c -h activation: fundamentals and recent developments...2017/09/05 · c -h activation:...
TRANSCRIPT
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C-H Activation: Fundamentals and Recent Developments
Giovanni [email protected]
11th INTERNATIONAL SCHOOL OF ORGANOMETALLIC CHEMISTRY San Benedetto del Tronto, 2-6 September 2017
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Focus on the Transformation
Historical Background
Overview of Mechanisms
Selection of Specific Examples
Plan: Focus on the Transformation
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Focus on the Transformations
type of C-H C(sp) C(sp2)arom C(sp2)vinyl C(sp3)1° C(sp3)2° C(sp3)3° C(sp3)allylic
structure
BDE
(kJ/mol) 552.2 473.0 460.2 410.8 397.9 389.9 361.1
pKa ~25 43 44 ~50 ~50 ~50 43
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The Holy Grail of Chemistry
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Feng, Y.; Chen, G. Angew. Chem., Int. Ed., 2010, 49, 958Breslow, R.; Yang, J.; Yan, J. Tetrahedron 2002, 58, 653
“Liberating chemistry from the tyranny of functional groups”… Of course, reactive groups have tobe tolerated
Multi-step Syntheses and C-H Activation /Functionalization
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Adapted from: Caballero, A.; Perez, P. J. Chem. Soc. Rev. 2013, 42, 8809
Feedstock Use and C-H Activation /Functionalization
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Focus on the Transformation
Historical Background
Overview of Mechanisms
Selection of Specific Examples
Plan: Historical Background
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Hofmann-Löffler-Freytag (HLF) Reaction
(a) Hofmann, A. W. Ber. Dtsch. Chem. Ges. 1883, 16, 558; Hofmann, A. W. Ber. Dtsch. Chem. Ges. 1885, 18, 5.(b) Löffler, K.; Freytag, C. Ber. Dtsch. Chem. Ges. 1909, 42, 3427.(c) Corey, E. J.; Hertler, W. R. J. Am. Chem. Soc. 1958, 80, 2903.(d) Buchschacher, P.; Kalvoda, J.; Arigoni, D.; Jeger, O. J. Am. Chem. Soc. 1958, 80, 2905.(e) Corey, E. J.; Hertler, W. R. J. Am. Chem. Soc. 1959, 81, 5209.
August Wilhelm von Hofmann
highly reactive intermediates……and structural proximity
photochemical decomposition of N-haloamines
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Kharasch, M. S.; Isbell, H. S. J.Am. Chem. Soc. 1931, 53, 3053.
Jacob Volhard
Otto Dimroth
Morris Kharasch
Pioneering Electrophilic C-H Metalations of Arenes
Volhard, J. Justus Liebigs Ann Chem . 1892, 267, 172.
Dimroth, O. Ber. Dtsch. Chem. Ges. 1898, 31, 2154; 1899, 32, 758; 1902, 35, 2032 and 2853.
Goldshleger, N. F.; Eskova, V. V.; Shilov, A. E.; Shteinman, A. A. Russ. J. Phys. Chem. 1972, 46, 785.
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Alexander Shilov
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Kleiman, J. P.; Dubeck, M. J. Am. Chem. Soc. 1963, 85, 1544
Green, M. L. H.; Knowles, P. J. J. Chem. Soc., Chem. Comm. 1970, 1677.
Pioneering Nucleophilic Metalations of Arenes
First C-H ortho-metalation
Chatt, J.; Davidson, J. M.; J. Chem. Soc. (A) 1965, 843.
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Lewis, L. N.; Smith, J. F. J. Am. Chem. Soc. 1986, 108, 2728.
Catalytic aromatic ortho C-H activation
Iverson, C. N.; Smith III, M. R. J. Am. Chem. Soc. 1999, 121, 7696
Borylation of Arenes
Other Important Pioneering Steps Forward
First catalytic C-H activation / functionalization
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Focus on the Transformation
Historical Background
Overview of Mechanisms
Selection of Specific Examples
Plan: Overview of Mechanisms
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We can mechanistically classify the metal-catalyzed C-H activation / functionalizationprocesses into two main classes.
