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byJeremy ZIMBRON
RhMe
Me
OO
R2
R1
chiral Cpx*Rh(I) complex, 1
O
NH
OBoc
R'
R"
R'"+2 mol% 1, 2 mol% DBPO
EtOH, 23°C, 16h
O
NH
R'R"
R'"
Literature Meeting November 27th, 2012
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Cyclopentadienyl ligands (Cp)
1. H. Werner, Angew. Chem. Int. Ed. 2012, 51, 6052-6058.
Common anionic ancillary ligand in organometallic chemistry
Ferrocene is the classic cyclopentadienyl compound
Fe
Discovered and identified by Woodward, Wilkinson and Fischer in the 1950s1
Tigger important developments in modern organometallic chemistry
Wilkinson and Fischer dancing at the final reception of the Conference on Organometallic Chemistry in July 1974 in Ettal
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Cyclopentadienyl ligands (Cp)
1. H. Werner, Angew. Chem. Int. Ed. 2012, 51, 6052-6058.2. Waymouth et al., Angew. Chem. Int. Ed. 1995, 34, 1143-1170.3. F. Viton, G. Bernardinelli and E. P. Kündig, J. Am. Chem. Soc., 2002, 124, 49684. A. D. Bolig, M. Brookhart, J. Am. Chem. Soc. 2007, 129, 14544.5. A. H. Hoveyda, J. P. Morken, Angew. Chem. Int. Ed. Engl. 1996, 35, 1262. 6. M. Zhou, N. D. Schley, R. H. Crabtree, J. Am. Chem. Soc. 2010, 132, 12550.
Present in some of the most active catalysts:
ZrCl
Cl
Stereospecific olefin
polymerization2
RuL
Ar2PP
OO
PhPh
Ar2
Enantioselective Diels-Alder3
Rh
Me3Si
SiMe3
Hydroacylation ofolefins with
aromatic aldehydes4
Enantioselective C-C and C-H Bond
Formation5
TiCl
ClHydroxylation of
alkanes6
Ir
ClCl
ClIr
Cl
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About Cp and Cp* ligands
Inert to both nucleophilic or electrophilic reagents
Strong binding to metal centers
Large array of possible structural modifications of the ligand
In asymmetric catalysis Cp ligands have been bypassed by chiral ligands
Only few examples of chiral Cp inducing enantioselection
Co
O
N
R
h (= 420 nm)
N
R
O
82-93% ee
A. Gutnov et al., Angew. Chem. Int. Ed. 2004, 43, 3795 and A. Gutnov et al., Organometallics 2004, 23, 1002-1009.
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Designing chiral Cp metal complexes1
ClCl
Ti
1. R. L. Halterman. Chem. Rev. 1992, 92, 965-994.
Cyclopentadienyl-derived chirality
OCPh3P
Fe
O
OCON
Mo
Cl
Metal-centered chirality
Combined metal-centered and Cp-derived chirality
XL
M
Y
R
X,Y: N, O, P
*
Mono-bidentate chiral ligands
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Designing chiral Cp metal complexes1
1. R. L. Halterman. Chem. Rev. 1992, 92, 965-994.
Cyclopentadienyl-derived chirality
OCPh3P
Fe
O
OCON
Mo
Cl
Metal-centered chirality
Combined metal-centered and Cp-derived chirality
No C2 symmetry in chiral Cp ligands: form diastereomers during coordination of the metal
Separate diastereomeric complexes
ClCl
Ti
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1,2-substituted cyclopentadiene with C2-symmetric Cp derivatives
Ligand features to achieve the required selectivity:
R
R
OO
R2
R1C2-symmetry coordination
of the metal R
R
OO
R2
R1
RhI
RhI
Provides onechiral complex
Designing chiral Cp ligand
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1,2-substituted cyclopentadiene with C2-symmetric Cp derivatives
Ligand features to achieve the required selectivity:
Designing chiral Cp ligand
Restriction of rotation around the Cp moiety: a single preferential alignment of substrates
M
M
SS
SL
SSSL
M
SL
SS
stericclash
stericclash
M
SLSS
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1,2-substituted cyclopentadiene with C2-symmetric Cp derivatives
Ligand features to achieve the required selectivity:
Designing chiral Cp ligand
Restriction of rotation around the Cp moiety: a single preferential alignment of substrates
A shield from a remote substituent: direct the approach of the incoming reactant
M
SL
SS
M
SLSS
Shield Rc
Shield RcSelective coordination M
SL
SS
RcAsymmetric reaction
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Structure of chiral Cpx*Rh(I) complexes
Different backside shielding from the corresponding C2-symmetric Cp precursors
Relatively air-stable and easy to handle
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Synthesis of chiral Cpx*Rh(I) complexes
Synthesis of the C2-symmetric cyclopentadienes 13
15-crown-5,THF54%
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Synthesis of chiral Cpx*Rh(I) complexes
tBu2Si(OTf)22,6-lutidine, 56%
Xanthanone(OMe)2PPTS, 59%
(Ph)2C(OMe)2PPTS, 33%
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C–H bond functionalization using Rh catalysts1
1. G. Song, F. Wang, X. Li, Chem. Soc. Rev. 2012, 41, 3651-3678.2. D. N. Tran, N. Cramer, Angew. Chem. Int. Ed. 2011, 50, 11098-11102.
