Leyendas puertorriquenas por Cayetano Coll y Toste (volumen IV) T2
New Progress of Gold in Organic Chemistry Recent Contribution of F. Dean Toste
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New Progress of Gold in Organic Chemistry Recent Contribution of F. Dean Toste Department of Chemistry University of Montreal March 17 th , 2009 William S. Bechara Charette Group Literature Meeting
description
Department of Chemistry University of Montreal March 17 th , 2009. New Progress of Gold in Organic Chemistry Recent Contribution of F. Dean Toste. William S. Bechara Charette Group Literature Meeting. Outline. General Properties of Gold - PowerPoint PPT Presentation
Transcript of New Progress of Gold in Organic Chemistry Recent Contribution of F. Dean Toste
New Progress of Gold in Organic ChemistryRecent Contribution of F. Dean Toste
Department of Chemistry University of Montreal
March 17th , 2009
William S. Bechara
Charette Group Literature Meeting
2
Outline
• General Properties of Gold
• Particularities and advantages of Gold in Homogeneous Catalysis
• Relativistic effects of Gold (Quantum Chemistry studies)
• Examples of the Relativistic Effect
• Initial Tryouts with Gold in Organic Chemistry
• Contribution of F. Dean Toste in Homogeneous Gold(I) Catalysis
• Mechanistic Studies
• Applications in Total Synthesis
3
General Properties of Gold
• Oxidation States : Au-I to AuIII and AuV but AuI and AuIII dominate.
• Electronegativity : Au 2.54 (~highest electronegativity of all metals)
• Industrial use : medicine, dentistry, electronics, jewelry, food, etc good resistance to
oxidative corrosion, good conductor of heat and electricity, ductile, malleable….
• Organic Chemistry : heterogeneous and homogeneous catalysis (Au0) (AuI and AuIII)
AuI AuIII
Linear Square Planar
Au : [Xe] 6s1 4f14 5d10
J. Phys. Chem. A, 2006, 110 , 11332
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Advantages of Gold in Organic Chemistry
• Most reactions catalyzed by Au can be done without precautions to exclude air
and humidity (sometimes done in water or MeOH).
• Gold catalysts can be used for heterogeneous and homogeneous catalysis.
• Relatively fast reactions.
• Good potential to stabilize cationic reaction intermediates.
• Versatile Lewis Acid Gold species can activate various substrates, specially
unsaturated molecules. e. g. alkynes, alkenes, allenes, diynes, allenynes,
enynes...
• A wide array of nucleophiles can be added to the activated substrates in an
intramolecular or intermolecular fashion. e.g. O, N, C, F, S.
F. Dean Toste Nature, 2007, 446, 395F. Dean Toste J. Am. Chem. Soc., 2008, 130, 4517Hashmi Angew. Chem. Int. Ed. 2005, 44, 6990
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Particularities of Gold in Homogeneous Catalysts
• Gold catalysts are considered as soft and mostly carbophilic Lewis acid.
• Au(I) complexes are known to activate C-C -bonds towards nucleophilic
addition.
• Au(III) can also complex carbonyls and other heteroatoms (e.g. N, O, S)
• Au(I) species are not nucleophilic (relative to the copper complexes).
• Gold catalysts have a low propensity for β-H elimination and reductive
elimination.
• Au(I) and Au(III) complexes do not readily cycle between oxidation states in the
catalysis. Difficult for cross-coupling.
• Au(I) can pass through a cationic intermediate and a carbenoid species in the
reaction mechanism.
• Strong relativist effect. Relativistic effects are crucial to understanding the
electronic structure of heavy elements.F. Dean Toste Nature, 2007, 446, 395P. Pyykko Angew. Chem. Int. Ed. 2004, 43, 4412 F. Dean Toste Chem. Rev., 2008, 108 , 3351
Relativistic Effect of Gold
• Relativistic Quantum chemistry describes the electron dynamics, chemical bonding and
particularly the behaviour of the heavier elements of the periodic table (specially the
elements in which the 4f and 5d orbitals are filled), aurophilicity (strong Au-Au interaction),
etc.
