Sulfoxides preparation

Unsaturated -Keto Esters, (3-Diketones, and a /3-Keto Sulfoxide Prepared by Selenoxide Elimination... 

Scheme 5.13 Chiral sulfoxide preparation and olefin reduction with borane.

An efficient chiral sulfoxide preparation of 40 was developed which was the key to set the two chiral centers. 

Treatment of the sulfoxide prepared from p-cresol and thionyl chloride with a mixture of TFAA and KHCO3 in acetonitrile at -30°C led to formation of an orthoquinone mono(monothioketal). Desulfurisation with NiCl2(PPh3)2 gave 2-(4-methylphenoxy)-4-methylphenol in 38% overall yield. 

Among addition reactions of imines, malonate esters have been added to dihydroiso-quinolines (27) at C(l), to give the corresponding tetrahydro derivatives in high ee,74 and enantiopure aromatic sulfoxides (prepared by o-dircctcd metallation) have been added enantioselectively to imines.75... 

Sulfoxides, prepared by the oxidation of sulfides with NaI04 or peracid, undergo elimination to give the alkenes at temperatures similar to the amine oxides (Scheme 4.12). 

Dissolve 10 mg rifampicin (rifamycin SV) in 1.0 ml dimethyl sulfoxide. Prepare also a 5% (w/v) solution of trichloroacetic acid (TCA). 3-107. Place exactly 0.1 ml H-leucine solution (step 3-105) in a 125 ml Erlenmeyer flask and place the flask in the bath. 

Enantlomerically pure (R)-(+)-methyl p-tolyl sulfoxide, prepared from (-)-menthyl p-tolylsulfinate,3 4 was described with the following specific rotations [a]g +145.5° (acetone),3 [a]g5 +168° (acetone, e 1.8), [a]g +189° (CHClj, a 1). The submitters checked a sample prepared3,4 and kindly provided by Professor G. Solladle (Strasbourg), which was recrystal 11zed from hexane [a]g +146° + 1 (acetone, e 1), mp 76-77°C. HPLC analysis carried out on a chiral stationary phase shows the absence of the enantiomer (Dr. Tambute, private communication). The same analysis shows that the product obtained by the procedure described above is of 99.5% ee. 

Lithiated a-amino nitriles derived from an enantiomerically pure secondary amine have been used to achieve the asymmetric synthesis of trfl 5-dibenzylbutyrolactones (scheme 10) [58]. Enantiomeric excesses of greater than 96% were obtained after removing the chiral auxiliary. When aromatic aldehydes were used as electrophiles the benzylic alcohols were obtained as a mixture of the two epimers with a diastereomeric excess of 60-75%. Addition of a chiral sulfoxide, prepared using a modified Sharpless oxidation, to butenolide has also been utilised as part of an expeditious synthesis of podophyllotoxin (scheme 11) [59]. 

Taylor has demonstrated that conversion of the title sulfoxide, prepared by oxidation of the known sulfide, shown in Scheme 4.67 [124], into two desired enones which were required as starting materials for the synthesis of thiathromboxane analogues, could be carried out using trimethylsilyl chloride (TMSCl) in refluxing tetrachloromethane. At the time, this was the first occasion on which TMSCl had been used in order to effect a Pummerer rearrangement for such species (Scheme 4.67) [125a,b]. 

Some enantiomerically pure sulfoxides prepared from sulfite (S)-l (ref 28) and R of Figure 6 are on the left and on the right respectively on the drawings... 

Other potential syntheses of cefaclor based on 3-methylenecepham preparations reviewed earlier in this chapter are outlined in Schemes 11 and 12. A synthesis similar to that starting with phthalimido-p-chloro-methylpenicillin a-sulfoxide was not investigated in the phenoxyme-thylpenicillin series (Kukolja et al., 1976b). The exocyclic dehydrobrom-ination of 3-bromo-3-methylcepham ester sulfoxide, prepared by the method of the Fujisawa group (Kamiya et al., 1973), was discovered only recently. This chemical route to cefaclor has been explored only in laboratory-scale reactions (Corfield and Taylor, 1978). 

Acid anhydrides and chlorides are reactive as the electrophile for activation of dimethyl sulfoxide. Preparatively useful procedures based on acetic anhydride/ trifluoroacetic anhydride,and oxalyl chloride have come into general use. The pyridine-SOa complex is also useful.Scheme 10.3 gives some representative examples. Entry 4 is an example of the use of a water-soluble carbodiimide as the activating reagent. The modified carbodiimide facilitates product purification by providing for easy removal of the by-product urea formed from the carbodiimide. 

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