Recent Advances in Directed and Intramolecular Transition Metal Catalyzed Oxidative ...€¦ ·...
Transcript of Recent Advances in Directed and Intramolecular Transition Metal Catalyzed Oxidative ...€¦ ·...
Recent Advances in Directed and Intramolecular Transition Metal Catalyzed Oxidative Functionalizations of Carbon-
Hydrogen Bonds
John Heemstra Jr.April 18, 2006
HC
HHR
XC
HHR
cat [M]
oxidant
1 step
X = NR2, OR, halogen
HC
HHH (g) + 1/2 O2 (g)
OHC
HHH
(l) ΔHo = -30.7 kcal/molcatalyst?
However, two major problems:
HC
HHH
OHC
HHH
Chemoselectivity: product more reactive toward oxidant than starting alkene
93 kcal/mol104 kcal/molif oxidation involves abstractionof H atom, overoxidation to CO2will be observed
Regioselectivity: radical and electrophilic reagents oxidize 3o>2o>1o
However, the selectivity is often not high
RMeEti-Prt-Bu
R-H -> R + H104.9101.198.696.5
Stahl, S.S.; Labinger, J.A.; Bercaw, J.E. Angew. Chem. Int. Ed. 1998, 37, 2180
Oxidative Functionalization of Alkanes
Selectivity: kinetic and thermodynamic preference to form the lesssterically hindered C-M intermediate (1o sp3 > 2o sp3 >>> 3o sp3)
HC
HHR
MLn
CHH
R
H
MLn
CHH
R+ H+
or
XC
HHR
C-H activation functionalization
MLn
90-105 kcal/mol
50-80 kcal/mol
X = anything other than H
X
oxidative addition
heterolytic cleavage
C-H Functionalization via the ‘Inner-Sphere’ Mechanism(alternatively termed ‘organometallic’)
C-H Activation Via Late, Nucleophilic Complexes
σ*
• Typically involves coordinatively and electronically unsaturated Rh(I) and Ir(I) intermediate complexes
• Prone to non-productive reductive elimination in the presence of oxidants andnon-productive protonolysis in the presence of protic reagents.
σ-bonding: C-Hσ -> Mdσπ-backbonding: Mdπ -> C-Hσ∗
• Heterolytic cleavage results in no oxidation state change in metal.
• Electrophilic complexes in their highest stable oxidation state are typicallyused (eg. PtII and PdII)
• Compatible with oxidants (including O2) and provide a route to oxidative functionalization.
C-H Activation Via Late, Electrophilic Complexes
σ-bonding: C-Hσ -> Mdσπ-backbonding: Mdπ -> C-Hσ∗
The Shilov System
Stahl, S.S.; Labinger, J.A.; Bercaw, J.E. Angew. Chem. Int. Ed. 1998, 37, 2180
RCH3 + H2O
PtIICl ClCl Cl
2- (K+)2
K2Pt(IV)Cl4 (ox.)120 oC
RCH2OH + RCH2Cl
(cat.)
First reported by Shilov and coworkers In 1972…….a paradigm shift
“Even though these results were mostly ignored or met with disbelief at first, they are now seen as the origin of the organometallic class of alkene oxidations.”
Robert Crabtree
1o > 2o > 3o
H3C CH3 H3C
CH3HO OHHO
OHH2O+H3C CH3+
OH3 1
H2O+"Pt"
"Pt"
Although excellent chemioselectivity is observed, only modest regioselectivitieshave been obtained for unfunctionalized alkanes.
