Recent Developments in Homogeneous Gold Catalysis · Recent Developments in Homogeneous Gold...
Transcript of Recent Developments in Homogeneous Gold Catalysis · Recent Developments in Homogeneous Gold...
Recent Developments in Homogeneous Gold Catalysis David A. Nagib
MacMillan Group Literature Meeting
03.17.2010
Relativistic Effects in Gold Catalysis
Relativistic effects – phenomenon resulting from the need to consider velocity as significant relative to the speed of light
m = m°/√1-(v/c)2
Consequences: • Relativistic mass increases as velocity approaches c • Increased mass results in decreased Bohr radius • Contracted 6s orbital better shields (expands) 5d orbital
Relativistic contraction of 6s orbital
• Faster • Heavier • Nearer
Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395-403 Pyykkö, P.; Desclaux, J. P. Acc. Chem. Res. 1979, 12, 276-281
Filled 4f orbital
Filled 5d orbital
79Au
Relativistic Effects in Gold Catalysis
Relativistic effects – phenomenon resulting from the need to consider velocity as significant relative to the speed of light
m = m°/√1-(v/c)2
Consequences: • Relativistic mass increases as velocity approaches c • Increased mass results in decreased Bohr radius • Contracted 6s orbital better shields (expands) 5d orbital
• Faster • Heavier • Nearer
Au
Increased π-acidity
R
Ag
R>
Increased e− delocalization(i.e. backbonding)
Au Ag
AgAu
>
Modes of Reactivity in Homogeneous Gold Catalysis
Au
Nu
Au
Nu E
Nu Au
E
Nu
Au
Nu E
E
cationderived products
cation cyclizationrearrangement
H
Nu
carbenoidderived products
C-H insertioncyclopropanation
trans-addition
increased e− delocalization(expanded 5d orbital)
♦ Au backbonding E+ = alkene, ylide, etc.
♦ proto-deauration E+ = H+ (Nu-H)
Lewis acidderived products
ring expansioncycloisomerization
increased π-acidity(contracted 6s orbital)
♦ aprotic nucleophile E+ = alkene, alcohol, etc.
Lewis acidderived products
heterofunctionalizationheterocyclization
Modes of Reactivity in Homogeneous Gold Catalysis
Au
Nu
Au
Nu E
Nu Au
E
Nu
Au
Nu E
E
cationderived products
cation cyclizationrearrangement
H
Nu
carbenoidderived products
C-H insertioncyclopropanation
trans-addition
increased e− delocalization(expanded 5d orbital)
♦ Au backbonding E+ = alkene, ylide, etc.
♦ proto-deauration E+ = H+ (Nu-H)
Lewis acidderived products
ring expansioncycloisomerization
increased π-acidity(contracted 6s orbital)
♦ aprotic nucleophile E+ = alkene, alcohol, etc.
Lewis acidderived products
heterofunctionalizationheterocyclization
Activation of π-systems Towards Nucleophiles
Oxygen nucleophiles
Other nucleophiles
Hydration: Fukuda, Y.; Utimoto, K. J. Org. Chem. 1991, 56, 3729-3734 Teles, J.; Brode, S.; Chabanas, M. Angew. Chem. Int. Ed. 1998, 37, 1415-1418
Hydro-amination: Mizushima, E.; Hayashi, T.; Tanaka, M. Org. Lett. 2003, 5, 3349-3352
Hydro-fluorination: Akana, J.; Bhattacharyya, K.; Muller, P.; Sadighi, J. J. Am. Chem. Soc. 2007, 129, 7736-7727
Trostʼs Synthesis of Bryostatin
Trost, B.; Dong, G. Nature 2008, 456, 485-488
Gold-catalyzed 6-endo-dig cyclization provides highly sensitive dihydrofuran C ring under mild conditions
Employing Carbon Nucleophiles: Hydroarylation
Reetz, M.; Sommer, K. Eur. J. Org. Chem. 2003, 18, 3485-3496
Au(I) & Au(III)-catalysts provide complete regioselectivity in the hydroarylation of terminal alkynes
o/p
Employing Carbon Nucleophiles: Enolate Alkylation
Kennedy-Smith, J.; Staben, S.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 4526-4527
