CDC Reaction Involving α -C-H Bonds ofNitrogen in Amines

李南 2012.6.16

Yoshida, J. Am. Chem. Soc. 1999, 121, 9546.

一般形式

R3 H

NR1R2 oxidant

R3

NR1R2 Nu-

R3 Nu

NR1R2

N

CO2Me

- 2e

- H+ N

CO2MeN

CO2MeEox = 1.91V

Eox = 1.75V

SiMe3

N

CO2Me

Murahashi, S.-I. J. Am. Chem. Soc. 2003, 125, 15312.Murahashi, S.-I., Angew. Chem., Int. Ed. 2005, 44, 6931.Murahashi, S.-I., J. Am. Chem. Soc. 2008, 130, 11005.

Conditions A: 2.5 equivH2O2; Conditions B: 60 oC, 1 atmO2.

N CH2R3R2

R1

+ NaCN/AcOH 1.2 eq/6 eq

5 mol% RuCl3,

CH3OHCondition A or B

N CHR3R2

R1

CN

N CH2Me

Ph

CNN CH2

Me CN

Br

N

Ph

CN NPh

CN

A: 80%B: 88%

A: 67%B: 88%

A: 69% A: 97%B: 76%

Ofial, Chem. Commun., 2009, 45, 5024.Bir Sain, Chem. Commun., 2009, 45, 2371. Zhu, C.-J., Chem. Commun., 2011, 47, 2354.

N + TMSCN

10 mol% FeCl22.5 eq tBuOOH

R.T. MeOHN

CN

N + TMSCN

10 mol% Cat

1.2 eq tBuOOH

R.T. MeOHN

CN

N N

AuCl Cl

Cl-

Catyield up to 98%

yield up to 92%

N + NaCN/AcOH

5 mol% V2O5O2

60 oC, MeOHN

CN

yield up to 97%

Li, C.-J. J. Am. Chem. Soc., 2004, 126, 11810.

Ar N + H R

5 mol% CuBr

(1.0 - 1.2 eq) tBuOOH

100 oC, 3hAr N

R

N + H Ph

5 mol% CuBr

(1.0 - 1.2 eq) tBuOOH

100 oC, 3hN

Ph

36%

yield up to 82%

NPh

+ H OMe

5 mol% CuBr

(1.0 - 1.2 eq) tBuOOH

100 oC, 3h

NPh

OMe

74%

N+ H Ph

5 mol% CuBr

(1.0 - 1.2 eq) tBuOOH

100 oC, 3h

N

Ph

12%

Fu Hua, J. Org. Chem., 2008, 73, 3961.Li, C.-J., Org. Lett., 2004, 6, 4997. Li, C.-J., Tetrahedron: Asymmetry, 2006, 17, 590.

+N

Ar

H R

10 mol% CuOTf

15 mol% PyBOx

(1.0 - 1.2 eq) tBuOOH

100 oC, THF

NAr

R

NO

N N

O

Ph Ph

yield up to 72%ee up to 74%

N + H R3

40 mol% CuBr2eq NBS

80 oC, 6h

NR3

R2

R1

R2

R1

yield up to 65%

NR2 R1

H

+ R

10 mol% FeCl22 eq (tBuO)2

100 oC, airN

R2

R1R

yield up to 93%

N + SiEt3

10 mol% FeCl22 eq (tBuO)2

100 oC, airN

SiEt3

82%

1.2 eq TBAF

THFN

H

89%

10 mol% FeCl22 eq (tBuO)2

100 oC, air

n-Oct N

N N n-Oct

67%

Pierre Vogel, Org. Lett., 2009, 11, 1701.

Li, C.-J., J. Am. Chem. Soc. 2005, 127, 6968.

NPh

+ Ar-H

10 mol% CuBr

(1.0 - 1.3 eq) tBuOOH

50 oC

NPh

Ar

NPh

NH

NPh

NH

Cl

NPh

NHO2N

NPh

NMe

79% 44% 73% 85%

NPh

NHMe

NPh

OH

NPh

OH

NPh

OH

Br OMe

49% 53% 49% 55%

NNH

5 mol% CuBr

1.5 eq tBuOOH

N

NH H R1

O

H

H

R2

R30 mol%

NH

PhCO2H

5 mol% CuBr, 1.5 eq tBuOOH

N

R

R1

O

yield up to 78% yield up to 73%

Huang, Z.-Z. Org. Lett. 2010, 12, 5214.Che, C-M., Chem. Commun. 2010, 46, 2739.

