Me O Me EtMe Me O Me HO2C Me OHMe OH OH LnM O R O Me Me MeO Me Me OH[O] Me O Me Et Me Me O Me HO2C Me OHMe OH OH M OR O Me Me MeO Me Me OH O O O Me O Me EtMe Me O Me HO2C Me OHMe OH OH O LnM OOOOO Me MeO Me HO2C HO Me Me Me H H OHMe H Me H OHMe H OOOOO Me MeO Me HO2C HO Me Me Me H H OHMe H Et H OHMe H C. A. Morales Chem 206Olefin Addition Rxns in Polyether Synthesis-1 One plausible biosynthetic proposal for polyether natural products: Monensin B Cane, D. E. JACS, 1983, 105, 3394.Cane, D. E. JACS, 1982, 104, 7274. An alternate biosynthetic proposal: Townsend, C. A.; Basak, A. Tetrahedron, 1991, 47, 2591. from lecture 7 (Z,Z,Z)-premonensin triene [2+2] Monensin reductive elimination Me OH Me Me MeMe PCC HOAc Me OH Me Me Me Me PCC HOAc OO H Me Me Me O OO H Me Me Me O OHOO H Me H Me Me Me Me OHOO H Me H Me Me Me Me OHOO H Me H Me Me Me Me OHOO H Me H Me Me Me Me OR S RL H RZ RE OH O Cr H RZ RE RL RS H H O O OH i-Pr OHMe Me Me PCC HOAc O CrRL RS H H O O OH H RE RZ O CrRL RS H H O OH H R E RZ O O H i-Pr Me O Me C. A. Morales Chem 206Olefin Addition Rxns in Polyether Synthesis-2 A biomimetic model for syn-oxidative polycyclization: McDonald, F. E. JACS, 1994, 116, 7921. 9% combined, 11:1 (trans:cis) 38%, 9.9:1 19% combined, 3.7:1 (trans:cis) 24%, 17:1 High syn-stereospecificity for tertiary alcohols But for secondary alcohols... ...simple oxidation occurs more rapidly than oxidative cyclization. Conformational model for syn-oxidative cyclization: [2+2] reductive elimination trans-substitutedtetrahydrofuran Does this explain the lower degree of "trans-cross-ring" selectivity observed for (E)-olefins? Me EtMe Me O MeMe Me OEtHHO Me O Me EtMe Me O Me HO2C Me OHMe OH OH LnM O Me Et Me Me HO OH O MeMe Me OHEtHAcO (Cl2CHCO2)ReO3 (Cl2CHCO)2O O MeMe EtHAcO O Me OHH H C D OOOOO Me MeO Me HO2C HO Me Me Me H H OHMe H Et H OHMe H C D HO O O Me OEt HH OH H OH H OH n-C12H25 n-C12H25O H n-C12H25OH Et O HH OH H OH H OH n-C12H25HO O O Me n-C12H25OH (Cl2CHCO2)ReO3 (Cl2CHCO)2O NHSO2CF3 NHSO2CF3 Application of the model for syn-oxidative polycyclization using an all (Z)-polyolefin: McDonald, F. E. Pure App. Chem., 1998, 70, 355. (Z,Z,Z)-premonensin triene Monensin C. A. Morales Chem 206Olefin Addition Rxns in Polyether Synthesis-3 AD-mix β CrO3(py)2 1) Ac2O, Et3Ncat. DMAP 2) NaBH4, CeCl3 5 Goniocin 5 (E,E,E)-pregoniocin triene Et2Zn, Ti(O-i-Pr)4 * * One stereocenter ( ) controls the induction of six additional centers.* Application of the model for syn-oxidative polycyclization on an all (E)-polyolefin: