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. Org. Lett. 2006, 8, 341. Rhodium-Catalyzed 1,4-Additions
! Carreira independently reports Rh-catalyzed 1,4 addition with C1-symmetric ligand
3.3 mol% Me OMe
O Me O
Me Me PhB(OH)2 1.5 mol% [RhCl(C2H4)2]2 Ph o KOH, dioxanes/H2O, 25 C 87% Y, 95% ee
O O O O
4-OMeC H 4-COMeC H Ph 6 4 6 4 Ph 85% Y, 96% ee 96% Y, 97% ee 91% Y, 94% ee 81% Y, 95% ee
Ph O Me O Ph O Ph
Me Ph Ph2N Me MeO Me O O 43% Y, 98% ee 68% Y, 89% ee 98% Y, 93% ee 93% Y, 88% ee
Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E. Org. Lett. 2004, 6, 3873. Rhodium-Catalyzed 1,4-Additions
! Carreira independently reports Rh-catalyzed 1,4 addition with C1-symmetric ligand
3.3 mol% Me OMe
O Me O
Me Me PhB(OH)2 1.5 mol% [RhCl(C2H4)2]2 Ph o KOH, dioxanes/H2O, 25 C 87% Y, 95% ee
! Ligand modification gives insight in catalyst binding
Me OMe
Me Me OMe OMe Me OMe Me Me
Me Me Me Me t-Bu
52% Y, 71% ee 93% Y, 58% ee < 10% conversion 87% Y, 95% ee
Rigid diene structure required for activity
Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E. Org. Lett. 2004, 6, 3873. Rhodium-Catalyzed 1,4-Additions: Ligand Development
! Fumaric compounds are amenable to transformation
3.2 mol% Mes
O Mes O Ph Ot-Bu PhB(OH) Ot-Bu t-BuO 2 t-BuO O 1.5 mol% [RhCl(C2H4)2]2 O o KOH, dioxanes/H2O, 50 C 90% Y, 90% ee
! Diene ligands are more selective than traditional ligands
OMe
O N
O O PPh2 PPh2 MeO PPh2 P NEt2 PPh2 O PPh2 MeO PPh2 O N O
OMe (R)-binap (R)-segphos (S)-P-phos (S)-phosphoramidite 96% Y, 21% ee 99% Y, 3% ee 94% Y, 13% ee 50% Y, 32% ee
Shintani, R.; Ueyama, K.; Yamada, I.; Hayashi, T. Org. Lett. 2004, 6, 3425. Rhodium-Catalyzed 1,4-Additions: Expansion of Scope
! Malemide compounds are amenable to transformation
3.2 mol% Mes O O Mes
N Cy ArB(OH)2 N Cy Ar 1.5 mol% [RhCl(C2H4)2]2 O o O KOH, dioxanes/H2O, 50 C 77-95% Y, 82-92% ee
! Diene ligands and phosphine ligand display orthogonal reactivity
O O O Ph 2.75 mol% ligand N Bn N Cy PhB(OH)2 Et N Cy Et 1.25 mol% [RhCl(C2H4)2]2 Ar Et O O O
(R)-Binap 85% 15%
Ph 10% 84% Ph
Shintani, R.; Ueyama, K.; Yamada, I.; Hayashi, T. Org. Lett. 2004, 6, 3425. Shintani, R.; Duan, W.-L.; Hayashi, T. J. Am. Chem. Soc. 2006, 128, 5628. Rhodium-Catalyzed 1,4-Additions: Ligand Development
! Benchmark reaction: Phenyl boronic acid 1,4-addition to cyclohexenone
O O 3 mol% diene ligand PhB(OH)2 1.5 mol% [RhCl(C2H4)2]2 Ph
! Hayashi's C2-symmetric ligands
Bn Bn Ph Ph Ph
Bn Ph Bn Ph Ph
90% Y, 95% ee 89% Y, 97% ee 97% Y, 95% ee 93% Y, 83% ee 98% Y, 90% ee not stable to air/light stable
Otomaru, Y.; Kina, A.; Shintani, R.; Hayashi, T. Tetrahedron: Asymmetry 2005, 16, 1673. Otomaru, Y.; Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem. 2005, 70, 2503. Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508. Rhodium-Catalyzed 1,4-Additions: Ligand Development
! Benchmark reaction: Phenyl boronic acid 1,4-addition to cyclohexenone
O O 3 mol% diene ligand PhB(OH)2 1.5 mol% [RhCl(C2H4)2]2 Ph 98% Y, 99% ee
! Hayashi's state of the art ligand
F
F F Ligand can be synthesized in 3 steps
F R High reactivity High selectivity R
R = (!)-menthol pre-catalyst
Nishimura, T.; Nagaosa, M.; Hayashi, T. Chem. Lett. 2008, 37, 860. Rhodium-Catalyzed 1,4-Additions: Ligand Development
! Benchmark reaction: Phenyl boronic acid 1,4-addition to cyclohexenone
O O 3 mol% diene ligand PhB(OH)2 1.5 mol% [RhCl(C2H4)2]2 Ph
! Prochiral ligands
R R R
R R R R S R S cyclooctatetraene cyclooctadiaene
Ph Ph ligand dissociates and racemizes Ph 90% Y, 43% ee 92% Y, 62% ee Using PhZnCl (fast) 89% Y, 81% ee Grützmacher Hayashi
Kina, A.; Ueyama, K.; Hayashi, T. Org. Lett. 2005, 7, 5889. Läng, F.; Breher, F.; Stein, D.; Grützmacher, H. Organometallics 2005, 24, 2997. Rhodium-Catalyzed 1,4-Additions: Ligand Development
! Benchmark reaction: Phenyl boronic acid 1,4-addition to cyclohexenone
O O 3 mol% diene ligand PhB(OH)2 1.5 mol% [RhCl(C2H4)2]2 Ph
! Other ligands under development
Ph H Me MsHN NHMs n-Bu TsN H Ph
95% Y, 88% ee 96% Y, 91% ee 89% Y, 91% ee 96% Y, 95% ee Laschat Xu and Lin Yu Du
Easy to synthesize Obtained from Rh allylic C-H Binding occurs through olefin Norbornadiene mimics activation/conjugated diene addn Complex has fast coordination/dissociation
Li, Q.; Dong, Z.; Yu, Z.-X.; Org. Lett. 2011, 13, 1122. Wang, Y.; Hu, X.; Du, H. Org. Lett. 2010, 12, 5482. Feng, C.-G.; Wang, Z.-Q.; Tian, P.; Xu, M.-H.; Lin, G.-Q. Chem. Asian J. 2008, 3, 1511. Helbig, S.; Sauer, S.; Cramer, N.; Laschat, S.; Baro, A.; Frey, W. Adv. Synth. Catal. 2007, 349, 2331. Rhodium-Catalyzed 1,4-Additions: Expansion of Scope
! 1,4-Addition into aldehydes 3.3 mol% Bn O O Ar
ArB(OH)2 Bn H R H R 1.5 mol% [RhCl(C2H4)2]2 83-95% Y, 88-97% ee R = alkyl, aryl Ar = e! rich, neutral, e! poor ! 1,4-Addition into cinnamaldehydes MeO Me
Bn