A wide range of β-keto esters serve as efficient nucleophiles for the mild and fast hydroalkylation of terminal alkynes
Deuterium studies support trans-addition mechanism and explain limitation towards internal alkynes
Cyclization of Silyl Enol Ethers
Staben, S.; Kennedy-Smith, J.; Huang, D.; Corkey, B.; LaLonde, R.; Toste, F. D. Angew. Chem. Int. Ed. 2006, 45, 5991-5994
Enol silanes are also suitable nucleophiles for quaternary (& now tertiary) carbon center construction
Water serves as the external proton source for the final proto-deauration
terminal-δ-alkyne
( )n
RTBSO
HR
O R
( )nH
5-exo-dig
6-exo-dig
internal additionfavored
O
AuL
TBS
H2O
H
Internal vs Terminal Alkynes
Markovnikov addition provides access to variously substituted cyclopentenes depending on alkyne substitution
Staben, S.; Kennedy-Smith, J.; Huang, D.; Corkey, B.; LaLonde, R.; Toste, F. D. Angew. Chem. Int. Ed. 2006, 45, 5991-5994
( )n
RTBSO
H
internal-γ-alkyneR
O R
( )nH
XX
X = Ar, I
5-endo-dig
benzylic/halo additionfavored
O
AuL
X
TBS
terminal-δ-alkyne
( )n
RTBSO
HR
O R
( )nH
5-exo-dig
6-exo-dig
internal additionfavored
O
AuL
TBS
H2O
H
R
O R
( )n
•
R
( )n
RTBSO
H H
terminal-β-allene
5-endo-trig
conformation governsaddition
•
O
AuL
TBS
H
H
H
Synthetic Applications of Cyclopentenes
The non-ester bearing quaternary cyclopentenes allow rapid synthetic access to a variety of Lycopodium alkaloids.
Staben, S.; Kennedy-Smith, J.; Huang, D.; Corkey, B.; LaLonde, R.; Toste, F. D. Angew. Chem. Int. Ed. 2006, 45, 5991-5994 Linghu, X.; Kennedy-Smith, J.; Toste, F. D. Angew. Chem. Int. Ed. 2007, 46, 7671-7673
For comparison, structurally similar Lycopodium alkaloids synthesized in 22-24 steps: Laemmerhold, K.; Breit, B. Angew. Chem. Int. Ed. 2010, ASAP
( )n
RTBSO
H
internal-γ-alkyneR
O R
( )nH
XX
X = Ar, I
5-endo-dig
benzylic/halo additionfavored
O
AuL
X
TBS
R
O
tBuO
O
Me H
O
1. Organocat.2. H+
3. β-allene add'n4. NIS
8 steps
H
O
MeH
O
Me
BocN
3 steps
BnO
N
(+)-lycopladine A8 steps
(+)-fawcettimine13 steps
Me
N
OHO
H
HO
TFA
Enantioselective Conia-Ene
A chiral Pd-complex was preferred due to the linear geometry of the ligand and substrates across the Au-catalyst
X-ray structures demonstrate the distance between the ligand framework and the pro-chiral substrate
4.58 Å 3.14 Å
Corkey, B.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 17168-17169 Shapiro, N.; Toste, F. D. Synlett. 2010, 5, 675-691
Au vs Pd
Enantioselective Gold Catalysis
Development of a Au(I)-catalyzed asymmetric hydroamination reaction
Coordinating counteranion provides increasing enantioselectivity due to the proposed model below
LaLonde, R.; Sherry, B.; Kang, E.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 2452-2453
All 3 species observed by 31P NMR of 2:1 L(AuCl)2:AgBF4 "
Coordinating counteranions shift equilibrium to left (higher ee)
Chiral Counterion Catalysis
Chiral induction still challenging due to the expanse of the linear gold complex
An interesting alternative
Hamilton, G.; Kang, E.; Mba, M.; Toste, F. D. Science. 2007, 317, 496-499 Perspective: Lacour, J.; Linder, D. Science. 2007, 317, 462-463
Chiral ligand strategy
Chiral counterion strategy
Increasing solvent polarity
Nucleophiles also include -NHSO2Ar & -CO2H
Modes of Reactivity in Homogeneous Gold Catalysis
Au
Nu
Au
Nu E
Nu Au
E
Nu
Au
Nu E
E
cationderived products
cation cyclizationrearrangement
H
Nu
carbenoidderived products
C-H insertioncyclopropanation
trans-addition
increased e− delocalization(expanded 5d orbital)
♦ Au backbonding E+ = alkene, ylide, etc.
