Ketene thioacetals preparation

Despite the latent reactivity of ketene thioacetals,3-4 some members of this class such as the title compound have been little studied, perhaps because of preparative inaccessibility. The only previously reported route to 2-methylene-1,3-dlthiolane involves monoacetylation of 1,2-ethanedithiol, cyclization to 2-methyl-1,3-dithiolan-2-yl perchlorate, and exposure of this salt to diisopropylethylamine in acetonitrile 5... 

Substituted derivatives 219 were prepared from 1,2,3,4-tetrahydroiso-quinoline-l,4-dione 217 and sulfonyl ketene thioacetals 218. The same products were also obtained from 220 and 221 (Scheme 52) (79YZ1234). 

Ketene thioacetals can also be used as ketene equivalents in the preparation of cyclobutanones and cyclobutanes. Boron trifluoride catalyzes the [2 + 2] cycloaddition of 2-[(l-pyrro-lidinyl)mcthylene]-1,3-dithiane (39) with dimethyl maleate (40).17 Although the cycloadduct is obtained in good yield, stereochemical integrity is not maintained and the thermodynamically most stable isomer predominates. 

Reaction of the anion prepared by deprotonation of a ketene thioacetal (799) (LDA or s-butyllithium) with a carbonyl compound has been shown to afford generally the product of y-addition (800) (80JOC2236). Mercury ion-assisted hydrolysis of the 5-hydroxy ketene thioacetal provides access to a y-lactone (801 Scheme 187). The y-selectivity of carbonyl substrates is to be contrasted with the a-selectivity generally exhibited by alkyl halides in... 

Thiol esters RC(0)SR have been prepared by nucleophilic cleavage of polystyrene-bound /V-acylsulfonamides with mixtures of a thiol and sodium thiophenolate [377] or LiBr [378], or by treatment of Wang or PAM resin bound carboxylic esters with ethanethiol in the presence of a Lewis acid (AlMe2Cl or AlMe3, DCM, 20 °C, 3 h [379,380]). The latter method can also give rise to the formation of orthoesters RC(SEt)3 and ketene thioacetals, which can, however, be hydrolyzed to the desired thiol esters by treatment with TFA [379]. 

Thiol esters RC(0)SR are stronger acylating agents than simple alkyl esters, and have been prepared on solid phase mainly as synthetic intermediates. The preparation of thiol esters as intermediates for the synthesis of support-bound thiols is discussed in Section 8.1. Further examples of the preparation of thiol esters on insoluble supports include the aldol addition of ketene thioacetals to polystyrene-bound aldehydes... 

Construction of the suitably substituted geranic acid for making the furan ring has been effected too. For example, Poulter et al. have prepared the substituted geranate 865 by reaction of 4-methyl-3-pentenylcopper with the acetylenic ester 866. The ester 865 then underwent cyclization in the presence of acid to the lactone 867, related to scobinolide (161), and the action of acid on the lactol produced from 867 with diisobutylaluminum hydride gave perillene (849). The lactone 867 has also been prepared by a slightly different method the C9 alcohol 868 was made (in poor yield) from isobutenol and prenyl chloride with butyllithium. The extra carbon atom was introduced by the action of sodium cyanide on the epoxide of 868, and hydrolysis of the cyano group followed by dehydration yielded the lactone 867. The dimethylthioacetal of 867 has been used to synthesize perillene (849). This thioacetal was made from the suitably substituted ketene thioacetal 869 and dimethylsulfonium methylide. Thus the ketene thioacetal 870 (readily prepared from acetone, carbon disulfide, and sodium amylate, followed by methylation °) can be prenylated with lithium... 

Conjugated ketene thioacetals have been successfully prepared starting with aldehyde dimethylhydra-zones. In these reactions, the first-formed azaallyllithium reagent was allowed to react with carbon disulfide to form an intermediate lithium 3-dimethylhydrazonoalkanedithiolate. A second deprotonation of this dithiolate with a second equivalent of LDA then generated a dianion that was successfully alkylated with two equivalents of methyl iodide to yield the ketene thioacetal (e.g. 55 equation 25). This two step sequence avoided competing formation of a methyl dithiocarbamate by addition of LDA to carbon disulfide. 

Similar to the ketene thioacetal. vinyl and alkynyl thioelhers react with 2-oxazolidinone derivatives of s ,/ -unsaturated acids to give the corresponding cyclobutanes and cyclobutenes with almost complete asymmetric induction0,31-35. From a [2 + 2] adduct, prepared by use of a chiral titanium Lewis acid, a carbocyclic analog of the four-membered nucleoside oxetanocin A has been readily prepared in optically pure form10. 

