Configuration apparent retention

Three reaction sequences, all of a similar nature, have been published by Fujita and coworkers. The first175 is an alkene synthesis in which only three examples that involve sulphones are given. The most useful of these is a conversion of nerly phenyl sulphone (from neryl chloride) into aCn triene (75%), with the extra carbon atom being supplied by the iodomethylstannane reagent. The reaction proceeds spontaneously, with apparent retention of configuration at the Z alkene, as in equation (72). 

Initial attack by base on (34) yields the alkoxide anion (36), internal attack by this ROe then yields the epoxide (37) with inversion of configuration at C (these cyclic intermediates can actually be isolated in many cases) this carbon atomf, in turn, undergoes ordinary SN2 attack by eOH, with a second inversion of configuration at C. Finally, this second alkoxide anion (38) abstracts a proton from the solvent to yield the product 1,2-diol (35) with the same configuration as the starting material (34). This apparent retention of configuration has, however, been brought about by two successive inversions. 

Reductive decyanation. This reaction is a key step in a route to syn-l,3-diol acetonides from P-trimethylsilyloxy aldehydes (1). Reaction of 1 with trimethylsilyl cyanide followed by acetonation gives a 1 1 mixture of a protected cyanohydrin (2). This mixture is converted into a single isomer (3) on alkylation of the anion of the cyanohydrin acetonide. Reductive decyanation with Na-NH3 at -78° produces a syn-diol acetonide (4). The apparent retention of configuration in the reduction results from preferential formation of an intermediate axial anion. 

The dearomatizing anionic cyclization of r-naphthamides bearing chiral fV-substitu-ents occurs with >99% retention of configuration. Apparently anion translocation following ortho lithiation occurs for only one of the two atropisomers at —78 °C the resulting a-lithiated species can cyclize to only one diastereoisomer of the product. 

Each reaction in the sequence shown is reported to proceed with retention of configuration, yet the starting material has the R configuration and the product has the S configuration. Reconcile this apparent contradiction. 

Step 1 is fundamentally an SN2 reaction (kinetics related to structural variations of the reactants,16 8 retention of stereochemistry at phosphorus912), except in those instances wherein a particularly stable carbocation is produced from the haloalkane component.13 A critical experiment concerned with verification of the Sn2 character of Step 1 by inversion of configuration at the carbon from which the leaving group is displaced was inconclusive because elimination rather than substitution occurred with the chiral secondary haloalkane used.14 An alternative experiment suggested by us in our prior review using a chiral primary substrate apparently has not yet been performed.2... 

In the rearrangement of l-methylbicyclo[3.1.1]heptan-6-one (8) the tertiary carbenium ion 9 in which the configuration at C6 is still retained is apparently more stable than the secondary ion, thus leading to ra-5-methyIbicyclo[3.2.0]heptan-6-one (10) with retention of its chiral information.44... 

Many such examples are known. In most cases where the stereochemistry has been investigated, retention of configuration is observed,225 but stereoconvergence (the same product mixture from an E or Z substrate) has also been observed,226 especially where the carbanionic carbon bears two electron-withdrawing groups. It is not immediately apparent why the tetrahedral mechanism should lead to retention, but this behavior has been ascribed, on the basis of molecular orbital calculations, to hyperconjugation involving the carbanionic electron pair and the substituents on the adjacent carbon.227... 

If we assume that the above dehydration occurs with retention of configuration at C-7, the ready formation of the anhydro derivative from platynecine and the inertness of dihydroxyheliotridane apparently indicate a cis-relationship of the C-7 hydroxyl group with respect to the hydroxymethyl group in platynecine and a Iraws-conformation in dihydroxyheliotridane.1,78 A reversed relationship would follow from the alternative assumption of inversion at C-7. 

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