The Shilov System
CH4
PtIICl OH2
Cl OH2
PtIIClCl OH2
CH3
H
Cl-
PtIICl CH3
Cl OH2
PtIVCl CH3
Cl OH2
Cl
Cl
PtIVCl CH3
Cl OH2H
PtIVCl ClCl Cl
CH3
PtIICl ClCl Cl
OH2
HCl
- K+
- K+
K2195Pt(IV)Cl6
K2195Pt(II)Cl4
or
Cl-
H2O
- K+H2O
2 H2O
2 Cl-
2- (K+)2
CH3OH
PtIICl ClCl Cl
2- (K+)2
H2O
Pt is late “soft” metal, allowingC-H to compete with waterfor binding to Pt
No oxidation state change to metal
Inversion of stereochemof deuterium labledsubstrates
Stahl, S.S.; Labinger, J.A.; Bercaw, J.E. Angew. Chem. Int. Ed. 1998, 37, 2180
Chelate-Directed C-H Bond Functionalizations
Basickes, N.; Sen, A. Polyhedron 1995, 14, 202
Substrate Product Yield
Conditions:17 mol% K2Pt(II)Cl4, 50 mol% K2Pt(IV)Cl6,D2O, 110-120 oC, 3 days
For alcohols:α-CH << β-CH < γ-CH ≤ δ-CH
Selectivity arises form the tendence to form the metallacycle with the least ring strain
Trend also observed for carboxylic acids,Sulfonic acids, and phosphonic acids
Kinetic product formed by reductive elim.?
O
OHNH2
O O
NH2dr 2:1
NH
CO2H+ 214 : 1
O
OHNH2
O O
NH2dr 2:1
NH
CO2H+ 154.5 : 1
NH2
O O + nd2 : 3O O
NH
CO2H no reaction
O
OH
241:3NH2
OHNH2
HO+
substrate products γ− / δ− products
isolatedyield,%
conditions: 0.05 equiv K2PtCl4, 7 equiv CuCl2, H2O, 160 oC, 10h
Dangel, B.D.; Johnson, J.A.; Sames, D.S. J. Am. Chem. Soc. 2001, 123, 8149
Chelate-Directed C-H Bond Functionalizations
The chelation effect in amino acids can override the inherent selectivity of the C-H activation step.
Proposed Catalytic Cycle
Dangel, B.D.; Johnson, J.A.; Sames, D.S. J. Am. Chem. Soc. 2001, 123, 8149
PtIICl OH
ClH2N
O
CH3
PtIIClCl
H2N
H3C
OOH
PtIIClCl
H2N
OOH
+
C-H activation
PtIVClCl
H2N
CH3
OOHCl
Cl
CuCl2
PtIICl ClCl Cl
O
OHH3C
OH NH2
O O
NH2
H3C
or
O
OHH3C
NH2
HN
K+ -
K+ -
(K+)2 2-
HO2C
reductive elimination
Alternatively….
O
OHNH2
ClHNHO2C
alkylation+
γ-selective pathway = oxygenation δ-selective pathway = chlorination
• Has been instrumental in the understanding of mechanistic and selectivity issues related to alkane oxidation by homogeneous transition metal complexes
• Moderate to excellent regioselectivity can be achieved in the oxidation of functionalized alkanes (eg. alcohols and acids) via the chelate effect
• However, the platinum mediated chemistry is plagued by low catatystturnover numbers.
• Pt(IV) is not a practical stoichiometric oxidant (cost) and attempts at replacing it with other oxidants have afforded decreased chemoselectivity.
• Deposition of platinum metal erodes selectivities and the oxidation of Pt(0) tends to be difficult. Palladium on the other hand……..
RCH3 + H2O
PtIICl ClCl Cl
2- (K+)2
K2Pt(IV)Cl4 (ox.)120 oC
RCH2OH + RCH2Cl
(cat.)
Summary of Platinum Mediated Alkane Oxidations
Stahl, S.S.; Labinger, J.A.; Bercaw, J.E. Angew. Chem. Int. Ed. 1998, 37, 2180
• The chelating group believed to both direct and accelerate unactivated sp3 C-H activation
• High reactivity for 1o β−C-H likely reflects preference for forming 5-membered palladacycles and strong steric preference for formation less hindered 1o Pd-alkyls.
N
R1 R4
R2 R3
MeO5 mol% Pd(OAc)2
1/1 AcOH/ Ac2O100 oC,
N
R1
MeO
R2R3
Pd
AcO
2PhI(OAc)2 N
R1
R2 R3
MeO
OAc
1.1 equiv
Palladium-Catalyzed Oxygenation of Unactivated sp3 C-HBonds
Unlike Pt(II), only 10 β-C-H bonds undergo functionalization!