♦ proto-deauration E+ = H+ (Nu-H)
Lewis acidderived products
ring expansioncycloisomerization
increased π-acidity(contracted 6s orbital)
♦ aprotic nucleophile E+ = alkene, alcohol, etc.
Lewis acidderived products
heterofunctionalizationheterocyclization
Non-Canonical Reactivity
Compared with nucleophilic activation provided by canonical metal catalysis, gold offers orthogonal electrophilic activation
Ring Expansions
Compared with nucleophilic activation provided by canonical metal catalysis, gold offers orthogonal electrophilic activation
Non-canonical nucleophiles that lack metal-coordination sites (i.e. C-C σ-bond) are suitable partners in Au-catalysis
Markham, J.; Staben, S.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 9708-9709 Kleinbeck, F.; Toste, F. D. J. Am. Chem. Soc. 2009, 131, 9178-9179
Modes of Reactivity in Homogeneous Gold Catalysis
Au
Nu
Au
Nu E
Nu Au
E
Nu
Au
Nu E
Lewis acidderived products
ring expansioncycloisomerization
E
cationderived products
cation cyclizationrearrangement
H
Nu
Lewis acidderived products
heterofunctionalizationheterocyclization
carbenoidderived products
C-H insertioncyclopropanation
trans-addition
increased π-acidity(contracted 6s orbital)
increased e− delocalization(expanded 5d orbital)
♦ proto-deauration E+ = H+ (Nu-H)
♦ aprotic nucleophile E+ = alkene, alcohol, etc.
♦ Au backbonding E+ = alkene, ylide, etc.
Enyne Cycloisomerizations
Simple olefins can also serve as nucleophiles when tethered to a π–activated alkyne (1,6-Enynes)
A series of skeletal rearrangements involving carbenoid and cationic intermediates may be invoked for this transformation
96% yield
2% (PPh3)AuSbF6CH2Cl2, r.t., 10 min
5-exo-dig
MeE
E EE
Me
Nieto-Oberhuber, C.; Muñoz, M.; Buñuel, E.; Nevado, C.; Cárdenas, D.; Echavarren, A. Angew. Chem. Int. Ed. 2004, 43, 2402-2406
Product selectivity is highly dependant on the substitution of the α,ω–enyne starting materials
H
AuL
H
Me
carbene
E
E
H
H
Me
E
E AuL
E
E
MeH
LAu
cation
E
ELAu
cation
HMe
Enyne Cycloisomerizations Revisited
Simple olefins can also serve as nucleophiles when tethered to a π–activated alkyne (1,5-Enynes)
Mamane, V.; Gress, T.; Krause, H.; Fürstner, A. J. Am. Chem. Soc. 2004, 126, 8654-8655 Kleinbeck, F.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 9178-9179
1,5-Enynes (from propargyl alcohols) reliably provide synthetic access to the cis-fused 3,5-ring systems
8 examples> 94% yield
2% (PPh3)AuSbF6CH2Cl2, r.t., 5 min
5-exo-digAuL
RR
R
H
RR
RAuL
RR
R
H
1,2-H shift
98% yield
Bn
OHTMS
5% (dppm)ReOCl35% NH4PF6, MeNO2, 65°C
1% LAuSbF6
CH2Cl2, r.t.BnBn
H
propyl
79% yield
propyl
propyl
Free alcohols can replace the benzyl substituent and provide access to propane-fused cyclopentenone
Enyne Cycloisomerizations Revisited
Simple olefins can also serve as nucleophiles when tethered to a π–activated alkyne (1,5-Enynes)
Mamane, V.; Gress, T.; Krause, H.; Fürstner, A. J. Am. Chem. Soc. 2004, 126, 8654-8655 Kleinbeck, F.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 9178-9179
Propargyl deuterium label is selectively incorporated in the vinyl position of the product
8 examples> 94% yield
2% (PPh3)AuSbF6CH2Cl2, r.t., 5 min
5-exo-digAuL
RR
R
H
RR
RAuL
RR
R
H
1,2-H shift
AuL
carbenoid
