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

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
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
4
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, 395 F. Dean
Toste J. Am. Chem. Soc., 2008, 130, 4517 Hashmi
Angew. Chem. Int. Ed. 2005, 44, 6990
5
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 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
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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 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
7
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.

V. Gevorgyan J. Am. Chem. Soc., 2005, 127,
10500 F. Dean Toste Nature, 2007, 446, 395
8
Initial 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
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Contribution 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).
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Conia-Ene Reaction of b-Ketoesters with Alkynes
F. Dean Toste J. Am. Chem. Soc., 2004, 126 , 4526
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Proposed Mechanism
F. Dean Toste J. Am. Chem. Soc., 2004, 126 , 4526
12
Allenyne Cycleisomerisation Activated Ene
Reaction
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
13
Mechanistic Studies Ene Type Reaction
? Intramolecular proton transfer
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
14
Mechanistic Studies
Ene Reaction
Metallacycles
Vinylidenes
p-Coordinations
Mono Gold Phosphine
Dual Gold Phosphine
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
15
Mechanistic Studies
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
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Mechanistic Studies
Metallacycles

• Experimentally
• Computationally

? Similar computational results for dual
phosphine gold intermediate
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
17
Mechanistic Studies
Vinylidenes

• Very unstable by computational energy
• minimization, hight DG

F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
18
Mechanistic 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
19
Mechanistic Studies

• Intermediate I also approved
• by computational analysis

F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
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Catalytic Cycle
F. Dean Toste J. Am. Chem. Soc., 2008, 130 , 4517
21
Synthesis of Benzopyrans
F. Dean Toste J. Am. Chem. Soc., 2009, 131 , 3463
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Proposed Mechanism
Rearrangement of allylic oxonium intermediate
F. Dean Toste J. Am. Chem. Soc., 2009, 131 , 3463
23
Mechanistic 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
24
1,3-Dipolar Cycloaddition of Munchnones
F. Dean Toste J. Am. Chem. Soc., 2007, 129 ,
12638
25
Proposed Mechanism
F. Dean Toste J. Am. Chem. Soc., 2007, 129 ,
12638
26
Intramolecular Cyclopropanation
F. Dean Toste J. Am. Chem. Soc., 2009, 131 ,
2056
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Proposed Mechanism

• Carbenoid
• Intermediates

F. Dean Toste J. Am. Chem. Soc., 2009, 131 ,
2056
28
Stereoselective Olefin Cyclopropanation

• Cis cyclopropanes major product

F. Dean Toste J. Am. Chem. Soc., 2005, 127 ,
18002
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Reaction 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
30
Pyrrole Synthesis Acetylenic Schmidt Reaction
F. Dean Toste J. Am. Chem. Soc., 2005, 127 ,
11260
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Reaction Mechanism
F. Dean Toste J. Am. Chem. Soc., 2005, 127 ,
11260
32
Intramolecular Hydroamination of Allenes
F. Dean Toste J. Am. Chem. Soc., 2007, 129 , 2452
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Cyclization of Silyl Enol Ethers
F. Dean Toste Angew. Chem. Int. Ed. 2006, 45, 5991
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Ring Expanding Cycloisomerisation
F. Dean Toste Org. Lett.. 2008, 10, 4315
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Proposed Mechanism
Nazarov-type electrocyclisation
Backbonding
F. Dean Toste Org. Lett.. 2008, 10, 4315
36
Applications 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
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)

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Are 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

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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 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.