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
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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!