O 3.3 mol% O Ar1 Me Ar2B(OH) i-Bu H Ar1 2 H Ar2 1.5 mol% [RhCl(C2H4)2]2 63-90% Y, 89-93% ee Ar1,2 = e! rich, neutral, e! poor ! 1,1-Diarylethanes via one-pot addition/decarbonylation
O CH3 1.5 mol% [RhCl(diene]2 4-MeOC6H4B(OH)2 H Ph then [{Rh(cod)Cl}2], dppp OMe 71% Y, 93% ee
Hayashi, T.; Tokunaga, N.; Okamoto, K.; Shintani, R. Chem. Lett. 2005, 34, 1480. Paquin, J.-F.; Defieber, C.; Stephenson, C. R. J.; Carreira, E. M. J. Am. Chem. Soc. 2005, 127, 10850. Fessard, T. C.; Andrews, S. P.; Motoyoshi, H.; Carreira, E. M. Angew. Chem. Int. Ed. 2007, 46, 9331. Rhodium-Catalyzed 1,4-Additions: Expansion of Scope
! 1,4-Addition into esters MeO Me
Bn 3.3 mol% O O Ar2 2 Me i-Bu Ar B(OH)2 t-BuO Ar1 t-BuO Ar1 1.5 mol% [RhCl(C2H4)2]2 62-95% Y, 89-93% ee Ar1,2 = e! rich, neutral, e! poor Ar1 includes heteroaromatics ! 1,4-Addition into Weinreb amides 3.3 mol% Bn O O Ar Me ArB(OH) Bn Me N R 2 N R OMe 1.5 mol% [RhCl(C2H4)2]2 OMe 83-92% Y, 80-92% ee R = alkyl, aryl Ar = e! rich, neutral ! 1,4-Addition into "-silyl carbonyls 3.3 mol% Bn O O Ar ArB(OH)2 RO SiMe Ph Bn 2 RO SiMe2Ph
1.5 mol% [RhCl(C2H4)2]2 89-96% Y, 93-99% ee R = alkyl, aryl Ar = e! rich, neutral, e! poor Shintani, R.; Kimura, T.; Hayashi, T. Chem. Comm. 2005, 3213. Paquin, J.-F.; Stephenson, C. R. J.; Defieber, C.; Carreira, E. M. Org. Lett. 2005, 7, 3821. Shintani, R.; Okamoto, K. Hayashi, T. Org. Lett. 2005, 7, 4757. Rhodium-Catalyzed 1,4-Additions: Expansion of Scope
F ! 1,4-Addition into N-phthalimides F F
diene*= O F R O Ar ArB(OH)2 RO NPhth RO NPhth R R = 2,6-dimethylphenyl 81-99% Y, 93-99% ee 1.5 mol% [RhCl(diene*)2]2 Ar = e! rich, neutral, e! poor, vinyl ! 1,4-Addition to form quaternary centers Me O
O Me O diene*= Ph Ar4BNa O-2Np R
R Me 83-92% Y, 80-92% ee linear and cyclic carbonyls 2.5 mol% [RhCl(diene*)2]2 R = Me, Et, CO2Me Ar = e! rich, neutral ! 1,4-Alkynylation of cyclic enones Bn O O 6 mol% HO Bn Si SiiPr i-Pr 3 i-Pr 5 mol% [RhCl(C2H4)2]2 SiiPr 91% Y, 86% ee 3
Nishimura, T.; Tokuji, S.; Sawano, T.; Hayashi, T. Org. Lett. 2009, 11, 3222. Shintani, R.; Tsutsumi, Y.; Nagaosa, M.; Nishimura, T.; Hayashi, T. J. Am. Chem. Soc. 2009, 131, 13588. Nishimura, T.; Wang, J. Nagaosa, M.; Okamoto, K.; Shintani, R.; Kwong, F.-Y.; Yu, W.-Y. Chan, A. S. C.; Hayashi, T. J. Am. Chem. Soc. 2010, 132, 464. Rhodium-Catalyzed 1,2-Additions
! Seminal publication: Hayashi, 2004
Ph Ts Ts N diene* = HN
Ph H Ph (PhBO)3 Cl 1.5 mol% [RhCl(diene*)2]2 Cl
challenging with phosphine ligands 96% Y, 98% ee benchmark reaction
! Scope
Ts Ts Ts Ts HN HN HN HN
