Ketene dithioacetals rearrangement

Methyl 3-hydroxybutanedithioate (R = Me) (0.6 g 4 mmol) was added dropwise to a solution of LDA (2 eq) in THF cooled at -78°C. The mixture was stirred for 20 min. The yellow dithioester colour disappeared. Allyl bromide (1 eq) was added. Stirring was maintained for 45 min. The solution was quenched by an aqueous solution of ammonium chloride. The mixture was partitioned between ether and brine. The organic layer was washed with brine, dried with magnesium sulfate and concentrated. The crude ketene dithioacetal was left at ambient temperature for X d to achieve the rearrangement. A yellow oil was isolated by flash chromatography (elution with a 90 10 mixture of cyclohexane/ethyl acetate), yield 74%, as a 90 10 syn/anti mixture of diastereoisomers. 

Vinyl sulfoxides (221), which are aldehyde a-cation equivalents, and vinylthiolium ions (230), which are a.jj-unsaturated carbonyl 3-cation equivalents, are also suitable acceptors for silyl ketene acetals and enol silyl ethers (Scheme 36). Kita reports that the bulky r-butyldimethylsilyl ketene acetals and tri-methylsilyl ketene acetals form 1 1 adducts (224) and 1 2 adducts (225) with (221), respectively 91 mechanistically, these additions proceed via an initial Pummerer rearrangement The vinylthiolium ion additions are notable for their synthetic flexibility for example, additions to the ketene dithioacetal (229) proceed with higher diastereoselectivity than the corresponding enolate additions to a,3-unsaturated esters.9 lc,91d... 

With a ketene dithioacetal function in the 4-position as in 335, FVP results in loss of CO2 and PhCN to give 336, which rearranges to the dithioalkyne 337161. The... 

A new type of asymmetric induction in this area has been achieved in our group. The need for absolute stereocontrol with the aid of a removable chiral centre, and the observation that the sulfinyl group, recently introduced for Diels-Alder reactions, has not yet been introduced in substrates prone to [3.3] sigmatropic processes, were our motivations. The requisite racemic ketene dithioacetals bearing a sulfinyl group have been prepared and their rearrangement was shown [202] to proceed at ambient temperature. The asymmetric induction was extremely effective, with diastereoselectivi-ties ranging from 93 7 to 99 1, in favour of the (2S,SS) isomer. 

Chirahty transmission can also be induced in thio-Claisen reactions by a chiral center adjacent to the allyl vinyl sulfide core. The group of Metz-ner examined the diastereoselectivity of the rearrangement of acyclic S-allyl ketene dithioacetals bearing a chiral center adjacent to carbon 6. hi these substrates, the sigmatropic shift proceeded smoothly and with modest syn anti diastereoselectivity [74]. In contrast, higher selectivities are foimd for thio-Claisen precursors bearing a chiral center adjacent to carbon 1 mainly due to steric effects and allylic strain [75]. In 1991, the group of Beslin examined the effect of a hydroxyl substituted chiral center attached to C-1 of Z and E S-allyl ketene dithioacetals [76,77] (Scheme 7). Under the reaction conditions, these... 

Reaction of ketene dithioacetals 260 with thioamides gave 5-substituted 2-methyl(phenyl)-6-methylthio-4-thioxopyrimidine (262) (92H1573). The reaction mechanism involves the addition of the thioamide to the ketene dithioacetal 260 to afford 2-cyano-3-methylthio-3-thioamido-propenoni-trile or -propenoate intermediate, which cyclizes in situ by site-selective nucleophilic attack of the sulfur on the cyano group to give 6-imino-l,3-thiazine 261, which rearranged to 262 (Scheme 84). 

Ketene dithioacetals are deprotonated with LDA-HMPA and complexed with copper(l) iodide (Scheme 36). This reagent reacts with allylic halides exclusively at the y-position with allylic rearrangement (5n20. The reaction of the lithium reagent with simple alkylating reagents gives mostly a-attack. Ketene dithioacetals can be converted to esters by aqueous mercury(II) chloride. 

Pummerer rearrangement of 4-benzenesulfinyl-l-naphthols generates naphthoquinone phenylsulfonium ions. These react with enol ethers to afford annulated furanyl ethers. Another Pummerer rearrangement on aryl substituted ketene dithioacetal monoxides provides 2-methylthiobenzothiophenes. ... 

Ketene Dithioacetal Formation and Thia-Claisen Rearrangement General Procedure624 ... 

In contrast to chelation-controlled anionic Claisen rearrangements of /(-hydroxy esters [where chelation control only allows the formation of (i -lithium enolates see p 3420], all four diastereomeric A-crotylic a-hydroxy ketene dithioacetals can be prepared either by deprotona-... 

The reaction of dithio-esters (19) with bromoalkynes in the presence of potassium amide in liquid ammonia yields the keten dithioacetal (20), which upon heating undergoes an electrocyclic rearrangement to the allenic dithio-esters (21). Acid-catalysed or strongly base-catalysed cyclization yields the thiophen derivatives (22), whereas weak bases yield the 2H-thiopyran (23). 

Five Ring Nitrogen Systems.—Pynolines and Pyrrolidines. Ketene dithioacetals react with aziridines to give vinyl aziridines which undergo an iodine catalysed rearrangement to pyrrolines yields are high (Scheme 61). The novel spiro-com-pound (172) has been obtained by this route. A hetero-vinyl cyclopropane... 

The efFicienqr of sulfoxides as chiral inductors for the thio-Claisen rearrangement has been demonstrated with N,S-ketene acetals derived from racemic 2-sulfinyl dithioacetates [72], Moreover, these reactions were successfully extended to the enantiopure series using chiral thioamides as substrates [125]. The source of chirality is the easily available and cheap D-glucose [126]. Remarkably, both enantiomers of the starting 2-sulfinyl thioacetamides can be selectively obtained from the same D-glucose. 

Thioacylketen dithioacetals participate with alkenes and sulphenes in 1,4-cycloaddition reactions. Thio-Claisen rearrangement of 1-allylthio-l-aminoalkenes to thioamides or isothiocyanates, and of 5 -allyl-5 -methyl-keten mercaptals to dithioesters, has been described. 

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