NH

N+

Ph

3 mol% Cat

3 eq tBuOOH

MeCN/H2O, reflux

NPh

NH

80%

NPh

NMe

68%

NPh

70%

N

NPh

71%

N

Br

N

N N

CONH(CH2)3Si(OEt)3

Fe

NCMeMeCN NCMe

NH

N+

Ph

10 mol% V2O5O2

H2O, 100 oC

NPh

NH

83%

Ramaiah Prabhu, Chem. Commun., 2011, 47, 11787.

Kawakami, Y., Angew. Chem., Int. Ed. 2004, 43, 4231.

N

X

Me

O

H

+Y

R

H

H

0.5 mol% Zr(OTf)4

130 oC, 1 atm O2

Y

R

H

HN

X

MeO

yield up to 58%

N

O

Me

NPh

N

O

Me

NMe

N

O

Me

NMe

N

O

Me

S

O

O

ON

O

Me

NMe

24% 58%28%

C3: C2= 60: 4022% 14%

Itami, K., Chem. Asian J., 2009, 4, 1416.

NR2 R1

Het-H+10 mol% FeCl2 4H2O

10 mol% bipy

20 mol% KI

2 eq pyridine N-oxide

DMA, 130 oC

NR2 R1

HetH

yield up to 61%

SMeO

BnMeN

60%

SMeO

NMe

EtO2C

26%

S

BnMeN

OMe

40%

N NMe

NMeBn

56%

Li, C.-J. J. Am. Chem. Soc., 2005, 127, 3672.Li, C.-J. Green Chem., 2007, 9, 1047.

NR2 R1

R3 H

+NO2

H R4

5 mol% CuBr

Condition A or BN

R3 R4

NO2R1

R2

NPh

NO2A: 75%B: 79%

NPh

NO2A: 53% dr = 1.7:1B: 75% dr = 1.7:1

Me

Me

NMe

O2N

A: 62%B: 63%

N

Ph

NO2

A: 53%

yield up to 82%

Conditions A: 80 equiv nitroalkane, 1.0-1.2 equiv ∼ tBuOOH; Conditions B: 5 equiv nitroalkane, 1 atm O2, H2O, 40-60 oC.

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

NR2 R1

R3 H

+NO2

H R4

1mol% Ir(ppy)2(dtbpy)PF6

visible lightN

R3 R4

NO2R1

R2

yield up to 96%

NPh

NO2

A: 75%

NPh

NO2

A: 53% dr = 2 : 1

Me

A: 53% dr = 5 : 1

N

Ph

NO2

A: 53%

Np-BrC6H4

NO2Me

Zhu, C.-J., Angew. Chem., Int. Ed. 2012, 51, 1252.

NR2 R1

R3 H

+NO2

H R4

3 mol% Cat

air, 60 oCN

R3 R4

NO2R1

R2

yield up to 95%

N N

AuCl Cl

AuCl4-

Cat

NPh

NO2

A: 86%

NPh

NO2Me

A: 85%

Me NMe

NO2

A: 52%

Li, C.-J. Green Chem. 2007, 9, 1047.Li, C.-J. Eur. J. Org. Chem. 2005, 3173.

Conditions A: 2.5 equivH2O2; Conditions B: 60 oC, 1 atmO2, H2O.

5 mol% CuBr

Condition A or B

yield up to 86%

NR1

+CO2R2

CO2R2H

H

NR1

CO2R2R2O2C

NPh

CO2MeMeO2C

A: 74%B: 63%

NPh

CO2EtEtO2C

A: 65%B: 59%

NPh

CO2BnBnO2C

A: 70%

NPh

O O

O O

A: 86%

Mikiko Sodeoka. J. Am. Chem. Soc. 2006, 128, 14010.

NBoc

MeO

MeO+

CO2i-Pr

CO2i-PrH

5 mol% Pd cat

1.1eq DDQ in DCM(slow addtion over 5h)

DCM, R.T.