• It describes that Gold has a relativistic contraction of the 6s and 6p orbitals and an expansion
of the 5d orbitals. This correspond to a lowering of the lowest unoccupied molecular orbital
(LUMO) and therefore a strong Lewis acid.
• It also results in greatly strengthened Au–L bonds (which can induce high chirality).
• Different oxidation state influences the activity of the catalyst.
•
79Au78Pt
77Ir73Ta
80Hg
76Os
81Ti
82Pb
Contraction of 6s and expansion of 5d orbitals
6
6s 4f 5d
Au:
F. Dean Toste Nature, 2007, 446, 395 , P. Pyykko Angew. Chem. Int. Ed. 2004, 43, 4412
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Influence of Oxidation States
• Gold(I) and (III) can furnish different regioisomers :
• Gold(III) catalyses the reaction
by activating the ketone.
• Gold(I) catalyses the reaction
by activating the allene.
O n-Oct
Br
O
O
H
Br n-Oct
[Au]
Br n-OctO n-Oct
Br[Au]
O
Br
H n-Oct
AuCl3 (2 mol%)
PhCH3
Et3PAuCl (2 mol%)
PhCH3
O
[Au]
Br n-OctH
hydride shift
O n-Oct
Br
[(III)Au]
Br
O n-Oct[(III)Au]
< 1: 9995 : 5
V. Gevorgyan J. Am. Chem. Soc., 2005, 127, 10500F. Dean Toste Nature, 2007, 446, 395
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Initial tryouts with Gold in Organic Chemistry
• First attempts using gold catalysis was mainly for oxidations :
• Au(III) species
NH2
R2R1
HAuCl4 (0.3-0.5 eq)
H2O, NaOH (pH~6)
O
R2R1
9 - 72%
SR2R1
Bu4N(AuCl4) (5 mol%)
MeNO2, HNO3 10%S
O
R2R1
76 - 97%
R1, R2 = alkyl
R1 = alkylR2 = aryl or alkyl
J. Org. Chem., 1976, 41, 2742 Tetrahedron 1983, 39, 3181
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Contribution in Homogeneous Gold Catalysis
• Dean was born in 1971 in Azores, Portugal and soon moved to Canada. He majored in Chemistry and obtained a M.Sc. in Organic Chemistry at the University of Toronto with Prof. Ian W. J. Still. He then pursued his Ph.D. with Barry Trost at Stanford and a post-doctoral appointment with Robert Grubbs at Caltech. Dean is currently an Associate Professor of Chemistry at UC Berkeley.
• His main research interest is the Gold(I)-Catalyzed C-C Bond Formation.
• Published around 30 publications (~25 JACS) just on Gold chemistry in the past 5 years.
Prof. F. Dean Toste
Around 10 reviews on gold chemistry in the past few years (2 by Toste).
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Conia-Ene Reaction of -Ketoesters with Alkynes
OR2
O
R1
O
O
R1
R2OO
R3R4
R5
R3
R4
R5
O
R1
R2OO
Ph3PAuCl (1-5 mol%)AgOTf (1-5 mol%)
CH2Cl2, rt, 15min - 24h
O
Me
MeOO
O
Me
MeOO
O
Me
MeOO
O
Me
MeOO
Et PhPh
n-Pr
R1 = Me, R2 = Me 94%R1 = Ph, R2 = Et 93%R1 = Me, R2 = t-Bu 81%R1 = Me, R2 = CH2CCH 79%
95% (17:1) 86% (4.2:1) 96% (4:1) 97% (2.9:1)
H
CO2Me
OOOO
H R3
CO2R2CO2Me
H
CO2Me
O
O
H
CO2Me
