Vinyl sulfoxides cyclization

The synthesis of unnatural (+)-mesembrine (387) through the asymmetric synthesis of methyl (i )-l-[(3,4-dimethoxy)phenyl]-4-oxocyclohex-2-enyl acetate (390) by cycloaddition of enantiomerically pure vinyl sulfoxide with dichloroketene has been performed 189) (Scheme 43). Vinyl sulfoxide 388 [prepared by conjugate addition of enantiopure acetylenic sulfoxide with (3,4-dimethoxy)phenylcopper] reacted with trichloroacetyl chloride in the presence of freshly prepared zinc-copper couple in THF at 0°C to produce a mixture of mono- and dichloro lactones 389. Reduction of 389 with zinc in acetic acid followed by cyclization and methylation afforded methyl IR-[(3,4-dimethoxy)phenyl]-4-oxocyclohex-2-enyl acetate (390), treatment of which with methylamine brought about amidation and concomitant intramolecular Michael addition to provide 2-oxo-mesembrine (391). Successively, 391 was transformed to (+)-mesembrine (387) in 79% yield (three steps ketalization of an oxo group, reduction of lactam, and deketali-zation)(/S9). 

A simple and straightforward application was outlined in the synthesis of hydrohydrastinine as depicted in Scheme 10. Michael addition of 3,4-methyle-nedioxyphenylmethyl amine to vinyl sulfoxide 36 took place smoothly in refluxing methanol. Pummerer rearrangement in acetic anhydride afforded acetoxysulfide 37 in 90% yield and this was then cyclized to 38 with BF3 etherate in 93 % yield. Sulfide 38, which was rather unstable, was desulfurized with Raney nickel in 80 % yield. Hydrolysis of the acetyl group followed by reductive methy-lation afforded hydrohydrastinine (39) in good yield [24]. 

Dithiole-2-one (60), which can be readily transformed into its thio- or seleno-carbonyl derivatives, is a key intermediate for the synthesis of tetrathiafulvalene (Scheme 13)[31]. We first anticipated that compound 57, a Michael addition product of xanthate 54 to vinyl sulfoxide, might be an ideal intermediate for the synthesis of 60 via cyclization under Pummerer rearrangement conditions. However, although Michael addition of dithiocarbamate 53 to vinyl sulfoxide proceeded smoothly to yield compound 55, the addition reaction with xanthate 54 failed. We then turned to the alkylation approach. Xanthate 54 was alkylated smoothly with 56, which served as the synthetic equivalent of the vinyl sulfoxide, in ethanol under sonication in 90% yield [32]. Cyclization of 57 under Pummerer rearrangement conditions in the presence of trifluoroacetic acid afforded 58 in 79% yield. Sodium metaperiodate oxidation gave the unstable sulfoxide 59 which underwent thermal elimination to yield 60 in refluxing benzene in moderate yield. 

Chiral, isomeric vinyl sulfoxides (88) and (89) were treated separately with benzyltrimethylammonium hydroxide. On cyclization of the proposed incipient amino-anion, (l s)-( )-(88) gave a 63 37 mixture of the diastereoisomeric isoquinolines (90) and (91). An enhancement and reversal of diastereoselectivity was observed on base hydrolysis of (/ s)-(Z)-(89). This reaction gave a 16 84 ratio of (90) (91) in 96% yield from which diastereoisomerically pure (91) was obtained in 78% yield after column chromatography. 

They can also be used as vinylic carbanion species as shown by the asymmetric synthesis of the chro-man ring of vitamin The (E)/(Z) mixture of chiral sulfoxide (9) was readily isomerized into the ( )-isomer with LDA in THF (the exclusive formation of the ( )-isomer was due to the chelation of lithium with an oxygen of the acetal). Condensation to trimethylhydroquinonecarbaldehyde gave only one diastereoisomer and then the cyclization in presence of sodium methoxide was also fully stereoselective (the stereochemistry of the cyclization being controlled by that of the allylic hydroxy group which is eliminated during the cyclization Scheme 48). 

The synthesis of the preceding vinyl amino sulfone offers a very good example of a stereospecific sulfide-directed epoxidation (Scheme 76).Oxidation of optically active sulfide alcohol (12 readily made from epoxycyclopentadiene and resolved) with MCPBA affords the corresponding sulfoxide, which is in equilibrium with the sulfenate ester. Treatment with pyridine hydrobromide and then phenyl disulfide and bromine gives the bromodiol (13), which is simply cyclized to the epoxide with aqueous sodium hydroxide solution (83% overall yield from the sulfoxide). Treatment of the P-epoxy sulfone with DBU followed by in situ silylation with f-butyldiphenylsilyl chloride affords an 86% yield of vinyl sulfone (14). Mesylation of the alcohol moiety followed by immediate treatment with dimethylamine produces the amino vinyl sulfone via a syn Sn2 substitution. ... 

In many respects the Pummeter reaction can be regarded as the sulfur version of the Polonovski reaction (and vice versa), and by analogy to the Polonovski reaction the central intermediate is a sulfur-stabilized carbocation (thionium ion). Although the existence of this species is only transient, it reacts to give a number of different products, e.g. a-acetoxy sulfides, vinyl sulfides, cationic cyclization products, etc., depending upon the sulfoxide structure and reaction conditions. Other reaction pathways ate specific to the Pummerer reaction as a result of sulfur s ability to expand its valence shell (additive Pum-merer reactions). A moderate degree of asymmetric induction is also observed in certain Pummerer reactions, where optically pure sulfoxides are substrates. 

Catalytic asymmetric synthesis of the key intermediate 11 in the preparation of 3/1.8/ , 10a-trihydroxycapnellene and 3/ ,8/J,10a,14-telrahydroxycapnellene is achieved upon treatment of 5-methyl-5-(3-trifluoromethanesulfonyloxy-3-butenyl)-1.3-cyclopentadiene (10) with catalytic amounts of palladium(II) acetate, (S)-BINAP and tetrabutylammonium acetate in dimethyl sulfoxide. The (.STS..S (-enantiomer of 11 is obtained in 89% yield and 80% ce23,8 . In a similar cyclization reaction of the substrate which contains a vinyl iodide unit in the side chain, a much lower asymmetric induction w7as observed. 

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