A, p-Unsaturated sulfones

The Barton-Zard (BZ) pyrrole synthesis is similar both to the van Leusen pyrrole synthesis that uses Michael acceptors and TosMlC (Section 6.7) and the Montforts pyrrole synthesis using a,P-unsaturated sulfones and alkyl a-isocyanoacetates." An alternative to the use of the reactive nitroalkenes 1 is their in situ generation from P-acetoxy nitroalkanes, which are readily prepared via the Henry reaction between an aldehyde and a nitroalkane followed by acetylation. Examples are shown later. 

There is generally little or no competition from 1,2 addition (to the C=0). However, when R is allylic,l,4 addition is observed with some substrates and 1,2 addition with others. The compound R2CuLi also add to a,P-unsaturated sulfones but not to simple aP-unsaturated nitriles. Organocopper reagents RCu (as well as certain R2CuLi) add to ocP-unsaturated and acetylenic sulfoxides. ... 

Sulfones have become increasingly important in organic synthesis in recent years and a, P-unsaturated sulfones especially are known to be excellent Michael acceptors. Following our concept of using SAMP derivatives as chiral equivalents of ammonia, the enantioselective aza-Michael addition has been investigated in order to provide a new method for the synthesis of P-aminosulfones [15]. 

Reduction of a,P-unsaturated sulfones.1 Sodium amalgam (7, 326-327) is not satisfactory for reductive cleavage of alkenyl sulfones, R CH=CR2S02C6H5. These substrates are best reduced to alkcncs wth potassium-graphite (65-85% yields). 

Some additional examples, where the stereochemical outcome of the cycloaddition to chiral alkenes has been explained in terms of the Houk-Jager model, should also be mentioned. The diastereomer ratio found in the reaction of y-oxy-a,p-unsaturated sulfones (166), with Morita-Baylis-Hillman adducts [i.e., a-(a -hydro-xyalkyl)-acrylates (167)] (Scheme 6.27), with dispiroketal-protected 3-butene-1,2-diol (168), and with a,P-unsaturated carbonyl sugar and sugar nitroolefin (169) derivatives, all agree well with this model. 

The basc-catalysed condensation of aldehydes with sulfones gives a,p-unsaturated sulfones [449]. 

Vinyl fluorides,1 Fluoro(phenylsulfonyl)methylithium (2), obtained by reaction of 1 with BuLi in THF at — 78°, reacts with carbonyl compounds to form fluorohydrins (3), which are dehydrated to (E)-a-fluoro-a,p-unsaturated sulfones (4) in 67-92% yield with CH3S02C1 or orthophosphoric acid. Conversion of 4 into vinyl fluorides (5) is effected with aluminum amalgam (—90% yield). The vinyl fluorides are obtained as a 1 1 mixture of (E)- and (Z)-isomers. 

Review. Use of C8K as a heterogeneous reagent in organic synthesis has been reviewed, particularly as a reducing agent for C=C and C—N bonds, and for reductive cleavage of the C—S bond of a,p-unsaturated sulfones. C8K has been used to obtain active metals dispersed on graphite by reduction of metal halides. 

Stereocontrol (vide infra) can be efficiently engineered in the addition of acetate to ir-allylpalladium complexes (equation 49).168-171 The regioselective addition of acetate of allylpalladium complexes to prepare y-acetoxy-( )-a,0-unsaturated esters172 and y-acetoxy-a.P-unsaturated sulfones has also been achieved (equations 50 and 51).173-174... 

This review continues from one entitled The Chemistry of a,P-Unsaturated Sulfoxides which was recently published in a monograph of organosulfur chemistry. 1 In addition, the coverage has been extended to include the analogous a,P-unsaturated sulfones. The focus of the present review are recent advances in the chemistry of a,P-unsaturated sulfoxides and sulfones, especially those which have been published since 1993. The synthesis of a,P-unsaturated sulfoxides and sulfones has already been reviewed extensively by Rayner2 and hence will not be covered here. Only the chemistry of vinyl (alkenyl) sulfoxides and sulfones will be considered. The chemistry of other a,P-unsaturated sulfoxides and sulfones such as dienyl, allenyl, and propargyl (alkynyl) sulfoxides and sulfones is beyond the scope of this review. Considerable emphasis has been placed on stereo- and enantioselective reactions, reflecting the current interest in this area. 

