palladium-catalyzed allylic amination

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Palladium-catalyzed allylic amination

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Palladium-catalyzed allylic amination. Chem. Rev. 1998 , 98, 1689 Angew. Chem. Int. Ed. 2008 , 47, 4733. Amination of Functionalized Alkenes. Richard D. Connel l et al. J. Org. Chem . 1988 , 53, 3845. Bystorm S. E. et al. Tetrahedron Letters , 1985 , 26 , 1749. - PowerPoint PPT Presentation

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Page 1: Palladium-catalyzed allylic amination

Palladium-catalyzed allylic amination

Page 2: Palladium-catalyzed allylic amination

R

H+R'ZNH

[Pdll]

[O]

Oxidative allylicamiantion

[Pdll]

[O]

aza-Wacker oxidation

ZR'N R

and/or

R

NR'Z

NR'Z

R

H

ii

R1 R2

XPd(0),Nu-

oxidative additionR1 R2

Pd

Nu

Xi

Pd(0),X

R1 R2

Nu

+R1 R2

Nu

Chem. Rev. 1998, 98, 1689Angew. Chem. Int. Ed. 2008, 47, 4733

Page 3: Palladium-catalyzed allylic amination

Amination of Functionalized Alkenes

OAc

N(Boc)2

N(Boc)2 N(Boc)2+ (Boc)2N Li ++

4 mol% Pd(dba)2

5.5 mol% diphos

THF-DMF(2:1)

36h, 25oC

total 94%42:50:8

Richard D. Connell et al. J. Org. Chem. 1988, 53, 3845

Bystorm S. E. et al. Tetrahedron Letters, 1985, 26, 1749

+

Cl

OAcTsNH Na

5 mol% Pd(PPh3)

THF-DMSO(4:1)

4.5h, 25oC

80%

NHTs

OAc

Ph Ph

OAc

+ Ph Ph

N(CHO)2

up to 94% ee

NaN(CHO)2

2.5 mol% (C3H5PdCl)26 mol% (S)BINAP

NEt(1 eq.)

ClCH2CH2Cl

0oC

Kuiling Ding, et al. J. Org. Chem. 2001, 66, 3238

Page 4: Palladium-catalyzed allylic amination

R Ligand(mol%)

Pd(mol%)

X Reaction tme(h)

Yield(%) Ee(%)

Ph 1 (2.6) 2.5 CO2Et 31 80 79

Ph 2 (2.6) 2.5 CO2Et 37 93 97

Ph 3 (4.5) 3.0 CO2Et 12 90-95 99

Ph 4 (4.5) 3.0 CO2Et 12 90-95 97

Ph 5 (4.5) 3.0 CO2Et 12 90 99

Ph 6 (3.0) 3.0 CO2Me 1 98 94

Ph 7 (3.0) 3.0 CO2Me 2 93 88

Me 6 (10.0) 3.0 CO2Me 15 93 30

Me 7 (10.0) 3.0 CO2Me 96 87 57

Me 2 (2.0) 1.0 P(O)Ph2 13 84 73

Tamino Hayashi, et al, J. Am. Chem. Soc. 1989, 111, 6301 Togni, A. et al. J. Am. Chem. Soc. 1996, 118, 1031 Helmchen, G., et al.Tetrahedron: Asymmetry 1994, 5, 573.

