Title: New Progress of Gold in Organic Chemistry Recent Contribution of F. Dean Toste
1 New Progress of Gold in Organic ChemistryRecent
Contribution of F. Dean Toste
William S. Bechara Charette Group Literature
Meeting
- Department of Chemistry
- University of Montreal
- March 17th , 2009
2Outline
- 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
3General Properties of Gold
Au Xe 6s1 4f14 5d10
- 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)
J. Phys. Chem. A, 2006, 110 , 11332
4Advantages 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, 395 F. Dean
Toste J. Am. Chem. Soc., 2008, 130, 4517 Hashmi
Angew. Chem. Int. Ed. 2005, 44, 6990
5Particularities 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 p-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 ß-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, 395 P. Pyykko
Angew. Chem. Int. Ed. 2004, 43, 4412 F. Dean
Toste Chem. Rev., 2008, 108 , 3351
6Relativistic 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 AuL
bonds (which can induce high chirality). - Different oxidation state influences the activity
of the catalyst. -
Contraction of 6s and expansion of 5d orbitals
76Os
82Pb
73Ta
81Ti
77Ir
80Hg
78Pt
79Au
F. Dean Toste Nature, 2007, 446, 395 , P.
Pyykko Angew. Chem. Int. Ed. 2004, 43, 4412
7Influence 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.
V. Gevorgyan J. Am. Chem. Soc., 2005, 127,
10500 F. Dean Toste Nature, 2007, 446, 395
8Initial tryouts with Gold in Organic Chemistry
- First attempts using gold catalysis was mainly
for oxidations - Au(III) species
J. Org. Chem., 1976, 41, 2742 Tetrahedron 1983,
39, 3181
9Contribution in Homogeneous Gold Catalysis
Prof. F. Dean Toste
- 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.
? Around 10 reviews on gold chemistry in the past
few years (2 by Toste).
10Conia-Ene Reaction of b-Ketoesters with Alkynes
F. Dean Toste J. Am. Chem. Soc., 2004, 126 , 4526
11Proposed Mechanism
F. Dean Toste J. Am. Chem. Soc., 2004, 126 , 4526
12Allenyne Cycleisomerisation Activated Ene
Reaction
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
13Mechanistic Studies Ene Type Reaction
? Intramolecular proton transfer
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
14Mechanistic Studies
Ene Reaction
Metallacycles
Vinylidenes
p-Coordinations
Mono Gold Phosphine
Dual Gold Phosphine
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
15Mechanistic Studies
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
16Mechanistic Studies
Metallacycles
- Experimentally
- Computationally
? Similar computational results for dual
phosphine gold intermediate
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
17Mechanistic Studies
Vinylidenes
- Very unstable by computational energy
- minimization, hight DG
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
18Mechanistic Studies
p-Coordinations
- 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
19Mechanistic Studies
- Intermediate I also approved
- by computational analysis
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
20Catalytic Cycle
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
21Synthesis of Benzopyrans
F. Dean Toste J. Am. Chem. Soc., 2009, 131 , 3463
22Proposed Mechanism
Rearrangement of allylic oxonium intermediate
F. Dean Toste J. Am. Chem. Soc., 2009, 131 , 3463
23Mechanistic Studies
3,3-rearrangement
2,3-rearrangement
1,4-sigmatropic rearrangement
Inversion of allyl moiety
Impossible inversion
F. Dean Toste J. Am. Chem. Soc., 2009, 131 , 3463
241,3-Dipolar Cycloaddition of Munchnones
F. Dean Toste J. Am. Chem. Soc., 2007, 129 ,
12638
25Proposed Mechanism
F. Dean Toste J. Am. Chem. Soc., 2007, 129 ,
12638
26Intramolecular Cyclopropanation
F. Dean Toste J. Am. Chem. Soc., 2009, 131 ,
2056
27Proposed Mechanism
F. Dean Toste J. Am. Chem. Soc., 2009, 131 ,
2056
28Stereoselective Olefin Cyclopropanation
- Cis cyclopropanes major product
F. Dean Toste J. Am. Chem. Soc., 2005, 127 ,
18002
29Reaction Mechanism
- Complete loss of ee, consistent with the
formation of a vinyl gold(I) species
F. Dean Toste J. Am. Chem. Soc., 2005, 127 ,
18002
30Pyrrole Synthesis Acetylenic Schmidt Reaction
F. Dean Toste J. Am. Chem. Soc., 2005, 127 ,
11260
31Reaction Mechanism
F. Dean Toste J. Am. Chem. Soc., 2005, 127 ,
11260
32Intramolecular Hydroamination of Allenes
F. Dean Toste J. Am. Chem. Soc., 2007, 129 , 2452
33Cyclization of Silyl Enol Ethers
F. Dean Toste Angew. Chem. Int. Ed. 2006, 45, 5991
34Ring Expanding Cycloisomerisation
F. Dean Toste Org. Lett.. 2008, 10, 4315
35Proposed Mechanism
Nazarov-type electrocyclisation
Backbonding
F. Dean Toste Org. Lett.. 2008, 10, 4315
36Applications in Total Synthesis
- Ventricosene Ring Expanding Cycloisomerization
- ()-Lycopladine A Cyclisation os Silyl Enol
Ether
F. Dean Toste Org. Lett.. 2008, 10, 4315 F. Dean
Toste Angew. Chem. Int. Ed. 2006, 45, 5991
37Conclusion
- 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)
38Are Gold Chemicals Expensive???
/g
Au
Ag
Ti
Cu
Pd
Pt
Rh
TiCl2Cp2 2
AuCl140
PtCl2 135
AgCl3
CuCl5
RhCl(PPh3) 98
PdCl2 42
TiCl4 0.13
AuCl3 94
AgF6Sb 12
CuBr2 0.5
PtCl4 114
Pd(OAc)2 59
RhCl3 438
TiCl3 0.5
AgOTf 6
Cu(OTf)47
Rh2(OAc)4 371
PPh3AuCl 108
Pd(PPh3)4 66
PtCl2(PEt3) 2 149
39Myths 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 philosophers 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 todays chemistry.