Ph Ph Ph Ph O MeO F3C Me2N
97% Y, 95% ee 96% Y, 99% ee 94% Y, 98% ee 99% Y, 99% ee
Ts Ts Ts HN HN HN
Cl Me OMe
99% Y, 99% ee 96% Y, 99% ee 97% Y, 96% ee
Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584. Rhodium-Catalyzed 1,2-Additions
! Seminal publication: Hayashi, 2004
Bn Ts Ts N diene* = HN
Bn H Ph (PhBO)3 Cl 1.5 mol% [RhCl(diene*)2]2 Cl
challenging with phosphine ligands 96% Y, 98% ee benchmark reaction
! Stereochemical model
Ph Ph Ph Ts Rh Ar Rh Ts N Ph N Ph Ar Ph Rh Ph H H Ph N H Ph Ar Ts favored disfavored
Ts Ts HN High enantioselectivity HN
Ph results from Ts and Ar in Ph unsubstituted quadrants Cl Cl
Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584. Rhodium-Catalyzed 1,2-Additions
! Benchmark reaction: 1,2 Ts- and Ns-imine addition
R R N HN 1.5 mol% [RhCl(diene*)2]2 H Ph (PhBO)3 Cl Cl R = Ts, Ns R = Ts, Ns
! Ligand development and survey
Me
Ph Ph Bn Ph Me O Ts O-2,6(Me)2Ar Ph Ph Bn Ph Me 95% Y, 99% ee 88% Y, 94% ee 98% Y, 92% ee 96% Y, 99% ee 98% Y, 98% ee
Me
Ph Ph Bn Ph Me O Ns O-2,6(Me) Ar Ph Ph 2 Bn Ph Me 96% Y, 98% ee 99% Y, 90% ee 88% Y, 81% ee 92% Y, 99% ee 96% Y, 99% ee
Otomaru, Y.; Hayashi, T.; Rawal, V. H. Chem. Comm. 2009, 4815. Otomaru, Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005, 7, 307. Otomaru, Y.; Kina, A.; Shintani, R.; Hayashi, T. Tetrahedron: Asymmetry 2005, 16, 1673. Rhodium-Catalyzed 1,2-Additions
! Benchmark reaction: 1,2 Ts- and Ns-imine addition
R R N HN 1.5 mol% [RhCl(diene*)2]2 H Ph (PhBO)3 Cl Cl R = Ts, Ns R = Ts, Ns
! Ligand effects on rate: electron deficient ligand (1a) accelerates transmetallation
Me Bn Me O
Bn O-2,6(Me)2Ar
3b: 98% Y, 92% ee Me 1a: 98% Y, 98% ee
Ph Ph
Ph Ph
3a: 96% Y, 99% ee 5: 95% Y, 99% ee
Otomaru, Y.; Hayashi, T.; Rawal, V. H. Chem. Commun. 2009, 4815. Otomaru, Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005, 7, 307. Otomaru, Y.; Kina, A.; Shintani, R.; Hayashi, T. Tetrahedron: Asymmetry 2005, 16, 1673. Rhodium-Catalyzed 1,2-Additions
! Benchmark reaction: 1,2 Ts- and Ns-imine addition
R R N HN 1.5 mol% [RhCl(diene*)2]2 H Ph (PhBO)3 Cl Cl R = Ts, Ns R = Ts, Ns
! Ligand development and survey
Ph H OMe Ts
H SO2NMe2 Ph HN 81% Y, 99% ee
Ph H OMe
Ns 82% Y, 84% ee OMe H Ph Du 94% Y, 99% ee
Lin Cao, Z.; Du, H. Org. Lett. 2010, 12, 2602. Wang, L.; Wang, Z.-Q.; Xu, M.-H.; Lin, G.-Q. Synthesis 2010, 3263. Wang, Z.-Q.; Feng, C.-G.; Xu, M.-H.; Lin, G.-Q. J. Am. Chem. Soc. 2007, 129, 5336. Rhodium-Catalyzed 1,2-Additions
