Post on 31-Mar-2015
1
Homogeneous Gold Catalysis – A Homogeneous Gold Catalysis – A
Reactivity PerspectiveReactivity Perspective
Dongxu ShuDongxu Shu
Tang Research GroupTang Research Group
12, 10, 200912, 10, 2009
2
ContentsContents
Relativistic effect and reactivity
π-acidity reactivity
Gold catalyzed coupling reaction
Summary
3
Features of Gold CatalysisFeatures of Gold Catalysis
π-acidity: soft Lewis acid, preferentially activate π-systems
AuI and AuIII
AuI: d10, linear bicoordinate geometry, difficult in asymmetric catalysis
Noβ-H elimination
Reluctant to undergo oxidative addition and reductive elimination
4
Relativistic Effect Relativistic Effect
Lower 6s and 6p, higher 5d
Pyykko, P. et al. Acc. Chem. Res. 1979, 12, 276.
5
Origin of Origin of ππ–acidity and Alkynophilicity–acidity and Alkynophilicity
• π-acidity of R3PAu+
1) lower LUMO
2) poor back donation
• Alkynophilicity
1) kinetic in origin
2) LUMO of alkyne is lower
Hertwig, R. H. et al. J. Phys. Chem. 1996, 100, 12253.
Toste, F. D. et al. Nature. 2007, 446, 395.
ΔG ≈ -10 kcal/mol
AuR3P
AuAu
AuNu faster than AuNu
6
ContentsContents
Relativistic effect and reactivity
π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene
Gold catalyzed coupling reaction
Summary
7
ππ-Acidity-Acidity ReactivityReactivity
RearrangementEliminationNu attack
CyclopropanationC-H insertion
AuR
L
AuLR
Au
Au
Nu E
Nu
Nu
Au
E
Nu
E
Nu
Au
E
8
Carbene or CarbocationCarbene or Carbocation
Fürstner, A. et al. Angew. Chem. Int. Ed. 2009, 48, 2510.
Au Au
O O[(R3P)Au] [NTf2]
O O
AuPPh3
OO
Ph3PAu1
2
3
-78oCNTf2 NTf2
OO
Ph3PAu1
2
3 <7.2 kcal/molOO
Ph3PAu1
2
3
9
Carbene or CarbocationCarbene or Carbocation
Goddard, W. A. Toste, F. D. et al. Nature Chem. 2009, 1, 482.
O
O Ph
Ph
LAuCl, AgSbF6
CD2Cl2 O
O
Ph
Ph
O
O Ph
Ph
LAuCl, AgSbF6
CD2Cl2 O
O
Ph
Ph
Ligand Yield
P(OMe)3 0%P(OPh)3 11%PPh3 52%PMe3 56%NHC 80%
OO
Ph3PAu1
2
3
<7.2 kcal/mol
Au
PMe3
Calculated: 22.5 kcal/mol
Au
PMe3
10
Early ResearchEarly Research
Thomas, C. B. et al. J. Chem. Soc. Perkin Trans. II 1976, 1983.
Teles, J. H. et al. Angew. Chem. Int. Ed. 1998, 37, 1415.
Ph Ph + MeOH
Ph3PAuMeMeSO3H
solvent-free
20-50 0C
OMe
PhPh
TOF: Ph3P (610 h-1) < (MeO)3P (1200 h-1) < (PhO)3P (1500 h-1)
TON: Ph3P (5000) > (PhO)3P (2500)
R1 R2
7 mol% H[AuCl4]
MeOH/H2O, 650C
R1R2
O
+ R1R2
O
+ R1
OMe
R2
+ R1
Cl
R2
AuPh3P MeSO3
AuL X
11Hashmi, A. S. K. et al. Angew. Chem. Int. Ed. 2009, 48, 8247.
Stereoselectivity and RegioselectivityStereoselectivity and Regioselectivity
Au
Nu
Au
Nu
antiStereoselectivity
R
AuAuR
Au
RRegioselectivity
•
Au AuAu
HN
OPh
R
Au
R = H5-exo-dig
R = H6-endo-dig
O
NPh
O
NPh
R
Au(IPr)
Can be isolated
O
NPh
R
HH
C Hg
12
ContentsContents
Relativistic effect and reactivity
π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene
Gold catalyzed coupling reaction
Summary
13
Reactivity Pattern of EnyneReactivity Pattern of Enyne
Furstner, A. et al. Angew. Chem. Int. Ed. 2008, 47, 5030.