AuLAuL
R'R"
R'R"
R'R"
cation hybrid
AuL
R'R"
R R R R
D D D D
R'R"
RD
1,2-Disubstituted olefins underwent cycloisomerization stereospecifically
Further mechanistic considerations
Gold-carbenoid character is strongly suggested by these mechanistic observations …
Carbene Controversy
Fürstner strongly argues that these gold-catalyzed processes exhibit more non-classical carbocationic features
Fürstner, A.; Morency, L. Angew. Chem., Int. Ed. 2008, 47, 5030-5033 Seidel, G.; Mynott, R.; Fürstner, A. Angew. Chem., Int. Ed. 2009, 48, 2510-2513
Employing a carboxylate trap as a mechanistic probe, Fürstner demonstrated the 1,6-enynes arise from cationic mechanism
R1
R2
OH
OE E
OOH
LAu
E
E R1
R2
R1
R2
OHO
EE
LAu
OO
E
E R1
R2
OO
E
E
R1
R2
if R2 =
Me if R1 = Me
R1 = H R2 = H
R1 = H R2 = MeR1 = Me R2 = H
if R1 = Me if R2 = Me
19% yield 11% yield- 80% yield
82% yield -
cationicmechanism
carbenemechanism
AuPPh3H
O
O
AuPPh3H
O
O
carbene cation
NMR studies strongly suggest that the cation mesomer better represents the complex
Fürstner isolated and characterized a stable alkyl-gold complex that could exist as a carbene
Carbenes Defended
Toste held that many of their methodologies strongly resembled reactivity associated with carbenic systems
Toste & Goddardʼs bonding model for gold(I) carbene complex involves both σ- and π- bonding, with a bond order ≤ 1
Toste & Goddard refute Fürstnerʼs NMR experiments with bond rotation calculations and measurements of their own
Benitez, D.; Shapiro, N.; Tkatchouk, E.; Wang, Y.; Goddard, W.; Toste, F. D. Nature Chem. 2009, 1, 482-486 Horino, Y.; Yamamoto, T.; Ueda, K.; Kuroda, S.; Toste, F. D. J. Am. Chem. Soc. 2009, 131, 2809-2811
[Au]
( )n( )n
( )n
[Au] [Au]+
( )n ( )n
(n = 1-4)
9 examples82-99% yields
12 examples60-86% yields
C-H insertion
(n = 1,2) (n = 3,4)
HH
C-C migration AuPPh3H
O
O
Furstner'snon-carbene
Toste/Goddardcarbene
AuLH
O
O
O
O
Ph Ph
vs
Ph Ph
80% yield
Carbene Controversy Concluded
An entire literature meeting could be devoted to this subject …
The carbocation-carbenoid continuum best offers a helpful mnemonic to explain and predict many facets of gold catalysis
Carbocationic ONLY
Carbene ONLY
Carbocationic Carbenoid Continuum
Ongoing debate on the cationic and carbene character of gold catalysis suggests a continuum of tunable reactivity
Methods of Generating Gold Carbenes
Gold carbenes from alkynyl sulfoxides offer an orthogonal approach to reactivity previously associated with diazocarbonyls
Shapiro, N.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 4160-4161 Gorin, D.; Davis, N.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260-11261
Azides are analogous carbene precursors
LG+
[Au]+
Nu
[Au]+
Nu-LG+[Au]+ 5-exo-dig
[Au]
NuLG+
gold carbene
LGNu-
S
[Au]+
O
[Au]+
OSPh
[Au]+ 5-exo-dig
[Au]
OSPh
gold carbene
O
Ph
SPh
S
OC-H insertion
94% yield
Methods of Generating Gold Carbenes
Gold carbenes from alkynyl sulfoxides offer an orthogonal approach to reactivity previously associated with diazocarbonyls
Shapiro, N.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 4160-4161 Gorin, D.; Davis, N.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 11260-11261
[Au]+
O
gold carbene
SMe
Me
SMe Me 5% IPrAuCl
5% AgSbF6CH2Cl2, r.t.
