Visible Light Induced C(sp3)-H Bonds

Functionalization

LSPN SeminarBAO, Xu

13. 09. 2018

1912. Light had the potential to serve as an inexpensive, abundant, renewable,and nonpolluting reagent for chemical synthesis.

G. Ciamician, Science, 1912, 36, 385

1978.

D. M. Hedstrand, W. H. Kruizinga, R. M. Kellogg, Tetrahedron Lett. 1978, 19, 1255

COOH

N2

BF4 RR = H, Br or OMe

[Ru(bpy)3]Cl2 (5 mol% )

CH3CN, > 410 nm

COOH

R

1984.

H. Cano-Yelo, A. Deronzier, J. Chem. Soc., Perkin Trans. 2, 1984, 1093.

2003.

J. M. Zen, S. L. Liou, A. S. Kumar, M. S. Hsia, Angew. Chem. Int. Ed. 2003, 42, 577

2008.

M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am. Chem. Soc. 2008, 130, 12886

History of Photoredox Catalysis LSPN Seminar Bao, Xu

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Pandey’s work: Oxidation and Amination

DCA could also serve as PC

a Pandey, G.; Laha, R.; Singh, D., J. Org. Chem. 2016, 81, 7161;b Pandey, G.; Laha, R., Angew. Chem.Int. Ed. 2015, 54, 14875.

Acridinium ion as PC

Fukuzumi, S. et al, Chem. Commun.2010, 46, 601

Zhang, L.; Yi, H.; Wang, J.; Lei, A., Green Chem. 2016, 18, 5122

Xiang, M.; Xin, Z.-K.; Chen, B.; Tung, C.-H.; Wu, L.-Z., Org. Lett. 2017, 19, 3009.

Benzylic C(sp3)-H oxidation LSPN Seminar Bao, Xu

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Reactive Intermediate: Iminium ion & α-Aminoalkyl radical

Mechanism for Iminium ion formation

Stephenson, C. R. J. et al J. Am. Chem. Soc. 2010, 132, 1464.

NPh

R1 Ir(ppy)2(dtbppy)PF6

RCH2NO2 (no degassed)visible light

NPh

R1

NO2Rup to 96% yield

Aza-Henry reaction

Stephenson, C. R. J. et al J. Am. Chem. Soc. 2010, 132, 1464.Strecker reaction

NR2

ArR1

R1 = Ar, Alkyl, HR2 = Alkyl, H

Ir(ppy)2(bpy)PF6

KCN, AcOH, MeCNvisible light

up to 97% yield

NR2

ArR1

CN

Rueping, M. et al Chem Commun. 2011, 47, 12709.

NAr

R1

Mannich reaction

Ru(bpy)3(PF6)2 (1 mol%)L-Proline (10 mol%)MeCN, visible light

47 – 95% yield

+R2

ON

ArR1

R2

ORueping, M. et al Chem Commun. 2011, 47, 2360.

NR1

+R2

OSiMe3

R1 = Ar, alkyl

Ru(bpy)3Cl2 (5 mol%)MeOH, blue LED72 – 98% yield

NR1

R2

O

Xia, W. et al Chem. Commun. 2012, 48, 2337

NPh

Ru(bpy)3Cl2 (5 mol%)

MeOH, blue LED NPh

OH

NPh

OMe

+

43% 57%

4

α-Amino Functionalization Iminium Ion Intermediate LSPN Seminar Bao, Xu

Friedel-Crafts amidoalkylation

R1 N R3

O

R2+ Nu

Ru(bpy)3Cl2 (1 mol%)(NH4)2S2O8, 25-30 oC R1 N R3

O

R2

Nu

alkylamides:

H

O

N

O

N N

O

Electron-rich aromatics

OMe

MeO OMe

OMe

OMe

OMe

OMe

OMeNR

R = H,Me,Ph,Bn

Stephenson, C. R. J. J. Org. Chem. 2012, 77, 4425; Org. Lett. 2012, 14, 94

NR1

R2

+ R3HNO

R4R5

Ru(bpy)3Cl2 (10 mol%)

O2, blue LEDsDCM, 40 oC

43 – 75% yieldN

R1

R2

R5

R3HN O

R4

Li, J.-H. J. Org. Chem. 2012, 77, 8705.