99%86%R2 = Et, R3 = H 90%R2 = Me, R3 = Me 83%
88%n = 1 90%n = 2 90%
n
F. Dean Toste J. Am. Chem. Soc., 2004, 126 , 4526
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Proposed Mechanism
Au
D
OH
Me
Au+
O
Me
Au+
CO2Me
CO2Me
OMe
O
Me
O
Au
AcMeO2C
AcMeO2C
AcMeO2C
H+
H+
A
B
OMe
O
Me
O
O
Me
DH
MeOO
O
Me
HD
MeOO
Ph3PAuOTf
H
H
OMe
O
Me
O
Ph3PAuOTf
D
X
O
Me
DAu
MeOO
via in both cases
Syn
Anti
F. Dean Toste J. Am. Chem. Soc., 2004, 126 , 4526
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Allenyne Cycleisomerisation – Activated Ene Reaction
Me
Me
Me
n
n
[(Ph3PAu)3O]BF4 (1-5 mol%)
CHCl3, 60oC, 6-48h
Me
R1
R2
R3
R4
R1
R2
R4R3
H
H
H
Me
H
H
Bn
Me
H
Ph
H
Me
H
CO2Me
CO2Me
H H
H H
Me
CO2EtCO2Et
H
H
HMe
Ph
H
H
HPh
Me
2.4 1
7:1Z:E +
84% 88% 89% 99% 40%
64% 78% 70% 70%cis trans
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
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Mechanistic Studies – Ene Type Reaction
D3C
Me
CD3Catalyst
+
DH2C
DH2C
Me
D
DD
CH2DCatalyst
+
CH2D
D
DDD
D
Me
Me
D3C
D3C
BnPMP+
Me
+
CD3
D
DDH
BnPMP
Catalyst
Me
Me
Me
H
Me
H
Intramolecular proton transfer
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
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Mechanistic Studies
Me
Me
Me
H
Me
H
Me
Me
PPh3Au
Ph3PAu
MeMe
H
Me
MeH
AuPPh3
Ph3PAu
MeMe
PPh3Au
PPh3Au
AuPPh3
MeMe
Me
Me Me
MePh3PAu
Me
Me
Ph3PAu
PPh3Au
AuPPh3
Me
Me
AuPPh3
PPh3Au
A B C D E
F G H I
MonoGold
Phosphine
DualGold
Phosphine
Ene Reaction Metallacycles Vinylidenes -Coordinations
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
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Mechanistic Studies
Me
Me
PPh3Au
A
Me
Me
Bn
H
LDA, THF, -78oC
then Ph3PAuCl Me
Me
Bn
PPh3Au
CHCl3, 60oCNo reaction
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
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Mechanistic Studies
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
Me
Me
Au
Me
HAuPPh3
OxidativeAddition
-HydrideElimination
Ph3PAu
MeMe
H
ReductiveEliminationH
Ph3P
Me
Ph3PAu
MeMe
H
Me
Me
AuPPh3
Computational
Energy Minimization
Ph3PAu
MeMe
H
Ph3PAu
MeMe
PPh3Au
B F
X X XAuPPh3
• Experimentally :
• Computationally :
Similar computational results for dual phosphine gold intermediate
Metallacycles :
17
Mechanistic Studies
Me
MeH
AuPPh3
PPh3Au
AuPPh3
MeMe
Me
Me
AuPPh3
PPh3Au
Computational
Energy Minimization
Me
MeH
AuPPh3
PPh3Au
AuPPh3
MeMe
C G
Very unstable by computational energy minimization, hight G+
Vinylidenes :
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
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Mechanistic Studies
Formation of unstabilized vinyl cation
Need of concerted C-C bond formation and asynchronous hydrogen transfer to avoid
unstable intermediate.
