Vinyl sulfoxides diastereoselectivity

The enantiomerically pure, doubly activated a, /j-olefinic sulfoxides 46-5095 98 undergo highly diastereoselective Diels-Alder cycloadditions with cyclopentadiene, and pyridyl vinylic sulfoxide 5199 reacts diastereoselectively with furan. It is noteworthy that olefins singly-activated by only a sulfinyl group are not effective partners in Diels-Alder cycloadditions, as we have found after many attempts and as has been reported recently98. 

Diastereoselective reactions of azomethine ylides with chiral vinyl sulfoxides have also been conducted (Scheme 12.35) (162-164). The 1,3-dipolar cycloaddition of (R)s-p-tolyl vinyl sulfoxide (106) with l-methyl-3-oxidopyridinum (105) gave three of the four possible diastereomers, and one of these isomers 107 was used for the enantioselective synthesis of the (75)-(—)-2a-tropanol 108 (162). 

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... 

Reactions of 3,5-dichloro-2,4,6-trimethyl benzonitrile oxide 241 with fluoro-methyl substituted alkenes 242, bearing a chiral sulfinyl group at -position of the double bond, afford diastereoisomeric 4,5-dihydroisoxazoles 243 and 244 [180] with a stereoselectivity lower than 2 1 (Scheme 110). The authors conclude that the efficiency of allyl sulfoxides to control diastereoselectivity of 1,3-dipolar cycloadditions with nitrile oxides is lower than that of vinyl sulfoxides. 

Pradilla et al. have shown that simple p-tolyl vinyl sulfoxides undergo nucleophilic epoxidation with metal alkyl peroxides to give enantiopure sulfinyl oxiranes.138 This process takes place with fair to excellent diastereoselectivities. The same group recently reported the epoxidation of diastereomeric hydroxy vinyl sulfoxides, bearing an additional stereocenter adjacent to the reactive carbon-carbon double bond. Hydroxy vinyl sulfoxides 256 and 258 underwent epoxidation with lithium ferf-butyl peroxide with high anti selectivity. However, when potassium ferf-butyl peroxide was used, only hydroxy vinyl sulfoxide 256 showed anti... 

Cycloaddition with nitrile oxides is also efficient with trisubstituted enol ethers and enolates. With fluoro-substituted chiral vinyl sulfoxides 10. cycloadditions performed with aryl chloroaldoximes, at room temperature in carbon tetrachloride in the presence of triethylaminc, are slow but give the homochiral dihydroisoxazoles 11 with high regio- and diastereoselectivity. ... 

Piperidine and benzylamine have been utilized in diastereoselective addition reactions to other a,/ -unsaturated vinyl sulfoxides bearing the R absolute configuration92,93 at sulfur. A conjugate addition of piperidine to (f )-l-methyl-4-[(Z)-l-propenylsulfinyl]benzene (20) in a polar solvent such as methanol gives an 83 17 (21A/21B) diastereomeric mixture of adducts94,95. 

While the stereochemical outcome of the reactions with chiral (Z)-vinyl sulfoxides can be simply explained in terms of a reactive conformation, the outcome of reactions with chiral (f.)-vinyl sulfoxides cannot be satisfactorily explained. The latter reactions generally proceed with poorer selectivity and with either opposite or the same 7t-face selectivity compared to their Z counterparts94 95. Investigations with chiral (E)- and (Z)-vinyl (/Ci-sulfoxides 23 and ben-zylamine show, besides a solvent effect, that both reaction types proceed with similar diastereoselectivities. The reaction products are formed irreversibly and the extent of interconversion between the ( )- and (Z)-vinyl sulfoxide isomers is small (l-2%)96. 

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. 

Vinyl sulfoxides have been converted to sulfinyl oxiranes <1996JOC3586>. Protected hydroxyl substituents can have an effect on the diastereoselectivity <2002JOC8166, 2003JOC4797, 2006JOC1569> (Equation 76). 

Miscellaneous. A vinylic sulfoxide was prepared firom (J )-methyl p-tolyl sulfoxide and benzophenone. Cyclopropanation of the double bond with Dimethylsulfoxonium Methylide gave a good diastereoselectivity (eq 14). ... 