NR1

R2

+NH O

OR4Ir[(ppy)2(bpy)]PF6 (1 mol%)

Zn(OAc)2, blue LEDsMeCN, 40 oC42 – 86% yield

NR1

R2

HN O

OR4R3Ar

Rueping, M. et al Chem Commun. 2012, 48, 11960.

5

α-Amino Functionalization Iminium Ion Intermediate LSPN Seminar Bao, Xu

DiRocco, D. A.; Rovis, T., J. Am. Chem. Soc. 2012, 134, 8094

6

α-Amino Functionalization Iminium Ion Intermediate LSPN Seminar Bao, Xu

α-Amino Functionalization Arylation and Reductive Umpolung of Carbonyl Derivatives LSPN Seminar Bao, Xu

Ooi, T. et al J. Am. Chem. Soc. 2015, 137, 13768

Ar1 H

NAr2

+ NAr

RH

[Ir(ppy)2(dtbbpy]PF6 (1 mol%)

DMA, Li2CO3 (20 mol%), Blue LEDs25 oC, 72 h

Ar1

HNNR

Ar

Ar2

36 – 97% yield

Ar H

O+ N

p-Tol

MeH

[Ir(ppy)2(dtbbpy]PF6 (0.5 mol%)

DMA, PhCOOH (20 mol%),Blue LEDs, 25 oC, 6 -24 h

Ar

OHN

p-Tol

46 – 75% yield

Rueping, M., et al Angew. Chem. Int. Ed. 2016, 55, 6776.

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α-Amino Functionalization Alkylation and Addition of α-aminoalkyl radical LSPN Seminar Bao, Xu

X+

Br

X = NBoc, O, S

Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1 mol%)N (10 mol%)

[Ni] (2 mol%), K2CO3, MeCN/H2OBlue LEDs

MeO

OMe

Ni Br

Br

X

41 – 82% yield

MacMillan, D. W. C.et al Nature, 2017, 547, 79.

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O-α-C(sp3) H Functionalization (1) Functionalization of ethers LSPN Seminar Bao, Xu

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Molander’s mechanism Doyle’s mechanism

O-α-C(sp3) H Functionalization (2) C-Alkylation and Arylation of alcohols LSPN Seminar Bao, Xu

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O-α-C(sp3) H Functionalization (2) C-alkylation of alcohols LSPN Seminar Bao, Xu

H

X

X = OR, OH, SR, NRAc

H

O

(sp3)C H

O

Br

BrHO

COOH

OBr

Br

eosin Ysolvent, white LED light

X

EWG

O

EWG

(sp3)C EWG

EWG =aldehydeketoneesteramideimidecyanidesulfonenitropyridine

Wu, J. et al Angew. Chem. Int. Ed. 2018, 57, 8514.

O

Br

BrHO

COOH

OBr

Br

eosin Y

O

Br

BrHO

COOH

OHBr

Br

eosin Y

O

Br

BrHO

COOH

OBr

Br

*eosin Y

whiteLEDs

O

O

Ph CNCNOPh CN

CNO

PhCN

CN

11

Allylic CH Functionalization LSPN Seminar Bao, Xu

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Benzylic CH Functionalization LSPN Seminar Bao, Xu

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Aliphatic CH Functionalization LSPN Seminar Bao, Xu

Alexanian, E. J. et al J. Am. Chem. Soc. 2014, 136, 14389.

Alexanian, E. J. et al J. Am. Chem. Soc. 2016, 138, 13854.

Alexanian, E. J. et al J. Am. Chem. Soc. 2016, 138, 696.Alexanian, E. J. et al Chem. Sci. 2018, 9, 5360 Alexanian, E. J. et al J. Am. Chem. Soc. 2016, 140, 4213. 14

Aliphatic CH Functionalization LSPN Seminar Bao, Xu

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Remote CH Functionalization Amidyl radical induced CH Functionalization LSPN Seminar Bao, Xu

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Remote CH Functionalization Iminyl Radical Induced CH Functionalization LSPN Seminar Bao, Xu

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Remote CH Functionalization Iminyl Radical Induced CH Functionalization LSPN Seminar Bao, Xu

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Visible Light Induced C(sp3)-H Bonds Functionalization LSPN Seminar Bao, Xu

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Advantage mild condition

good compatibility with several functional group

Formation of C-C and C-X bonds are possible

Disadvantage Poor regioselectivity

Poor siteselectivity

Enantioselectivity challenge

Many areas left to explore!