R R

X+ BnNH2

Pd/L40oC

THF R R

NHBn PPh2

PPh2

NR1R2Fe

1: R1=Me,R2=(CH2)2OH2: R1=R2=(CH2)2OH

PPh2

NFe N R

3: R=Adamantyl4: R=3-NO2-Ph5: R=Cp2Ru

PPh2 N

O

R6: R=Ph7: R=t-Bu

Chiral N-P Ligands

Page 5: Palladium-catalyzed allylic amination

OAc + PhthN (C6H13)4N

2.5 mol% (C3H5PdCl)27.5 mol% a

n=5-784%-95%

n-4n-4 NPhth

94-98% ee

HNO

X2

NHO

X1

a: X1=X2=PPh2b: X1=PPh2 X2=PAr2, Ar= O O

O

HNO

NHO

PPh2 Ph2P

c

O+ PhthNH

2.5 mol% (C3H5PdCl)27.5 mol% a or c

PhthNOH

a: 76% eeb: >98% ee

Trost, B. M. et al. J. Am. Chem. Soc. 1992, 114, 9327.Trost, B. M. et al. J. Am. Chem. Soc. 1994, 116, 4089.Trost, B. M. et al. J. Am. Chem. Soc. 1997, 119, 5962.

Ph Ph

OAc

+ BnNH2Ph Ph

NHBnPd2(dba)3.CHCl3, 1

THF, 40oC

up to 99% ee

PPh2

N

O

POPh2

CN+

H2N

HO

1

Paul S. Pregosin, et al. Organometallics 1999, 18, 1207

Page 6: Palladium-catalyzed allylic amination

Lixin Dai, Xuelong Hou, et al. J. Am. Chem. Soc. 2001, 123, 7471

Fe

BrN O

R

(1) n-BuLi

(2) (Et2N)2PCl

Fe

PN O

R

Et2N

Et2N

(R)-BINOLFe

PN O

R

R'O

Et2N

Fe

PN O

R

Et2N

R'O+

(S)-BINOL

R=i-PrFe

PN O

i-Pr

R''O

Et2N

Fe

PN O

i-Pr

Et2N

R''O+

6a R=i-Pr6b R=t-Bu6c R=Ph6d R=Bn

7a R=i-Pr7b R=t-Bu7c R=Ph7d R=Bn

8a R=i-Pr8b R=t-Bu8c R=Ph8d R=Bn

9a R=i-Pr9b R=t-Bu9c R=Ph9d R=Bn

10 11

O

OH

O

OHR'= R''=

Page 7: Palladium-catalyzed allylic amination

Up to 98% ee

Chiral P-S ligands

Michael C. Willis, et al. Tetrahedron: Asymmetry , 2003, 14, 705;J. W. Faller, et al. Org. Lett., 2004, 6, 1301; J. W. Faller, et al. Org. Lett. 2005, 7, 633.

Ph Ph

OAc

+ BnNH2Ph Ph

NHBnPd2(dba)3.CHCl3, 1

THF, 40oC

up to 99% ee

Carlos CarreteroJ. Org. Chem. 2003, 68, 3679

Page 8: Palladium-catalyzed allylic amination

Chiral phosohine oxides

Yasumasa Hamada, et al. J. Am. Chem. Soc. . 2004, 126, 3690Yasumasa Hamada, et al. Org. Lett., 2007, 9, 927

Chatt, J.; Heaton, B. T. J. Chem. Soc. A 1968, 2745

MeOOC

OO

OMe

N

NH2

Boc

+

Pd(C3H5)Cl (2 mol%)(S,Rp)-1a(4 mol%)

BSA(2.5 equiv.)

CH3CN, -30oC

99%

N

HN

BocMeOOC

(S)-5 95% ee

NH

NOHH

HH

(-)-TangutorineOrg. Lett., 2010, 12, 872

Page 9: Palladium-catalyzed allylic amination

Proticacid generated during the reaction is the prerequisite for product isomerization

J. Am. Chem. Soc. 2005, 127, 17516; J. Am. Chem. Soc. 2004, 126, 5086;J. Am. Chem. Soc. 2007, 129, 14172

Andrei Yudin

DBU keeps the reaction under kinetic control, but achieving a high b/l ratio requires greater discrimination between isomeric allyl palladium intermediates, which is achieved through ligand control.