Overview of Mechanisms
outer sphere
inner sphere
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1. Insertion of a C-H bond into the ligand of a transition metal (TM) complex
2. Coordination of the C-H bond to a metal vacant site to create an organometalliccomplex. The hydrocarbyl species stays in the inner-sphere during the C-Hcleavage event.
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Metalloradical pathway (metal oxene)
Metal carbenes (or nitrenes)
Outer Sphere
Nature does it very well
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Inner Sphere: Nucleophilic vs Electrophilic Character
M
M
H
H
C
C
Reverse CT (ECT1)M CH
Nucleophilic C-H activation
Forward CT (ECT2)M CH
d
d
C-H
C-HM
M
H
H
C
C
Forward CT (ECT2)M CH
Reverse CT (ECT1)M CH
Electrophilic C-H activation
d
d
C-H
C-H
-donation >>-back-bonding
MH
C
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three steps
Oxidative Addition vs Sigma-bond Metathesis
-Bond metathesis (σ-BM )Metal assisted σ-bond metathesis (MAσ-BM), Oxidatively added transition state (OATS)
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σ-Complex assisted metathesis (σ-CAM),Oxidative hydrogen migration (OHM)
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The Isohypsic Electrophilic Mechanisms
Intramolecular concerted mechanisms (AMLA / CMD)
(a) Fagnou, K. et al. J. Am. Chem. Soc. 2008, 130, 10848; (b) J. Org. Chem. 2012, 77, 658; (c) Chem. Lett. 2010, 39, 1118.(b) Davies, D. L.; Macgregor, S. et al. Dalton Trans. 2009, 5820.(c) Oxgaard, J.; Goddard III, W. A. Organometallics 2007, 26, 1565.
Ambiphilic metal-ligandactivation (AMLA)Concerted metalationdeprotonation (CMD)Internal electrophilicsubstitution (IES)
External heterolytic cleavage
-donation >>-back-bonding
MH
C
CH
[M]
+
CH
[M]
X
X[M]
CH
X
1,2-addition
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Redox Concepts in C-H Cross Couplings
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PdX2-cat. Oxidative Transformations
Z and QX2: 2e- sacrificial oxidants; DG: directing group
Acceptorless oxidation
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Dehydrometalation / Hydrometalation
Transition metal alkyl complexes bearing a β-H atom that can adopt syncoplanar position withrespect to the metal undergo easily β-hydride elimination (dehydrometalation).The metal must have a vacant coordination site (empty orbital) that can interact with the Hatom of the alkyl ligand. So, a dehydrometalation step can be regarded as a special case ofinner-sphere intramolecular C-H activation.d0 metal complexes (i.e. Ag+, Hg 2+) lacking the possibility to participate in d-orbital bonding arenormally stable to β-hydride elimination:
Thorn, D. L. Hoffmann, R. J. Am. Chem. Soc. 1978, 100, 2079
G. Poli
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The Case of the PdX2 Catalyzed allylation of a NuH
Liron, F.; Oble, J.; Lorion, M. M.; Poli, G. Eur. J. Org. Chem. 2014, 5863 MicroreviewLorion, M. M.; Nahra, F.; Ly, V.-L.; Mealli, C.; Messaoudi, A.; Liron, F. ; Oble, J.; Poli, G. Chem Today 2014, 32, 30Lorion, M. M.; Oble, J.; Poli, G. Pure Appl. Chem. 2016, 88, 381.