Ar1 Ar2
NH+
R1
[{Rh(coe)2(OH)}2] (2.5 mol%),L (6 mol%)
toluene, 100-120°C, 16h
Ar2 NH2
R2
R1
R2
up to 98:2 er
P
P
MeO
MeO
tBu
OMe
tBu
tBu
OMe
tBu
2
2
L:
Cramer: enantioselective [3+2] cycloaddition2
imine directing group
[Rh]
NH
Ar
DTBM-MeOBiphep
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C–H bond functionalization using Rh catalysts1
1. G. Song, F. Wang, X. Li, Chem. Soc. Rev. 2012, 41, 3651-3678.2. D. N. Tran, N. Cramer, Angew. Chem. Int. Ed. 2011, 50, 11098-11102.3. S. Rakshit, C. Grohmann, T. Besset, F. Glorius, J. Am. Chem. Soc. 2011, 133, 2350-2353.4. N. Guimond, S. I. Gorelsky, K. Fagnou, J. Am. Chem. Soc. 2011, 133, 6449-6457.
Ar1 Ar2
NH+
R1
[{Rh(coe)2(OH)}2] (2.5 mol%),L (6 mol%)
toluene, 100-120°C, 16h
Ar2 NH2
R2
R1
R2
up to 98:2 er
P
P
MeO
MeO
tBu
OMe
tBu
tBu
OMe
tBu
2
2
L:
Cramer: enantioselective [3+2] cycloaddition2
C-H functionalization using an oxidizing directing group3,4
• Glorius work3
• Fagnou work4
NH
O
H
+ R'
[Cp*RhCl2]2 (2.5 mol%),CsOPiv (30 mol%), PivOH (20 mol%)
EtOH, 80°C, 16h
NH
R
OOPiv
• Excellent directing group• Internal oxidant• Mild conditions• High functional group compatibility N
H
O
H
+R2
[Cp*RhCl2]2 (0.5 mol%), CsOAc (2 eq)
MeOH, RT, 16h
NH
R3
O
OPiv R3
R2
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Optimization of the asymmetric C-H functionalization
R
R
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Optimization of the asymmetric C-H functionalization
R
R
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Optimization of the asymmetric C-H functionalization
R
R
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Optimization of the asymmetric C-H functionalization
R
R
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Optimization of the asymmetric C-H functionalization
R
R
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Substrate scope: olefin acceptors
Variety of styrenes are competent reaction partners
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Substrate scope: olefin acceptors
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Substrate scope: aryl hydroxamates
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Presumed catalytic cycle for the cyclization
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Postulated model for the stereochemical preference
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Presumed catalytic cycle for the cyclization
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Presumed catalytic cycle for the cyclization
7-membered rhodacycle is stabilized with the extra coordination of the carbonyl oxygen of BOC
Migration of the OtBu from N to RhRh
N
OOBoc
Cpx*
R
(III)
N
R
RhCpx*
OBocO(III)
NRh
Cpx*
OBoc
O
Rh
N
O
R
OBoc
Cpx*(V)
nitrene intermediate
RhN
O O
Cpx*
R
(III) O
OtBu
Reductive elimination
L. Xu, Q. Zhu, G. Huang, B. Cheng, Y. Xia, J. Org. Chem. 2012, 77, 3017.
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Presumed catalytic cycle for the cyclization
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Conclusion
A class of chiral Cpx* analogs with low molecular weight
Desymmetrize a Rh(III)-catalyzed directed C–H bond functionalization
Reaction proceeds under mild conditions and is high yielding and enantioselective
Unlock the potential of chiral Cp ligands in enantioselective catalysis with half-sandwich complexes
Asymmetric catalytic amination of alcohols
R. Kawahara, K-i. Fujita, R. Yamaguchi, Adv. Synth. Catal. 2011, 353, 1161–1168.
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How to induce chirality with Cp complexes?
Coordination of chiral ligands: diamines or phosphines
Chiral, non racemic cyclopentadienyl ligands
Biochemical approach: Cp-complex embedded into a chiral protein environment
(R)
NH2(R)
NH
Ph Ph
S
O
O
(1R,2R)-(-)-N-p-Tosyl-1,2-diphenylethylenediamine
(1R,2R)-TsDPEN
(R) PPh2
PPh2
(R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl
(R)-BINAP
MMM
ML
L
L
host protein
spacer
Linker ML
L
L
NHO
H
HN
H S
O
NH
Biotinylated Cp complexSav protein
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Oxidizing Directing Groups in CH Activation Reactions
Cui and Wu previous work1
1. J. Wu, X. Cui, L. Chen, G. Jiang, Y. Wu, J. Am. Chem. Soc. 2009, 131, 13888.2. N. Guimond, C. Gouliaras, K. Fagnou, J. Am. Chem. Soc. 2010, 132, 6908
Fagnou previous work2
Quinoline N-oxides: directing group and internal oxidant
Benzhydroxamic acid: directing group and internal oxidant