! 1,2-Addition into aldehydes F F F
diene* = F Fc O OH Fc H Ph (PhBO)3
1.5 mol% [RhCl(diene*)2]2 95% Y, 86% ee ! Reaction scope
OMe OH OH OH OH
Ph Ph Ph Ferrocenyl Ph
Me Br 99% Y, 85% ee 99% Y, 78% ee 85% Y, 78% ee 94% Y, 85% ee
OH OH OH OH
2-ClC H Mes 2-OMeC6H4 4-MeC6H4 6 4
97% Y, 85% ee 90% Y, 85% ee 91% Y, 86% ee 87% Y, 94% ee
Nishimura, T.; Kumamoto, H.; Nagaosa, M.; Hayashi, T. Chem. Commun. 2009, 5713. Carborhodation with Chiral Diene Ligands
! Rhodium-catalyzed addition/cyclization
7.5 mol% Bn BnO Me Me H Bn BnO Ph BnO PhB(OH)2 O 3.5 mol% [RhCl(C2H4)2]2 BnO OH KOH, dioxanes/H2O 60 oC 89% Y, 94% ee
! Catalytic cycle product [Rh]-OH PhB(OH) hydrolysis 2 transmetallation H2O B(OH)3 Me
BnO Ph [Rh]-Ph BnO O[Rh] BnO Me Me H cyclization Ph addition BnO BnO O [Rh] BnO O Shintani, R.; Okamoto, K.; Otomaru, Y.; Ueyama, K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54. Carborhodation with Chiral Diene Ligands
! Rhodium-catalyzed addition/cyclization into alkynes 5 mol% Bn O OH R H Bn
Me R B(OH)2 2.5 mol% [RhCl(C2H4)2]2 Me R=C(Me)(CO2Me)2 KOH, dioxanes/H2O 35 oC 97% Y, 81% ee
! Rhodium-catalyzed addition/cyclization into alkenes
F F F 10 mol%
F O OSiPh3 OH
H Ph3SiO n-hex n-hex
BF3K 5 mol% [IrCl(coe)2]2 o Et3N, PhMe/H2O, 60 C 83% Y, 93% ee
Shintani, R.; Okamoto, K.; Hayashi, T. Chem. Lett. 2005, 34, 1416. Nishimura, T.; Yasuhara, Y.; Nagaosa, M.; Hayashi, T. Tetrahedron: Asymmetry 2008, 17, 1778. Carborhodation with Chiral Diene Ligands
! Rhodium-catalyzed addition/cyclization 7.5 mol% Bn Et MeO2C Et Bn MeO C PhB(OH) 2 Ph MeO2C 2 CO Me CO Me 3.5 mol% [RhCl(C2H4)2]2 2 2 MeO2C KOH, dioxanes/H2O 60 oC 93% Y, 99% ee
! Rh/diene catalysts favor alkyne arylation over 1,4-addition
MeO2C Me MeO2C Et
MeO2C MeO2C Me CO2Me
[Rh] PhB(OH)2 [Rh] PhB(OH)2
Et MeO2C Me Ph Ph MeO2C MeO2C
CO2Me MeO2C Me Binap 76% < 3% (rec SM) cod 81% 80%
Shintani, R.; Tsurusaki, A.; Okamoto, K.; Hayashi, T. Angew. Chem. Int. Ed. 2005, 44, 3909. Carborhodation with Chiral Diene Ligands
! Rhodium-catalyzed addition/cyclization 7.5 mol% Bn Et MeO2C Et Bn MeO C PhB(OH) 2 Ph MeO2C 2 CO Me CO Me 3.5 mol% [RhCl(C2H4)2]2 2 2 MeO2C KOH, dioxanes/H2O 60 oC 93% Y, 99% ee
! Rh/diene catalysts favor alkyne arylation over 1,4-addition
MeO2C Me MeO2C Et
MeO2C MeO2C Me CO2Me
[Rh] PhB(OH)2
Et MeO2C Me Ph Ph MeO2C MeO2C
CO2Me MeO2C Me
cod 7% 76%
Shintani, R.; Tsurusaki, A.; Okamoto, K.; Hayashi, T. Angew. Chem. Int. Ed. 2005, 44, 3909. Carborhodation with Chiral Diene Ligands