Very hight activation energy (computational calculus) F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
Me
Me
Ph3PAu
Me
Me
Ph3PAu
PPh3Au
D H
H2CMe
Ph3PAu
H
H2CMe
Ph3PAu
HPPh3Au
-Coordinations :
19
Mechanistic Studies
Intermediate I also approved by computational analysis
Me
Me
AuPPh3
Me
Me
AuPPh3
PPh3Au
E I
Me
MeCatalyst
R
R = PhR = Me
No reaction
Me
Me
Bn
PPh3Au
CatalystMe
Bn
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
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Catalytic Cycle
Me
Me
Me
Me
Ph3PAuAuPPh3
Me
Ph3PAuAuPPh3
Me
H
Ph3PAu AuPPh3
Me
C-C Bond formation
1,5-Hydrogen shift
HHH
Catalyst transfer
+
OAuPPh3
AuPPh3
Ph3PAu
-BF4
Me
Me+
OAuPPh3
AuPPh3
Ph3PAu
-BF4
+
OH
AuPPh3
-BF4
Aurophilicity
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
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Synthesis of Benzopyrans
OPivR1
O R2 OR
OPivR1 R2
R
O
OPiv
O
OPivX
O
OPiv
X = Cl 69% 97% ee= Br 60% 94% ee= t-Bu 65% 99% ee= Ph 64% 97% ee= OPh 60% 97% ee
t-Bu
64%98% ee
Ar = Ph 74% 97%eem-MeO-C6H4 78% 99%eep-Cl-C6H4 72% 98%eeo-Me-C6H4 58% 98%ee
O
OPivEt
(R)-MeO-DTBM-BIPHEP(AuCl)2 (5 mol%)AgSbF6 (10 mol%)
MeCN, rt
O
OPiv
Ar Ph Ph Ph
Ph
O
OPiv
Ph
53%99% ee
35%98% ee
44%99% ee
O
OPiv
55%97% ee
O
OPiv
51%97% ee
O
OPiv
49%91% ee
> 95:5, E:Z
F. Dean Toste J. Am. Chem. Soc., 2009, 131 , 3463
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Proposed Mechanism
OPivMe
O
PhO
OPivMe
Ph
AuL
OPivMe
O
Ph
AuL
Me
O
Ph
AuL
OPiv
Me
O
Ph
AuL
OPiv
Me
O
Ph
AuL
OPiv
?
Backbonding
1,2-Migration ofpropargyl ester
Nucleophilicattack
Rearrangement of allylic oxonium intermediate
F. Dean Toste J. Am. Chem. Soc., 2009, 131 , 3463
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Mechanistic Studies
Inversion of allyl moiety
Me
O
Ph
AuL
OPiv
O
OPivMe
Ph
O
OPiv
Me
AuL
O
OPiv
Me
Ph
Ph
OPivMe
O
O
OPivMe
OPivMe
O
OMe
OMe
O
OPivMe
(R)-MeO-DTBM-BIPHEP(AuCl)2 (5 mol%)AgSbF6 (10 mol%)
MeCN, rt
(R)-MeO-DTBM-BIPHEP(AuCl)2 (5 mol%)AgSbF6 (10 mol%)
MeCN, rt
X
X3,3-rearrangement2,3-rearrangement
1,4-sigmatropic rearrangement
Impossibleinversion
F. Dean Toste J. Am. Chem. Soc., 2009, 131 , 3463
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1,3-Dipolar Cycloaddition of Munchnones
O
N
O
RAr
NO O
Ph
+
(S)-Cy-SEGPHOS(AuOBz)2 (2 mol%)PhF (0.5 M)
then TMSCHN2or CH2N2
N
N
Ar
OO
CO2MeR
Ph
N
N
Ph
OO
CO2MeMe
Ph
N
N OO
CO2MeMe
Ph
N
N
Ph
OO
CO2MeH
Ph
N
N
Ph
OO
CO2Me
Ph
N
N
Ph
OO
CO2MePh
Ph
X = p-OMe 77% 95%eep-Br 75% 93%eep-Cl 72% 92%eep-NO2 98% 91%ee
N
N
Ph
OO
CO2MeBn
Ph
N
N OO
CO2Me
Me
Ph
N
N OO
CO2Me
Me
Ph
X MeO
76%95% ee
84%98% ee
86%87% ee
35%78% ee
71%68% ee
77%95% ee
73%86% ee
1.5 equiv.
