1 chiral phosphoric acids-catalyzed multi-component reactions for synthesis of structurally diverse...
TRANSCRIPT
1
Chiral Phosphoric Acids-Catalyzed Multi-Component Reactions for Synthesis of Structurally Diverse Nitrogenous Compo
unds
Feng Shi
Dec. 18th, 2010
2
Multi-component Reactions (MCR)
The reaction between three or more reagents in a single vessel which have been added together (or nearly) to form a new compound that contains significant portions of all the components.
The definition of MCR:
The advantages of MCR:•superior atom economy, atom utilization and selectivity
• lower level of by-products
• simpler procedures and equipment
• lower costs, time, and energy
•more environmentally friendly
Introduction:
3
• Amino-acid derivatives• Brønsted acids • Lewis bases• Nucleophilic Carbenes
Chiral Organocatalyzed Multi-component Reactions
Chiral Organocatalysts:
Combined catalysis of organo and metal catalysts
4
Chiral Brønsted Acids
For review, see: T. Akiyama*, Chem. Rev. 2007, 107, 5744.
X
R
H
B
Bronsted acid catalysis
X=O, NR'
N N
S
H H
R R
O
OAr Ar
OHOH
Ar Ar
X
OH
OH
X
X
O
O
X
POH
O
Hydrogen-bonding Catalysts Stronger Bronsted Acid Catalysts
Jacobsen, Takemoto Seebach, Rawal
Aklyama, Terada
5
Other newly developed Brønsted Acids:
X
SO3H
SO3H
X
Ishihara
X
SO2
SO2
X
NH
List
X
O
O
X
PNHTf
O
X
COOH
COOH
X
Maruoka
O
O OO
P OHO
OPO
OH
Gong
Yamamoto
6
The first examples of Phosphoric Acids-catalyzed Reactions
HO
N
Ph
OEt
OSiMe3
(1.5 equiv)
1a (10 mol %),PhMe, -78oC, 24h
HO
HN
PhCO2Et
Me
+
HO
HN
PhCO2Et
Me
87% (96% ee) 13%
N
Ph
Boc 1b (2 mol%)
acac (1.1 equiv)CH2Cl2, RT, 1h
HN
PhAc
Ac
Boc
*
99% (95% ee)
X
O
O
X
POH
O
1a: X=4-NO2C6H41b: X=4-(beta-Naphthyl)C6H4
T. Akiyama*, J. Itoh, K. Yokota, K. Fuchibe, Angew. Chem. Int. Ed. 2004, 43, 1566.
D. Uraguchi, M. Terada*, J. Am. Chem. Soc. 2004, 126, 5356.
7
For related reviews, see: (a) M. Terada*, Synthesis, 2010, 1929; (b) A. Zamfir, S. Schenker, M. Freund, S. B. Tsogoeva*, Org. Biomol. Chem., 2010, 8, 5262; (c) S. J. Connon*, Angew. Chem. Int. Ed. 2006, 45, 3909.
The Structural Features of Chiral Phosphoric Acids:
X
O
O
X
POH
O
Stereo-controlling group
Lewis basic site
Bronsted acidic site
Stereo-controlling group
8
Chiral Phosphoric Acids-Catalyzed Multi-Component Reactions
Biginelli Reaction
Cyclization Reactions
1,3-Dipolar Cycloaddition
Kabachnik–Fields Reaction
Friedel-Crafts Aminoalkylation Hantzsch Reaction
Povarov Reaction
Direct Mannich Reaction
Aza-D-A Reaction
Ugi-type reaction
9
Q.-X. Guo, H. Liu, C. Guo, S.-W. Luo, Y. Gu, L.-Z. Gong*, J. Am. Chem. Soc. 2007, 129, 3790.
1a: R=4-ClC6H4
R
O
O
R
POH
O
O
R1H R3
OO
R3
HN
R1
+ +
5 mol% 2b or 2c
PhCH3, 10 oC
NH2
R2
R2
up to76% yield, 86% ee
Direct Mannich Reaction:
2a: R=C6H52b: R=4-FC6H42c: R=4-ClC6H4
O
OP
O
OH
R
R
PO O
O O
H
O
H
NR3
R1
R2R4
*
Transition state
X
O
+ PhNH2 +H R
O0.5 mol% 1aor 2 mol% 2a
PhCH3, 0oCX
O
R
NHPh
up to 98% ee, 98/2 dr
10
up to 99/1 dr, 99% ee
R1CHO + ArNH2 +
NHCbz
R2
Cat. 0oCCH2Cl2, EtOH
then NaBH3CN,pTSA
NH NHCbz
R1
R2
ArO
OP
O
OH
R
R
Cat.: R=4-ClC6H4
G. Dagousset, F. Drouet, G. Masson, J. Zhu*, Org. Lett., 2009, 11, 5546.
R1CHO
NHCbz
R2
NH NHCbz
R1
R2
Ar
ArNH2
+P
O
OO
O
N
H R1
ArPO
OOH
O
H
HR2
HN
R1
N
Cbz
H
Ar
HO
OP
O
ONH N
R1
R2
Ar HCbz OP
O
O
O
HO
Et
PO
OOH
ONH NHCbz
R1
R2
Ar
OEt
H-
I II
enecarbamate
* *
* *
*
Using Enecarbamates as Nucleophiles
11
R H
O+ PMP
NH2
+
OEt
O TBS 3mol% Cat.
-50oC R OEt
ONHPMP
up to 97% yield, 97% ee
M. Sickert, F. Abels, M. Lang, J. Sieler, C. Birkemeyer, C. Schneider*, Chem. Eur. J. 2010, 16, 2806.
O
OP
OH
O
t-Bu
t-BuCat.
Vinylogous Mannich Reaction
R H
N
OEt
O TBS
R OEt
ONHPMP
PMP
PO
O OH
O
*
R H
NPMP
PO
O O
O
*H
R OEt
ONHPMP TBS
PO
O O
O
*
H2O
+ TBS OH
I
12
Biginelli Reaction:
P. G. Biginelli*, Chim. Ital. 1893, 23, 360.
General mechanism:
O
Ar H
O
H2N NH2
O O
OEt HNNH
CO2Et
Ar
O
Me+ +
Conditions
HCl
OH
Ar HO
H2N NH2
OH O
OEt
NH
HNCO2Et
Ar
O Me
ONH2
H2NOH
Ar-H2O
ONH2
HNAr
O
H2N NH
CO2Et
Ar
OH NH
HNCO2Et
Ar
O MeOH N
H
HNCO2Et
Ar
O MeOH2
H+-H+
-H2O
N-acyliminium ion
open chain ureide hexahydropyrimidine
13X.-H. Chen, X.-Y. Xu, H. Liu, L.-F. Cun, L.-Z. Gong*, J. Am. Chem. Soc. 2006, 128, 14802.
O
OP
O
OH
Ph
Ph
Cat.
The first organocatalytic highly enantioselective Biginelli reaction
O
R1 H
x
H2N NH2
O O
R2 OR3 HNNH
CO2R3
X
R2
+ +10 mol% Cat.
CH2Cl2, RTR1
up to 86% yield, 97% ee
X=S,O
O
R1 H
x
H2N NH2
O O
R2 OR3 HNNH
CO2R3
X
R2
+ + R1*
O PO
OH
O -H2O
R1
N
X
NH2 OH
O
R2
R3O
HO
PO
O
O
-H2O*
* HNNH2
R1 R2
O OR3
X
*
O
1 2 34
5 3 6
14
N. Li, X.-H. Chen, J. Song, S.-W. Luo*, W. Fan, L.-Z. Gong*, J. Am. Chem. Soc. 2009, 131, 15301.
Biginelli and Biginelli-Like Condensations
beta-keto esters and cyclic ketones
O
R1 H +
X
H2N NH
R1
N
X
N
NH
NR4
R3
XR1
*
OH
R4
R3
R2
H
+
R2
H
R2
R3
R4
O10% Cat. 1 or 2
Conditions
O PO
OH
O-H2O
OP
O
O
O
-H2O
up to 98% yield, 99% ee
*
*
•Reversal of the stereochemistry by tuning the 3,3’-disubstituents of phosphoric acids
O
OP
O
OH
Ph
Ph
Cat.