! Rhodium-catalyzed [4+2]
Ph diene* = Ph MeO C Ph 2 Me Ph MeO2C
MeO2C Me 2.5 mol% [RhCl(diene*)2]2 MeO2C o H AgSbF6, CH2Cl2, 25 C 87% Y, 94% ee
! Catalytic cycle
product MeO2C Ph [RhI] reductive elimination MeO2C Me coordination Ph
RhIII MeO C Ph MeO2C 2 Me RhI MeO C 2 MeO2C Me H Ph 1,3 allyl migration oxidative cyclization MeO2C RhIII
MeO2C H
Me
Shintani, R.; Sannohe, Y.; Tsuji, T; Hayashi, T. Angew. Chem. Int. Ed. 2007, 46, 7277. Carborhodation with Chiral Diene Ligands
! Rhodium-catalyzed cyclopropanation
MeO C CO Me O O 2 mol% [RhCl(diene*)2]2 2 2
Ph MeO OMe F o NaBAR 4, PhMe, 40 C Ph N2 86% Y, 89% ee
! Rh/diene catalyst
F
F F
i-Pr2N O F
Rh O Cl Ni-Pr2
Nishimura, T.; Maeda, Y.; Hayashi, T. Angew. Chem. Int. Ed. 2010, 49, 7324. Chiral Dienes in Resolutions
! Carreira's seminal publication: kinetic resolution of allyl carbonates
Me OMe
Me
3.6 mol% OCO2Me OCO2Me OPh t-Bu R R R 1.5 mol% [IrCl(COE)2]2 28-46% Y, 80-98% ee 0.5 equiv PhOH
! Resolution of BIPHEP MeO Me OH Me Ar MeO Ph Ph Me Me PPh2 P Rh PPh2 diene* = Me P 57% Y, 12% ee Ph Ph t-Bu hydroboration of styrene [RhCl(diene*)2]2 racemizes at room temp
Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E. J. Am. Chem. Soc. 2004, 126, 1628. Faller, J. W.; Wilt, J. C. J. Organomet. Chem. 2006, 691, 2207. Chiral Dienes in Suzuki!Miyaura Coupling
! First enantioselective reaction employing Pd-diene catalyst
Ph H
diene* =
H Ph Me Me 5 mol% Pd(diene*)Cl Br B(OH)2 2 15 mol% diene* Cs2CO3, PhMe, rt 78% Y, 90% ee
! Scope
MeO MeO
Me Me CHO BnO Me PMBO Me Me Me
90% Y, 84% ee 90% Y, 73% ee 93% Y, 65% ee 83% Y, 65% ee 72% Y, 48% ee
Zhang, S.-S.; Wang, Z.-Q.; Xu, M.-H.; Lin, G.-Q. Org. Lett. 2010, 12, 5546. Classes of Chiral Olefins
M M
!-allyl diene
P N M M phosphane-olefin amine-olefin Chiral Phosphane-Olefin Ligands
! Hybrid ligands combine advantages of phosphanes and olefins
good chiral environment strong coordination ability P about metal M
! Classes of chiral phosphane-olefin ligands
PPh2 PPh2 O Ph P N R PPh O
Grützmacher Hayashi Carreira Widhalm
OEt Me O OTr PPh2 Fe PPh2 Re PPh2 OC CO Me O OC Ph2PO Du Stepnicka Bolm Boysen Chiral Phosphane-Olefin Ligands
! Phosphane-olefin ligands also participate in 1,4-additions
PPh2
O ligand = O
Ph PhB(OH)2
[RhCl(ligand)]3 (5 mol% Rh) Ph o KOH, dioxanes/H2O, 50 C 94% Y, 93% ee
! Reactivity is similar to diene ligand
[Rh] trimer
catalyst OH O [Rh] sol
