fluoride-mediated oxidative gold chemistry ...lalonde, r. l.; wang, j. z.; mba, m.; lackner, a. d.;...

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%