SiPh3
O
O
SiPh3
POH
O
1
2
15
Reaction Mechanism
PO
OH
N S
NR2H
R1
O
O
O
R1 + H2N NH
S
R2H
R4
R3
OH
R4R3
O
HN
R1
R4R3
OH
SNH
R2
PO
O
O
O
HN N
S
R3
R2
R1
R4OH2
HN N
S
R3
R2
R1
R4
H
P
OO
OO
+H2O
*
*
*
-H2O
OO
P
OO
HN
NH
R1
S
R2
R4 = Alkyl or ester groupO
OP
OO
HN
NH
R1
S
R2
R3
O
R4
H
I
IIIII
IV
*
*
*
*
*
16
NH
NH
S
MeO2C
F
F
H2O2, NH4OH
EtOAc, 50oC20 min N
H
NH
O
MeO2C
F
F
Ph(CH3)3NBr3
CH2Cl2, rt, 30min
73%, 2steps NH
NH
O
MeO2C
F
F
Br
92% ee91% ee
NaOMe, MeOH
reflux, 20 min
81%
NH
NH
O
MeO2C
F
F
MeO
92% ee
NH
N
O
MeO2C
F
F
MeO
(S)-L-771688
NH
O
N
N
1 2 3
4 5
Synthetic applications:
17
Asymmetric Amplification in Phosphoric Acid-Catalyzed Biginelli Reaction:
N. Li, X.-H. Chen, S.-M. Zhou, S.-W. Luo, J. Song, L. Ren, L.-Z. Gong*, Angew. Chem. Int. Ed. 2010, 49, 6378.
Cat.
SiPh3
O
O
SiPh3
POH
OS
H2N NH2 NH
NHEtOOC
S
10% Cat.
50oC
NO2
CHO
+ +OEt
O O
O2N
•Positive nonlinear effect
18
OO
Ar
Ar
PO
OH
Ar= 9-phenanthrenylCat.
+ +R2 OR3
O O
N
R1
R2
CO2R3
Ar
R1
CHO *
PhCN, 50 oC, 24 h
10 mol% CatArNH2
up to 83% yield, 98% ee
J. Jiang, J. Yu, X.-X. Sun, Q.-Q. Rao, L.-Z. Gong*, Angew. Chem. Int. Ed. 2008, 47, 2458.
Cyclization Reactions Leading to Dihydropyridine Derivatives:
N
CO2Et
PMP
67% yield, 96% ee
+N
OH
EtO2C Cl
Et3N (2 equi)
Et2ON
CO2Et
PMP
NO
EtO2C H
H
NO2 NO2
Synthetic applications:
19
N
R1
R3
CO2R4
R2 OH
H
II
R3
O
R4O
O
R1 N
R2
H O
R3
O
R4O
OH
R1 N
R2
H
H
*
H
H+ R2NH2
O
R1
R1 NR2
-H2OR3 OR4
O O
N
R1
R2R3
CO2R4
H2O
6
I
III
*
* PO
O
O*
HOP
O
O
O*
HOP
O
O
O*
OP
O
O
O*
Reaction Mechanism:
20 J. Jiang, J. Qing, L.-Z. Gong*, Chem. Eur. J. 2009, 15, 7031.
Cat.
SiPh3
O
O
SiPh3
POH
O
Cyclization leading to dihydropyridinone derivatives:
+ +15-20 mol% Cat.
N
R2
O
HN
Ar
0oC, CHCl3ON
R1
Ph
O
R1
Ph
O
ArNH2R2 CHO
Up to 96% ee, 90%yield
NH2
CO2EtCO2Et
+O
NPh
O
Me
+ N
CO2EtCO2Et
N
CO2EtCO2Et
R
Me
O
Me
O
NHCOPh
NHCOPh
20 mol% Cat.
