Allylation sulfone electrophiles

Phenylsulfonyl-1,3-dienes are versatile synthetic intermediates. They can participate in cycloaddition reactions and Michael-type additions leading to adducts which can be further functionalized. In the latter case the resulting allylic sulfone can be functionalized by electrophiles, nucleophiles, or both (Figure 1). 

Several new leaving groups have been discovered recently which merit special discussion. Allyl sul-fones, surprisingly, function as substrates for palladium catalysis.86 As the sulfone group had previously been proven to be able to stabilize an adjacent carbanion, this result allowed allyl sulfones now to be considered as synthons for 1,1- and 1,3-dipoles (equation 10). That is, the allyl sulfone can be used alternately as a nucleophile and electrophile, greatly extending its synthetic utility. 

Sulfones can also be used in Friedel-Crafts-type cyclizations. One example is shown in Scheme 85, where the cyclization in the presence of aluminum chloride of the allylic sulfone occurred in high yield, showing that sulfones can also become electrophiles. Since a tertiary carbanion has about the same stability as a simple allylic cation, tertiary sulfones can also be cyclized (Scheme 85). These last examples illustrated the umpolung provided by the sulfone since carbanion chemistry was used to introduce the 2-methyl groups. 

Chinchilla, R., Galindo, N., and Najera, C., Dimethyl 2-(tosylmethyl)fumarate. An allyl sulfone as electrophilic reagent for the synthesis of itaconate ester derivatives. Tetrahedron, 52, 1035, 1996. 

The relative reactivity of the derivatives follows the trend allyl carbonate > allyl phosphate > allyl acetate (see Equations 20.5-20.7)." This difference in reactivity allows for chemoselective substitutions of one allylic alcohol derivative over another. Other allylic electrophiles, such as allylic sulfonates, which undergo cleavage of the carbon-sulfur bond, allylic nitro compounds, which undergo cleavage of the C-N bond, - and allylic... 

Allylic sulfones are important and versatile intermediates in organic synthesis due to the ability of the sulfone to impart both nucleophilic and electrophilic properties to the a-carbon. Pleasingly, the use of sodium benzenesulfinate in an AAA reaction of meso substrate 78 furnished the... 

Allylic sulfones react as electrophiles through palladium(O) activation as illustrated in Scheme 22.24. With Pd(Ph3P)4 as catalyst, alkyl sulfone 86 generates an allylpalladium intermediate 87 with inversion of configuration. The latter is attacked by the nucleophile with inversion of configuration on its least stericaUy hindered carbon center giving 88 as the major product. Thus, allylsulfones can be considered 1,3-dipole equivalent 89 because the a-center reacts as nucleophile and the 7-center as electrophile. 

SCHEME 22.24. Reaction of allylic sulfones as electrophiles through palladium(O) activation. 

The reactivity of the allylic sulfide double bond with electrophiles is largely masked by the presence of the heteroatom. However, on oxidation to the sulfone the alkene is found to be surprisingly inert toward such species, and this has been taken as further evidence for a transannular effect of the —SO2— unit greater than that seen for the sulfur atom in tetrahydrothiopyrans (77MI22502). 

The proton serves as the simplest electrophile to displace the silyl group stereo- and regioselectively. Numerous conditions have been used for the electrophilic protodesilylation of allyl- and vinylsilanes19. ( )-vinyl sulfones 2 are prepared from the silylallylic sulfones 1 in the presence of protic acids in high yield (equation l)34. Diastereoselective protodesilylation of allylsilane 3 gives 4 with excellent control of the geometry of the double bond exocyclic to the ring (equation 2)35. 

In general, allylic and propargyllic electrophiles are much more reactive than alkenyl and alkynyl electrophiles. Thus, a wide variety of electrophiles containing halogens, e.g. I, Br, and Cl, and oxygen groups, e.g. sulfonates, phosphates, carboxylates, carbonates, alkyl and aryl ethers, and even silyl... 

This reaction illustrates a stereoselective preparation of (Z)-vinylic cuprates, 5 which are very useful synthetic Intermediates. They react with a variety of electrophiles such as carbon dioxide,5,6 epoxides,5,6 aldehydes,6 allylic halides,7 alkyl halides,7 and acetylenic halides 7 they undergo conjugate addition to a,6-unsaturated esters,5 6 ketones,6 aldehydes,6 and sulfones.8 Finally they add smoothly to activated triple bonds6 such as HCSC-OEt, HC3C-SEt, HC=C-CH(0Et)2. In most cases these cuprates transfer both alkenyl groups. The uses and applications of the carbocupration reaction have been reviewed recently.9 The configurational purity in the final product 1s at least 99.951 Z in the above transformations. 

All types of electrophiles have been used with 2-lithio-l,3-dithiane derivatives, including alkyl halides, sulfonates, sulfates, allylic alcohols, arene-metal complexes, epoxides, aziridines, carbonyl compounds, imines, Michael-acceptors, carbon dioxide, acyl chlorides, esters and lactones, amides, nitriles, isocyanates, disulfides and chlorotrialkylsilanes or stannanes. The final deprotection of the dithioacetal moiety can be carried out by means of different types of reagents in order to regenerate the carbonyl group by heavy metal coordination, alkylation and oxidation184 or it can be reduced to a methylene group with Raney-nickel, sodium or LiAIII4. 

Mulzer (Scheme 8 upper left) obtained the a,/(-unsaturated ester 33 with Z configuration from aldehyde 26a via a Still-Gennari olefination with phosphonate ester 34. Reduction of the ester with DIBAH and application of L-imidazole-PPhj gives allylic iodide 35. This acts as electrophile on the -anion of sulfone 36. After reductive removal of the phenylsulfone, group 28b is obtained [23]. 

R = alkyl, aryl R = 1° or 2 alkyl, allyl, benzyl, activated aryl, acyl X - Cl, Br, I, OTs electrophile epoxide, dialkyl sulfate, alkyl sulfonate, alkyl nitrate base = NaOR NaH base = KOf-Bu, cone. NaOEt, NaH solvent = R OH, f-BuOH, benzene, ether, DMF... 

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