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Focus on the Transformation
Historical Background
Overview of Mechanisms
Selection of Specific Examples
Plan: Selection of Specific Examples
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Inner Sphere: C-H Functionalization (nucleophilic reactivity)
(a) Janowicz, A. H.; Bergman, R. G. J. Am. Chem. Soc. 1982, 104, 352(b) Hoyano, J. K.; Graham, W. A. G. J. Am. Chem. Soc. 1982, 104, 3723(c) Jones, W. D.; Feher, F. J. Organometallics 1983, 2, 562
Low temperature IR flash kinetic spectroscopy C-H selectivity: sp2 > 1o sp3 (Rh easier than Ir) The hydrido(alkyl)metal complex is unproductive The oxidative addition is thermodynamically favored. Rh: thermodynamic control. Ir: kinetic control
The Bergman Breakthrough
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Electrophilic Paths: The Pivotal Role of C-Pd-X
Pd XC1
C1 X
- Pd(0)
PdX2-MX
C1 Met
PdX2-HX
C1 H
C2 C3
C2 C3
C1
a
b
d
I
C2 MetC1 C2
II
C2 H C1 C2
III
carbopalladation/dehydropalladation
transmetallation
C-H activation
oxidative addition
transmetallation
C-H activation
- Pd(0)
- Pd(0)ZX2
Pd XC1X
X
Z
C2 HC1 C2
V
reductive eliminationor SN2
C1 Ce
nucleopalladation
- PdX2
C1 X
C-H activationVI
VII
Pd(0)
- PdX2
C2 XC1 C2
IVoxidative addition
- PdX2
CPdXC1 C
ccarbopalladation
Nu-H, -HX, -Pd(0)NuC1CNu
C1CNu dehydropalladation
C
-HX -Pd(0)
nucleofunctionalization
PdX2-HX
VIII
IX
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Oxidative Addition Triggered Arylations
(a) Nakamura, N.; Tajima, Y.; Sakai, K. Heterocycles 1982, 17, 235(b) Akita, Y. Ohta, A. Heterocycles 1982, 19, 329(c) Fagnou, K. et al. J. Am. Chem. Soc. 2006, 128, 16496
Electrophilic reactivitycoupling type c, path (a + III)
aryl/aryl
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Oxidative Addition Triggered Arylations
(a) Park, C-H.; Ryabova, V.; Seregin, I. V.; Sromek, A. W.;Gevorgyan, V. Org. Lett. 2004, 6, 115
(b) Campeau, L.-C.; Rousseaux, S.; Fagnou, K. J. Am. Chem.Soc. 2005, 127, 18020
PdR3P
OO
Me
H
PdR3P
OO
Me
H
PdR3P
OOH
Me
E
PdR3P
OO
Me
H
Edist
activation strain analysis
Eint
coupling type c, path (a + III) Electrophilic reactivityaryl/aryl
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Stuart, D. R. Fagnou, K. Science, 2007, 316, 1172
Cross Dehydrogenative Couplings (CDC)coupling type d, path (d + III)
Dwight, T. A.; Rue, N. R.; Charyk, D.; Josselyn, R.; DeBoef, B. Org. Lett. 2007, 16, 3137-3139
Electrophilic reactivity
aryl/aryl
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Fujiwara-Moritani reaction
aryl/vinyl
Moritani, I.; Fujiwara, Y. Tetrahedron Lett. 1967, 8, 1119
aryl/vinyl, coupling type d, path (d + I) Electrophilic reactivity
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(a) Fahey, D. R. J. Organometal. Chem. 1971, 27, 283.(b) Eberson, L. J. et al. Liebigs Ann. Chem. 1977, 233; Stock, L. M. et al. J. Org. Chem. 1981, 46, 1759. Crabtree R. H. et al. J. Mol. Catal.
A: Chem. 1996, 108, 35(c) Sanford, M. S. et al. J. Am. Chem. Soc. 2004, 126, 2300.
Oxidative Pd(II)/Pd(IV) Sequences
coupling type e, path (d + V + VII)
C-H nucleofunctionalizations
C HPdX2Ln, QX2
C X
C PdX
- HX
QX2, -QPd
X
XL
CL X
AMLA/CMD
oxidative addition
PdX2Ln
reductive elimination(IV)
Sanford, M. et al. J. Am. Chem. Soc. 2005,127, 12790
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C-H activation at Pd(II) vs Pd(IV)
alkene 1,2-aminoalkylationcoupling type g, path (e + V + VI)
NH
OMe
MeMe
N O
Me
MeMe
Me
Pd(TFA)2 10 mol%NFSI 2 equiv.BHT 1 equiv.
3 Å MS, rt
Me+
200 equiv.
Me
anti-aminopalladation
oxidation
coordination
C-H activation
reductiveelimination
- XH
NPd
O
Me
MeMe
X
L
NPd
O
Me
MeMe
X
L
N(SO2Ph)2
F
NFSI
NPd
O
Me
MeMe
X N(SO2Ph)2
F Me
HH
NPd
O
Me
MeMe
N(SO2Ph)2F
Me
PdX2- XH
84%H
(a) Sibbald, P. A.; Rosewall, C. F.; Swartz, R. D.; Michael, F. E. J. Am. Chem. Soc. 2009, 131, 15945. (b) Rosewall, C. F.; Sibbald, P. A.; Liskin, D. V.; Michael, F. E. J. Am. Chem. Soc. 2009, 131, 9488.