Radical addition to Y-hydroxy-(a-methylsulfinyl)-a,P-unsaturated sulfone (32) was observed in excellent yield and high stereoselectivity for the syn diastereoi-somer (33) (Scheme 8).29,30... 

Intramolecular 6-exo-radical cyclization of 7-bromo-3-methoxy-l-methylthio-1 -(p-tolylsulfonyl)-1 -heptene (66) exhibited a highly efficient 1,2-asymmetric induction to yield the trans ring-closure product 67 (Scheme 17).45 Also reported are radical cyclizations ofy-oxygenated-a,P-unsaturated sulfones, often with very high observed stereoselectivity.45,46... 

Carretero and co-workers reported that the a-sulfonyl radicals resulting from such radical additions to y-oxygenated-a,P-unsaturated sulfones are useful intermediates for the generation of a second carbon-carbon bond via intramolecular addition to a suitably located carbon-carbon double bond.46,47 The highly functionalized acyclic y-hydroxy vinyl sulfone 68 underwent a novel cascade process, based on two sequential radical cyclizations, affording the bicyclic compounds 69 and 70 in good yield (Scheme 18). 

Allylic trichloroacetimidates, generated in situ from cyclic y-hydroxy-a,P-unsaturated sulfones, undergo intramolecular conjugate addition to the vinyl sulfone moiety to afford oxazolines. Acid hydrolysis of the oxazolines generated... 

Carretero et al. reported that enantiopure y-oxygenated-a.P-unsaturated sulfone (143) underwent a completely regioselective 1,3-dipolar cycloaddition with ace-... 

The synthesis of electron-deficient diene 285 was achieved by the Stille coupling of P-trifluoromethanesulfonyl-a,P-unsaturated sulfone (284) with a 3-stannyl-a,P-unsaturated ester (283) (Scheme 74).148 Similarly, the preparation of a diverse range of enantiomerically pure 1- and 2-sulfinyl dienes has been achieved via Stille coupling of halovinyl sulfoxides and vinyl stannanes.149,150 Enantiomerically pure 1- and 2-sulfinyl dienes have been used extensively in asymmetric Diels-Alder reactions.111... 

Aminosulfones (68) may be prepared by conjugate 1,4-addition of amines to a,p-unsaturated sulfones or by a Mannich-type reaction of a sulfinic acid with an aldehyde in the presence of an amine (Scheme 31). 

A route to ( , )-2,4-alkadienoic esters involves the Johnson-Claisen rearrangement of y-hydroxy-a,P-unsaturated sulfones and subsequent elimination of PhSO H with DBU. Stereoselective access to trisubstituted enol ethers initiated by iodoalkoxylation of disubstituted alkenes (with PyjIBF, 2HBF, ROH) is concluded by treatment with DBU.5... 

Catalyst 19, which contains the 3-fluorophenyl methyl ether, was found to be the most effective for the epoxidation of (fc)-a,P-unsaturated sulfones (Scheme 5.17). Of note, the (Z)-configured sulfone was converted under the same optimized conditions into the corresponding ds-a,P-cpoxysulfonc, but with a lower enantios-electivity (16% ee). 

Extrapolations and improvements to this approach continue to enlarge its usefulness - a,P-unsaturated sulfones react with isocyano-acetates and isocyano-nitriles to give pyrroles. Potassium carbonate can be used as the base, vinyl arenes and hetarenes react at the side-chain double bond to give 3-aryl(hetaryl)-pyrroles, and acetylenic-esters produce pyrrole-2,4-dicarboxylates, methyl t-butyl ether as solvent to avoid peroxides. ... 

Epoxidation of a, p-unsaturated sulfones. Epoxidation of cir-1-phenyl-2-(p-tolylsulfonyl)ethene (1) with alkaline hydrogen peroxide in aqueous acetone... 

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