C-C σ-bondmigration O
ArS
N2
OSMe
Me
[M]
Another Method of Generating Gold Carbenes
Propargyl carboxylates allow synthetically facile access to gold carbenes via a 1,2-acyloxy migration
Johansson, M.; Gorin, D.; Staben, S.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 18002-18003
Modular synthesis of propargyl carboxylates coupled with gold carbene pathways allow for rapid complexity generation
OO
R'R
[Au]+
OOR
R'[Au]+
OO
R'R
[Au]+ 5-exo-dig
1,2-acyloxy migration
[Au]
OO
R R'
gold carbene
70% yield> 20:1 dr, 81% ee
O
O
R
R'
Ph
Ph
L*
O
R'R
OX
ketone
acid derivative
alkyne
2 steps
Propargyl Carboxylate Reactivity
Substitution patterns dictate formation of vinyl gold versus gold carbene species
Wang, S.; Zhang, G.; Zhang, L. Synlett. 2010, 5, 692-706
OO
R'R
EWGor H
[Au]+
OOR
R'[Au]+
OO
R'R
[Au]+ 5-exo-dig
1,2-acyloxy migration
[Au]
OO
R R'
[Au]+
gold carbene
tBu
[3,3]-rearrangement
[Au]+
OO
R'R
OO
⋅R
OO
R'[Au]
OO
RR'
[Au]
6-endo-dig[Au]
α-carbonylvinyl gold
R R�'
Vinyl Gold Intermediate
Substitution patterns dictate formation of vinyl gold versus gold carbene species
Wang, S.; Zhang, G.; Zhang, L. Synlett. 2010, 5, 692-706
Vinyl gold species can also be exploited in a variety of rapid complexity generating transformations
OE
R'R
ONu
R'R
or
[3,3]-rearrangement
[Au]+
OO
R'R
OO
⋅R
OO
R'[Au]
OO
RR'
[Au]
6-endo-dig[Au]
α-carbonylvinyl gold
R R�'
Electrophilic Trapping of Vinyl Gold
Electrophilic trapping by N-halo-succinimides affords α-halo -enones and -enals from propargyl acetates
Yu, M.; Zhang, G.; Zhang, L. Org. Lett. 2007, 9, 2147-2150 Yu, M.; Zhang, G.; Zhang, L. Tetrahedron. 2009, 65, 1846-1855
butyl
OBr
Me
butyl
OI
butyl
or
NBSorNIS85% yield
> 99:1 dr94% yield> 20:1 dr
[3,3]-rearrangement
[Au]+
OO
R'R
OO
⋅R
OO
R'[Au]
OO
RR'
[Au]
6-endo-dig[Au]
α-carbonylvinyl gold
R R�'
Electrophilic Trapping of Vinyl Gold
Catalytic molybdenum oxide allows for the use of propargyl alcohols in addition to propargyl carboxylates
Yu, M.; Zhang, G.; Zhang, L. Org. Lett. 2007, 9, 2147-2150 Ye, L.; Zhang, L. Org. Lett. 2009, 11, 3646-3649
butyl
OBr
Me
butyl
OI
butyl
or
NBSorNIS85% yield
> 99:1 dr94% yield> 20:1 dr
OH
HMe
butyl
[3,3]-rearrangement
[Au]+
OMo
O
R'R
O
⋅R
OMo
O
R'[Au]
OMo
O
RR'
[Au]
6-endo-dig[Au]
α-carbonylvinyl gold
- MoO2
+ H2O1% MoO2
R R'
Nucleophilic Trapping of Vinyl Gold
Oxidation of the vinyl gold intermediate allows access to Au(III) oxidation state and corresponding nucleophilic trapping
Peng, Y. Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2009, 131, 5062-5063
A variety of intermolecular nucleophilic functionalizations can be envisioned to access α-substituted enones and enals
