Aristolactone Wittig rearrangement

The pioneering work on enantioselective [2,3]-Wittig rearrangement was carried out by Marshall and Lebreton in the ring-contracting rearrangement of a 13-membered cyclic ether using lithium bis(l-phenylethyl) amide (63) as a chiral base (equation 34). Upon treatment with a (S,S)-63 (3 equivalents) in THF at —70 to —15 °C, ether 64 afforded the enantioenriched [2,3]-product 65 in 82% yield with 69% ee. The reaction was applied in the synthesis of (+)-aristolactone (66). 

Chiral lithium bases have been used for enantioselective deprotonation to yield configurationally stable a-oxy carbanions. This holds potential for asymmetric [2,3]-Wittig rearrangement in stereoselective synthesis. Thus, treatment of propargylic ether 72 with (S,S)-3 in THF at — 70 °C to —15 °C afforded propargylic alcohol 73 in 82% yield and in 69% ee of the shown enantiomer96,97. This product was successfully employed as a precursor of (-l-)-Aristolactone (Scheme 55). 

Figure 6.7. Natural products using the [2,3]-Wittig rearrangement as the key step (a) ant pheromone [58] (b) t aromycin A (J768) (c) Prelog-Djerassi lactone (J771) (d) aristolactone...

SCHEME 17.10. Synthesis of ( )-aristolactone 43 by a [2,3]-Wittig rearrangement-ring contraction of propargylic ether 41. 

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