F. Dean Toste J. Am. Chem. Soc., 2007, 129 , 12638
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Proposed Mechanism
H
LAu O
N
O
MePh
O
N
O
MePh
AuL
LAuOBz
OBz
OBz
HOBz
O
N
O
MePh
AuLNO O
Ph
N
O
N
N
Ph
OO
CO2MeMe
Ph
O
Ph
Me
N
O
OPh
HOBz
AuL
Generation of 1,3- dipole1,3-DipolarCycloaddition
F. Dean Toste J. Am. Chem. Soc., 2007, 129 , 12638
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Intramolecular Cyclopropanation
R1 OR2
OAc OAc Me OAc
Me OAc Et OAc
n n
R1OR2
MeOAc
HOAc
HOPiv
R3R3
OAc
OO
Me
91%49% ee
49%15% ee
44%85% ee
94%92% ee
91%92% ee
98%90% ee
80%90% ee
96%90% ee
88%75% ee
L*(AuCl)2 (2.5 mol%)AgSbF6 (5 mol%)
MeNO2 (0,1 M), -25oC
F. Dean Toste J. Am. Chem. Soc., 2009, 131 , 2056
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Proposed Mechanism
Carbenoid Intermediates
OPiv
OR2
AuPPh3 OPiv
AuPPh3
OPiv
AuPhPh3
1,2-Shift
Backbonding
AuPhPh3
OPiv
SynAnti
Ph
PhOPiv
Ph
Ph
F. Dean Toste J. Am. Chem. Soc., 2009, 131 , 2056
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Stereoselective Olefin Cyclopropanation
OR
+
R2
R4
R3
R1
RO
R2R1
R3
R4
Ph3PAuCl (5 mol%)AgSbF6 (5 mol%)
MeNO2, rt
PivO
Ph
AcO
TMS
PivO
C5H11
PivO
O
H
HPivO
H
H
n
PivOPh
Ph
BzOPivO
Ph
HAcO
H
Me
AcO
MeMe
MeMe
74% (6:1)(cis:trans)
62% (1.3:1) 48% (1.3:1) 61% (>20:1) n = 1 68% (>20:1)n = 2 69% (1.2:1)
73% 73% 84% (5:1) 69% (1.2:1) 67%
Cis cyclopropanes – major product
F. Dean Toste J. Am. Chem. Soc., 2005, 127 , 18002
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Reaction Mechanism
Ph
OAcLAu
Ph
OAc
AuLLAu
Ph
OAc
AuL
Ph
B
AAuL
H
HH
Ph
OAc
Ph
AuL
H
HPh
H
OAc
Ph
PhOAc
Ph
PhOAc
Ph
Syn
Anti
Ph
OAcHPh3PAuCl (2 mol%)AgSbF6 (2 mol%)
MeNO2, rt
91% ee
PivO
Ph
65% (95:5 cis:trans)0% ee
Z
Z
Z
Z
Complete loss of ee, consistent with the formation of a vinyl gold(I) species
F. Dean Toste J. Am. Chem. Soc., 2005, 127 , 18002
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Pyrrole Synthesis – Acetylenic Schmidt Reaction
R1 N3
R2
R3
(dppm)Au2Cl2 (2,5 mol%)AgSbF6 (5 mol%)
DCM, 35oC
HNR1
R2
R3
HNn-Bu n-Bu
HNH n-Hex
HNn-Bu
HN Ph
HN
H
HNn-Bu
Ph
82% 76% 78% 41% 73%
HN
H
HN
H
HN
H
HNH
O
61% 68% 88% 93% 87%MeO
CF3
I
F. Dean Toste J. Am. Chem. Soc., 2005, 127 , 11260
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Reaction Mechanism
LAu
N3
R
N
R
N2
LAu
N2
N N2
RLAu
N
RLAu
H
N
RH
NH
R3
1,2-proton shif t
Backbondingstabilises cation
intermediate
F. Dean Toste J. Am. Chem. Soc., 2005, 127 , 11260
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Intramolecular Hydroamination of Allenes
R1
R1NHTsR1
R1TsNR2
R2
n
n
R2 R2
Me
MeTsN
Et
EtTsN TsN
TsN TsN
Me
MeTsN
Me
MeTsN
Me Me
Me
MeTsN
Ph Ph
TsN
MeMe
TsNTsN O
O
Me
Me
Et
EtTsN TsN
Me
MeTsN
MeMe
Me
MeTsN
PhPh
Me
MeTsN
(R)-xylyl-Binap(AuOPNB)2 (10 mol%)
DCE
98%99% ee
94%93% ee
90%99% ee
75%83% ee
99%70% ee
99%87% ee
88%98% ee
