palladium-catalyzed allylic amination
DESCRIPTION
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 PresentationTRANSCRIPT
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
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
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
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
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''=
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
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
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
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
Xuelong Hou, et al. Org. Lett., 2009, 11, 1789
Kinetic Resolution of Indolines
HNO
Ph2P
NHO
PPh2
L10
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
Beccalli, E. M. et al; J.Org. Chem. 2004, 69, 5627.Chem. Rev ,2007, 107 5318
Beccalli, E. M
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
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
J. AM. CHEM. SOC. 2009, 131, 11701
Brønsted Base activition
Lewis acid and Brønsted Base promoting intermolecular functionalization
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
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.