0 oC, CHCl3
CH2Cl2, -15 oC
R
6 2 1a
7
8
R'R'
R'
CHO
R
BF3.Et2O
Up to 97% ee, 75%yield
21
O
NR2
ONR4
R3
R1
N
R3
R4O
R1NHCOR2
N
R3
R4
O
NR1
O
R2
H
R3 H
O
O
NR2
O
R1
++ R4NH2
III
POO
OO
H H
*
Reaction Mechanism:
formal [4+2] cycloaddition
22
Hantzsch reaction:
C. G. Evans, J. E. Gestwicki*, Org. Lett. 2009, 11, 2957.
O
OP
OH
O
Cat.
O
O
R CHOOEt
O
O
NH4OAc
+Cat. (10mol%)
ACN, rt NH
O R
OEt
O
up to 94% yield, up to 99% ee
*
23
Aza-Diels-Alder Reaction :
H. Liu, L.-F. Cun, A.-Q. Mi, Y.-Z. Jiang, L.-Z. Gong*, Org. Lett. 2006, 8, 6023.
O
OP
O
OH
X
XCat. X=4-ClC6H4
O
+5 mol% Cat.
PhCH3, rt N
O H
ArN
O Ar
H+
1 3 4
Ar=4-ClC6H4, 70% yield (3+4), 78/22 endo(3)/exo(4), 83% ee (3)Ar=4-BrC6H4, 68% yield (3+4), 76/24 endo(3)/exo(4), 84% ee (3)Ar=3-CH3C6H4, 71% yield (3+4), 87/13 endo(3)/exo(4), 85% ee (3)
Ar H
O+
NH2
OCH3
PMP PMP
O
+N
H R
R' 5 mol% Cat.
PhCH3, 20oC NR'
O H
RNR'
O R
H+
1 2 3 4up to 82% yield (3+4), 84/16 endo(3)/exo(4),87% ee (3)
N
H R
R'
H+
OH H
HN
HO H
R
R'HN
HO R
H
R'5
6
7 8
+
24
Povarov reaction:
OO
Ar
Ar
PO
OH
Ar= 4-ClC6H4
Cat.
H. Liu, G. Dagousset, G. Masson,* P. Retailleau, J. Zhu*, J. Am. Chem. Soc. 2009, 131, 4598.
NH2
R + R1CHO +CbzHN Cat. (0.1 equi)
CH2Cl2, 0oC NH
NHCbz
R1R
N R1R
CbzN H
PO
O
O
OH
*
N
NHCbz
R1
R
Isomerization
Up to 90% yield, 99% ee
An inverse electron-demand aza-Diels-Alder reaction between 2-azadienes and electron-rich olefins.
25
Ugi-type reaction:
Cat.
Ar
O
O
Ar
POH
O
Ar=2,4,6-(CH3)3C6H2
T. Yue, M.-X. Wang,* D.-X. Wang, G. Masson, J. Zhu*, Angew. Chem. Int. Ed. 2009, 48, 6717.
R1
O+ ArNH2 + CN
R2NR3R4
O
R1
NHAr
PO
O
O
OH
*
PO
O
O
O
*
CN
R2NR3R4
O
N
R2NR3R4
OR1
NHArP
O
O
O
O
*N
ONR3R4R1
R2 H
NHAr
PO
O
O
O
*
N
OR1
R2
NHAr
NR3R4
Cat. (0.2 equiv)
toluene, -20oCup to 90% ee
26
1,3-Dipolar cycloaddition: O
O OO
P OHO
OPO
OHCat.
X.-H. Chen, W.-Q. Zhang, L.-Z. Gong*, J. Am. Chem. Soc. 2008, 130, 5652.
R
N
R1
IIa
CO2R2
H
POO
O O
H
N
R1
CO2R2
H
POO
O O
H
R
N
R1
O
OR2
R
PO
O
O
OH
IIb
H
+
NH
R1
CO2R2
R
CO2R3
R3O2C
H2N CO2R2
R1
RCHO
CO2R3
CO2R3
*
* *
+ +
NH
R1
CO2R2
RCO2R3
CO2R3
CH2Cl2, RT
CO2R3
R3O2C
H2N CO2R2
R1
RCHO10 mol% Cat.
up to 99% ee, 97% yield
27
X.-H. Chen, Q. Wei, H. Xiao, S.-W. Luo, L.-Z. Gong*, J. Am. Chem. Soc. 2009, 131, 13819.