NBoc

CO2i-Pri-PrO2C

MeO

MeO

yield = 82%ee = 86%O

O

O

O

PAr2

PAr2

Ar = 3,5-Me2C6H3

Li, C.-J. Angew. Chem., Int. Ed. 2008, 47, 7075.

PMPNH

NR1R2

H

O

+ Ar

10 mol% CuBr

1.0 tBuOOH

DCM, R.T.

PMPNH

NR1R2

O

Ar

yield up to 78%

PMPNH

NR1R2

H

O

+CO2R3

CO2R3R4

2 eq Cu(OAc)2, 20 mol% Cs2CO3

20 mol% di(pyridyl) ketone

tol, 150 oC PMPNH

NR1R2

O

R4OR3

O

R3O

O

yield up to 94%

ArNH

NR1R2

H

O

+CO2R3R4

10 mol% CuOTf2, 12 mol% L1.0 eq DDQ

THF, -40 oC

yield up to 82%ee up to 96%dr up to 7 : 1

O R1

PMPNH

NR1R2

O

R4OR3

O

R1

O

O

N N

O

NPh

+CO2Et

PO(OEt)2HH

10 mol% CuOTf2, 12 mol% L1.0 eq DDQ

THF, 0 oC

NPh

(EtO)2OP CO2Et

yield 72%ee 90%dr 19 : 1

Wang, Rui, Angew. Chem., Int. Ed. 2011, 123, 10613.

Klussmann, M. Chem. Commun. 2009, 45, 3169.Guo, C-C., Chem. Commun. 2009, 45, 953.

NAr

R

R

+R2

O 10 mol% VO(acac)210 mol% Proline

1,5 eq tBuOOH

MeOH, R,T,

NAr

R

R

R2

O

yield up to 69%

+R4

O

R1N

R2

R3

5 mol% CuI1 atm O2

80 oCR3

ONR1 R2

yield up to 73%

NPh

Ph

O

62%

NPh

O

62%

Me NMe O

Me

70%

NAr

R

R

1 mol% [Ru(bpy)3](PF6)210 mol% Proline

MeCN5W lamp

NAr

R

RR2

O

yield up to 95%

+R2

O

Magnus Rueping, Chem. Commun., 2011, 47, 2360.

Chi, R. Y. Angew. Chem. Int. Ed. 2012, 51, 3649.Klussmann, M. Synlett 2009, 10, 1558.

R1

R1N

Ar+

O

HR2

1) 30 mol% Cat 10 mol% CuBr2 50 mol% AcOH 1.5 eq tBuOOH

CHCl3/Et2O R.T.

2) NaBH4, EtOH

0 oC

R1

R1N

ArH

R2

HHO

yield up to 71%ee up to 99%dr up to 3 : 1N

H

Ar

OTMS

Ar

Ar = 3,5-(CF3)2C6H3

R1

R1N

Ar

+OTMS

10 mol% CuCl2H2O

MeOH, O2, R.T.

R1

R1N

Ar

O

R

yield up to 96%

N

OTMS

R+

10 mol% CuCl2H2O

MeOH, O2, R.T. NH O

PMP46%

Huang, Z.-Z. Angew. Chem., Int. Ed. 2010, 49, 10181.

X= O, S, CH2, (CH2)2

O+

Ar

HN

OR1

O10 mol% Cu(OAc)230 mol% pyrrolidine

1.5 eq tBuOOH, R.T.COOR1

O HNAr

yield up to 73%

X

O

+PMP

HN

OR1

O10 mol% Cu(OAc)230 mol% pyrrolidine

1.0 eq DDQ, CHCl3

0 oC- R.T. X

O

NH

PMP

COOR1

yield up to 83%

Conclusion

1. Although using simple and inexpensive building blocks is an attractive alternative to consuming more functionalized and costly reagents, chemo- and regioselectivity remain issues that limit the broad usage of these methods.2. Practical approaches to C-H bond oxidation using reagents that are more environmentally friendly, such as oxygen, electricity, and visible light, are desirable and are being developed.3. In terms of asymmetric catalysis, enantioselective C-C bond formation by C-H bond oxidation is still in its infancy, although ligand-accelerated transition metal catalysis and organocatalysis has enabled some growth.