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Substrate Control: Directed Aromatic ortho Activations
Two mechanistically different strategies
Seminal papers on directed ortho activation: (a) S. Murahashi J. Am. Chem. Soc. 1955, 77 (1955) 6403-6404; (b) J. P. Kleiman, M.Dubeck, J. Am. Chem. Soc. 1963, 85, 1544-1545.
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Nucleophilic Directed C-H Activation: The Murai Reaction
Aromatic ortho C-H activation, the Murai-Chatani-Kakiuchi reaction
Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N. Nature 1993, 366, 529.
Nucleophilic reactivity
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Directed Fujiwara-Moritani
Ortho-metalation Pd(II)
(a) Miura, M.; Tsuda, T.; Satoh, T.; Pivsa-Art, S.; Nomura, M. J. Org. Chem. 1998, 63, 5211(b) Boele, M. D. K.; van Strijdonck, G. T. P. F.; de Vries, A. H. M.; Kamer, P. C. J.; de Vries, J. G.; van Leeuwen, P. W. N. M. J. Am.
Chem. Soc. 2002, 124, 1586
Electrophilic reactivity
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Directed Aromatic C-H Activation
Oi, S.; Fukita, S.; Hirata, N.; Watanuki, N.; Miyano, S.; Inoue, Y. Org. Lett. 2001, 3, 2579
Ortho-metalation Ru(II) Electrophilic reactivity
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Different directed Pd-catalyzed ortho functionalization
Yu. et al. J. Am. Chem. Soc. 2008, 130, 17676
Pd(II)/Pd(IV)
Pd(II)/Pd(0)
Daugulis, O. et al. Angew. Chem., Int. Ed. 2005, 44, 4046.
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C-H Borylation
Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010, 110, 890
Selectivity 1° > 2°
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C-H Borylation
Iverson, C. N.; Smith III, M. R. J. Am. Chem. Soc. 1999, 121, 7696.Chen, H.; Hartwig, J. F. Angew. Chem. Int. Ed. 1999, 38, 3391.Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010, 110, 890.
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1/2O
OBB
O
O+
Rh
150°C
O
OB
82%
0.5 mol%
Rh
Cp*(III)
H BpinBpin Bpin
- HBpinRh
Cp*(III)
Bpin Bpin
16 VE
Cp*Rh(I)( 4-C6Me6)- 4-C6Me6
Rh
Cp*(III)
Bpin BpinPh H
Ph-HRh
Cp*(III)
Bpin BpinPh H
Rh
Cp*(III)
Bpin Bpin
Ph H
Rh
Cp*
Bpin H16 VE
(Bpin)2
Cp*Rh( 4-C6Me6)
Rh
Cp*
Bpin H
BpinBpin
-CAM
18 VE
HBpin released isalso efffective forborylation18 VE
18 VE 18 VE 18 VE
18 VE
(III)(III)
H
(Bpin)2
start here !
(I)
oxid. add.
why hexamethylbenzene is bent?
Rh
Cp*(III)
BpinBPh
H
18 VEpin
rotation
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To Read More On This Topic…
Roudesly, F; Oble, J; Poli, G. J. Mol. Cat. A. Chem. 2017, 426, 275
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The Jeffery ligandless conditions
Jeffery, T. J. Chem. Soc., Chem. Commun. 1984, 1287Jeffery, T. Tetrahedron, 1996, 52, 10113.
Gittins, D. I.; Caruso, F. Angew. Chem. Int. Ed., 2001, 40, 3001Astruc, D. Inorg. Chem., 2007, 46, 1884
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Cookson, Platinum Metals Rev., 2012, 56, 83Carrow, B. P.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 79
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Homeopathic amounts of catalyst
de Vries, A. H. M.; Mulders, J. M. C. A.; Mommers, J. H. M. ; Henderickx, H. J. W. ; de Vries, J. G. Org. Lett., 2003, 5, 3285.Fairlamb, I. J. S.; Kapdi, A. R.; Lee, A. F.; Sánchez, G.; López, G.; Serrano, J. L.; García L.; Pérez, E. Dalton Trans., 2004, 3970.
