M C. White, Chem 153 Hydrogenation-166- Week of october 21. 2002 Stereochemical model Hydride transfer via a four-centered transition state. leads to the formation of a new stereogenic center at the disubstituted carbon of the olefin. in this model the olefin approaches from the front"of the complex with hydrometallation resulting in formation of the less sterically hindered Ti alkyl bond H--TiH e najor product, >99% transition state A HTi VS The olefin arrangement shown in transition state a Me minimizes the steric interactions between the large substituents on the olefin and the cyclohexyl portion of the MeH→Ti tetrahydroindenyl ligand. The rate of reduction for Z olefins is slower than the rate of reduction for e olefins Can this result be rationalized based on this model for the transition state? nsition state b
M.C. White, Chem 153 Hydrogenation -166- Week of October 21, 2002 H Ti Me MeH Ti H Me H TiH (R) (S) Me Me vs. ‡ ‡ major product, >99% e.e. transition state A transition state B Hydride transfer via a four-centered transition state. leads to the formation of a new stereogenic center at the disubstituted carbon of the olefin. In this model, the olefin approaches from the "front" of the complex with hydrometallation resulting in formation of the less sterically hindered Ti alkyl bond. The olefin arrangement shown in transition state A minimizes the steric interactions between the large substituents on the olefin and the cyclohexyl portion of the tetrahydroindenyl ligand.The rate of reduction for Z olefins is slower than the rate of reduction for E olefins. Can this result be rationalized based on this model for the transition state? Stereochemical model
M.C. White Chem 153 Hydrogenation-167- Week of october 21. 2002 Asymmetric hydrogenation of cyclic imines Ti-H Meo 、父.M Meo H2 NH H 81 yield, 98%ee 82% yield, 98%ee RHN H L Ti e. g. Kinetic studies suggest that the hydrogenolysis of the Ti-N bondR' L*Ti this catalytic cycle *Ti the ethylene bridge Buchwald JACS 1994(1168952 H
M.C. White, Chem 153 Hydrogenation -167- Week of October 21, 2002 N MeO MeO Me Ti H H2 NH MeO MeO Me 82 % yield, 98 % e.e. Asymmetric hydrogenation of cyclic imines N H Ti H H2 NH 81 % yield, 98 % e.e. L*Ti H H N R R'' R' R' R'' RHN H2 H R N R' R'' H L*Ti N R H R' R'' RN R'' R' L*Ti L*Ti * * * ‡ ‡ * Kinetic studies suggest that the hydrogenolysis of the Ti-N bond may be the rate-determining step in this catalytic cycle Ti H N R ‡ e.g. the ethylene bridge is omitted for clarity Buchwald JACS 1994 (116) 8952
M.C. White Chem 153 Hydrogenation -168 Week of october 21. 2002 Asymmetric hydrogenation of acyclic imines TisH syn isomers. This property proves relevant in the asymmetric hydrogenation of these 93% yield, 76%ee c-hex n Ph Ti_,c-hex→ (R) Me disfavored Buchwald JACS 1994(116)8952 the ethylene bridge is omitted for clarity
M.C. White, Chem 153 Hydrogenation -168- Week of October 21, 2002 Me N Ph Ti H H2 Me N Ph anti/syn : 11/1 93 % yield, 76 % e.e. Asymmetric hydrogenation of acyclic imines Acyclic imines exist as mixtures of anti and syn isomers. This property proves relevant in the asymmetric hydrogenation of these substrates. Ti H N c-hex Ph Me Ti H N Me Ph c-hex Me N Ph Me N Ph Me N Ph favored disfavored anti Me N Ph Ti H N Me Ph Me Ti H N c-hex Ph c-hex Me N Ph Me N Ph favored disfavored syn Buchwald JACS 1994 (116) 8952 the ethylene bridge is omitted for clarity (R) (S)