Koizumi observed a diastereoselective cycloaddition between furan and chiral vinyl sulfoxides 6 [15]. While the analogous p-tolylsulfinyl acrylates were completely unreactive in this reaction, the 2-pyridyl (Py) substituent signifi-... 

An interesting application of the chiral cyclopalladated complexes is palladium-promoted asymmetric Diels-Alder reactions of l-phenyl-3,4-dimethylphosphole (Scheme 4). In the original report on the Diels-Alder reaction of the phosphole reported by Nelson and co-workers, the dichloropalladium species was employed as a promoter.f In 1994, Leung showed that a chiral cyclopalladated complex was capable of promoting the Diels-Alder reaction. In this reaction, the chiral palladacycle worked as a chiral auxihary and showed almost perfect diastereoselectivity. It has been revealed that simultaneous precoordination of a diene and a dienophile to the palladium center is essential for the reaction. Thus, both dienes and dienophiles should possess Lewis basic functionahty. The diene l-phenyl-3,4-dimethylphosphole has been the only substrate examined so far, while a variety of dienophiles, such as vinylphosphine, vinyl-sulfoxide, vinylsulfide, acrylamide, vinylarsine, vinylpyridine, vinyl-pyrrole, or methylenequinuchdinone, have successfully been applied to this asymmetric Diels-Alder reaction. 

The asymmetric induction on the 1,3-dipolar cycloaddition reaction of carbonyl ylides has also been studied using chiral dipolarophile. The Rh2(OAc)4-catalyzed reactions of o-(methoxycarbonyl)diazoacetophenone 89 with enantiomerically pure vinyl sulfoxides 103 afforded 4,10-epoxybenzo-[4,5]cyclohepta[l,2-c]furan-3,9-dione 105, in good or moderate yield with complete regioselectivity [113]. The endo stereoisomer 105a is favored with respect to the exo isomer 105b and interestingly, high diastereoselectivity and complete enantioselectivity have been achieved (Scheme 32). 

Tom and co-workers " have elegantly demonstrated the role of intramolecular hydrogen bonding for diastereoselectivity as well as reactivity towards radical addition onto MBH adducts. Thus, the reaction of (25,5s)-a-(1-hydroxyethyl)vinyl sulfoxide 387 with alkyl radical and BusSnH gave the... 

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. 

Recently, the fluoride ion-catalysed desilylation of p-tolyl l-(trimethylsilyl)vinyl sulfoxide (55) and reaction with aldehydes such as benzaldehyde (56) to give the corresponding allylic alcohol (57) has been studied (Scheme 5.18) [57]. The diastereoselectivity of the reaction was not evaluated and the products were obtained in moderate to good yields. The authors suggested possible mechanistic pathways for the reaction. 

Subsequent work has shown that simple, unactivated enantiomerically pure vinyl sulfoxides such as p-tolyl vinyl sulfoxide, without further substitution on the double bond, are not effective dienophiles for inducing diastereoselectivity in asymmetric Diels-Alder reactions. In the majority of cases, further substitution of the double bond by electron-withdrawing groups is necessary to achieve high stereoselectivity under mild conditions. However, a recent report by Ronan and Kagan [157,158] has shown that (5)-p-tolyl vinyl sulfoxide (26b) can be efficiently activated toward Diels-Alder cycloaddition by transformation into a sulfoxonium... 

Vinyl sulfoxides substituted at the p-position by electron-withdrawing groups have been used extensively as enantiomerically pme dienophiles in asymmetric Diels-Alder cycloadditions. Maignan and colleagues utilized methyl (Z)-(/ )-3-p-tolylsulfinyl propenoate (184), which reacted with cyclopentadiene under mild conditions high stereoselectivity and diastereoselectivity were observed [159] in formation of the endo and exo cycloadducts (185a) and (185b) (Scheme 5.60). 

Zard has studied the isomerization/Mislow-Evans rearrangement of vinyl sulfoxides such as 237, arising from enolate addition to alkynyl sulfoxides [Scheme 18.60). Isomerization of 237 to the allylic sulfoxide 238 enabled the [2,3]-sigmatropic rearrangement to a-hydroxy-a-vinyl ketone 239. In this case, diastereoselectivity was low in formation of the carbinol center within a steroid framework. Additions to allenyl sulfoxides provide a similar sequence, leading to 2-propenyl substitution at the tertiary alcohol center (not shown). 

---