Aristolactone synthesis

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). 

With only moderate dilution and without a template effect, the cyclic ether 24 which is an important precursor in the total synthesis of the racemic ger-macranolide-aristolactone (25) was obtained from the hydroxychloride 23 [35]. 

Applications of cyclocarbonylation to the preparation of natural products include the synthesis of ( )-aristolactone [12], (+ )-hamabiwa]actone B [13], (+ )-asimicin, and (+ )-bullatadn [14], all of which involve 4-hydroxybutenolide motifs (Scheme 2.4). 

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

Marshall JA, Lebreton J, DeHoff BS, Jenson TM. Total synthesis of the germacranolide ( )-aristolactone via [2,3]-Wit-tig ring contraction. Tetrahedron Lett. 1987 28(7) 723-726. 

Marshall JA, Lebreton J. Enantioselective synthesis of mac-rocyclic propargyUc alcohols by [2,3]-Wittig ring contraction. Synthesis of (-l-)-aristolactone and cembranoid precursors. 7 Arw. Chem. Soc. 1988 110(9) 2925 2931. 

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