O
OP
O
OH
Cat.
Methyleneindolinones as dipolarophiles to synthesize Spiro[pyrrolidin-3,3’-oxindoles]
with unusual regiochemistry
N
R3
O
R2
10 mol% Cat.
N
R3
O
NHR2
R5
CO2R6+ + H2N CO2R6
R5
R4
3A MS, CH2Cl2, 25 oC
R4-CHOR1R1
up to 98% ee, 97% yieldmethyleneindolinones
28
N
R5
H
CO2R6R4
PHO
O
O
O N
R5
CO2R6
H
POO
O O
H
R4Prototropy
Ia
NR1
R3
O
R2
N
R5
R6O2C
POO
R4
H
NR1
R3
O
R2 O O
H
NR1
R3
O
NHR2
R4
CO2R6
R5
NR3
O
NHR2
R4
R5 CO2R6
N
R3
O
N
R2R1
CO2R6R5
R4
PO
O
O
OH
IIIb
H
N
R3
O
N
R4
CO2R6
R2R1
R5
PO
O
O
O
H
H
IIIa
II
PHO
O
O
O
PHO
O
O
O
N
R5
CO2R6
PO
O O
H
R4
OH
Ib
majorminor
*
* *
*
**
*
R1
*
Reaction mechanism:
29
R H
O+
H2N CO2Et
CO2Et+ ArNH2 N
H
NR
EtO2C
EtO2C
R
Ar
up to 91/9 dr, 98% ee
10 mol% cat.
toluene, -10 oC2
O
OP
O
OH
Ar
Ar
Ar = 2,4,6-(i-Pr)3C6H2
cat
W.-J. Liu, X.-H. Chen, L.-Z. Gong*, Org. Lett. 2008, 10, 5357.
Imine as dipolarophile to synthesize imidazolidines
R H
O
ArNH2
NH
NR
EtO2C
EtO2C
R
Ar
H2N CO2Et
CO2Et
Cat.
-H2O
Cat.
-H2O
R
N
COOEtCOOEt
H
HO P
O
OO
*
R N
COOEtCOOEt
H
HO P
O
OO
*
ArN
H
R
OP
O
O
O
*Ar
NH
R
OP
O
O
O
*
[3+2]
30
O
O OO P OHO
OPOOH
Cat.
J. Yu, L. He, X.-H. Chen, J. Song, W.-J. Chen, L.-Z. Gong*, Org. Lett. 2009, 11, 4946.
2,3-Allenoate as dipolarophiles to create pyrrolidines along with C=C double bond
CO2Et
H2N CO2Et• 10 mol% Cat.
PhCH3, rt NH
CO2Et
CO2EtR
RO2C
CO2RR CHO
R2
R1 R3 R3R1
R2
up to 97% ee
Kinetic Resolution of Racemic 2,3-Allenoates N
H
CO2Et
CO2EtR'
R1
R2
R3
•R2
R1RO2C
R'CHO + H2NCO2Et
CO2Etracemic
RO2CR3
R3
•R1
R2RO2C ee up to >99%
ee up to 94%
10 mol% Cat.
PhCH3, rt
++
J. Yu, W.-J. Chen, L.-Z. Gong*, Org. Lett. 2010, 12, 4050.
‘‘
31
1,4-Naphthoquinone as dipolarophile to synthesize isoindolines
C. Wang, X.-H. Chen, S.-M. Zhou, L.-Z. Gong*, Chem. Commun. 2010, 1275.
O
OP
O
OH
Ar
Ar
Ar = 9-anthracenyl
Cat.
O
O
+
R1CHO
H2N CO2R3
R21) 10 mol% Cat.
