fluoride-mediated oxidative gold chemistry ...lalonde, r. l.; wang, j. z.; mba, m.; lackner, a. d.;...
TRANSCRIPT
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)2MeCN, 18 h, 50 oC
OPh
Ph B(OH)2+1.5 equiv Selectfluor
2.0 equivn-hexyl
n-hexyl
R'10 equiv EtOH
5 mol % dppm(AuBr)2MeCN, 18 h, 50 oC
O+1.5 equiv Selectfluor
2.0 equiv
n-hexyl
n-hexyl
10 equiv H2O OMeO2C
(HO)2B
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)2MeCN, 18 h, RT
Ph B(OH)21.5 equiv Selectfluor
2.0 equiv
NPh
TsNHTs+
(82%)
Isolation of an Active Au(III) Fluoride
N. P. Mankad, F. D. Toste, J. Am. Chem. Soc. 2010, 132, 12859–12861.
NN
Au
iPr
iPr iPr
iPr
F
Me
F+ F-
- F-
B(OH)2
R R
Me
2+
Au
F
N N
AuD
D
F
IPr
F PhB(OH)2
CDCl3
D
Dretention of stereochemistry
Proposed Mechanism For Oxidative Heteroarylation
E. Tkatchouk, N. P. Mankad, D. Benitez, W. A. Goddard III, F. D.Toste, J. Am. Chem. Soc.,2011, 133, 14293-14300.
Ph2P PPh2Au AuBr Br
Ph2P PPh2Au AuBr
Br F
Ph2P PPh2Au AuBr
Br F
X
Ph2P PPh2Au AuBr
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 NFCl
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.
OO
POO
i-Pr
i-Pr
i-Pr i-Pr
i-Pr
i-Pr
CR1
R1
OHOR1
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
HNO
P
PRh
HOOC Ph
PhOCH3
H3CO
Metal+ Chiral Ligand
Substrate
Traditional approach:
Chiral – Anion C
OH
Au
OOPOO*
PR3
Metal+ Substrate
Substrate+
Ph Ph
NucleophileA*
Ph Ph
H Nuc Chiral– Anion
Our approach:
Ph
Ph Cl
N 15 mol%
Ph
PhN
R2
R1 Ph
Ph O
NR1
R2
R3
Ag
0.6 equiv Ag2CO3
OO
POO*
R3HO
R1
R2
OO
POO*
50–95% yield90–99% ee
G. L. Hamilton, T. Kanai, F. D. Toste J. Am. Chem. Soc. 2008, 130, 14984.
Desymmetrization of Meso-aziridinium Ions
NHTs TsN
*NHTs
SP
SO
O HSN2'10 mol%
98% yield96% ee
OO
R
PS
SH
R
NCH3
H3CO
H3CO2C CO2CH3
NCH3
H3CO
H3CO2CCO2CH3
75% yield, 91% ee
C
OO
PSS* 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
CuX2
HX
NH
XCu
O Ph
NH
XCuO NH
X
Ph
NH
Cu
OPh
NH
O Ph
O NHPh
CuX
or
indole
m/z 930.87
m/z 1127.46
Mechanistic Proposal:
ORAr
OCOR'
(racemic)
OR OCOR'
• ArH[Au]+
OR OCOR'Ar
H[Au]
[Au]+
[3,3]6-endo-trig O
H ArR
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 examplesR' = H, 83 to 91 % ee
R' = CH2Ar, 95 to >99% ee
R
R
HN
NH
NH
NHN
N
AuCl
ClAu
Mechanistic Rationale:
Catalytic Enantioselective Protonation of Silyl Enol Ethers of Ketones
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, 133, 13248-13252
Wang, Z. J.; Casey, C. J; Bergman, R. G.; Raymond, K. N.; Toste, F. D. J. Am. Chem. Soc. 2011, 133, 7358-7360
Asymmetric Flourination
Enantioselective fluorination using insoluble electrophilic fluorinating agent and lipophilic, chiral anion as phase-transfer catalyst
10 examples, 84 – 95% ee
Kanno, O.; Kuriyama, W.; Wang, Z. J.; Toste, F. D.; Angew. Chem. Int. Ed. 2011, 42, 9919-9922
Rauniyar, V.; Lackner, A. D.; Hamilton, G. L.; Toste, F. D. Science, 2011, 334, 1681-1684
C(sp3)-F Reductive Elimination From Au(III) complexes
Mankad, N.; Toste, F. D. Chem. Sci. 2012, 3, 72-76
Au(I)/Menthol Cooperative Catalysis – Regio- and Enantioselective Hydroamination of Dienes
Hydroalkoxylation Catalyzed by Me3PAuX in water
Hydroalkoxylation Catalyzed by Encapsulated Me3PAu+ in water
18h, 48% 90h, 76%
4% 18%