The syntheses by Ban and co-workers of both Na-acetylaspidospermidine (180) and deoxylimapodine (181) (Scheme 32) utilize the important pentacyclic ketone (182), prepared earlier. The critical stage in both syntheses is a Michael reaction, apparently stereospecific, of (182) with methyl vinyl sulphone [-> (180)] and keten thioacetal monoxide [—>(181)], respectively. The later stages in the synthesis are unexceptional. Mercuric acetate oxidation of deoxylimapodine enabled the first synthesis of iVa-acetylaspidoalbidine (183) to be completed. ... 

Solvolysis of ketene thioacetals. Reaction of ketene thioacetals (2), prepared as shown, with NCS, an alcohol, and acetonitrile provides a useful route to a-chlorocarboxylic acid esters (3). NCS can be replaced by NBS with equaUy satisfactory results. ... 

Ketene thioacetals. A recent preparation of these useful intermediates is shown in equation... 

Ketene thioacetals. a-Lithiovinyl phenyl sulfide is useful for preparation of ketene thioacetals and related compounds. ... 

Alkylulen ltJ-ditUanesj These useful ketene thioacetals can be prepared as formulated in equation (I). The preparation involves N-tosylsulfilimines, which are cleaved readily to 2-alkylidene-l,3-dithianes. 

Note that the Wittig synthesis of ketene thioacetals can only be used with aldehydes. Of course, the reaction can be used for preparation of other thioacetals. ... 

The first examples of the use of the Knoevanagel-type condensation for the synthesis of a,p-unsaturated sulfoxides were made by Ogura and Tsuchihashi, who prepared racemic ketene thioacetal monoxides by the condensation of methyl... 

Thiophilic addition to dithioesters followed by capture of the thioacetal anion with an electrophile provides a useful approach to the formation of carbonyl compounds such as (42) and (43), and has been elegantly employed in the total synthesis of the macrocycles ( )-maysine and ( )-4,5-deoxymaysine. Trimethyl borate has been used to convert bis(phenylthio)methyl-lithium into the keten thioacetal (45) via the boron-containing carbanion (44), as shown in Scheme 4. Bis(phenylthio)methyl-lithium and related compounds are also the key reagents in the preparation of 2-(phenylthio)-enones, 2-(phenylthio)-butadienes, a-(phenyl-... 

Carolinoside (1), isolated from Solanum carolinense as the host plant specific feeding induction factor for Manduca sexta, has been further characterised and shown to incorporate a 2,6-dideoxy-3-C-methyl- -L-flra6/ o-hexopyranose unit. Alkylation (LDA/Mel) of ketone (2) has afforded the 3-C-methyl derivative (3) which was converted to the A/ -benzylformamide compound (4), an TV-forraylkanosamine glycosyl donor. Aldol condensation (LDA/THF) of ester (5) with aldehyde (6) produced predominantly the isomer (7) which was converted into L-cladinose (8). An aldol condensation of mi s-but-2-enal with a ketene thioacetal has been employed with a chiral catalyst in a preparation of 4-C-methyl-D-ribose/... 

Hydroxyorthothioesters, e.g. (66), which can be prepared from orthothioesters and aldehydes or ketones, are transformed into keten thioacetals, e.g. (67), on treatment with P2I4 and triethylamine. /3-Hydroxythioacetals furnish vinyl sulphides under the same conditions, and the method works equally well with the selenium analogues. The ylide generated from the stable phosphonium salt (68) is a convenient reagent for the transformation of aliphatic or aromatic aldehydes (but not ketones) into keten dithioacetals. ... 

Aminoalkenes (72) are readily prepared from dimethylaminopropyl chloride, magnesium, and the corresponding ketones (R R CO) in a one-pot procedure which is reported to result in higher yields than those obtained by a stepwise method. Another one-pot method involves the reaction between an alkyl halide (R R CHX), magnesium, and CS2 followed by LDA-R X to yield keten-thioacetals (73). ... 

Keten thioacetals (428) are useful synthetic intermediates and a general method for their preparation is reaction of metalated silyl thioacetals with carbonyl derivatives. ... 

Keten thioacetals such as (85) have been prepared by two routes. The first gives yields of 50—70% n = 2), and involves the reaction of bis(dimethyl-alumino)propane-l,3-dithiolate with esters it is patterned after the reaction earlier described, involving the analogous ethane-1,2-dithiolate. In the second method, a Grignard reagent is condensed with CS2, the product is converted into its lithium salt, allowed to react with Br(CHa) Cl, and then cyclized. ... 

Other catalytic applications of HBF4 include alkene isomerizations, alkylation of alcohols with diazoalkanes, preparations of substituted pyridines, hydrolysis of a-hydroxyketene or a-(methylthio)ketene thioacetals to a,p-unsaturated thioesters, and terpene formation from isoprenic precursors. ... 

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