Tetrahedron Letters,Vo1.25,No.25,pp 2627-2630,1984 0040-4039/84 $3.00 + .OO Printed in Great Britain 01984 Perqamon Press Ltd. zyxwvutsr (S)-(+)-2-(ItTOLYLsULFINYL)-2-BUTEN-COLIDE: AN ENANTIOMERICALLY PURE MICHAEL ACCEPTOR FOR ASYMTRIC ~YN~tiEsxs OF 3-sUBsTmTED 4dwTbwoLIDEs. (--)-PODORHIZ~N. Gary H. Posner,* Timothy P. Kogan, Stephen R. Haines and Leah L. Frye Department of Chemistry, The Johns Hopkins University, Baltimore, Maryland 21218 SUMMARY: A short, reliable, and practical synthesis of (S)-(+)-2-(e-tolylsulfinyl)-2-buten- 4-olide has been developed, and the utility of this Michael acceptor for highly enantiocontrolled synthesis of 3-substituted 4-butanolides has been demonstrated. Because of the importance of many S-substituted cycloalkanones as biologically active natural products and as widely useful synthetic intermediates, we have developed a program for asymmetric synthesis of these chiral molecules in high enantiomeric purity.l Our methodology is based on faithful i,3-transfer of chirality from the sulfur atom of a temporarily attached, chiral, auxiliary sulfoxide group to the b-vinyl carbon atom of a conjugated enone system during organometallic conjugate addition to enantiornerically pure 2-(arylsulfinyl)-il-cyclo- alkenones 1 (Ar = e-tolyl or panisyllf; R'=H, Mele, orptolylle; n=5 or 6; W=CH2; M=Mg, Zn, or Ti). B"ecause of the importance of many 3-substituted and 2,3-disubstituted 4-butanolides (y-butyrolactones) as biologically active (e.g. anticancer2, anti-glaucoma3, pheromone4, and inducer of streptomycin biosynthesis5) natural products and as broadly useful synthons, we have now prepared &)-(+)-2-(e-tolylsulfinyl)-2-buten-4-olide [(+)-la, W=O, Ar=e-tolyl, R=H, - n=5) in virtually complete enantiomeric purity, and we have illustrated its effectiveness as a Michael acceptor for asymmetric synthesis of 3-substituted 4-butanolides by preparation of a vicinally-disubstituted lignan lactone6 of high enantiomeric purity. Despite its structural simplicity, relatively small size, and accessibility in racemic form,7 enantiomerically pure butenolide (+)-la is indeed an exceptionally challenging syn- - thetic target. For example, although we have been able to prepare cyclic bromovinylic ortho- ester 2a from 2-bromo-2-buten-4-olide8 (anhydrous and freshly distilled BF3, ethylene oxide, O'C, 42 hr),g all attempts at bromine + metal exchange1s10 using I-butyllithium, t-butyl- lithium, sodium-containing lithium metal, or Rieke magnesium were unsuccessful, as were all attempts at direct lithiation at the 2-position of the corresponding cyclic orthoester 2b. Following thorough retrosynthetic analysis (bonds a-f in structure la) and unsuccessful e;- -- periments to form bonds b-f in butenolide (+)-la, we are now very pleased to report a suc- cessful, short, reliable, and practical (i.e. gram scale) synthesis of butenolide (furan- 2(5H)-one) (+)-la in virtually complete enantiomeric purity via the accompanying scheme. __ 2627