Au
Au Au
Au Au
Further transformation
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Cycloisomerization of 1,6-Enyne With Cycloisomerization of 1,6-Enyne With Skeletal RearrangementSkeletal Rearrangement
Echavarren, A.M. et al. Angew. Chem. Int. Ed. 2004, 14, 2402.
Echavarren, A.M. et al. Angew. Chem. Int. Ed. 2005, 44, 6146.
MeOOC
MeOOC
[AuCl(PPh3)]/AgSbF6 (2 mol%)
CH2Cl2, r.t., 25min91%
MeOOC
MeOOC
1 2
34
12
3
4
MeOOC
MeOOC
[AuCl(PPh3)]/AgSbF6 (2 mol%)
CH2Cl2, r.t., 5min95%
MeOOC
MeOOC
MeMe1 2
3
4
1 24
3
Single Cleavage
Double Cleavage
P Aut-Bu
t-Bu NCMe
SbF6
A
15
Mechanism – From Cyclobutene?Mechanism – From Cyclobutene?
Echavarren, A.M. et al. Chem. Eur. J. 2006, 12, 5916.
Z
H
AuH
Z
H
Conrotatory openingAu
MeOOC
MeOOC
COOMe
Pd catalyst,
60 oC COOMe
MeOOC
MeOOC
P Aut-Bu
t-Bu NCMe
SbF6
A
MeOOCMeOOC A (2 mol%)
CH2Cl2, r.t.(80%)
MeOOC
MeOOC
H
HH
25.7
21.6
16
Mechanism of Skeletal RearrangementMechanism of Skeletal Rearrangement
R2
AuR1
H
R2 R1
Au
HR2
R1
R2
R1
AuR1
H
R2
R2
H
AuR1
R1
R2
R2
R1
Single Cleavage
Double Cleavage
Echavarren, A.M. et al. Chem. Eur. J. 2006, 12, 5916.
17
Toste, F. D. et al. J. Am. Chem. Soc. 2007, 129, 5838.
Mechanism of Skeletal RearrangementMechanism of Skeletal Rearrangement
H
MeOOC
MeOOCPh
AuH
H
MeOOC
MeOOCPh
Au OSR2
O=SR2
H
MeOOC
MeOOCPh
OH
H
H
H AuMeOOCMeOOC
O=SR2
H
H
H OMeOOCMeOOC
Ph
HMeOOC
MeOOC
MeOOC
MeOOC N NR RL=
18
ContentsContents
Relativistic effect and reactivity
π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene
Gold catalyzed coupling reaction
Summary
19
Propargylic Ester Reactivity PatternPropargylic Ester Reactivity Pattern
Nolan, S. P. et al. Angew. Chem. Int. Ed. 2007, 46, 2750.
O O
R1
R2
R3Au
5-exo-dig
6-endo-dig
AuR3
OR2
O R1
R2 •
R3
OR1
OAuO O
R1
R2
Au
OO
R1
R2
AuR3
Carbene-typereactivity
alleneactivation
overall [3,3] rearrangement
R3
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5-exo-dig VS 6-endo-dig5-exo-dig VS 6-endo-dig
Nolan, S. P. et al. Angew. Chem. Int. Ed. 2006, 45, 3647.
Toste, F. D. et al. J. Am. Chem. Soc. 2009, 131, 4513.
OAc
RAu
5-exo-dig OAc
RAuR = H
C-H insertionOAc
1,2-shift
•OAc
R
Au
ROac
[3,3]R = alkyl
1
2
R
Ph
O
Ph
O
t-Bu
18
•
Ph
O
Ph
O t-Bu18
Ph
Ph
O t-Bu
O18
6-endo-dig
21
Carbene Reactivity through 5-exo-digCarbene Reactivity through 5-exo-dig
Uemura, S. et al. Tetrahedron Lett. 2003, 44, 2019.
Toste, F. D. et al. J. Am. Chem. Soc. 2005, 127, 18002.
OAc
Ph
OAcPh
[RuCl2(CO)3]2
AuCl3 also work
OAc
Ar
OAcAr
2.5% [Au], 5% AgSbF6
MeNO2, 25 oC, 20min
[Au] =
O
O
O
O
PAr2AuCl
PAr2AuClAr =
t-Bu
OMe
t-Bu
76-94% e.e.
22
Allene Activation through 6-endo-digAllene Activation through 6-endo-dig
Zhang, L. et al. J. Am. Chem. Soc. 2005, 127, 16804.