[Rh(OH)(cod)]2 PhB(OH)2 Ph rate insertion/hydrolysis det. transmetallation O step
B(OH)3 H2O Ph [Rh] sol Duan, W.-L.; Iwamura, H.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2007, 129, 2130. Chiral Phosphane-Olefin Ligands
! Wilhalm's ligand improves reactivity/selectivity
Ph O O P Ph
Ph PhB(OH) 88% Y, 98% ee 2 0.5 mol% [RhCl(ligand)]2 o KOH, dioxanes/H2O, 50 C
! Tropp ligands are versatile
O
Ph2P O
Ph
Ph PhB(OH) > 85% conv, 95% ee 2 5 mol% [Rh(OH)2(ligand)2] o KOH, dioxanes/H2O, 50 C
Kasak, P.; Arion, V. B.; Widhalm, M. Tetrahedron: Asymmetry 2006, 17, 3084. Piras, E.; Lang, F.; Ruegger, H.; Stein, D.; Worle, M.; Grutzmacher, H. Chem. Eur. J. 2006, 12, 5849. Chiral Phosphane-Olefin Ligands
! Hemilability of tropp ligand facilitates hydrogenation
Ph2P menthol Ph O Ph N NH
Ph Me Ph Me [Ir(tropp)(cod)]OTf, H2 > 98% Y, 86% ee
! Olefin hydrogenation
Ph2P O O Ph MeO Me MeO MeO MeO O O 0.01 mol% [Ir(ligand)2]OTf > 85% conv, 60% ee H2, CH2Cl2
Maire, P.; Deblon, S.; Breher, F.; Geier, J.; Bohler, C.; Ruegger, H.; Schonberg, H.; Grutzmacher, H. Chem. Eur. J. 2004, 10, 4198. Piras, E.; Lang, F.; Ruegger, H.; Stein, D.; Worle, M.; Grutzmacher, H. Chem. Eur. J. 2006, 12, 5849. Chiral Phosphane-Olefin Ligands
! Hemilability of tropp ligand facilitates hydrogenation
P P Ir pre-catalyst is bound to P and olefin
3 H2 hydrogenation is reversible
P H H tropp ligand is hydrogenated L Ir in active catalyst P L X H2
Y
P L P H Ir X H L P Ir Y P
Maire, P.; Deblon, S.; Breher, F.; Geier, J.; Bohler, C.; Ruegger, H.; Schonberg, H.; Grutzmacher, H. Chem. Eur. J. 2004, 10, 4198. Piras, E.; Lang, F.; Ruegger, H.; Stein, D.; Worle, M.; Grutzmacher, H. Chem. Eur. J. 2006, 12, 5849. Chiral Phosphane-Olefin Ligands
! Pd-allyl chemistry is now also possible
MeO2C CO2Me OAc O O [PdCl(allyl)]2
Ph Ph MeO OMe Ph Ph
Ph PPh2 Me O OEt PPh2 OTr Fe PPh2 Ph Me O Ph2PO Ph
98% Y, 95% ee 87% Y, 96% ee 100% Y, 43% ee 90% Y, 61% ee
Liu, Z.; Du, H. Org. Lett. 2010, 12, 3054. Minuth, T.; Boysen, M. M. K. Org. Lett. 2009, 11, 4212. Kasak, P.; Arion, W. B.; Widhalm, M. Tetrahedron: Asymmetry 2006, 17, 3084. Shintani, R.; Duan, W.-L.; Okamoto, K.; Hayashi, T. Tetrahderon: Asymmetry 2005, 16, 3400. Chiral Phosphane-Olefin Ligands
! Carreira demonstrates allylic amination with Ir/P-olefin system
O OH P N O NH3Cl
6 mol%
H NSO 3 mol% [IrCl(coe) ] 3 3 2 2 70% Y, 70% ee DMF, rt ! Stereoretentive allylic amination
OH conditions NH3Cl