Desai, L.D.; Hull, K.L.; Sanford, M.S. J. Am. Chem. Soc. 2004, 126, 9542
Palladium-Catalyzed Oxygenation of Unactivated sp3 C-HBonds
1.5 h
5 min
Desai, L.D.; Hull, K.L.; Sanford, M.S. J. Am. Chem. Soc. 2004, 126, 9542
These Pd-catalyzed reactions typically proceed under significantly milder conditions, with higher TON (often ≥50) and with broader substrate scope than those with Pt catalysts
Single diastereomer
N
H 1-5 mol% Pd(OAc)2
75-100 oC NPd
AcO
2N
X1-2 equiv oxidant
12 h
Dick, A.R.; Hull, K.L.; Sanford, M.S. J. Am. Chem. Soc. 2004, 126, 2300
Yoneyama, T.; Crabtree, R.S. J. Mol. Catal. A 1996, 108, 35
Palladium-Catalyzed Oxygenation of Unactivated sp2 C-HBonds
X
+ PhI(OAc)2AcOH
100 oC, 21h
+
1 equiv
Pd(OAc)2
1 equivlargeexcess
X
OAc
Substrate yield o:m:p
Benzene 39Anisole 40 44:5:51Toluene 39 43:26:31
Low levels of regioselectivity observed
Dioxidation of substrates: Conditions: 2.3 equiv of PhI(OAc)2, 6-8 mol% Pd(OAc)2, 100 oC, 12h, CH3CN
Chelate-Directed Oxidation of sp2 and sp3 C-H Bonds
Monooxidation of substrates: Conditions: 1.1-1.6 equiv of PhI(OAc)2, 1-6 mol% Pd(OAc)2, 100 oC, 12-20 h, CH3CN
in MeOH
Dick, A.R.; Hull, K.L.; Sanford, M.S. J. Am. Chem. Soc. 2004, 126, 2300
Conditions:5 mol% Pd(OAc)2, 1.1-3.0 equiv PhI(OAc)2,AcOH, C6H6 or C6H6/Ac2O, 100 oC, 0.5-4 h
Unlike directed ortho-lithiation and Ru-catalyzedC-H activation reactions, OMe, OMOM, and FDid not exhibit secondary directing effects
Kalyani, D.; Sanford, M.S. Org Lett. 2005, 19, 4149
Palladium-Catalyzed Acetoxylation of Meta-SubstitutedAryl pyridines
Conditions:5 mol% Pd(OAc)2, 1.1-2.2 equiv PhI(OAc)2,AcOH, AcOH/Ac2O, 100 oC, 3-12 h
Palladium-Catalyzed Acetoxylation of Aryl Pyrrolidinones
Selectivity for A may be general over many classes of directing groups in PdII-catalzedC-H activation/oxidative functionalizations.
Kalyani, D.; Sanford, M.S. Org Lett. 2005, 19, 4149
Palladium-Catalyzed Acetoxylation of Substrates with Potential Dual Chelating Groups
Kalyani, D.; Sanford, M.S. Org Lett. 2005, 19, 4149
Conditions:5 mol% Pd(OAc)2, 1.5-1.8 equiv PhI(OAc)2,C6H6 or C6H6 /Ac2O, 100 oC
?
75-100 oCN
PdII
AcO
2N
OAcequiv PhI(OAc)2
12 h comparible yield
NPdII
AcO
2
CH3CN
75-100 oC12 h
CH3CNno reaction
N75-100 oC
12 h
CH3CNno reaction+ Pd(OAc)2
benzoquinoneor
Cu(OAc)2
Dick, A.R.; Hull, K.L.; Sanford, M.S. J. Am. Chem. Soc. 2004, 126, 2300
Proposed Catalytic Cycle for Palladium-Catalyzed Acetoxylation of Benzo[h]quinone
Mechanistic Investigations of C-O Bond-Forming Reductive Elimination of Pd(IV) Complexes
Dick, A.R.; Kampf, J.W.; Sanford, M.S. J. Am. Chem. Soc. 2005, 127, 12790
Expected mechanism A most likely by analogy to C-O bond-forming reactions with PtIVHowever….• no observed rate acceleration in more polar solvents and no correlation with solvent
dielectric constant• ΔS = +4.2 ± 1.4 and -1.4 ± 1.9 eu in d6 DMSO and CDCl3 respectively (ionic reductive
eliminations typically show highly negative values of ΔS).• ρ = -1.36 ± 0.04 (PtVI C-O bond forming reductive elimination ρ = +1.44)• Thermolysis in the presence of 5 equiv NBu4OAc resulted less than 5% incorporation
of the acetate in CHCl3 or DMSO
Stable at rt
What experiments would you perform to distinguish between Mech. B and C?