Zhang, L. et al. J. Am. Chem. Soc. 2007, 129, 11358.
Pt>
Au
[3, 3] O
O
N
•
Bu
[M]
O
O
N Bu
M
N
O
O
Bu
[M]
M=Au
M=Pt
N
O
O
Bu
N
O
O
Bu
Bu
MeO
ON
N
O
O
Bu
Pt
23
ContentsContents
Relativistic effect and reactivity
π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene
Gold catalyzed coupling reaction
Summary
24
Vinyl Allene as SubstrateVinyl Allene as Substrate
Malacria, M. et al. J. Am. Chem. Soc. 2009, 131, 2993.
R1 R2R1 R2
•n-C5H11
m-CPBA
CH2Cl265%
On-C5H11
[O]
On-C5H11O
n-C5H11
Au
n-C5H11
Au
Aun-C5H11
•n-C5H11
Au n-C5H11
•n-C4H9
AuCl(PPh3) / AgSbF6 (2 mol%) n-C4H9
CH2Cl2, r.t., 10min80%
25
Vinyl Allene as SubstrateVinyl Allene as Substrate
Malacria, M. et al. J. Am. Chem. Soc. 2009, 131, 2993.
OAc
( )n
AuAcO
( )n( )n
AcO AcO HH
( )n
n = 1, 83%n = 2, 97% n = 3, 86% n = 4, 100%
n = 5, 99%
OAc
( )n•
OAc
( )n
Au
AcO
AcO Au AcO
Au
AcO
H
Au
AcO
H
AcO
Au
AcO
H
AcO
HH
[3,3]
26
Toste, F. D. et al. J. Am. Chem. Soc. 2009, 131, 6348.
Mascarenas, J. L. et al. J. Am. Chem. Soc. 2009, 131, 13020.
TsN
•
1
L*-AuCl, AgSbF6
CH2Cl2, -15 oCTsN
H
H
yield: 92%ee: 92%
O
OP N
Ph
PhL =
Allene for CycloadditionAllene for Cycloaddition
•MeOOC
MeOOCD
5%, LAuCl5%, AgSbF6
CH2Cl2, r.t.
MeOOC
MeOOCH
HDH
MeOOC
MeOOCH
D
H
1 2 3
L 2:3
P(OPh)3 100:0PPh3 67:33P(t-Bu)2(o-biPh) 4:96
H
27
ContentsContents
Relativistic effect and reactivity
π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene
Gold catalyzed coupling reaction
Summary
28
Early InvestigationEarly Investigation
Kochi, J. K. et al. J. Organomet. Chem. 1974, 64, 411.
Kochi, J. K. et al. J. Am. Chem. Soc. 1976, 98, 7599.
AuPh3P Me I Me
Au
Me
I
PPh3
Me
AuMe PPh3AuI PPh3
Au
Me
Me
PPh3
Me
Me Me
I Me AuMe PPh3 AuI PPh3Me Me
29
Gold Catalyzed Coupling ReactionGold Catalyzed Coupling Reaction
Corma, A. et al. Angew. Chem. Int. Ed. 2007, 46, 1536.
Guo, R. et al. J. Am. Chem. Soc. 2009, 131, 386.
I
AuCl(PPh3)
K3PO4
Cl (HO)2Bnano Au (0.05 mol%)
NaOH, H2O
Combine the Combine the ππ-acidity and Coupling -acidity and Coupling Reactivity Reactivity
Au
Au
NuNu
H
Nu
M (Pd)
M
Nu
R-M (B)Nu
Au
R
Nu
R
H
Combine the Combine the ππ-acidity and Coupling -acidity and Coupling Reactivity Reactivity
OH
•5mol% AuCl3 O
47%O
O
10%
Hashmi. A. S. K. et al. Eur. J. Org. Chem. 2006, 1387.
OH
•
AuIII
O
R
R
AuIII
O
R
R
AuIII
AuIII
R
R
AuIII
O
O
R
R
R
RO
O
R
R
R
R
Combine the Combine the ππ-acidity and Coupling -acidity and Coupling Reactivity Reactivity
Wegner. H. A. et al. Chem. Eur. J. 2008, 14, 11310.
O O HAuCl4 (5 mol%)
tBuOOH
O
O
O
O
yield: 13% - 67%
Zhang. L. et al. Angew. Chem. Int. Chem. 2009, 48, 3112.