88%98% ee
76%96% ee
79%98% ee
80%98% ee
88%81% ee
41%74% ee
70%98% ee
70%88% ee
66%97% ee
F. Dean Toste J. Am. Chem. Soc., 2007, 129 , 2452
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Cyclization of Silyl Enol Ethers
Ph3PAuCl (10 mol%)AgBF4 or AgOTf (10 mol%)
CH2Cl2 or toluene/H2O or MeOH40oC or 0oC
R1PGO
MeO2C CO2Me
O R1
R2
MeO2CCO2Me
n n
O Me
HMeO2C
CO2Me
R1
R2
MeO2CCO2Me
Me
HMeO2C
CO2Me
OO
R2
OO
TsN
OO H
HMe
O
H
R
Me
O
H
Me
O
H
MeO
H
Me
OS
TsN
78% 80% 77% 91%
75%77% 85% 73% 75% 91%
R1 = H, R2 = H 83%R1 = Ph, R2 = H 83%R1 = Me, R2 = Me 90%
PG = TBS or TIPS
O Me
H
94%
MeO2C CO2Me
I
F. Dean Toste Angew. Chem. Int. Ed. 2006, 45, 5991
34
Ring Expanding CycloisomerisationEtO2C CO2Et
X
CO2EtEtO2CPh3PAuCl (5 mol%)AgSbF6 (5 mol%)
DCM, rt
CO2EtEtO2C
X
CO2EtEtO2C CO2EtEtO2C CO2EtEtO2C CO2EtEtO2C CO2EtEtO2C
EtO2C CO2Et CO2EtEtO2C
Ph3PAuCl (5 mol%)AgSbF6 (5 mol%)
DCM, rtI
I
91%82%ee
MeCl
Cl
Me
MeMe
I
75% 75% 91% 35% 44% 86%
F. Dean Toste Org. Lett.. 2008, 10, 4315
35
Proposed Mechanism
F. Dean Toste Org. Lett.. 2008, 10, 4315
EtO2C CO2Et CO2EtEtO2C
LAu
AuL
EtO2CEtO2C
LAu
EtO2CEtO2C
Backbonding
Nazarov-type electrocyclisation
36
Applications in Total Synthesis
CO2Me HO
H
HO
H
HPh3PAuCl (3 mol%)AgSbF6 (3 mol %)
CH2Cl2, 23oC, 2h87%
O OTBS
OBnI
H
Ph3PAuCl (10 mol%)AgBF4 (10 mol %)
CH2Cl2/MeOH, 40oC95%
O
H
BnO
I O
H
HO
N
Ventricosene
(+)-Lycopladine A
• Ventricosene : Ring Expanding Cycloisomerization
• (+)-Lycopladine A : Cyclisation os Silyl Enol Ether
F. Dean Toste Org. Lett.. 2008, 10, 4315F. Dean Toste Angew. Chem. Int. Ed. 2006, 45, 5991
37
Conclusion
• Properties and Avantages of Gold in Homogeneous Catalysis
• Relativistic Effects of Gold and Examples
• Applicationd of Gold in Organic Chemistry
• Very Versatile and Useful Catalyst (Hight Yields and ee)
• Large Contribution of F. Dean Toste
• Mechanistic Studies
• Applications in Total Synthesis
Future Work : Further the understanding of Enantioselective and Seteroselective
Mechanisms. (Transition States with Chiral Ligands)
38
Are Gold Chemicals Expensive???
AuAu Pd Pd
PtPtRhRh AgAg
AuCl
140$
AuCl3
94$
PtCl2
135$
PtCl4
114$
PtCl2(PEt3) 2
149$
PdCl242$
Pd(OAc)2
59$
Pd(PPh3)4
66$
RhCl(PPh3)
98$
RhCl3
438$
Rh2(OAc)4
371$
PPh3AuCl
108$
AgCl
3$
AgF6Sb
12$
AgOTf
6$
TiTi
TiCl2Cp2
2$
TiCl4
0.13$
TiCl3
0.5$
CuCu
CuCl
5$
CuBr2
0.5$
Cu(OTf)4
7$
$/g$/g
$$$$$$
39
Myths – Does the Chemistry Comes from Gold????
• A very long time ago, the main goal of the alchemists was to produce
gold from other substances, such as lead — presumably by the
interaction with a mythical powerful substance called the philosopher’s
stone. Although they never succeeded in this attempt, the alchemists
promoted an interest in what can be done by reacting different
substances and this apparently laid a foundation for today‘s chemistry.
