Macrocyclic 2,31-Wittig rearrangements

Sigmatropic Wittig rearrangement of macrocyclic allyl propargyl ethers to carbocycles 91TA1. 

Marshall has reported an innovative application of the Wittig rearrangement in the synthesis of the 14-membered cembrenoid carbocycles (Scheme 16.21) [104], The stereoselectivity of this process is coupled with the conformational preferences of the macrocyclic ether. The rearrangement reaction of the 17-membered macrocycle 187 provided a 90% yield of the 14-membered alcohols, with 188 as the major diastereomer (dr=81 7 6 7). This represents a remarkable example of macrocyclic stereocontrol (see also Chapter 1) to effect a stereoselective ring-contraction by use of a Wittig rearrangement. 

Macrocyclic ethers with remote sp stereocenters can undergo diastereoselective 2,3-Wittig ring contractions. Thus, the alcohol (266a equation 58) and several of its ether derivatives (266b) and (266c) upon treatment with Bu"Li in pentane-THF-TMEDA afforded the four diastereomeric rearrangement... 

For the rearrangement of conformationally constrained [2,3] Wittig substrates, chiral bases can exert a more pronounced influence on the stereochemical outcome of the reaction, as evidenced by the macrocyclic ring contraction of cyclic ether 47 86. 

The [2,3]-Wittig-Still rearrangement of the phenyl sulfide 51 (n = 0) afforded a mixture of 52 and 53 from a and p approach in 8 92 ratio fScheme 17.9T From the corresponding sulfone 51 (n = 2), use of 2 equiv. n-BuLi selectively yielded 54 in 65% yield with the a stereochemistry, resulting from lithium-ion chelation with the sulfonyl methyl and oxymethyl lithium (51a). The synthesis was continued to attach the side chain, and alkylative macrocyclization gave diol 57 (Scheme 17.9). ... 

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