catellani reaction
DESCRIPTION
Catellani Reaction. 2011.04.09. Contents. Introduction. Mechanism. Synthetic Applications. Conclusions. Introduction. The Nobel Prize in Chemistry 2010. Richard F Heack University of Delaware, Newark,DE,USA. Ei-ichi Negishi Purdu University, West Lafayetle,IN,USA. Akira Suzuki - PowerPoint PPT PresentationTRANSCRIPT
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化 学 系Department of Chemistry
Catellani Reaction
2011.04.09
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Introduction
Mechanism
Synthetic Applications
Contents
Conclusions
2
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The Nobel Prize in Chemistry 2010
Richard F HeackUniversity of Delaware,Newark,DE,USA
Ei-ichi NegishiPurdu University,West Lafayetle,IN,USA
Akira SuzukiHokkaido University,Sapporo,Japan
For palladium-catalyzed cross-coupling reactions in organic synthesis.
Introduction
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Marta Catellani
1971,obtained Italian laurea under supervition of Prof. G. Casnati at the University of Parma . 1977,started to work on homogeneous Catalysis with group metals, Ⅷ G.Casnati Group 1978-1979, Postdoc, UC, Prof. J. Halpern 1989-1990, short periods in Sheffied,Tsukuba,Russia and China. 1990-present, full professor at Uiversity of Parma.
Catellani M, Angrew. Chem. Int. Ed. 1997,36,119-122.
Introduction
H
I
H+ I R1
R2+
Pa(0) cat, base
DMA, 20oC, 30hR1 R1
R2
Yield: 31~100%E type: 89~95%
R
R=H, Me, CO2MeR1=n-Bu, BnCH2,n-OctR2=CO2Me, Ph, n-Hex
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Introduction
Role of Norbornene :1. Essential for this reaction to occur;2. Plays as a catalyst;3. More than stoichiometric norbornene is necessary
norbornene
.
.
.
Catellani Reaction is defined as
Norbornene-mediated
Ortho C-H Functionalization.
5
R1
R2
R
H
X
R
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Mechanism
R1= Alkyl, ArylR2=Aryl, Alkenyl, H, CNR = H, or bulky substisuents
R1
PdllX
RPd0
H
PdllX
R
H
R
R2-Y
R1
R2
R
H
X
R
XPdll
Base
Base•HX
R
Pdll
R1-X
R
PdlV
X
R1
R
R1
XPdll
Ternination
Oxidative Addition 1
Carbopalladation with norbornene
Palladacycle
Oxidative Addition 2
Reductive Elimination
Norbornene Extrusion
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Oxidation Addition 1
Pd0
H
X
R
R1-X
H
PdllX
R
R1-PdllX
R1=alkyl, path 1 predominates.
R1=aryl , it depends on Ligands.
Path 1
Path 2
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Carbopalladation of Norbornene
Pd0
H
PdllX
R
tranditional cross-copling
carbopalladation of norbornene
R2-Y
H
R2
R
H
R
XPdll
X-Y +
?
1. High reactivity (strain energy 90.4 kJ/mol)
2. Superstoichiomeric quantities
Favored
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PdllCl
ClPdll
Phenylnorbornylpalladadium(Ⅱ) dimer
PNP dimer
Inoue M, Tedrahendron Lett.,1974(15),8,647-650.
I
+ I n-BuCO2Me
+
K2CO3(2.0 eqv)
DMA, 20oC, 30h
n-Bu n-Bu
CO2Me
Yield:93%
10mol%PNP dimer
1.0 eqv 1.5 eqv2.0 eqv
+
1.0 eqv
Catellani M, Angrew. Chem. Int. Ed. 1997,36,119-122.
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Carbopalladation of Norbornene
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Palladacycle Formation
-Hybride Elimination
H
R
XPdll
?
