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TRANSCRIPT
Proposed Mechanism For Oxidative Heteroarylation
Isolation of an Active Au(III) Fluoride
N. P. Mankad, F. D. Toste, J. Am. Chem. Soc. 2010, 132, 12859–12861.
E. Tkatchouk, N. P. Mankad, D. Benitez, W. A. Goddard III, F. D.Toste, JACS 2011, in press.
Gold-Catalyzed Intermolecular Oxyarylation
A. D. Melhado, W. E. Brenzovich, Jr., A. D. Lackner, F. D. Toste, J. Am. Chem.
Soc., 2010, 132, 8885–8887.
5 mol % dppm(AuBr)2
MeCN, 18 h, 50 oC
O
PhPh B(OH)2+
1.5 equiv Selectfluor
2.0 equiv
n-hexyl
n-hexyl
R'10 equiv EtOH
5 mol % dppm(AuBr)2
MeCN, 18 h, 50 oC
O+1.5 equiv Selectfluor
2.0 equiv
n-hexyl
n-hexyl
10 equiv H2O OMeO2C
(HO)2B
W. E. Brenzovich, Jr., J.-F. Brazeau, F. D. Toste, Org. Lett., 2010, 12, 4728–4731.
Arylsilanes allow for divergent reactivity:
Me3Si
B O
N
OO
O
Me
R
OMe
B O
N
OO
O
Me
Me3Si
Gold CatalysisPalladium Catalysis
cat. dppm(AuBr)2
Ph-Br,
SPhos, K2CO3
olefin, MeOHSelectfluor
cat. Pd(OAc)2
Fluoride-Mediated Oxidative Gold Chemistry
W. E. Brenzovich, Jr., D. Benitez, A. D. Lackner, H. P. Shunatona, E. Tkatchouk,
W. A. Goddard, III, F. D. Toste, Angew. Chem. Int. Ed. 2010, 49, 5519–5512.
Gold-Catalyzed Intramolecular Heteroarylation
3 mol % dppm(AuBr)2
MeCN, 18 h, RT
Ph B(OH)2
1.5 equiv Selectfluor
2.0 equiv
N
Ph
TsNHTs
+
(82%) Q uic k Tim e™ an d aPNG dec om pr e s s or
ar e n eed ed t o s e e t his pic t ur e .
NN
Au
iPr
iPr iPr
iPr
F
Me
F
+ F-
- F-
B(OH)2
RR
Me
2+
Au
F
N N
Au
D
D
F
IPr
F PhB(OH)2
CDCl3
D
D
retention of stereochemistry
Ph2P PPh2
Au Au
Br Br
Ph2P PPh2
Au Au
Br
Br F
Ph2P PPh2
Au Au
Br
Br F
X
Ph2P PPh2
Au Au
Br
Br F
XR
B(OH)2
X
R
XH
Selectfluor
H+
F B(OH)2
R B(OH)2
D
D
D
D
oxidation
anti-heteroauration
concertedbimolecularelimination
2 BF4
N NF
Cl
Metal ion NaBH4
SBA15 Loading
Complexation Reduction
62 Tertiary
Amines
64 Terminal
Groups 4th Generation
PAMAM Dendrimer G4OH
Transition Metal Nanoparticle Catalysis
Collaboration with the Somorjai Group
t-Bu
Rh40 G4OH/SBA-15 (0.5 mol %)
toluene, H2/CO = 2/1(500 psi), 100 C t-Bu
Me
CHO
Catalyst Preparation:
Rh-catalyzed Hydroforylation:
Witham, C. A.; Huang, W.; Tsung, C.; Kuhn, J. N.; Samorjai, G. A.; Toste, F. D. Nature Chem 2010, 2, 36-41
Huang, W.; Liu, J. H.; Alayoglu, P.; Li, Y.; Witham, C. A.; Tsung, C.; Toste, F. D.; Somorjai, G. A. J. Am. Chem.
Soc. 2010, 132, 16771-16773.