+PhCH3, 0 oCR
R2) Ac2O, Et3N, DMAP, CH2Cl2, 0oC
OAc
OAc
NHR2
R1
CO2R3
R
R
up to 97%ee, 98%yield
O
O
+
R1CHO
H2N CO2R3
R2 1) B*-H+
O
O
NHR2
R1
CO2R3
R
R
R
R
Ac2O/ Et3N
OAc
OAc
NHR2
R1
CO2R3
R
R
R1 N R2
CO2R3
O
O
R
R
+ B*-H
Without purification
2) Ac2O/ Et3N
EnantioselectiveOrganocatalyticDouble-Arylation
32
Kabachnik–Fields reaction:
The reaction of a carbonyl compound, an amine, and a phosphite by in situ imine hydrophosphonylation.
RH
Ar
O
+ PMPNH2 + PO
H
O
O10 mol% Cat.
cyclohexane,50oC
RP
Ar
NHPMP
O
OO
Up to 89% yield, 22:1 dr, 96:4 er
O
OP
O
OH
Cat.
i-Pr
i-Pr
Ar
i-Pr
i-Pr Ar
Ar= 9-anthracenyl
X. Cheng, R. Goddard, G. Buth, B. List*, Angew. Chem. Int. Ed. 2008, 47, 5079.
+ PMPNH2 + PO
H
Oi-Pr
Oi-Pr10 mol% Cat.
toluene, 40oC P
NHPMP
Oi-Pr
Oi-PrO
R H
O
Ar
R
R=Ar,Up to 87% ee, 91% yield
L. Wang, S.-M. Cui, W. Meng, G.-W. Zhang, J. Nie, J.-A. Ma*, Chin. Sci. Bull. 2010, 55, 1729.
OO
Ar
Ar
PO
OH
Ar = 3,5-(CF3)2C6H3
33
Friedel-Crafts aminoalkylation: OO
Ar
Ar
PO
OH
Ar = 2,4,6-(i-Pr)3C6H2
G.-W. Zhang, L. Wang, J. Nie, J.-A. Ma*, Adv. Synth. Catal. 2008, 350, 1457.
F3COH
OMe
+
R1
NH2
+
NH
10 mol% Cat.
CH2Cl2, rtNH
R2 R2
NH
CF3
R1
up to 99% yield, 99% ee
F3COH
OMe
+
R1H2N
NH
NH
R2
R2
NH
CF3
R1
OHP
O
O
O
*
R1HN
F3C OH
R1N
F3C
R1HN
F3C
OP
O
O
O
*
OP
O
O
O
* R1N
CF3H
H
N
R2
H
OHP
O
O
O
*
N,O-acetal
34
Combined catalysis of phosphoric acid and metal catalysts:
Relay Catalysis
Cooperative Catalysis
35
W. Hu*, X. Xu, J. Zhou, W.-J. Liu, H. Huang, J. Hu, L. Yang, L.-Z. Gong*, J. Am. Chem. Soc. 2008, 130, 7782.
O
OP
O
OH
Ar
Ar
Ar = 9-phenanthryl
*PA
Ar1 CO2R
N2 + ArCH2OH + NAr2
H Ar3
2 mol% Rh2(OAc)42 mol % *PA
CH2Cl2, -20oC
ROOC
ArH2CO Ar1
Ar3 NHAr2
Up to 98% yield, >99/1 dr, >99% ee
Mannich-type multi-component reaction:
Cooperative Catalysis:
36
Ar1
RO2CN2
ArCH2OH
N
Ar3
Ar2
ROOC
ArH2CO Ar1
Ar3 NHAr2
N
Ar3
Ar2 H OP
O
OO*
OHP
OO
O
*
N
Ar3
Ar2H O
PO
OO*
HO
CH2Ar
RO2C Ar1
RhLn
Ar1
RO2CRhLn
HO
CH2Ar
Ar1 CO2R
-RhLnH
OCH2Ar
Ar1 CO2RRhLn
I
IIaIIb
III
IV
Organo-catalyzed cycle Metal-catalyzed cycle
Reaction mechanism:
