Chiral alcohols rearrangements

Acid-induced wagner-meerwein rearrangements in chiral alcohols. In view of the considerable interest on ion-molecule complexes involved in gas-phase analogues of solvolytic reactions," ° " a sustained research effort has been directed to the study of Wagner-Meerwein rearrangements in cationized )8-arylaIkyl systems, under conditions excluding nucleophilic assistance by the solvent which in these systems normally interferes with anchimeric assistance of groups adjacent to the... 

The next example makes more involved use of these [2,3]-sigmatropic allylic sulfoxide-allylic alcohol rearrangements. It comes from the work of Evans (he of the chiral auxiliary) who, in the early 1970s, first demonstrated the synthetic utility of allylic sulfoxides. Here he is using this chemistry to make precursors of the prostaglandins, a family of compounds that modulate hormone activity within the body. 

Based on the ability of Pd(OAc)2 to accelerate the [2,3]-rearrangement of amine iV-oxide 114, we explored chiral palladium(ll) salts to catalyze the enantioselective rearrangement. When we treated amine iV-oxides 116 with Pd(OAc)2 and chiral phosphoramidite 118, chiral O-allylhydroxylamines 117 were isolated in 80-85% ee (Scheme 1S.28V Subsequent optimization revealed the beneficial effect of methanol and meta-chlorobenzoic acid (m-CBA) as additives, allowing the isolation of chiral nonracemic O-allylhydroxylamines 117 with greater than 90% enantioenrichment. This palladium-catalyzed enantioselective [2,31-rearrangement can tolerate a wide variety of functional groups in the amine N-oxide substrate. For example, we can synthesize chiral allylic hydrojq lamine products with reactive functional groups such as alcohols and aldehydes, which are inconpatible with many other methods for the synthesis of chiral alcohol derivatives. 

Similarly, Cooper used the orthoester Johnson-Claisen rearrangement for the stereospecific construction of nonracemic allene 348 from the chiral alcohol 347 with efficient rearrangement of the propargylic system." ... 

Wood et have shown how the product from such a reaction can set up the system to undergo a subsequent Claisen rearrangement (Eq. 14.86). Instead of the expected ketone 14.13, however, the nature of the final product suggests that the intermediate is enol 14.14, formed by transfer of the alcohol proton to O rather than C. Starting with one enantiomer of the chiral alcohol leads to good transfer of chirality to the final product. 

What do we mean by transfer of chirality Reactions in which the stereoselective formation of one stereogenic center is connected to the destruction of another stereogenic center involve transfer of chirality. Sigmatropic rearrangements are a large family of intramolecular reactions that often can be used to transfer chirality. We will look at two examples (1) the Claisen rearrangement (of allyl vinyl ethers to j8,7-unsaturated carbonyl compounds) and (2) the Mislow-Evans rearrangement (of allylic sulfoxides to allylic alcohols via sulfenate esters). 

A tandem ylide formation/[2,3]-sigmatropic rearrangement between donor/acceptor rhodium carbenoids and chiral allyl alcohols has been reported as a convergent C-C bond-forming process generating two vicinal stereogenic centres. Any of the four possible stereoisomers can be selectively synthesized by the appropriate combination of the chiral catalyst Rh2(DOSP)4 and the chiral alcohol (Scheme 144). °... 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

Overman LE, Owen CE, Pavan MM, Richards CJ (2003) Catalytic asymmetric rearrangement of allylic N-aryl trifluoroacetimidates. A useful method for transforming prochiral allylic alcohols to chiral allylic amines. Org Lett 5 1809-1812... 

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