M C. White Chem 153 Hydrogenation -169 Week of october 21. 2002 Substrate-Directed Ketone hydrogenations Ru hydride must have black box chemistry Ph2 some hydridic character (R}1(0.lmol%) MeOH, H2(100 atm), 23C, 48h 41% yield (R}l(0.1mol%) 2 equ. HX(X=Cl, Br, D) EtOH, H,(50 atm), 23C, 12h 72% yield Ru(llr-BINAP dicarboxylate catalysts were found to be ineffective for ketone hydrogenation molecular weight unknown mediated via a or B-oxygenated functionality. These hydrogenations could be effected in high yields and ee's with poorly defined halogen-containing Ru complexes. The dicarboxylate catalysts May Note: opposite sense of stereoinduction OH Ruxzl(R)-binapl 0 1 EtoH, H,(50-100 atm),rt Lewis basic 97% yield 0 functionality ogenation of ketones performe under forcing conditions(recall that May pre-coordinate to olefin hydrogenations were performed RuX(S)-binapl give the(s)enantiomer center via a at 4 atm with this catalyst) 0 EtoH, H(50-100 atm),rt NoyoriJACS 1987(109)5856 quantitative yield Noyori JACS 1988(110)629 98%ee quantitative yield >99% ee(best substrates
M.C. White, Chem 153 Hydrogenation -169- Week of October 21, 2002 Substrate-Directed Ketone Hydrogenations P Ph2 Ru(II) Ph2 P O O O O OEt O O OEt OH O P Ph2 Ru(II) Ph2 P O O O O 2 equ. HX (X= Cl, Br, I) RuX2[(R)-binap] molecular weight unknown black box chemistry N O N OH (S) Ru(II)-BINAP dicarboxylate catalysts were found to be ineffective for ketone hydrogenations mediated via α or β-oxygenated functionality. These hydrogenations could be effected in high yields and ee's with poorly defined halogen-containing Ru complexes. The dicarboxylate catalysts were effective for ketone hydrogenations mediated via highly basic α (or β) amino functionality. (0.1 mol%) MeOH, H2 (100 atm), 23oC, 48h (R)-1 41% yield 4% ee binap 72% yield 96% ee (R) EtOH, H2 (50 atm), 23oC, 12h (R)-1(0.1 mol%) Ru hydride must have some hydridic character. Hydrogenation of ketones performed under forcing conditions (recall that olefin hydrogenations were performed at 4 atm with this catalyst). R O X Lewis basic functionality RuX2[(R)-binap] 0.1 mol% EtOH, H2 (50-100 atm), rt May pre-coordinate to the Ru center via a 5-membered ring chelate R OH X (R) OH OH OEt OH O N(Me)2 OH O OH Br OH Br (R) quantitative yield 92% ee quantitative yield >99% ee (best substrates) quantitative yield >96% ee 97% yield 92% ee <1% yield 30% ee R O RuX2[(R)-binap] 0.1 mol% EtOH, H2 (50-100 atm), rt May pre-coordinate to the Ru center via a 6-membered ring chelate R OH (R) X X OH OH quantitative yield 98% ee OH <1% yield 74% ee RuX2[(S)-binap] gives the (S) enantiomer Noyori JACS 1987 (109) 5856 Noyori JACS 1988 (110) 629. Note: opposite sense of stereoinduction
M C. White. Chem 153 Hydrogenation -170- Week of octo ber 21. 2002 Noyori substrate-directed ketone hydrogenation: mechanism Rux2l(Rp-binapl 0 1 mol the ru center via a EtOH, H2(50-100 atm),rt 6-membered ring chelate 2 eq HX(X=Cl, Br, D) Rux2l(R)-binapl RuHXI(R)binal Ru(ln) monohydric
P Ph2 Ru(II) Ph2 P O O O O 2 eq HX (X= Cl, Br, I) RuX2[(R)-binap] molecular weight unknown R O RuX2[(R)-binap] 0.1 mol% EtOH, H2 (50-100 atm), rt May pre-coordinate to the Ru center via a R 6-membered ring chelate OH (R) X X HCl H2 RuHX[(R)-binap] Ru(II) monohydride O O R O P Ru P H X * O O R O P Ru P H X * O O R O P Ru P X * H H2 R OH X (R) M.C. White, Chem 153 Hydrogenation -170- Week of October 21, 2002 Noyori substrate-directed ketone hydrogenation: mechanism