Chiral Olefins as Ligands for Asymmetric Catalysis M Hui-Wen Shih Group Meeting April 20, 2011 Johnson, J. B.; Rovis, T. Angew. Chem., Int. Ed. 2008, 47, 840. Defieber, C.; Grutzmacher, H.; Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482. A Brief History ! 1827: Zeise reports first metal-olefin complex H H K H H Cl Pt Cl Cl Zeise's salt ! 1962: Cope prepares the first chiral olefin H H Cl Cl H Pt racemic Pt H Cl NH Cl NH fractional Me Ph crystallization Me Ph Zeise, W. C. Poggendorffs Ann. Phys. 1827, 9, 632. Cope, A. C.; Howell, C. F.; Knowles, A. J. Am. Chem. Soc. 1962, 84, 3191. A Brief History ! 1981: Hosokawa and Murahashi develop catalytic asymmetric reaction with chiral allyl ligand Me Me OAc Pd Me 2 O OH Cu(OAc)2, O2, MeOH ! 2003: Field begins to accelerate with Hayashi's report of chiral diene ligands in rhodium catalysis 3.2 mol% Bn O O 2 Bn R R B(OH)2 R 1.5 mol% [RhCl(C2H4)2]2 R1 R2 R1 Hosokawa, T.; Uno, T.; Inui, S.; Murahashi, S.-I. J. Am. Chem. Soc. 1981, 103, 2318. Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11509. Metal-Olefin Binding ! Dewar!Chatt!Duncanson model M M # donation $ back-donation Metal-olefin bond strength is determined by $ back-bonding Back-donation increases with metal principle quantum number ! Comparison of ligand binding energies, "Eint ! "Eint HAu L HAu* L* H H H H Me Me N C O HAu P HAu C HAu HAu HAu N Me HAu Me Me Me N H H H H 26.6 27.6 29.9 34.2 43.8 52.7 Defieber, C.; Grutzmacher, H.; Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482. Metal-Olefin Binding ! Olefins have large preparation energies for binding ! "Eint "Eprep XnM L XnM L* L* double bond elongation "Eprep sp2 to sp3 rehybridization ! Factors that affect binding strength strain release > > > entropy O O O substituent electronics > CN > Ph > n-Bu CO2Me sterics > CO2Me Hartley, F. R. Chem. Rev. 1973, 73, 163. Tolman, C. A. J. Am. Chem. Soc. 1974, 96, 2780. Defieber, C.; Grutzmacher, H.; Carreira, E. M. Angew. Chem., Int. Ed. 2008, 47, 4482. Classes of Chiral Olefins M M !-allyl diene P N M M phosphane-olefin amine-olefin Classes of Chiral Olefins M M !-allyl diene P N M M phosphane-olefin amine-olefin Chiral Allyl Ligands ! 1981: First catalytic asymmetric reaction (Hosokawa and Murahashi, Osaka University) Me Me OAc Pd Me 2 O OH Cu(OAc)2, O2 or t-Bu-OOH MeOH 64% Y, 18% ee 43% Y, 17% ee MeO Me Cl MeOC O O O O 37% Y, 26% ee 63% Y, 21% ee 65% Y, 6% ee 71% Y, 1% ee 16% Y, 22% ee 28% Y, 18% ee 47% Y, 5% ee 38% Y, 0.1% ee Hosokawa, T.; Okuda, C.; Murahashi, S.-I. J. Org. Chem. 1985, 50, 1282. Hosokawa, T.; Uno, T.; Inui, S.; Murahashi, S.-I. J. Am. Chem. Soc. 1981, 103, 2318. Chiral Allyl Ligands ! 1981: First catalytic asymmetric reaction (Hosokawa and Murahashi, Osaka University) Me Me OAc Pd Me 2 O OH Cu(OAc)2, O2 or t-Bu-OOH MeOH 64% Y, 18% ee 43% Y, 17% ee Me Me Me Pd Me H Me OAc Pd 2 HO Me OH LPdII LPd-OH Me O LPd-H Hosokawa, T.; Okuda, C.; Murahashi, S.-I. J. Org. Chem. 1985, 50, 1282. Hosokawa, T.; Uno, T.; Inui, S.; Murahashi, S.-I. J. Am. Chem. Soc. 1981, 103, 2318. Chiral Allyl Ligands ! 1981: First catalytic asymmetric reaction (Hosokawa and Murahashi, Osaka University) Me Me OAc Pd Me 2 O OH Cu(OAc)2, O2 or t-Bu-OOH MeOH 64% Y, 18% ee 43% Y, 17% ee Me Me Me Me Me Me Pd Me H 1 Pd O 1 Me H HO Ph Modified catalyst Me sits in space under C-1 bridgehead Phenoxy coordination Phenyl blocks space under C-1 olefin is trans to ligand generates opposite enantiomer no enantioselectivity attack occurs from back face Hosokawa, T.; Okuda, C.; Murahashi, S.-I. J. Org. Chem. 1985, 50, 1282. Hosokawa, T.; Uno, T.; Inui, S.; Murahashi, S.