A novel palladium-catalyzed intramolecular oxidative alkylation of unactivated olefins is described. This protocol was devised to solve one of the drawbacks of the original palladium-catalyzed cycloalkenylation that we developed. We call this new procedure the ‘second generation palladium-catalyzed cycloalkenylation’. This protocol has been applied to the total syntheses of cis-195A trans-195A boonein scholareins A C D and α-skytanthine.
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PeiT, WangX, WidenhoeferRA. (2001) Palladium-catalyzed intramolecular addition of 1,3-diones to unactivated olefins. Journal of the American Chemical Society, 125, 648-649. In 2001, Widenhoefer and coworkers discovered that 1,3-diones could add unactivated olefins in 6-endo-trig manner in the presence of a catalytic amounts of PdC2(MeCN)2: (2001) Pei T, Widenhoefer RA, Palladium-Catalyzed Intramolecular Addition of 1,3-Diones to Unactivated Olefins. Journal of the American Chemical Society, 123, 11290–11291.
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ToyotaM, WadaT, IharaM., (2000) Total syntheses of (-)-methyl atis-16-ene-19-oate, (-)-methyl kaur-16-en-19-oate, and (-)-methyl trachyloban-19-oate by a combination of palladium-catalyzed cycloalkenylation and homoallyl-homoallyl radical rearrangement. Journal of Organic Chemisty, 65, 4565–4570.
7.
ToyotaM, OdashimaT, WadaT, IharaM., (2000) Application of palladium-catalyzed cycloalkenylation reaction to C20 gibberellin synthesis: formal syntheses of GA12, GA111, and GA112. Journal of the American Chemical Society, 122, 9036–9037.
8.
ToyotaM, SasakiM, IharaM., (2003) Diastereoselective formal total synthesis of the DNA polymerase α inhibitor, aphidicolin, using palladium-catalyzed cycloalkenylation and intramolecular Diels-Alder reactions. Organic Letters, 8, 1193–1195.
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ToyotaM, AsanoT, IharaM., (2005), Total synthesis of serefendic acids A and B employing tin-free homoallyl-homoallyl radical rearrangement. Organic Letters, 7, 3929–3932.
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HibiA, ToyotaM., (2009) Development of palladium(II)-catalyzed oxidative cyclization of olefinic keto and/or lactone esters. Tetrahedron Letters, 50, 4888–1891.
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17.
A recent review of gibberellin synthesis: ManderLN. (2003) Twenty years of gibberellin research. Natural Product Reports, 20, 49–69.
18.
Our recent gibberellin synthesis: ToyotaM, OdashimaT, WadaT, IharaM., (2000) Applications of palladium-catalyzed cycloalkenylation reaction to C20 gibberellin synthesis: formal syntheses of GA12, GA111, and GA112. Journal of the American Chemical Society, 122, 9036–9037.
19.
A review of aphidicolin synthesis: ToyotaM, IharaM., (1999) Total synthesis of aphidicolane and stemodane diterpenes. Tetrahedron, 55, 5641–5679.
20.
Our recent aphidicolin synthesis: ToyotaM, SasakiM, IharaM. (2003) Diastereoselective formal total synthesis of the DNA polymerase α inhibitor, aphidicolin, using palladium-catalyzed cycloalkenylation and intramolecular Diels-Alder reactions. Organic Letters, 5, 1193–1195.
21.
TakedaK, ToyotaM., (2011) Scope and application of second generation palladium-catalyzed cycloalkenylation. Stereoselective total syntheses of iroiridomyrmecin, isodihydronepatalactone, and α-skytanthine. Tetrahedron, 67, 9909–9921.
22.
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23.
Recent total syntheses: (a) GirardN, HurvoisJ.-P, MoinetC, ToupetL. (2005) Total synthesis of (±)-pumiliotoxin C: An electrochemical approach. European Journal of Organic Chemistry, 2269–2280.
24.
AmatM, GrieraR, FabregatR, MolinsE, BoschJ. (2008) A biomimetic enantioselective approach to the decahydroquinoline class of dendrobatid alkaloids. Angewandte Chemie International Edition, 47, 3348–3351.
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LausonS, TremblayF, GagnonD, GodboutC, ChabotC, Mercier-ShanksC, PerreaultS, DeSeveH, SpinoC. (2008) Sterically biased 3,3-sigmatropic rearrangement of chiral allylic azides: Application to the total syntheses of alkaloids. Journal of Organic Chemistry, 73, 6239–6250. Our syntheses
26.
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27.
ToyotaM, AsohT, FukumotoK. (1996) Palladium catalyzed reductive cyclization reaction in alkaloid synthesis-an enantioselective total synthetic route to (+)-pumiliotoxin C. Tetrahedron Letters, 37, 4401–4404.
28.
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30.
FengT, CaiX-H, DuZ-Z, LuoX-D. (2008) Iridoids from the bark ofAlstonia scholaris, Helvetica Chimica Acta, 91, 2247–2251.
31.
KawaiY, SaekiM, ToyotaM., (2012) The first syntheses of scholareins A, C, and D employing 2nd generation palladium-catalyzed cycloalkenylation. Heterocycles, 86, 1093–1101.
32.
KanedaK, HondaT., (2008) Stereocontrolled synthesis of (+)-α-skytanthine by means of an intramolecular Pauson–Khand reaction. Tetrahedron, 64, 11589–11593.
33.
SaekiM, ToyotaM., (2011) Second generation palladium-catalyzed cyclolakenylation in iridoid lactone synthesis: total syntheses of (±)-onikulactone and (±)-mitsugashiwalactone. Heterocycles, 82, 1705–1708.
34.
TakedaK, ToyotaM., (2012) 2nd generation palladium-catalyzed cycloalkenylation in iridoid synthesis: diastereoselective total syntheses of isoirodomyrmecin and isodihydronepetalactone. Heterocycles, 84, 1271–1276.