Effect of palladium/substrate ratio on the yield of the Mizoroki-Heck reaction between PhBr and n-butyl acrylate at 135 °C
k1 > k2 at very low (homeopathic)concentration of catalyst (~40ppm Pd)
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From heterogeneous to quasi homogeneous catalysis
Chem. Rev. 2009, 109, 302.; ACS Macro Lett. 2014, 3, 260.
Merrifield resins, aerogels
Dendrimers Polymer Chains
Insoluble Soluble
Polymer supports in catalysis
nonlinear kinetic behavior unequal distribution and/or access to the chemical reaction solvation problems associated with the nature of the support synthetic difficulties in transferring standard organic reactions to the solid phase
quasi-homogeneous catalysis
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A. Biffis, J. Mol. Catal. A : Chem. 2001, 165, 303-307
Functionalised microgels to stabilise metal colloids
Clear colloidal suspension
100 nm
10-20 nm particle size
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Smart well-defined catalytic nanoreactors
Sanson, N. ; Rieger, J. Polym. Chem., 2010, 1, 965–977
X XX
X X
+
X
xDr. Rieger (IPCM@UPMC)
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Core Shell
Macromol. Rapid Commun. 2008, 29, 1965.Macromol. Rapid Commun. 2015, 36, 1458.Chem. Rev. 2015, 115, 9745.
Hybrid core-shell nanogels
Globular shaped cross-linked polymers in the range of 10-500 nm
Different polymers in the shell and the core
Swell in the presence of good solvents
Confine metallic species (recycling, nanoreactors)
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Synthesize Core-Shell nanogels with metal coordinating monomers
Functionalisation with metallic species
Study the catalytic properties of the hybrid materials
Understanding system robustness and recyclability
BA
C
Pd
Pd
L
LL
Objectives
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Reversible addition−fragmentation chain-transfer polym
Rizzardo, E. Thang, S. H. Macromolecules, 1998, 31, 5559.Matyjaszewski K. et al. Materialstoday 2005, 8, 26; Prog. Polym. Sci. 2007, 32, 93.
Mechanism superimposed on a conventional free radical polymerization Predictable size and narrow Mn distribution (chain length and molar mass distribution depend
directly on the monomer/control agent ratio). Large range of monomers: (meth)acrylates, (meth)acrylamides, vinyl, … Fast initiation, absence of termination… Polymer architecture (alternate or gradient copolymers; one or more blocks; ...)
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1/2 Init Init
+
Init
Pn (n=1)
Pn
Pn+1Pn
kppropagation
initiation
n n+1
S S
ZR+
S S
ZRP
kadd
k-add
k
k-
S S
ZP + R reversible chain transfer
/ propagation
R +R
Pmre-initiation
S S
ZPm
+S S
ZPmPn
kadd
k-add
k
k-
S S
ZPn +
degenerativechain equilibration/ propagation
M
M
Pn
kp
Pn
kp M
M
Pm
kp M
terminationPn+ Pn Pmkt
Pn
Reversible addition−fragmentation chain-transfer polym.
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Reversible addition−fragmentation chain-transfer polym.
