Nucleophilic attack stereoselectivity

Electrophilic attack on the sulfur atom of thiiranes by alkyl halides does not give thiiranium salts but rather products derived from attack of the halide ion on the intermediate cyclic salt (B-81MI50602). Treatment of a s-2,3-dimethylthiirane with methyl iodide yields cis-2-butene by two possible mechanisms (Scheme 31). A stereoselective isomerization of alkenes is accomplished by conversion to a thiirane of opposite stereochemistry followed by desulfurization by methyl iodide (75TL2709). Treatment of thiiranes with alkyl chlorides and bromides gives 2-chloro- or 2-bromo-ethyl sulfides (Scheme 32). Intramolecular alkylation of the sulfur atom of a thiirane may occur if the geometry is favorable the intermediate sulfonium ions are unstable to nucleophilic attack and rearrangement may occur (Scheme 33). 

The stereoselectivity of organometallic additions with carbonyl compounds fits into the general pattern for nucleophilic attack discussed in Chapter 3. With 4-r-butylcyclohex-anone, there is a preference for equatorial approach but the selectivity is low. Enhanced steric factors promote stereoselective addition. 

The stereochemical course of the reaction may be explained by assuming a fivc-membered chelate with the nucleophile attacking the less hindered side of the C—N double bond (alkoxy-mediated S -attack)18. This model is supported by the fact that (he stereoselectivity of the reaction clearly diminishes if smaller nucleophiles, e.g., ethylmagnesium bromide, are employed. The use of valinol methyl ether effects slightly better results19. 

In accord with previous proposals, Pfaltz and co-workers (30) suggested that this reaction proceeds by initial formation of copper carbenoid 47 (Scheme 3). Pfaltz does not invoke a metallacyclobutane intermediate but rather suggests that nucleophilic attack of the alkene on 47 with concomitant pyramidalization at the reacting centers forms two possible transition states with stereoselectivities deter-... 

Mechanistically, it has been recently postulated that the C5-carboxylate ester prefers to occupy an axial position in the oxycarbenium intermediate, thereby favoring the formation of the 3H4 half-chair over the 4H3 conformer. Nucleophilic attack on the 3H4 half-chair intermediate occurs in a (1-lashion, providing the 1,2-m-mannuronates with excellent stereoselectivity (Fig. 6).64 The stereocontrol of mannuronate esters is independent of the type of donor employed and agrees well with this postulate.65... 

A study of debrominations of vtc-dibromides promoted by diaryl tellurides and din-hexyl telluride has established several key features of the elimination process the highly stereoselective reactions of e/7f/tro-dibromides are much more rapid than for fhreo-dibromides, to form trans- and cw-alkenes, respectively the reaction is accelerated in a more polar solvent, and by electron-donating substituents on the diaryl telluride or carbocation stabilizing substituents on the carbons bearing bromine. Alternative mechanistic interpretations of the reaction, which is of first-order dependence on both telluride and vtc-dibromide, have been considered. These have included involvement of TeAr2 in nucleophilic attack on carbon (with displacement of Br and formation of a telluronium intermediate), nucleophilic attack on bromine (concerted E2- k debromination) and abstraction of Br+ from an intermediate carbocation. These alternatives have been discounted in favour of a bromonium ion model (Scheme 9) in which the role of TeArs is to abstract Br+ in competition with reversal of the preequilibrium bromonium ion formation. The insensitivity of reaction rate to added LiBr suggests that the bromonium ion is tightly paired with Br. ... 

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