites was extensive (Table II). The proportion of molinate sulfoxide increased from 1.2% on day 1 to 10.2% by the 14th day. Molinate, hydroxylated at the 4 position, decreased from 10.8% to 4.6% in 14 days. However, 4-keto and 3-hydroxy molinate together gradually increased over the 14 days from 6.9% to 77.7%. Another metabolite, a keto HMI,... 

Oikawa and Yonemitsu reported a general method for the synthesis of 2-hydroxy-carbazoles (529) by the acid-catalyzed cyclization of the p-keto sulfoxide 528 (511). The required p-keto sulfoxide was derived from nucleophilic attack of dimethyl sulfoxide on methyl 3-indolepropionate. 

The key step in this synthesis is an intramolecular nucleophilic attack on the electron-rich indole nucleus by the carbocation derived from the p-keto sulfoxide in the presence of acid. Finally, the intermediate tetrahydrocarbazole aromatizes by elimination of methanethiol under the conditions of the reaction to produce the hydroxycarbazole (511) (Scheme 5.12). 

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