PDMAAm =
Hawker, C. J.; et al. J. Am. Chem. Soc 2007, 129, 14493
MacroRAFTMn
LS = 14.2 kg/mol Mw/Mn
PMMA = 1.3
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V-50
Water, 70°C
PDMAAm-b-P(DEAAm-co-DMAEA-co-MBA) NG
Solvophobic
Solvophilic
Insoluble
Soluble
DEAAm85%
PDMAAm DMAEA10%
MBA5%
macroRAFT
Core monomerLCST~30-40°C Cross-linker
Pd coordination
Nanogel synthesis
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V-50
Water, 70°C
PDMAAm-b-P(DEAAm-co-DMAEA-co-MBA) NG
DEAAm85%
PDMAAm DMAEA10%
MBA5%
macroRAFT
Core monomerLCST~30-40°C Cross-linker
Pd coordination
Nanogel synthesis
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SEC
MacroRAFTMn
LS = 14.2 kg/mol Mw/Mn
PMMA = 1.3
NGMn
LS = 13.4 x 103 kg/molMw/Mn
PMMA = 1.8Nagg = 240
DLS @ 20°C
TEM
Nanogel characterization
Solvent DZ(nm) PDI
___ H2O 67 0.09
- - - DMAc 82 0.13
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rt, 24h
NG + Pd(OAc)2PdNP@NG
precipitationDCM + EtOH
40°C, 24h
i) Pd(OAc)2DCM, rt
ii) EtOH, 40ºC
Functionalisation with Pd nanoparticles
dialysislyophilized
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XPS
Dn = 2.9 ± 0.6 nm~868 Pd atoms /NP
Oxidation state (%)
PdII Pd0
24 76
Pd content (wt%)
ICP-MS XPS TGA
0.95 1.3 1.4
Characterization of PdNP@NG
TEM
1 10 100 1000 10000
Inte
nsity
Dh /nm
NG
PdNP@NG
DLS 20°C (H2O)
Dh = 104 nm
Pd 3d 5/2Pd 3d 3/2
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The Mizoroki-Heck reaction
Spectroscopic yields
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Isolated yields
X = Br X = I
The Mizoroki-Heck reaction
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Isolated yields
The Mizoroki-Heck reaction
X = Br X = I
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Isolated yields
The Mizoroki-Heck reaction
X = Br X = I
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The Mizoroki-Heck reaction
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0
1000
2000
3000
4000
5000
0,00
20,00
40,00
60,00
80,00
100,00
1st 2nd 3rd 4th
Accumulated TON(mol accumulated product / mol Pd)
Yield (%)
Spectoscopic yieldIsolated yield
Acc. TON
97 999292 95
88
970
1960
28803210
33
Hybrid Nanogel Recycling
tenfold scale up
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Reactionmixture
Precipitation in Et2O
products (and
substrates)
Dissolved in water
Solid
LyophilisationCatalyst Recycling
Solution
Dialysis
PdNP@NG Recycling
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4 cycles
TEM XPS
After 4 cycles of catalysis
ICP-MS XPS
PdNP@NG Pd cont (wt%) %Pd(II) %Pd(0)
t0 0.95 24 76
After 4 cycles 0.22 93 7
TEM
Pd leaching out of the NG
Pd content
Phase ppm % total Pd
Organic 76.6 19
Aqueous 0.04 2
Ostwald ripening
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Spectroscopic yield
Addition of 4-PVP (Mn = 50 kg/mol)
Pd leaching test #1
4-PVP
Macromolecular base
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PEG-methacrylate: Mn=1.1 kg/mol
Pd leaching test #2
Macromolecular substrate
R yield(%)Bu-n 60
[CH2CH2]nOMe 60 Br
O OPEG
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Proposed mechanism for the PdNP@NG cat Mizoroki-Heck rxn
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alkeneinsertion
E
R
XPdII
R
XPdII
E
alkenecoord.
R
XPdIIE
R
XPdII
E
H
B
BHX
dehydropalladation
reductiveelimination
Pd0
partialredeposition ?
R X
N
O
O
O
N HN O
HN
OO
N
N
O
O
O
NNHONH
O O
N
Pd0
Pd0
Pd0Pd0
Pd0Pd0
Pd0
Pd0
Pd0
PdNp@NG
increasiglylarge Pd0
clusters
PdNp@NG - Pd0
PdNp@NG - Pd0
oxidativeaddition/ leaching
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Well defined core-shell nanogels NG have been synthesised and characterised
RAFT aqueous dispersion polymerisation process
Pd0 NP were incorporated (~1.3 wt%) PdNP@NG
Long-term stability even under air and moisture
Nanogel Pd is an active catalyst in the Mizoroki-Heck reaction in 0.1 wt%
Substrates: bromo- and iodo-arenes (accumulated TOF: 2880)
The hybrid materials can be recycled up to three cycles
Leaching of Pd lead to the formation of Pd(II)
Conclusion part I
Pontes da Costa, A.; Rosa Nunes, D.; Tharaud, M.; Oble, J.; Poli, G.; Rieger, J. ChemCatChem, 2017, 9, 2167 -2175
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From agricultural waste to furfural
Furfural and Derivatives – Ullmann’s Encyclopedia of Industrial Chemistry 2012, Wiley-VCHZeitsch, K. J. The chemistry and technology of furfural and its many by-products, 2000 vol 13, Elsevier Lichtenthaler F. W. Acc. Chem. Res. 2002, 3, 201
corn cobs oat hulls wood chips bagasse
O CHO
furfural
alkaliacid
acid
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From furfural to bulk chemicals
López Granados, M.; et al., Energy Environ. Sci. 2016, 9, 1144
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Look for new reactivities on furfural
Formyl function Aromatic nucleus Three different aromatic C-H bonds
The challenge: C3 alkylation of furfural via catalytic directed C-H activation
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Related “cat C-H” activation precedents
Doucet H. et al. Chem. Cat. Chem. 2012, 4, 815
Miura M. J. et al. J. Org. Chem. 2013, 78, 7126
Chatani, N.; Murai, S. et al. J. Org. Chem. 1997, 62, 5647.