R
Pdll
H
R
palladacycle formation
1.Inability of bicycle system for beta-Hybride elimination
2.Electrophilic aromatic substisution at ortho aromatic carbon
10
Sicher J. Angrew. Chem. Int. Ed. 1972,11,200-203
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Palladacycle Formation
XPdllPdll
L
+L
-X
PdllL
L
H
-H
R R R
EAS:
Parshall G W. Acc Chem Res,1970(3),139-144.Markies BA. J Chem Soc Chem Commun ,1992, 1420-1423.
Wheland-type Intermediate
rate limiting step.
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ESA: electrophilic aromatic substitution
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Pdll
Py
-KCl
Pdll-PhOH
R R
Py
ClPhOK
Pdll
Py
R
Py
PhO PyPy
O PdII
H
D
ClPh3P
PPh3
PhOK
or Ag2CO3
H
PdII
O
Ph3P PPh3
D
PdII
O
Ph3P PPh3
+
1 : 1
Supports ESA for deprotonation is not rate limiting.
Echavarren AM .Chem Eur J. 2001(7), 2341-2345.
R NO2 H OMe
Minutes for 50% conversation
240 100 10
Catellani M . J Organomet Chem ,1992, 425:151
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Palladacycle Formation
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Oxidative addition 2
R
Pdll
Palladacycle R
PdlV
X
R1R1-X
A side product ofen seen:
Pdll
Palladacycle
reductive elimination
Pd0
+X
1.0 eqv2.0 eqv
Pd(PPh3)4K2CO3
DMF,105oC
X=Br, ndX=I, 62%
Catellani M, Synthesis, 1996,769-772
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I
NTs
I
Pd(AcO)2(15 mol%)PPh3(33 mol%)norbornene(7 equiv)Cs2CO3(5 equiv)
DME, wave,180oC N
CO2tBu
Ts
CO2tBu+
14
Addition with Alkyl Halides
1,10-phenanthroline
Ligand:
Catellani M, J Organomet Chem, 1993 .458:C12
Lautens M. Angew Chem Int Ed,2007,1485-1488
Oxidative addition 2
80% ee 63%ee
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Addition with Aryl Halides
Catellani Mechanism:
R
Pdll
Palladacycle R
PdlV
X
ArylAryl-X
Echavarren Mechanism:
R
Pdll
Palladacycle
Aryl X
Pd0
Aryl PdIIX
R
Pdll
Pdll
X
Aryl
Oxidative addition 2
Catellani M, J Organomet Chem, 1991 .407:C30
Echavarren AM .J Am Chem Soc. 2006(128), 5033-5034.
Low energy
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Reductive Elimination
PdIIN
N
Br
O2N PdIV
O2N
Br
N
N
NO2
PdII Br
NN
NO2
PdII Br
NN
Catellani M. J Organomet Chem,1990.390:251
Not observed
sp2-sp3 bond formation
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sp2-sp2 bond formation
PdIIL
LPdIV
Aryl
R
Aryl
X
XL
L
R
R=bulkylPdII
X
L
LR
Aryl
R=H
PdII L
L
Aryl
X
The Ortho Effect
Reductive Elimination
Catellani M. J Organomet Chem,1991.407:C30
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Norbornene Extrusion
PdIICl
2
2F
Br
K2CO3
DMF
PdII
Br
F
F
L1
L1
L1=DMF
+ then
N
CO2MeF F
PdIIL2 L2
Br
L2
Steric factors!
Characterized by NMR
I
O
I
CO2t-Bu
Pd(AcO)2 15mol%PPh3(33mol%)
Cs2CO3(5 equiv)
DME, uwave,180oC
7 equiv
O
CO2t-Bu
47%Lautens M .J Org Chem, 2009(74). 289-293
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Terminating Events
R1
PdllX
R
Nu HR1
Nu
R
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Pd0
PdII
R1
R2
R1/R3
R2PdII
R3
Z
R1/R3
R2Z
R3
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Synthetic Applications
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Mizoroki-Heck
R1
R2I
R3 I+EWG+
Pd(AcO)2(20mol%)K2CO3(5.2 equiv)KOAc(5.2 equiv)
DMF, 55oC
2 equiv
R1/R3
R2
R3
EWG
Intermolecular
Catellani M, Angrew. Chem. Int. Ed. 1997,36,119-122.
