Vinylpalladation of norbornene using vinylmercurial 5 and Li2PdC14 affords the corresponding cis-exo adduct 6 which can be directly carbonylated to methyl ester 7 in 60% overall yield. Reduction to aldehyde 9 and subsequent chain elaboration provides the new prostaglandin endoperoxide analog 12. Epimerization of exo aldehyde 9 to endo aldehyde 13 and chain extension provides the first synthesis of optically active endoperoxide analog 15, a known potent inhibitor of PGE2 synthesis. Biological test results for compounds 12 and 15 are reported. The synthesis of stable analogs of the prostaglandin endoperoxides has received considerable attention in recent years. 2*3 The most cOrnnon routes to these compounds have involved either modification of naturally occuring prostaglandins or Diels-Alder approaches. Our interest in this area has lead to a number of new approaches involving n-allylic,4 benzylic.1*5 and thieny16s7 palladium compounds, as well as oxypalladation.* Recently, we reported that the facile addition of vinylic palladium species to bicyclic alkenes affords the corresponding stable, cis-exo adducts (eq l).gslo The substantial biological activity of the known endoperoxide analogs 1 (prepared previously as a racemic mixture of C-15 epimers l1 or a diastereomeric mixture of the two 15-S alcohols12) and 2 (prepared previously as a racemic mixture of C-15 epimers13), as well as our own cis-exo compound 4 (prepared previously as a racemic mixture of C-15 epimers4), encouraged us to examine this reaction as a possible new approach to prostaglandin endoperoxide analogs, particularly compound 1 (as a pair of 15-S diastereomers), and the unknown optically active 15-S stereoisomer 3 (as a pair of diastereomers). We report here the successful conclusion of those studies. 1, &endo, It-exo 4 2, 8-exo. 12-endo 3, 8-exo, 12-exo Results and Discussion The requisite vinylmercurial 5 for our synthesis of ccmpounds 1 and 3 is readily available Frm optically pure (S)-3-(t-butyldimethylsilyloxy)-1-octyne' using our recently improved iydroboration-mercuration procedure l4 (eq 2). tSiMe2(t-Bu) R. C. LARCCK ef al. Vlnylpalladationg*IO of norbornene (10 equiv) using organontercurial 5 afforded the stable adduct 6 in 78% isolated yield (eq 3). This palladium compound Is no doubt a mixture of two (3) bSiMe2(t-Bu) 6 diasterecmers resulting from addition of the vinylpalladium species to opposite ends of the carbon-carbon double bond. This is seen from the extra peaks observed in the 13C NMR spectra of the products of subsequent reactions. All subsequent reactions are assumed to contain the analogous pair of diastereomers, though they have not been drawn and could never be separated. Numerous unsuccessful attempts have been made on a model system to elaborate this type of organopalladium complex to the desired Z-carbon homologated aldehyde 10 in a minimum of steps. Those efforts involved reactions with ClHgCH2CH0, LiCH2CN. CUCH~CN, LiCH2C02-I-Bu, LiCrCOEt, LiCsCH. NaCH(C02Et)2. I-n-Bu3SnCH=CHOEt, Z-LiCH=CHOEt. E-Cp2ZrClCH=CHOEt and E-g-(C6H402)BCH-CHOEt in the presence or absence of triphenylphosphine. Few of these reactions showed any of the desired cross-coupled product. When reaction did occur, it was usually that of substitution of PdCl by hydrogen. R. C. LAROCK er al. acetic acid and 0.17 ml of plperldine. The reaction mixture was refluxed for 3 h. The reaction mixture was cooled, poured into ice water, and extracted with benzene. The benzene layer was washed with dilute HCl, saturated NaHC03 and brine. and dried over MgS04. The solvent was evaporated to give 0.44 g (80%) of aldehyde 13 along with aldehyde 9 in a ratio of -9:l as seen by 'H NMR spectral analysis. The endo aldehyde exhibits a peak at 6 9.75 and the exo aldehydlc proton appears at 6 9.60. Synthesis of aldehyde 14. Compound 14 was synthesized using the same sequence as for compound 9 using the 9:l mixture of aldehydes 13 and 9. Compound 14 was separated from the corresponding exo aldehyde by column chromatography using 9:l hexane/ethyl acetate: 25% unoptimized yield; 'H NMR (DCC13) 6 0.0 (6 H, 2 s, SiMe2), 0.8-1.0 (12 H, s and m, &-Bu and CH3), 1.2-2.6 (20 H, m. norbornyl and methylenes), 4.0 (1 H, m. C=CCHO-), 5.35-5.55 (2 H, m, vinyl), 9.70 (1 H, m, CHO); 13C NMR (DCC13) 6 -4.89, 13.80, 18.04, 21.90. 21.95. 22.41, 24.84, 25.71, 29.71. 31.57. 37.09. 38.27, 40.04, 40.17, 42.20, 42.72, 42.94, 45.73, 45.86, 51.71. 73.30, 73.37, 132.13, 133.10. 133.16. 201.97; mass spectrum, m/e 321.2247 [calcd for C1gH3302Si (M+-C4Hg), 321.22491. Synthesis of acid 15. Compound 15 was synthesized by the same reaction sequence as used for compound 12: 1H NMR (DCC13) 6 0.83-2.50 (29 H; m; norbornyl , methylene sidechain and methyl protons), 4.00-4.20 (1 H, m, C=CCHO-), 5.20-5.65 (4 H. m, vinyl), 6.0-7.0 (2 H, br s. OH and C02H); 13C NMR (DCC13) 6 14.00, 22.04, 22.63, 24.71. 25.15, 26.53, 26