H3NSO3 R R see above
46-70% Y, 74-98% enantio-retention
Roggen, M.; Carreira, E. M. J. Am. Chem. Soc. 2010, 132, 11917. Defieber, C.; Ariger, M. A.; Moriel, P.; Carreira, E. M. Angew. Chem. Int. Ed. 2007, 46, 3139. Chiral Phosphane-Olefin Ligands
! Carreira demonstrates allylic amination with Ir/P-olefin system
Me Me N
R O H IrIII Me Me N NH3
O H
SO3 NH3HSO4 Me Me N R OH O H I R Ir R
Roggen, M.; Carreira, E. M. J. Am. Chem. Soc. 2010, 132, 11917. Defieber, C.; Ariger, M. A.; Moriel, P.; Carreira, E. M. Angew. Chem. Int. Ed. 2007, 46, 3139. Classes of Chiral Olefins
M M
!-allyl diene
P N M M phosphane-olefin amine-olefin Chiral Amine-Olefin Ligands
! Ligand lability is a challenge
! Unlike phosphane ligands, less prone to oxidation
! Based on phosphanyl-dibenzo-cycloheptene (tropp) framework
CO2Me H Bn N N H
N
tropp Ph Ph
NH HN NH HN
Maire, P.; Breher, F.; Schönberg, H.; Grützmacher, H. Organometallics 2005, 24, 3207.
Vogt, M.; de Bruin, B.; Berke, H.; Trincado, M.; Grützmacher, H. Chem. Sci. 2011, 2, 723.
Grützmacher, H.; Büttner, T.; Maire, P.; Ramseier, M.; Scheschkewitz, D.; Zweifel, T. DE 102004027771, 2006; EP 05011539.3 Chiral Amine-Olefin Ligands
! Single example of asymmetric catalysis - Transfer hydrogenation Ph H N Ph OH O Ir NH 1 mol% Ir catalyst Cl CO Me Me 10 mol% KOtBu i-PrOH, 80 oC, 1h >98% conv, 82% ee (S,S)-[IrCl(CO)(trop2dpen)]
Ir is bound to both N1 and N2 and C=Ctropp
Ir!C=Ctropp =1.968 Å
C=Ctropp = 1.501 Å
Maire, P.; Breher, F.; Schönberg, H.; Grützmacher, H. Organometallics 2005, 24, 3207. Chiral Amine-Olefin Ligands
! Single example of asymmetric catalysis - Transfer hydrogenation Ph H N Ph OH O Ir NH 1 mol% Ir catalyst Cl CO Me Me 10 mol% KOtBu i-PrOH, 80 oC, 1h >98% conv, 82% ee (S,S)-[IrCl(CO)(trop2dpen)]
KOtBu i-PrOH IrCl(CO)(trop2dpen) Ir(CO)(trop2dpen-H) IrH(CO)(trop2dpen)
O
Me
C=O H-bond to NH Ir-H is equatorial
Maire, P.; Breher, F.; Schönberg, H.; Grützmacher, H. Organometallics 2005, 24, 3207. Final Thoughts
! Young and acelerating field
! Ligand classes:
M M M R2P R2N
diene phosphane-olefin amine-olefin
! Late transition metals: Pd, Rh, Ir
! Reaction types:
R O O R 1,4 carbo- Ar A A Cycloaddition rhodation R R' R EWG EWG
H H H2 X 1,2 X Chiral Resolution R R R R H R R' R
! Advantages: novel/improved reactivity, low catalyst loading, mild conditions, chiral about metal
! Disadvantages: field is still at start of development, ligand synthesis challenging