37
X. Xu, J. Zhou, L. Yang, W. Hu*, Chem. Commun. 2008, 48, 6564.
Ar1 CO2R
N2 + ArCH2OH +
2 mol% Rh2(OAc)42 mol % *PA
CH2Cl2, -20oC
ROOC
ArH2CO Ar1
Ar2 NHPMP
Up to 90% yield, >99:1 dr, 97% ee
PMPNH2
Ar2CHO
+
O
OP
O
OH
Ar
Ar
Ar = 9-phenanthryl
*PA
X. Xu, Yu Qian, L. Yang, W. Hu*, Chem. Commun. ASAP, DOI: 10.1039/c0cc03024d
Up to 88% yield, >97:3 dr, 98%ee
Ar
N2
O
+ Ar1CH2OH + PMPN R
2 mol% Rh2(OAc)45 mol% *PA
toluene, rtAr R
O HN
O Ar1
PMPO
OP
O
OH
Ar
Ar
Ar = 4-CF3C6H4
*PA
38
Consecutive Intramolecular Hydroamination/ Asymmetric Transfer Hydrogenation
Up to >99% yield, >99% ee
NH
R1
R2
Gold Catalyzed Hydroamination
N
R1
R2
B*-H Catalyzed Asymmetric Reduction
NH
R1
R2*NH2
R2Ph3PAuCH3 (5mol %)
*BH (15mol %)
Toluene, 25oC, 16h
Au(I)
R1
B*-H
NH2R2R1
HEH
NH
CO2RRO2C
+
I
II
Au(I)
H*B
(HEH)
O
OP
O
OH
Ar
Ar
Ar = 9-phenanthrenyl
*BH
Relay Catalysis :
Z.-Y. Han, H. Xiao, X.-H. Chen, L.-Z. Gong*, J. Am. Chem. Soc. 2009, 131, 9182.
39
Intermolecular Hydroamination and Transfer Hydrogenation Reactions
X.-Y. Liu, C.-M. Che*, Org. Lett., 2009, 11, 4204.
O
OP
O
OH
Ar
Ar
Ar = 2,4,6-(i-Pr)3C6H2
*BH
R1
NH2
+ R2 +
NH
EtO OEt
O O(t-Bu)2(o-diphenyl)PAuOTf (1-2mol%)
*BH (5-10 mol%)benezene, 40oC
R1
HN
R2
Up to 98%yield, 96%ee
R2
NH
R' R'
LAu
R2
AuL
R1 NH2H2N
R2 H
AuL
R1
N
R2
R1
HN
R2
R1
O
P OO
O*
H H
N
R'
R'
HH
H
OP O
OO
*
HN
R2
R1
O
P OHO
O*
HN
R2
R1
+
N
R' R'
1st stage:gold catalysis
2nd stage:chiral phosphoric acidcatalysis
40
R2
NH2
R1 + R3 CHO +NHCbz (1) *BH / Au(I)
CH2Cl2
(2) AcOH/NaBH(OAc)3
NR1
R2
R3CbzHN
up to 72% yield, >99% ee
O
OP
O
OH
Ar
Ar
Ar = 9-anthracenyl
*BH
C. Wang, Z.-Y. Han, H.-W. Luo, L.-Z. Gong*, Org. Lett., 2010, 12, 2266.
Povarov reaction and subsequent intramolecular hydroamination
NR1
R2
R3CbzHN
R2
NH2
R1+ R3 CHO +
NHCbz *BH / Au(I)N
R1
R2
R3CbzHN
HB*H2O
R2
NR1
R3
HB*
NHCbz
Organocatalytic[4+2] cyclization
NHR1
R3CbzHN
R2
Au(I) NHR1
R3CbzHN
R2
Au(I)
NaBH(OAc)3
AcOH
I II III
41
Conclusions1. Many asymmetric multi-component reactions have be
en successfully established by chiral PA.2. Tremendous progress has been made in the develop
ment of chiral PA catalysts.3. Combined catalysis of PA and metal catalysts is a ne
w orientation. Outlook
1. There are still numerous multi-component reactions to be transformed into their asymmetric versions.2. Further elaboration of novel PA derived from other types of chiral backbones is needed.3. A more detailed mechanistic understanding of PA catalysis is needed.4. It is full of challenge and opportunity to develop combined catalysis of PA and metal catalysts.
42
Sincere thanks for your attention and kind help!Sincere thanks for your attention and kind help!