Mechanistic Investigations of C-O Bond-Forming Reductive Elimination of Pd(IV) Complexes
Sanford and co-worker currently favor mechanism C
Selective C-H Activation/Halogenation catalyzed by Pd(OAc)2
Conditions:1 mol% Pd(OAc)2, 1.1 equiv of N-Halosuccinamide, MeCN, 100 oC,24-72 h
Giri, R.; Chen, X.; Yu, J.-Q. Angew. Chem. Int. Ed. 2005, 44, 2112
Dick, A.R.; Hull, K.L.; Sanford, M.S. J. Am. Chem. Soc. 2004, 126, 2300
O
NMe
MeMe t-Bu
O
NMe
Me t-Bu
I
O
NEt
MeMe t-Bu
O
NEt
Me t-Bu
I
O
NEt
MeEt t-Bu
O
NEt
Et t-Bu
I
Substrate Product Yield (%)
92
91 (63:37 dr)
88
Conditions:10 mol% Pd(OAc)2, I2 (1 equiv)PhI(OAc)2 (1 equiv), CH2Cl2, 24 oC, 48-72 h
Ethanolamine, 2-methyl-2-amino-propanol, or valinol derived oxazolinesproceed at much slower rate
Giri, R.; Chen, X.; Yu, J.-Q. Angew. Chem. Int. Ed. 2005, 44, 2112
O
NMe
MeMe t-Bu
Pd(OAc)2
CH2Cl224 oC, 24h
60% yield
C-Hactivation
Oxidative addition/reductive elimination
PhI(OAc)2 (1 equiv)
Pd(OAc)2PdI2I2 (1 equiv)
CH2Cl2, 24 h
Selective C-H Activation/Halogenation catalyzed by Pd(OAc)2
Summary of the Palladium Catalyzed sp3 and sp2 C-H bond Oxidative Functionalization
• Unactivated sp3 and sp2 C-H bonds of oximes, pyridine, pyrazole, imine, and azo-benzene substrates undergo highly regio- and chemoselective Pd(II) catalyzed oxygenations with PhI(OAc)2 as a stoichiometric oxidant.
• C-H bonds can also be replaced with ether functionality or halides when reaction are performed in alcohol solvants or in the presence of N-halosuccinamides, or I2.
• Pd-catalyzed chelate-directed acetoxylation of meta-substituted arene substratesexhibit high regioselectivity for functionalization at the less substituted ortho-position
• These Pd-catalyzed reactions typically proceed under significantly milder conditions, With higher TON (often ≥50) and with broader substrate scope than those with Pt catalysts.
• The almost exclusive selectivity for 1o C-H bonds is a could be a limitation if one wanted to develop a stereospecific or enantioselective process.
Selectivity: involves buildup of radical and/or cationic character at carbonand shows selectivity for weaker C-H bonds:benzylic, allylic, 3o, or α to heteroatoms.