-I. J. Am. Chem. Soc. 1981, 103, 2318. Chiral Allyl Ligands ! Yamamoto: Pd-allyl complexes for enantioselective allylation Cl Pd 2 R1 X R1 N 5 mol% HN X SnBu3 Me R H THF or DMF, 0 oC R Bn Ph Pr Bn HN HN HN HN Ph Ph Ph c-hex 62% Y, 81% ee 74% Y, 0% ee 62% Y, 70% ee 64% Y, 40% ee Bn Bn Bn Bn HN CO2Me HN CO2Me HN CO2Me HN CO2Me Ph c-hex 2-Nap S 81% Y, 82% ee 63% Y, 60% ee 69% Y, 88% ee 77% Y, 69% ee Fernandes, R. A.; Yamamoto. Y. J. Org. Chem. 2004, 69, 3562. Nakamura, H.; Nakamura, K.; Yamamoto., Y. J. Am. Chem. Soc. 1998, 120, 4242. Chiral Allyl Ligands ! Yamamoto: Pd-allyl complexes for enantioselective allylation Cl Pd 2 SnBu R1 3 R1 N HN 5 mol% Me SiMe R H 3 o R H2O, THF, 0 C TBAF Bn Bn HN HN Ph c-hex N N H H 86% Y, 85% ee 84% Y, 50% ee 63% Y, 18% ee 77% Y, 7% ee Bn Bn Bn HN HN HN HN Ph c-hex Ph 4-pyr 86% Y, 91% ee 86% Y, 52% ee 83% Y, 84% ee 98% Y, 67% ee Fernandes, R. A.; Yamamoto. Y. J. Am. Chem. Soc. 2004, 69, 735. Fernandes, R. A.; Yamamoto., Y. J. Am. Chem. Soc. 2003, 125, 14133. Chiral Allyl Ligands ! Yamamoto: Pd-allyl complexes for enantioselective allylation Cl Pd 2 SnBu R1 3 R1 N HN 5 mol% Me SiMe R H 3 o R H2O, THF, 0 C TBAF Me Me Me Me Me Me Me Me favored disfavored no stereochemical Me Me Pd Me Me Pd Pd bias Pd R N R N N H H N Bn Bn trans-imine Bn cis-imine Bn H H R R Fernandes, R. A.; Yamamoto., Y. J. Am. Chem. Soc. 2003, 125, 14133. Classes of Chiral Olefins M M !-allyl diene P N M M phosphane-olefin amine-olefin Chiral Diene Ligands ! Classes of Chiral Diene Ligands F F F R R F R R R nbd bnd bdd bod R tfb Hayashi Hayashi Hayashi Hayashi Hayashi Me OMe Ph Me OMe Ph R1 Me Ph R Me cod cod Hayashi Carreira Carreira Grützmacher Ar Ar H O MsHN NHMs Me Me H Ar O tetrahydropentalenes Ar Xu, Lin, Laschat Du Du Trauner Rhodium-Catalyzed 1,4-Additions ! Hayashi's Seminal Publication Bn O 3.2 mol% O Bn PhB(OH)2 1.5 mol% [RhCl(C2H4)2]2 Ph o KOH, dioxanes/H2O, 30 C 94% Y, 96% ee O O O O 4-OMeC6H4 2-Np 4-CF3C6H4 n-C5H11 89% Y, 95% ee 96% Y, 96% ee 90% Y, 99% ee 73% Y, 88% ee O O O O Me i-PrO Ph Ph i-Pr Ph i-Pr Ph 88% Y, 88% ee 81% Y, 90% ee 81% Y, 97% ee 73% Y, 92% ee Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508. Rhodium-Catalyzed 1,4-Additions ! Hiyashi's Seminal Publication Bn O 3.2 mol% O Bn PhB(OH)2 1.5 mol% [RhCl(C2H4)2]2 Ph o KOH, dioxanes/H2O, 30 C 94% Y, 96% ee ! Norbornadiene ligands are C2-symmetric Bn Ph Bn O Rh O O Ph Rh Bn Rh Ph Ph Bn Ph favored disfavored higher catalytic activity O O better reactivity compared to phosphine ligands Ph Ph Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508. Rhodium-Catalyzed 1,4-Additions ! Catalytic cycle H O [Rh] [Rh] O H catalyst resting state 2 -1 Kdimer = 3.8 x 10 M OH [Rh] sol O PhB(OH)2 Ph rate insertion/hydrolysis [Rh(OH)(cod)] transmetallation 2 det. -1 -1 -1 -1 K1 = 16 M s catalyst step K1 = 6.7 M s O B(OH) H2O 3 Ph [Rh] sol Kina, A.; Yasuhara, Y.; Nishimura, T.; Iwamura, H.; Hayashi, T. Chem. Asian J. 2006, 1, 707. Rhodium-Catalyzed 1,4-Additions ! Comparison of reaction kinetics: diene vs. phosphine ligand H O OH transmetallation Ph insertion/ OH [Rh] [Rh] [Rh] [Rh] [Rh] O sol sol sol H hydrolysis catalyst resting state active catalyst 2 -1 -1 -1 -1 -1 [Rh(OH)(cod)]2 Kdimer = 3.8 x 10 M K1 = 6.7 M s K2 = 16 M s 2 -1 -1 -1 [Rh(OH)(binap)]2 Kdimer = 8 x 10 M K1 = 0.5 M s [Rh(OH)(cod)]2 equilibrium content of active catalyst is higher transmetallation occurs faster [Rh(OH)(cod)]2 is 20 times more reactive Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002, 124, 5052. Kina, A.; Yasuhara, Y.; Nishimura, T.; Iwamura, H.; Hayashi, T. Chem. Asian J. 2006, 1, 707. Rhodium-Catalyzed 1,4-Additions: Catalyst Loading ! Catalyst loading can be decreased significantly 3.3 mol% Bn O Bn O (S,S)-Bn-bod) PhB(OH)2 1.5 mol% [RhCl(C2H4)2]2 Ph Benchmark PhB(OH)2 catalyst (mol% Rh) yield (%) ee (%) PhB(OH)2 1.0 quant 96 PhB(OH)2 0.1 quant 96 PhB(OH)2 0.05 79 96 PhB(OH) 0.01 0 -- impurity in boronic acid 2 deactivates catalyst (PhBO)3 0.01 quant 96 (PhBO)3 0.005 71 96 Chen, F.-X.; Kina, A.; Hayashi, T.