R3=alkyl
R1 I+EWG+
Pd(AcO)2(10mol%)PPh3(20 mol%)CsCO3(3-5 equiv)
CH3CN or DME, 80oC
6 equiv
X
I
X
EWG
R1
Mark. Lautens. Org Lett .2006,8,3939-3942.
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I+
Y
X
Y
X
( )n
( )n
R1 R3
R2
Pd(AcO)2(10-20mol%)PPh3(22-44mol%)
norbornene(3-5equiv)Cs2CO3(5 equiv)
DME, 60-180oC
I
R1
Y
Y ( )n
( )n
O
O
NHt-Bu
87%
TsN
O
Ot-Bu
S
S
O
Ot-Bu
O
ON
MeO
54% 52% 57%
O Si
Si
O
Ot-Bu
O
60%
Lautens M. Org Lett, 2003(5). 4827Lautens M. Synlett, 2006. 2629Lautens M. J Org Chem, 2007(72). 775Lautens M. Angew Chem Int Ed, 2007(46). 1485
Mizoroki-Heck
Intermolecular
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I+ CO2Me +
Br Br
NO2
OHPd(OAc)2(1.25mol%)norbornene(0.8 equiv)K2CO3(3.2 equiv)
DMF, 105oC
1 equiv 3.2 equiv 1 equiv
O
Br
NO2
CO2Me
86%
Catellani M, Org Lett. 2006(8). 3967Catellani M, Synthesis. 2008. 995
Oxyl-Micheal addition
Mizoroki-Heck
Intermolecular
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R1
R2 +Br
R3
R4
( )n
1 equiv 3-5 equiv
Pd(AcO)2(10 mol%)tri-2-furylphosphine(20 mol%)norbornene(2-6 equiv)Cs2CO3(2-6 equiv)
CH3CN or DME, 85-100oC
R1 R3
R2 R4
( )n
Lautens M (2000) Angew Chem Int Ed 39:1045Lautens M (2001) J Org Chem 66:8127Lautens M (2005) Tetrahedron 61:6283Lautens M (2002) J Org Chem 67:3972
Mizoroki-Heck
Intramolecular
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I
O
I
CO2t-Bu
Pd(AcO)2 (15 mol%)PPh3 (33 mol%)norbornene (7 equiv)Cs2CO3 (5 equiv)
DME, uwave,180oCO
CO2Me
H
82% ee 78%(80% ee)
Lautens M .Angew Chem Int Ed. 2007(46). 1485Lautens M .J Org Chem. 2009(74). 289
Mizoroki-Heck
Intramolecular
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I
R1
R2
+ R3 Br ArB(OH)2+
Pd(AcO)2 (1 mol%)norbornene(1 equiv)K2CO3(6 equiv)
DMF, rt.
Ar
R1/R3
R2 R3
MeO2C
MeO2C
90% 89%
89% 71%
Catellani M. Chem Commun, 2000. 157
OMe
MeO
MeO2C
MeO2C
88% 82%
89% 71%
I
R1
+ ArB(OH)2
Pd(AcO)2 (1 mol%)norbornene(1 equiv)K2CO3(4 equiv)
DMF, 105oC
R1
R1
Ar
Catellani M. J Mol Catal A: Chem. 2003. 115
Suzuki-Miyaura
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Cassar-Sonogashira
I+
R1
R2 X +Ph
Pd(AcO)2 norbornene
K2CO3
DMF,rt.
R2
R1 R2
Ph
Yield promoted By KOAc ,Excess alkyl halide
I+
F
R2 X +Ph
Pd(AcO)2(10 mol%) norbornene(1.2 equiv)
KOAc(6 equiv)
DMF,rt.F
Ph
1 equiv 4 equiv 1.2equiv79%
Catellani M. J Organomet Chem. 2004. 689:3741
Copper –free!