C-H Functionalization via the ‘Outer-Sphere’ Mechanism(alternatively termed ‘coordination’)
HC
HHR
XC
HHR
MLnLG=X
X MLn
CHH
R
X MLnH
X CR2: carbene NR: nitrene O: oxo
LG
LG N2 IPh IPh, ROH
direct insertion
H atom abstraction/rebound
H
HC
HHR
X MLn
First example of an intermolecular C-H amination
First example of an intramolecular C-H amination
89%
Breslow. R; Gellman, S.H. J. Chem. Soc., Chem. Commun. 1982, 1400
Breslow. R; Gellman, S.H. J. Am. Chem. Soc. 1983, 105, 6728
aryliodinane
Cat.Rh2(OAc)4
93% yieldAryliodinane intermediateshave poor shelf life
C-H Bond Amination via the ‘Outer-Sphere’ Mechanism
Tosylamine
First demonstration of the use of the oxidant PhI(OAc)2 and Rh catalyst system
OHRO
OHNR
O
NCOCl3
O
O NH2R
CCl3
O
K2CO3,MeOH
5 mol%Rh2(OR)4
PhI(OAc)2 (1.4 equiv )MgO (2.3 equiv )CH2Cl2, 40 oC
OHN
R
O
A = Rh2(OAc)4B = Rh2(tpa)4
One-pot procedure for formation of aryliodinaneand insertion of metallonitrenoids in C-H bond
Espino, C.G.; Du Bois, J. Angew. Chem. Int. Ed. 2001, 40, 598
Rhodium-Catalyzed Oxidative C-H Insertion Reaction forOxazolidinone Synthesis
O
OH2NH
MeMe
O
ONH
MeMe
PhIPhI(OAc)2
O
ONH
MeMe
(AcO)4Rh2
Rh2(OAc)2
OHN
MeMe
O
Mechanism of Oxazolidinone Formation
Data suggests a concerted, metal-directedN-atom insertion process
Espino, C.G.; Du Bois, J. Angew. Chem. Int. Ed. 2001, 40, 598
OH
R2R1
ClSO2NH2
pyridine,CH2Cl2
O
R2R1
SH2NOO 2 mol%Rh2(OR)4
PhI(OAc)2 (1.1 equiv )MgO (2.3 equiv )
O
R2R1
SHNOO
90% (A) 75% (B)single isomer
80% (A)single isomer
91% (B)13/1 syn/anti
78% (A) 85% (A)8/1 cis/trans
78% (B)4/1 cis/anti
60% (A)
Rhodium-Catalyzed Oxidative C-H Insertion Reaction forOxathiazinane Synthesis
A = Rh2(OAc)4B = Rh2(oct)4
sulfamate
Espino, C.G.; Wehn P.M.; Chow, J.; Du Bois, J. J. Am. Chem. Soc. 2001, 123, 6935
O
CO2EtPh
SHNOO S-O and S-N bond
lengths of 1.59 AN-S-O angle of 105o
O
CO2EtPh
SH2NOO
S-O and S-N bondlengths of 1.58 A
N-S-O angle of 103o
sulfamate OS
HN
CO2EtPh
OO
sulfamidate
oxathiazinane
N-S-O angle of 95o
favored
disfavored
Torsional strain inducedin developing product
Wehn P.M.; Lee, J.; Du Bois, J. Org. Lett. 2003, 5, 4823
Rhodium-Catalyzed Oxidative C-H Insertion Reaction forOxathiazinane Synthesis
Fleming, J.J.; Fiori, K.W.. Du Bois, J. J. Am. Chem. Soc. 2003, 125, 2028
Rhodium-Catalyzed Amidation of Ethereal Cα-H Bonds
Fleming, J.J.; Fiori, K.W.. Du Bois, J. J. Am. Chem. Soc. 2003, 125, 2028
• When C6 unsubstituted, 4,5-synfavored
• When C6 substituted, 4,6-anti favoredregardless of C5 configuration
Alkynlzinc Addition Reactions with N,O-Acetals
One-pot procedure: rxn mixture filtered to remove MgO and then treated with either1.5 equiv BF3 OEt2 and 4 equiv allyltrimethyl silane or 0.1 equiv Sc(OTf)3 and 4 equivof silyl enol ether
Fiori, K.W.; Fleming, J.J. Du Bois, J.Angew. Chem. Int. Ed. 2004, 43, 4349
Tandem Rhodium C-H Amination, Iminium Ion Coupling Reactions
a
a
b
a R = Me b R = CPh3
R = Me
Ketene acetals can also be employed
Stereochemical Models for Iminium Ion Additions
Fiori, K.W.; Fleming, J.J. Du Bois, J.Angew. Chem. Int. Ed. 2004, 43, 4349
Model for alkylzincReagents
Model for allylsilanesand silyl enol ethers
Highly selective additions to 5,6-syn-substituted iminium ions
78%20:1
72%20:1
Selectivity erodes with 5,6-anti-configured substrates