OH
Ph
Pt40 G4OH/SBA-15 (3.5 mol %),PhICl2 (10.5 mol %)
toluene, 100 C
OPh
Pt-catalyzed Hydroalkoxylation:
Zach Travis
Hydroalkoxylation Catalyzed by Au(I)
Encapsulated in A Suparmolecular Host
Collaboration with the Raymond and Bergman Groups
G. L. Hamilton, E. J. Kang, M. Mba, F. D. Toste Science, 2007, 317, 496.
Lalonde, R. L.; Wang, J. Z.; Mba, M.; Lackner, A. D.; Toste, F. D.
Angew. Chem. Int. Ed. 2010, 49, 598.
O
OP
O
O
i-Pr
i-Pr
i-Pr i-Pr
i-Pr
i-Pr
CR1
R1
OH
OR1
R1
HR2 R2
R3 R3
R3
R3
R2 R2
73-96% yield90-99% ee
P Au
2.5 mol%
P Au
Ph Ph
Ph Ph
2
CR1
R1
NBoc
OH NBocOR1
R1
HR2 R2
R2 R2
75-98% yield87-98% ee
Chiral Anions in Asymmetric Catalysis
HN
O
P
P
Rh
HOOC Ph
Ph
OCH3
H3CO
Metal+ Chiral
Ligand Substrate
Traditional approach:
Chiral –
Anion COH
Au
O
OP
O
O*
PR3
Metal+ Substrate
Substrate+
Ph Ph
NucleophileA*
Ph Ph
H Nuc Chiral–
Anion
Our approach:
Ph
Ph Cl
N 15 mol%
Ph
Ph
NR2
R1Ph
Ph O
N
R1
R2
R3
Ag
0.6 equiv Ag2CO3
O
OP
O
O*
R3HO
R1
R2
O
OP
O
O*
50Ğ95% yield90Ğ99% ee
G. L. Hamilton, T. Kanai, F. D. Toste J. Am. Chem. Soc. 2008, 130, 14984.
Desymmetrization of Meso-aziridinium Ions
NHTsTsN
*NHTs
S
P
S
O
O HSN2'10 mol%
98% yield96% ee
O
O
R
PS
SH
R
NCH3
H3CO
H3CO2C CO2CH3
NCH3
H3CO
H3CO2CCO2CH3
75% yield, 91% ee
C
O
OP
S
S* H
10 mol%
N. D. Shapiro, V. Rauniyar, G. L. Hamilton, J. Wu, F. D. Toste Nature 2011, 470, 245.
Thiophosphoric acid covalent catalysis of diene additions
Chiral Counteranion-mediated Au(I) Reactions
O Ar
NHR
5 mol% catalyst
C6H5F, 4A MS, rt, 12h
O
NH
Ar
R
*
16-94% yield73-94% ee
catalyst
Copper(II) Catalyzed Asymmetric Heterocyclization
Mechanistic Proposal:
OR
Ar
OCOR'
(racemic)
OR OCOR'
Ar
H[Au]+
OR OCOR'
Ar
H[Au]
[Au]+
[3,3]
6-endo-trigO
H Ar
R
OCOR'
Dynamic kinetic asymmetric transformation via achiralintermediate B
A
B
(enantioenriched)
OR'
R
Ar
OPiv
AgOTf (10 mol%)
O
R
Ar
OPiv
R'
Gold(I)-carbene (5 mol%)
18 examples
R' = H, 83 to 91 % ee
R' = CH2Ar, 95 to >99% ee
R
R
HN
NH
NH
NHN
N
AuCl
ClAu
Mechanistic Rationale:
PhPh
Me
OTMS
6a
Catalytic Enantioselective Protonation of
Silyl Enol Ethers of Ketones
Enantioselectivity and E/Z ratio during Protonation of 6a:
Enantioselective Synthesis of Chromanone Derivatives
via Novel Gold(I)-carbene Catalyst
Rauniyar, V.; Wang, J. Z.; Burks, H.; Toste, F. D. J. Am. Chem. Soc. 2011, 133, 8486-8489.
Wang, Y.-M.; Kuzniewski, C.N.;
Rauniyar, V.; Hoong, C.; Toste, F.D.
J. Am. Chem. Soc. 2011, 133,
12972-12975 Cheon, C. H.; Kanno, O.; Toste, F. D.; J. Am. Chem. Soc. 2011, ASAP
Wang, Z. J.; Casey, C. J; Bergman, R. G.; Raymond, K. N.; Toste, F. D. J. Am. Chem. Soc. 2011, 133, 7358-7360