~50%
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I
Pd(AcO)2norbornene
Ligand
n-BuIcranide source
bae
CN
CN
NC
NC
Lautens M. JACS. 2006,128, 14436-14437;
R1
I
H
R2 + Ar Br
Pd(AcO)2(2.5mol%)tri-furylphosphine (6mol%)
K4Fe(CN)(5.5 equiv)norbornene(1.5 equiv)
Cs2CO3(1.5 equiv)
CH3CN,130oC uwave
R1
CN
Ar
R2
CN
O
61%
CN
CF3
CN
OMe
94%
56%
Cl CN
SO2Me
62%
Cyanation
Lautens M . JACS. 2007,129, 15372-15372;
Zn(CN)2K4Fe(CN)6
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Direct Arylation
C-H activation of arene is difficultCatellani reaction is a powful strategy for direact arylation.
R
I2 R1C CR2+
Pd(AcO)2
(R2)R1 R1(R2)
R
R
Marta.Catellani. Org Lett. 2001,3611-3614.
Base effect : K2CO3&Bu4NBr >> Cs2CO3&KOAcSolvents : DMF>>DMA>>acetontrile
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60-94%
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Direct Arylation
O2N N
CO2Me
86%
Cl
OMe
OMe
NCO2Et
75%
N
O62%
N
N
N
O
O
39%
R1
I
H
R2+
Pd(AcO)2(10mol%)tri-furylphosphine (22mol%)
norbornene(2 equiv)Cs2CO3(2 equiv)
CH3CN, 90oC
R1
R2
YNH
R3
Br( )n
R4
1 equiv 1.5~2 equiv
NY
R3
( )nR4
Mark Lautens. JACS,2005,13148; JOC,2008,1888; OL,2006,3601OL, 2006,2043.
S
Cl
S
AcHNO
S
O2N
O
Cl
77% 70% 66% 53%
Mark Lautens. JOC,2008,8705; OL,2006,4827
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Buchwald-Hartwig Reaction
Marta Catellani. OL. 2004,4759
R1
I
H
+
Pd(AcO)2( 5mol%)tri-furylphosphine (10mol%)
norbornene(1.5 equiv)K2CO3(2 equiv)
CH3CN, 85oC
R1
1 equiv 1 equiv
Br
HN
R2
Ar
N
R2
O
Ar
N O N O
S
N O
O
N
N
O
Ph
Ph
80% 78%
48% 63%
R1
I
H
+
Pd(AcO)2( 10mol%)tri-furylphosphine (22mol%)
norbornene( 2 equiv)Cs2CO3( 4 equiv)
CH3CN, 135oC
R1
2 equiv 1 equiv
Br
HN
R3
R2
( )nR2
NR3
( )nN
NO2
N N
NO2
NCO2Et
86% 45%
55%66%
Mark Lautens. OL. 2007,5255
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Addition to C=O/C=N and C=C Bonds
R1
IR2 +
R3
X
R4
Y
Pd(AcO)2(10mol%)Ph3P(10-22mol%)
norbornene(0.5~3equiv)Cs2CO3(1-2 equiv)
H2O(0-48 equiv)
R1
R2
R4
R3YH
X= Clor
R1
R2
R4X= BrR=OMe
YDME, 90oC or 150oC
F
OH
F
NHSO
OMe O OH
86% 37%
83% 70%
I+ Br
NHBoc
+
O Ot-Bu
Pd(AcO)2(10mol%)tri-2-furylphosphine(20mol%)
norbornene(2 equiv)Cs2CO3(2 equiv)
DMF, 80oC NBoc
Ot-Bu
O
68%1 equiv2 equiv 2 equiv
Catellani M. Tetrahedron Lett, 2004(45),6903-6907.
Mark Lautens. AICE. 2009,1849
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Conclusions
Catellani reaction is a useful and mechanistically interesting method for the polyfunctionalization of aromatic
molecules.