Stereochemical Models for Iminium Ion Additions
81%1.5:1
82%2.5:1
Fiori, K.W.; Fleming, J.J. Du Bois, J.Angew. Chem. Int. Ed. 2004, 43, 4349
Carbamate C-H insertions sulfamate C-H insertions
Similar yields; however, Rh-catalyzed process proceeds at 40 oC
stereospecific
Both ligand and AgSalt commercially available
Cui, Y.; He, C. Angew. Chem. Int. Ed. 2004, 5, 4210
A Silver-Catalyzed Oxidative C-H Insertion Reaction forOxazolidinone and Oxathiazinane Synthesis
*Dirhodium complex afforded 8:1 cis:trans
Highly robust catalyst featuringup to 59 catalytic turnovers at 1.5 mol%,and up to 300 at 0.1 mol% catalyst loadings
Single isomer*
1.5 mol% 12 equiv PhI(OAc)2
2.5 equiv Al2O3CH2Cl2, 40 oC
Fe and Mn metalloporphyrins afforded lower yields
Intramolecular C-N Bond Formations Reactions CatalyzedBy a Ruthenium Porphyrin
Liang, J.-L.; Yuan, S.-X.; Huang, J.S.; Yu, W.Y.; Che, C.-M. J. Org. Chem. 2004, 69, 3610
Liang, J.-L.; Yuan, S.-X.; Huang, J.S.; Yu, W.Y.; Che, C.-M. J. Org. Chem. 2004, 69, 3610
However, intramolecular C-H aminationis stereospecific!
Data for intermolecular reaction supports H-atom abstraction mechanism
a) Carboradical is too shortlived to undergoconfiguration inversion
b) Nonsynchronous concerted mechanismbearing significant hydrogen abstractioncharacter
Intramolecular C-N Bond Formations Reactions CatalyzedBy Ruthenium Porphyrins
Espino, C.G.; Fiori,K.W.; Du Bois, J. J. Am. Chem. Soc. 2004, 126, 15378
Expanding the Scope of C-H Amination Through Catalyst Design
Chelate effect should disfavor complete ligand dissociation from metal center and confer added stability to complex
1.5 mol% 21.4 equiv PhI(OAc)2
2.5 equiv Al2O3
Liang, J.-L.; Yuan, S.-X.; Huang, J.S.; Yu, W.Y.; Che, C.-M. Angew. Chem. Int. Ed. 2002, 41, 3465
*
[d] in CH2Cl2 at 40 oC[e] in CH2Cl2 at 5 oC[f] in toluene at 0 oC
Chiral porphyrin ligand is bothexpensive and difficult to synthesize
Intramolecular C-N Bond Formations Reactions CatalyzedBy a Chiral Ruthenium
Liang, J.-L.; Yuan, S.-X.; Huang, J.S.; Yu, W.Y.; Che, C.-M. J. Org. Chem. 2004, 69, 3610
Imido phenyl group points toward the smaller methano-bridge
X-ray structure of the majorenantiomer
Intramolecular C-N Bond Formations Reactions CatalyzedBy a Chiral Ruthenium Porphyrin
More readily accessible and cheaperHowever low selectivity obtained
Intramolecular C-N Bond Formations Reactions CatalyzedBy Rhodium and Manganese complexes
Fruit, C.; Muller, P. Helv. Chim. Acta 2004, 87, 1607Zhang, J.; Chan, P.W.H.; Che, C.-M. Tetrahedron Lett. 2005, 46, 5403
Catalyst yield erA 55% 65:35B 48% 76:24
A B
L = Cl
JRH1
Slide 42
JRH1 John R Heemstra Jr, 4/17/2006
Summary of Intramolecular C-H Aminations via the ‘Outer-Sphere’ Mechanism
• The intramolecular C-H amination reaction is now a highly dependable and predictable transformation and has found application in the preparation of a variety of natural products.
• The intramolecular insertion of metallonitrenoids (M = Ag, Rh, Ru) into C-H bond is a stereospecific process.
• The new Rh2(esp)2 catalysts now allows very low catalyst loadings and extremely high catalyst TON (>600)
• Enantioselective methods are still in their infancy and a method that provides highselectivity is still lacking