Unsaturated sulfonates

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. 

The reaction of the enamines of cyclohexanones with a,ft-unsaluraled sulfones gives mixtures resulting from attack of the enamine at the a- and /(-carbons of the oc,/ -unsaturated sulfone. The ratio of x- and /1-adducts is dependent upon the reaction solvent, the geometry and structure of the sulfone1 4. The diastereoselectivity of these reactions is also poor. The reaction of lithium enolates of cyclic ketones with ( )-[2-(methylsulfonyl)ethenyl]benzene, however, gives bicyclic alcohols, as single diastereomers, that result from initial -attack on the oc,/ -unsaturated sulfone5. 

I.5.3.4.2. Diastereofacial Selectivity I.5.3.4.2.I. Chiral a,/i-Unsaturated Sulfones Addition of Enolates and Related Anions... 

The addition of methyllithium to -alkoxy-a-(trimethylsilyl)-of/ unsaturated sulfones, 3-alkoxy-5-phenyl-l-phenylsulfonyl-l-(trimethylsilyl)-l-pentene and subsequent desilylation gives syn-products. The syn to anti diastereoselectivity is generally high and essentially independent of the nature of the y-alkoxy substituent8-13. 

In contrast cyclic y-(rey/-butyldimethylsilyloxy)-a,/ -unsaturated sulfones undergo addition of organometallic reagents to give mainly trans-adducts after reductive removal of the sulfonyl group. 

The diastereoselective addition of [(S)-3-alkoxy-l-octenyl]lithium to an enantiomerically pure cyclic y-(rer/-butyldimethylsilyloxy)-o(,/S-unsaturated sulfone was employed in the synthesis of ( )-prostaglandin E219, with addition occurring exclusively anti to the sterically demand-... 

Addition of methyllithium to a cyclic /i, y -epoxy-a,/i-unsaturated sulfone gave predominately the m-alcohol as product20. 

This type of reaction however works only for methylmetallic reagents. A general synthesis of this type of substituted cyclopentenes has been developed employing /T-dimethylamino and P -trimethylammonio-o ,/i-unsaturated sulfones 21. 

The addition of a lithiated dithiane to a chiral a,/J-unsaturated sulfone has been reported, however, the stereochemical outcome and the diastereoselectivity was not addressed20. The addition of (lithiomcthylsulfonyl)benzenc to a chiral y-alkoxy-a-trimethylsilyl-aj-unsaturated sulfone gave exclusively the, vr -adduct1 2 3 4 5 7 8 9 10 11 12. 

TABLE 5. Survey of sulfonyl halide additions to unsaturated systems and hydrogen halide eliminations to unsaturated sulfones... 

In order to justify the validity of ketone-sulfone analogies, a series of CNDO/2 calculations on a number of model cyclic unsaturated sulfones and ketones was... 

The experimental carbon-carbon and carbon-sulfur bond-length values for the series 3 and 4 are in good agreement with the calculated values both in the saturated and unsaturated sulfones and sulfoxides (Table 1 and 3). Thus, it appears that the carbon-... 

An illustrative example of the Michael reaction is that of the thiirene dioxide 19b with either hydroxylamine or hydrazine to give desoxybenzoin oxime (87) and desoxybenzoin azine (88), respectively, in good yields6 (see equation 29). The results were interpreted in terms of an initial nucleophilic addition to the a, j8-unsaturated sulfone system, followed by loss of sulfur dioxide and tautomerization. Interestingly, the treatment of the corresponding thiirene oxide (18a) with hydroxylamine also afforded 86 (as well as the dioxime of benzoin), albeit in a lower yield, but apparently via the same mechanistic pathway6. 

As formal a, /i-unsaturated sulfones and sulfoxides, respectively, both thiirene dioxides (19) and thiirene oxides (18) should be capable, in principle, of undergoing cycloaddition reactions with either electron-rich olefins or serving as electrophilic dipolarophiles in 2 + 3 cycloadditions. The ultimate products in such cycloadditions are expected to be a consequence of rearrangements of the initially formed cycloadducts, and/or loss of sulfur dioxide (or sulfur monoxide) following the cycloaddition step, depending on the particular reaction conditions. The relative ease of the cycloaddition should provide some indication concerning the extent of the aromaticity in these systems2. 

It has long been known that a, / -unsaturated sulfones resemble a, /i-unsaturated ketones and aldehydes in undergoing addition reactions with nucleophilic reagents43. These reactions are initiated by nucleophilic attack at the carbon to the sulfone group ... 

Allylic sulfones and a, /5-unsaturated sulfones are known to be in equilibrium314-319. Allylic sulfones, such as 242, isomerize to a, /5-unsaturated sulfones 243 upon treatment with a catalytic amount of potassium t-butoxide in dry THF. The a, /5-unsaturated sulfones can be converted to the corresponding olefins upon desulfonation with sodium amalgam320 or aluminium amalgam294,321. Since treatment of allylic sulfones with potassium-graphite gives 2-alkenes, alkylation of allylic sulfones and subsequent desulfonation is a useful process for the synthesis of olefins, as shown in Scheme 6. 

When a mixture of p-anisaldehyde and dimethyl sulfone was treated with excess potassium t-butoxide in DMF at 60-65 °C, bis-unsaturated sulfone 277 was obtained. In the reaction at 50 °C using a small amount of base, the main product was a heterocyclic compound, i.e., 2,4-di-p-methoxyphenyl-l,4-oxathiane 4,4-dioxide 278358. 

In the base-catalyzed condensation of diethyl ethylsulfonylmethylphosphate with aldehydes or ketones, the corresponding a, /1-unsaturated sulfones were obtained in good yields297,364,365. 

This chapter deals with (1) the transformation of the sulfone functionality into other functional groups by nucleophilic substitution reaction, and (2) the addition and elimination reaction of a,/i-unsaturated sulfones. Particular attention will be paid to recent uses of sulfones in organic syntheses1. 

The central bond of the l-(arylsulfonyl)bicyclo[1.1.0]butane system behaves like the double bond of a, /i-unsaturated sulfones to give alkyl-substituted cyclobutyl aryl sulfones on treatment with organometallic reagents (equation 20)17. This method has been applied... 

Reaction of a-isocyano-a, / -unsaturated sulfones with primary aliphatic amines affords 1,5-disubstituted imidazoles 59 (equation 56)48. The reaction of aromatic amines such as aniline is too slow to be of practical use. Results of the preparation of 59 are listed in Table 5. 

Addition of amines to a,/J-unsaturated sulfones has been used in synthesis of key intermediates of biotin. In this reaction, benzylamine serves first as a base in the reaction with 60 to afford thiophene 1,1-dioxide (61) and also as a nucleophile to introduce two amino groups (equation 57)49. 

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