Sulfur nucleophiles regioselectivity

All of the various sulfur nucleophiles that have been studied, including PhSCh—, RS— and (Et0)2P(0)S—, have been demonstrated to add to ir-allylpalladium complexes by ligand addition. Interpretation of the regioselectivities of these nucleophiles must be tempered by the realization that the allyl— SChPh, -SR and -SP(0)(0Et)2 products are capable of isomerization by means of reentering the ir-allylpalladium manifold. 

In contradistinction to the alkylation result in the crotyl system described in the previous section (cf. Eq. 8E.9), a rare example depicted in Scheme 8E.33 demonstrates that chiral recognition in the first step of the catalytic cycle can be a source of enantioselectivity [171]. The alkylations of ( )- and (Z)-crotyl carbonate with a sulfur nucleophile generate the branched product in 92% and 29% ee s, respectively. On the other hand, the same reaction using the chiral substrate gives a nearly racemic product with a similar 5 1 regioselectivity. These results clearly indicate that the nucleophilic addition occurs more rapidly than the enantioface exchange process. 

The regioselectivity in the methoxydefluorination reactions of difluoroquinolines has been examined.48 Studies of the substitution patterns in 2-cyano-3-nitroimidazole[l,2-a lpyridine have shown that nitrogen and oxygen nucleophiles substitute the 2-cyano group whereas sulfur nucleophiles replace the 3-nitro group.49... 

By far most of the reports on addition reactions of hetero-nucleophiles to activated dienes deal with sulfur-nucleophiles " ° 20-t37 jjj particular in the synthesis of 7/1-sulfur-substituted steroids which, like their carbon-substituted counterparts (Section ILA), are of interest because of their ability to inhibit the biosynthesis of estrogens ° 129-137 Early investigations 120-122 concentrated on simple acyclic Michael acceptors like methyl sorbate and 2,4-pentadienenitrile. Bravo and coworkers observed the formation of a 3 1 mixture of the 1,6- and 1,4-adduct in the reaction of methyl sorbate with methanethiol in basic medium (equation 39). In contrast to this, 2,4-pentadienenitrile adds various thiols regioselectively at C-5, i.e. in a 1,6-fashion (equation 4O) 121.122, jjjg same is true for reactions of this substrate with hydrogen sulfide (equation 41), sodium bisulfite and ethyl thioglycolate. ... 

Catalytic Asymmetric Allylation Although significant progress has been made in the asymmetric allylic alkylation (AAA) reactions during the last four decades, the employment of sulfur nucleophiles to construct C—S bonds with high regioselectivity and enantioselectivity has met with little success until recently. In 1986, Hiroi and... 

The regioselective reductive ring opening of, V-substitutcd aziridine-2-carboxylates gives either a- or //-amino acids.122 Heteronucleophiles such as nitrogen,123 oxygen,124 sulfur,125 and chloride preferably attack the C-3 position to provide a-amino acid derivatives. However, a mixture of products will result when carbanion or azide is used as the nucleophile (Scheme 4-62). 

The high nucleophilicity of heterosubstituted allyllithium compounds makes them attractive reagents in synthetic organic chemistry. Structural studies of these compounds give a fundamental understanding about the control of the regioselectivity. Often, these studies are difficult due to the tendency of the compounds to form complex fluxional aggregates in solution. Piffl and coworkers have studied the dependency of the oxidation state of sulfur on the structure and electronic properties of the heterosubstituted... 

Fluorine and sulfur (in the form of a methylthio group) are added to nucleophilic olefins with Markovmkov regioselectivity and anti stereoselectivity by di-methyl(methylthio)sulfonium fluoroborate and triethylamine tris(hydrogen fluoride) [177] (equation 21)... 

The regioselectivity of the cleavage of cyclic sulfites depends on the nature of the nucleophile, and this dependence can be interpreted in terms of the hard and soft acid and base principle <2000T7051>. For instance, in reactions with PhONa, PhSNa, NaN3, NaCN, BnNH2, and Pr NI I2, the Sn2 attack occurs exclusively at the less sterically hindered carbon atom. In contrast, the harder, less polarizable nucleophiles BnNHNa, PhNHNa, BnONa, and BnSNa attack at both the carbon and the sulfur atoms, sometimes with a predominance at the latter <2000T7051>. 

The high reactivity towards nucleophiles, as compared to carbonyl compounds, is easily explained by frontier orbital treatment [119]. However the regioselectivity of addition, whether on sulfur or on carbon atoms, has not yet been fully rationalised. However this has not prevented numerous successful applications [1]. 

California Red Scale is a worldwide citrus pest which can be controlled by means of the pheromone 60. Cohen used reductive lithiation to generate versatile allylic nucleophiles applicable to this type of target.6 The allyl sulfide 61 is lithiated by BuLi and reacts with butenyl bromide a to sulfur to yield 63. Reductive lithiation (Li, DBB) of the product yields allyllithium 64. A regioselective reaction of this nucleophile with formaldehyde at the more substituted terminus is ensured by transmetallation to the allyl titanium 65, which gives 66 after treatment with formaldehyde and bromination. 

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