NNFCl
2 BF4
Selectfluor
Oxidative CouplingOxidative Coupling
OAc
Me
Bu
[Ph3PAu]NTf2 (5 mol%)
SelectfluorBu
Bu
O
OMe
Me O
BuH
Me
19% 11%
O
BuAu
Me
O
BuF
Me
Oxidative CouplingOxidative Coupling
Zhang. L. et al. Angew. Chem. Int. Chem. 2009, 48, 3112.
OAc
Me
Bu[LAuI]F
F
[LAuI]
OAc
BuAuI
Me
L
O
BuAuI
Me
L
H2O
H+, HOAc
NNFCl
2 BF4
NNCl
2 BF4
O
BuAuIII
Me
L
F
O
BuAuIII
Me
L
F
O
BuAuIII
Bu
O
MeMe
L F
BuBu
O
OMe
Me
R-M
O
BuAuIII
Me
L
F
R
L= Ph3P
O
BuR
Me
Reductive Elimination
• Au
OAcBu
Me
[3,3]
Zhang. L. et al. Angew. Chem. Int. Chem. 2009, 48, 3112.
AuPPh3 AuPPh3 Ph
transmetallation
AuPPh3 Ph
F
Ph
AuPPh3 F
PhPh
F-
PhBF3K
PhB(OH)3
OAc
Me
Bu
BXnPhCH3CN, 80 oC
Selectfluor (2 equiv)
O
BuPh
Me
BuBu
O
OMe
Me O
BuH
Me
Catalyst PhBXn Solvent
1 2 3
1 2 3
[Ph3PAu]NTf2 PhBF3K MeCN PhPhonly
[Ph3PAu]NTf2 PhB(OH)2 MeCN/H2O 20:1 50% 17% 9%
Ph3PAuCl PhB(OH)2 MeCN/H2O 20:1 72% 9% 6%
[Ph3PAu]NTf2 PhB(OCH3)2 MeCN 30% 60% 0%
36
Gold and Palladium Combined for Gold and Palladium Combined for Cross-CouplingCross-Coupling
Hashmi, A. S. K. et al. Angew. Chem. Int. Ed. 2009, 48, 8283.
Blum, S. D. et al. Organometallics. 2009, 28, 1275.
•Me
i-PrO
OEt
Au(PPh3)Cl (1.0 eq.)
AgOTf (1.0 eq.)O
O
AuPh3P Me
i-Pr
PdCl2(dppf)] (1 mol%)
MeCNIPhO
O
PhMe
i-Pr
[L2PdCl2] [L2Pd0]
IPh
PdIIL2
Ph
I
OO
AuPh3P Me
i-Pr
O
Me
i-Pr
PdIIL2
PhO
Me
i-Pr
Ph[Ph3PAuI]
37
SummarySummary
π-acidity reactivity Complexity
1. substrate design
2. coupled with known reactivity (Nazarov, cycloaddition, carbocation)
3. tandem
Gold catalyzed coupling reaction
Combine π-acidity reactivity and coupling reaction 1. Generate more complexity
2. from stoichiometric to catalytic
38
AcknowledgementAcknowledgement
Professor Weiping Tang
Tang Group
Practice talk attendees
Katherine Myhre
Jenny Werness Wei Zhang
Renhe Liu Dr. Suqing Zheng
Xiaoxun Li Dr. Min Zhang
Patrick Robichaux Na Liu
Kyle Dekorver Tianning Diao
39
Goddard, W. A.; Toste, F. D. et al. Org. Lett. 2009, 11, 4798.
Mascarenas, J. L. et al. J. Am. Chem. Soc. 2009, 131, 13020.
•MeOOC
MeOOC
AuR3P
MeOOC
MeOOC
AuR3P
MeOOC
MeOOC
AuR3P
Au
R3PAu
R3P
MeOOC
MeOOC
MeOOC
MeOOC
H
MeOOC
MeOOC
Relativistic Effect Relativistic Effect
• m=m0/[1-(v/c)2]1/2
• r decrease as m increase
• v increase, m increase, radius decrease, s and p orbital lower, d higher
• Unusual higher electronegativity, ionization energy, lower 6s and 6p (LUMO), higher 5d, strong Au-L bond
Pyykko, P. et al. Acc. Chem. Res. 1979, 12, 276.
General Reactivities of Gold CatalysisGeneral Reactivities of Gold Catalysis
[Au]Nu π-Acidity:
Traditional organometallic reactivity:
Oxidative addition and reductive elimination
Transmetallation
C-H activation:
Hydrogenation and Oxidation
H
H
AuIII Au
Au
EE
E