Darses, S.; Genet, J. P. et al. Angew. Chem. Int. Ed. 2006, 45, 8232 ; J. Am. Chem. Soc. 2009, 131, 7887.
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Start of the project
Murai, S.; Kakiuchi, F.; Chatani N. et al. Nature 1993, 366, 529
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The first - disappointing - trials
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From imino coordination to amino-imino chelation
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Amino-imines as chlelating groups
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Scope with vinylsilanes
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Scope with styrenes
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Scope from HMF derived substrates
Entry Imine R’ R’’ t(h) Yield (%)
chromat. w/t chromat
1 DEAEIF TBDMS Si(OEt)3 5 57
2 PEIF TBDMS Si(OEt)3 5 44
3 DEAEIF TBDMS Si(OMe)3 16 59
4 DEAEIF TBDMS SiPh3 17 62 66
5 DEAEIF Ac Si(OEt)3 5 NR
6 DEAEIF Bn Si(OEt)3 5 20
7 DEAEIF THP Si(OEt)3 5 NR
8 DEAEIF Tr Si(OEt)3 17 17
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Scope: C5 substituted furfurals
Entry R R’ t(h) yield (%) lin/br
9 CH3 Si(OEt)3 5 56 (64)
10 CH3 SiMe2(OEt) 5 40 (65)
11 CH3 Ph 17 38 88:12
12 Ph Si(OEt)3 16 20
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Energetic profile 1
A
TSAB
B
TSBC
C
C’
TSC’D
D
TSDE
E
0
9 914
5
10
23 23
G (kcal/mol)
Free energy (kcal/mol)M06/(3-21G + fpf Ru, 6-311++G** others, Toluene, PCM, SMD)//PBE0/(SDD + fpf Ru, 6-31G** others)
agostic C-H coord. oxidative additionamine decoord. / 2-alkene coord. 2-alkene rotation
14
+20
-20
TDI
TDTS
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Energetic profile 2
14
G (kcal/mol)
20
1012
20
-8
11
0
E
TSEF
FF’
TSF’G
G
TSGH
H
A
agostic C-H coord. agostic C-H switch
Free energy (kcal/mol)M06/(3-21G + fpf Ru, 6-311++G** others, Toluene, PCM, SMD)//PBE0/(SDD + fpf Ru, 6-31G** others)
alkene insertion
-16
0
+20
-20
reductive elimination
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39/41Global mechanism
1/3 [Ru3(CO)12]
2CO
O NN
Ru
ON
NRuH
= CO
O
N
N
Ru
HSi(OMe)3
O
N
N
RuH Si(OMe)3
O NN
Si(OMe)3
O NN
H
H
HH
H
H O NN
H
O NN
RuH
H
HSi(OMe)3
H
Ru
H
NO
Si(OMe)3H
Ru
H
NO
(MeO)3SiH
NN
RuN
O
(MeO)3Si
N
RuN
O
Si(OMe)3
N
HH
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Pezzetta, C.; Veiros, L. F.; Oble, J.; Poli, G. Chem. Eur., 2017, 23, 8385-8389
Conclusion part II
First example of directed olefin insertion at C3 of furfurals (Murai reaction)
Use of a removable iminoamine N,N’-bidentate directing group is the key to success
DFT calculations provided a plausible catalytic cycle to put forward.
Breakthroughs in the valorization of lignocellulosic biomass substrates
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