Sulfoxides, vinyl Michael addition

The (formal) Michael addition of nucleophiles to thiirene oxides and dioxides (formally vinyl sulfoxides and sulfones). 

An intramolecular version of enolate Michael addition to enantiomerically pure vinylic sulfoxides is represented by reaction of a cyclopentenone sulfoxide with dichloroketene (Scheme 5)90 this type of additive Pummerer rearrangement has been developed by Marino and coworkers91 into a highly effective way of constructing variously substituted lactones in very high enantiomeric purity (equation 43). 

Michael-Additions The most important application of this type of reaction is the carbon-carbon bond formation p to a carbonyl function by the addition of carbanion. The asymmetric version of the Michael-addition has been known since 1973. An optically active vinyl sulfoxide served as chiral auxiliary198). 

In a like manner, vinyl sulfoxides and sulfones can serve as the equivalents of vinyl and alkenyl cations via a process involving a Michael addition followed by an elimination.43 For example, addition of the enolate of the P-keto ester (168 Scheme 24) to phenyl vinyl sulfoxide (169) furnished, in 50% yield. 

Michael additions. Michael addition of nitroalkanes to vinyl sulfoxides (equation 1) and to ketene diethyl dithioacetal S-monooxide (equation II) proceeds in high yield when DBU is used as base. The adducts can be converted into a,/J-enals.1... 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

The structurally related optically active a-acyl vinyl p-tolyl sulfoxide 269 underwent asymmetric cyclopropanation. Michael addition of the carbanion of bromomalonate to 269 and the subsequent intramolecular alkylation yielded the corresponding optically active a-acyl-cyclopropane 271, with a high degree of diastereoselectivity (Scheme 70).142 It was proposed that the stereochemical outcome of the reaction can be rationalized by transition state 270, in which there is chelation of the oxygen atom of the carbonyl and sulfinyl groups to the metal cation. 

Tandem Michael addition and Homer olefination occur when a-phosphorylvinyl sulfoxides react with salicylaldehyde leading to a 3-sulfinyl-277-l-benzopyran. Any optical activity associated with the vinyl sulfoxide is retained in the product <06JOC8818>. 

The use of bis(dimethyiphenylsilyl)cuprate in the Michael addition to -substituted vinyl sulfoxides allows for stereoselective C-Si bond formation with moderate to good diastereoselectivity. The reaction proceeds in the same diastereofacial sense for ( )- and (Z)-isomers of the vinyl sulfoxide and, therefore, opposite ratios of the diastereomeric products are obtained for each isomer35. 

A mercury-free route to allyl vinyl ethers that relies on the Michael addition of allyl alcohols to unsubstituted alkenyl sulfoxides, followed by thermal loss of sulfenic acid and concurrent Claisen rearrangement has been described [145]. This methodology has been applied to the synthesis of isocar-bacyclin [146]. Posner reported an acid-catalyzed protocol that produces conjugated dienoate esters from allylic alcohols and a sulfinyl orthoester [147]. Additionally, the use of propargyl alcoholates and a chloro alkenyl sulfox-... 

Instead of preparing the sulfoxide chirophore via a separation of diastereoisomers, the dia-stereoselective oxidation of a sulfide offers an interesting alternative. Thus Michael addition of 10-mer-captoisobomeol (414) to methyl propiolate furnished (Z)-vinyl sulfide (415) which underwent a hydroxy-directed oxidation (MCPBA) to give the (sulfur-R)-vinyl sulfoxide (416) in a highly selective manner (Scheme 100). ... 

Asymmetric synthesis by a Michael reaction. Japanese chemists report that Michael addition to a, -unsaturated sulfoxides proceeds readily. Thus /vtolyl vinyl sulfoxide (2) reacts with diethyl malonatc and ethyl acctoaoctate in the presence of an equimolar amount of. sodium ethoxide in ethanol to give the Michael adducts (3) and (4). 

Michael addition of nitro compounds 246 to phenyl vinyl sulfoxides 247 in the presence of DBU in acetonitrile at room temperature gave adducts 248 in quantitative yields (82JOC5017). Other bases, such as triethylamine, potassium fluoride, and tetramethylguanidine, were not so effective as DBU. 

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]. 

Efficient syntheses of substituted furans and pyrroles continue to be of interest in view of the widespread occurrence of these systems in nature. Michael addition of /J-ketoester 47 to vinyl sulfoxides 36 and 46 proceeded smoothly in the presence of sodium alkoxide (Scheme 12) [29]. It was anticipated that... 

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. 

In summary, vinyl sulfoxide (or its equivalent 56) was adopted as a two-carbon synthon for the syntheses of alkaloids (39,43ab,45ab), furans (51), pyrroles (52), and l,3-dithiole-2-one (60). Our overall strategy is summarized in Scheme 14. Michael addition of Nu1 to the vinyl sulfoxide followed by intramolecular trapping of the presumed sulfenium ion Pummerer rearrangement intermedia-... 

Chiral a,P-unsaturated sulfoxides 1.136 (Y = Tol, R = R CH=CH) also have been used in asymmetric synthesis. These compounds are prepared either by treatment of 1.137 with vinylic organometallic reagents, or from saturated precursors by classical chemical transformations [102, 173, 476, 484-487], Michael additions to these electrophiles are interesting only if R = CF3 [161], Organometallic additions or [4+2] cycloadditions require the introduction of a second electron-withdrawing substituent [73, 102], and acyclic 1.138 and cyclic 1.139 gem-di substituted sulfoxides have seen many interesting applications [101, 102,... 

Under thermodynamically controlled conditions, enantiomerically pure ( )-vinyl sulfoxide (84) (as a mixture of epimers at the hydroxy centre), underwent intramolecular Michael addition to produce a mixture of the cis diastereoisomers (85a and 85b) in 88% combined yield (the two trans isomers were isolated in only 2.3% combined yield), as shown in Scheme 4.42. 

Tanikaga and coworkers have reported the addition of nitroalkane anions to a-halo-a,P-unsaturated sulfoxides [72]. Further development of this work led to the use of nitroalkanes as alkyl group equivalents in conjugate addition to a,P-unsaturated sulfoxides [73-75]. Primary or secondary nitroalkanes such as 2-nitropropane (77), with DBU as a non-nucleophilic base, add to a,P-unsaturated sulfoxides including phenyl vinyl sulfoxide (26) to give products such as (78), which can be denitrated to yield (79) (Scheme 5.25). The Michael addition of nitroalkanes, and of diethyl N-acetylaminomalonate, to racemic phenyl vinyl sulfoxide using solid-liquid phase-transfer catalysis in the absence of solvent has also been accomplished [76]. 

Meanwhile, 3-functionalized sulfoxides 20 can be easily obtained by Michael addition to a,p-unsaturated sulfoxides. The a,p-unsaturated sulfoxide starting materials 19 can be prepared by the oxidation of vinyl sulfides 21 and also by the Horner-Wadsworth-Emmons reaction, using commercially available sulfoxy phosphonates 18 fScheme 20.6a). Alternatively, cross... 

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