[3,3]-rearrangement
[Au]+
OO
R'R
OO
⋅R
OO
R'[Au]
OO
RR'
[Au]
6-endo-digAuI
α-carbonylvinyl gold
R R'
OO
9 examples56-78% yield
+ H2O
[O]
OOAuIII
OO
AuIII
OAuIII
OOR R'
R R' R R'R R'
- AuI
reductiveelimination
Gold Cross-Coupling
Addition of boronic acids under semi-aqueous conditions readily provides α-aryl enones and enals
Zhang, G.; Peng, Y. Cui, L.; Zhang, L. Angew. Chem. Int. Ed. 2009, 121, 3158-3161 Related transformation for homo-allylic alcohols: Zhang, G.; Cui, L.; Wang, Y.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 1474-1475
[3,3]-rearrangement
[Au]+
OO
R'R
OO
⋅R
OO
R'[Au]
OO
RR'
[Au]
6-endo-digAuI
α-carbonylvinyl gold
R R'
OAr
15 examples45-71% yield
[O]
OAuIII
Ar
R R'R R'
- AuI
reductiveelimination
OAuIII
R R'
ArB(OH)2
Major Milestones in Homogeneous Gold Catalysis Alkynophilic π–activation toward nucleophiles
Investigating & harnessing carbenoid character
Asymmetric catalysis; counteranion control
Novel propargyl carboxylate reactivity
P−Au+
P−Au−Y*
P−Au+
P−Au+
*
X− X− Y−
mono-cationicspecies
Greater enantiocontrol
di-cationicspecies
Lesser enantiocontrol
coordinatingcounteranion
non-coordinatingcounteranion
Au
RNu-H Nu
HRElectrophile(π) activation
C-C migration
C-H insertion cyclopropanation
proton shift
[Au]
R HR
R R
O
OO[Au]
α-carbonylvinyl gold
E
R'R
ONu
R'R
E+
Nu[O]
Gold-Catalyzed Organic Reactions Stephen, A.; Hashmi, K.; Chem. Rev. 2007, 7, 3180–3211
Gold-Catalyzed Organic TransformationsLi, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 8, 3239–3265
Chem Rev - Special Issue ʻ08Coinage Metals in Organic Synthesis
Alternative Synthetic Methods through New Developments in Catalysis by GoldArcadi, A. Chem. Rev. 2008, 8, 3266–3325
Gold-Catalyzed Cycloisomerizations of Enynes: A Mechanistic Perspective Jiménez-Núñez, E.; Echavarren, A. Chem. Rev. 2008, 8, 3326–3350
Ligand Effects in Homogeneous Au Catalysis Gorin, D.; Sherry, B.; Toste, F. D. Chem. Rev. 2008, 8, 3351–3378
and many more …
A Reactivity-Driven Approach to the Discovery & Development of Gold-Catalyzed Organic Reactions Shapiro, N. D.; Toste, F. D. Synlett., 2010, 5, 675-691
Gold-Catalyzed Reaction of Propargylic Carboxylates via an Initial 3,3-Rearrangement Wang, S.; Zhang, G.; Zhang, L. Synlett. 2010, 5, 692-706
Synlett ʻ10 Accounts
Recent Reviews on Homogeneous Gold Catalysis
Gold catalysis in total synthesisStephen, A.; Hashmi, K.; Rudolph, M. Chem. Soc. Rev. 2008, 37, 1766-1775
N-Heterocyclic carbenes in Au catalysis Marion, N.; Nolan, S. Chem. Soc. Rev. 2008, 37, 1776-1782
Chem Soc Rev - Special Issue ʻ08 GOLD: CHEMISTRY, MATERIALS & CATALYSIS