M.C. White Chem 153 Hydrogenation-143- Week of october 15, 2002 Wilkinson site selectivii Site selective hydrogenation: sterics ketone activated -disubstituted atm), rt aPPh3 high levels of selective MPPh Chlorotris(triphenylphosphine)rhodium I tetrasubstituted Strem catalog 2001-2003 I mol% 1g=$42 =0 H,(I atm), benzene/EtoH, rt Pedro!C19913815 Site selective hydrogenation: sterics and electronics HcO CH(CH3 CH CH(CH3)C2Hs HO TOH trisubstituted HO Mel cis-disubstituted only site of 92% m198023114e cis vs. trans-disubstituted olefins Ph3p COMe COrMe H,(I atm), benzene/acetone, rt rans-disubstituted OAc PGE PGEI Schneider JOC 1973(38)951M.C. White, Chem 153 Hydrogenation -143- Week of October 15, 2002 Wilkinson: site selectivity Ph3P Rh(I) Ph3P PPh3 Cl Ph3P Rh(I) Ph3P PPh3 Cl Strem catalog 2001-2003 1g = $42 O Chlorotris(triphenylphosphine)rhodium I O O O O O H O O 1 mol% O H2 (1 atm), benzene/EtOH, rt 95% Pd/C acetone, H2 (1 atm), rt 75% ketone activated cis-disubstituted tetrasubstituted O CH(CH3)C2H5 O O H OMe O O O H H3CO O O H MeO HO OH H conjugated diene trisubstituted trisubstituted cis-disubstituted O CH(CH3)C2H5 O O H OMe O O O H H3CO O O H MeO HO OH H Ph3P Rh(I) Ph3P PPh3 Cl ~30 mol% H2 (1 atm), tol, rt 92% only site of hydrogenation O HO CO2Me OAc cis-disubstituted trans-disubstituted Ph3P Rh(I) Ph3P PPh3 Cl H2 (1 atm), benzene/acetone, rt 80% cat. O HO OAc CO2Me cis vs. trans-disubstituted olefins: PGE Schneider JOC 1973 (38) 951. 2 PGE1 Site selective hydrogenation: sterics highly active heterogeneous catalysts often cannot achieve high levels of selectivity. Site selective hydrogenation: sterics and electronics Pedro JOC 1996 (61) 3815. Fisher J. Med. Chem. 1980 (23) 1134. Ivermectin