Giuliana Cardillo, et al. Org. Lett., 2008 10, 2425

Page 10: Palladium-catalyzed allylic amination

Shu, Kobayashi. et al. J. Am. Chem. Soc. 2009, 131, 4200

Aqueous Ammonia as Nucleophile

Amination of Allylic Alcohols

Shyh-Chyun Yang J. Org. Chem. 1999, 64, 5000

Page 11: Palladium-catalyzed allylic amination

Xuelong Hou, et al. Org. Lett., 2009, 11, 1789

Kinetic Resolution of Indolines

HNO

Ph2P

NHO

PPh2

L10

Page 12: Palladium-catalyzed allylic amination

Amination of Nonfunctionalized Alkenes

Hegedus, L. S J. Am. Chem. Soc. 1978, 100, 5800

Stahl, S. S. Org. Lett. 2006, 8, 2257.

R1 Procedure

Yield%2

Yield%3

Yield%4

H A - 86

H B - - 60

Ph A - 62 -

Me(Z/E)=(83:17)

A 84 4

Me(Z/E)=(83:17)

C 96 - -

Me(E) B 91 - -

Me(Z) D 94 - -

NHTs

R1

NTs

orN

TsR'

orNTs

Procedure A-D

1 2 3 4

Page 13: Palladium-catalyzed allylic amination

Beccalli, E. M. et al; J.Org. Chem. 2004, 69, 5627.Chem. Rev ,2007, 107 5318

Beccalli, E. M

Page 14: Palladium-catalyzed allylic amination

Christina M White

J. AM. CHEM. SOC. 2007, 129, 7274J. AM. CHEM. SOC. 2008, 130, 3316

Using this alternative palladium(II) source having a counterion that is a much weaker base, 1H NMR analysis at the same 2 h time point revealed predominant formation of a ð-allylPd complex (ca. 61%) and no significant formation of product 3a. The addition of an external acetate source to this ð-allylPd intermediateled to the formation of 3a with a similar yield and identicaldiastereoselectivity to that observed under standard catalytic conditions.

Yields decrease over time, which was most likely due to formation of Pd-H in the oxidative aminopalladation pathway that mediates olefin isomerization to 2a

Intramolecular

Page 15: Palladium-catalyzed allylic amination

Intermaolecular

Stoichiometric Studies To Evaluate the Role of (salen)CrCl2

The combination of Cr catalyst 2 with BQ was uniquely effective at promoting formation of aminated product 7 in 25% yield with regio- and stereoselectivities similar to those observed under standard catalytic conditions. Consistent with 2/BQ working together to promote functionalization,sterically hindered quinones such as 2,6-dimethyl quinone result in significantly diminished yieldsThese results suggest that Pd catalyst 1 mediates allylic C-H cleavage, while Cr catalyst 2 and BQ promote functionalization.

J. AM. CHEM. SOC. 2008, 130, 3316

Lewis acid activition

Page 16: Palladium-catalyzed allylic amination

J. AM. CHEM. SOC. 2009, 131, 11701

Brønsted Base activition

Lewis acid and Brønsted Base promoting intermolecular functionalization

Page 17: Palladium-catalyzed allylic amination

Org. Lett., 2009, 11, 2707

Theaminopalladation/-hydride elimination mechanism predicts formation of 22a-d2 but not 22b-d2. The observed formation of nearly equal amounts of products 22a-d2 and 22b-d2, however, argued against the possibility of aminopalladation/-hydride elimination pathway and in favor of a mechanism involving aπ-allyl-Pd intermediate.

J. AM. CHEM. SOC. 2010, 132, 11978

Page 18: Palladium-catalyzed allylic amination

Conclusions:

1. All Pd(0)-catalyzed allylic aminations was promoted by chiral phosphines can not avoid regioselectivity directly. No other kinds of chiral organomoleculars was used. Most of them need additives and excess substrates(3 eq. of amines or even more) to prevent bypath product.

2. Most of Pd(ll)-catalyzed allylic aminations need additives to obtain product and high regioselectivity. Substrates were limited to functionalized amines.Consice mechanisms needed to be studied.