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Asymmetric BINOL-Phosphate Derived Brønsted Acids: Development and
Catalytic Mechanism
Reporter: Song FeifeiSupervisor: Prof. Yong Huang
2015.10.12
1
2
Outline
Introduction
Catalytic mechanism
Development
Overview of Catalysts
Summary
Looking Forward
Acknowledgment
Introduction
3Akiyama, T. et al. Chem. Rev. 2015, 115, 9277.
S
O
O
F3C OH Tf2HC
CHTf2
CHTf2
OHHO
OH
NH
S
S
F3C
OO
F3C
OO
R
CO2H
CO2H
R
R
SO3H
SO3H
R
R
R
SO2
SO2
NH
R H
Brønsted Acids
R
O
O
R
PO
OH
Introduction
4
SO
O O
H
CO
O
H1
23
4
free rotation
SO
O
H1
23
4
free rotation
P
O
OH
a) solfonic acids b) carboxylic acids c) sulfinic acids
12
3
d) phosphotic acids
PO
O
O
O
H
substrate recognition site
dual function bymonofunctional catalyst
Lewis basic site
Brønsted acidic site
stereoelectronic effect
G
G
ringstruture
e) cyclic phosphoric acids
Terada, M. Chem. Commun., 2008, 4097.
Introduction
5Rueping, M. et al. Chem. Rev. 2014, 114, 9047.
R
O
O
R
PO
X H
Brønsted acidorganocatalysis
R
O
O
R
PX
O
M+
Lewis acidmetal catalysis
mono-dual-
bifunctional-activation
6
Catalytic Mechanism
Mono activation
Dual activation
Bifunctional activation
Counterion catalysis
Ligand Behavior in Presence of Metals
Independent relay processes in presence of metals
7
Mono / Dual Activation
Rueping, M. et al. Angew. Chem. Int. Ed. 2011, 50, 6364.; Rueping, M. et al. Chem. Soc. Rev. 2011, 40, 4539.
PPhO
PhO
O
O
NH R3
R2R1
PPhO
PhO
O
O
NR3
R2R1
H
ion-pairing hydrogen bonding
Brønsted acidity, solvent, imine structure
PO
O
O
O
XR3
R2
*
H
YR1
PO
O
O
O
*
H Y
X
R2R1
H
two contacts tothe acidic proton
two contacts tothe catalyst
Mono Activation
Dual Activation
8
Bifunctional Activation
Goodman, J. M. et al. J. Org. Chem. 2011, 76, 1775.
NR2
R1
R3
PO
O
O
O
HH
NuR R
R3 larger than R2
Type I
PO
O
O
O
HH
NuR R
R2 larger than R3
Type II
NR3
R2
R1
9
Counterion Catalysis
H Nu
PO O
OO
electrophiliccationic species
R
R
Rueping, M. et al. Chem. Rev. 2014, 114, 9047.
10
Behavior in Presence of Metals
Ligand or a counterion for the metals
Independent relay processes
starting materials products
intermediates
relay catalysis
Mn+ PO
O
OH
O*
O
OP
O
O
R
Rn
Mn+
3,3'-positions can be tunedfor reactivity/selectivity
Lewis basic site
Can function asa Lewis acid
Rueping, M. et al. Chem. Eur. J. 2010, 16, 9350.; Alemán, J. et al. Org. Biomol. Chem. 2012, 10, 5001.;Luo, S. et al. Chem. Commun. 2013, 49, 847.
Development
11
2004
1992
1978
1971
R
O
O
R
PO
X H
Background
12Jacques, J. et al. Tetrahedron Lett. 1971, 4617.
HN
NH
C3H7
Me
O
EtO
PA16 N HCl
2 N NH4OH
(±)
HN
NH
C3H7
Me
O
EtO
(+)
H
O
O
H
PO
OH
PA 1
The Starting Seeds: Phosphinic Acids
13Cornforth, J. Proc. R. Soc. London, Ser. B. 1978, 203, 101.
P
XY
XY
R
R
O
OH
tunablearomatic groups
narrow well-definedchannel for substrates
possiblity forbackbone
substituents
PR RO O
H
P
R
R
O
O H
H2OHO
H
P
R
R
O
O
Me
Asymmetric Synthesis Using Chiral Rhodium Phosphate
14
O
OP
O
OH
Na4Rh2(CO3)4 O
OP
O
O Rh2(HCO3)2
(S)-PA1 Cat.
Me
O O
N2O
Cat. (0.5 mol%)
CH2Cl2, 40 C O
O
Me
O
Me
N2 Cat. (0.5 mol%)
CH2Cl2, -30 CO
Me
92%, 32% ee
80%, 60% ee
COMe
McKervey, M. A. et al. Tetrahedron Lett. 1992, 33, 5983.
15Akiyama, T. et al. Angew. Chem. Int. Ed. 2004, 43, 1566.; Akiyama, T. et al. J. Am. Chem. Soc. 2007, 129, 6756.
R
HO
N
R1 H
OR3
OTMS
H
R2
+
R
HO
HN
R1
R2
CO2R3
PA 15 (10 mol%)
toluene, -78 C, 24 h
15 examples65-100% yield
86:14-100:0 syn/anti81-96% ee
transition state:
NH
R1 H
OH
PO
O O
O*
OR3
OTMS
H
R2
O
OP
O
OH
NO2
NO2
PA 15
Mannich-Type Reaction by Akiyama
16
Catalytic Reaction Types
Friedel-Crafts ReactionMannich
1,3-DiopolarCycloaddition
Miscellaneous
Diels-Alder
Transfer Hydrogenation
BINOL PACatalysis
17
Overview of Catalysts
Alternative variants of catalysts
General BINOL-PA
Miscellaneous chiral PA
Multiple chiral axis containing PA
N-Phosphoramide
N-Thiophosphoramide
Spiro PA
[H8]-PA
PA
NPA
NTA
PKahigh
low
18
Alternative Variants of Catalysts
O
OP
O
OH
R
R
O
OP
O
OH
R
R
(S)-PA [H8]-PA
19
General BINOL-PA
R
O
O
R
PO
OH
PA 1, R = H
PA 2, R = SiPh3
PA 3, R = Si(4-tBuC6H4)3
PA 4, R = adamanthyl
PA 5, R = 1-naphthyl
PA 6, R = 2-naphthyl
PA 7, R = 9-anthracenyl
PA 8, R = 9-phenanthryl
PA 9, R = 1-pyrenyl
O
OP
O
OH
R
R
PA 10, R = H
PA 11, R = tBu
PA 12, R = F
PA 13, R = Cl
PA 14, R = OMe
PA 15, R = NO2
PA 16, R = Ph
PA 17, R = 3,5-(CF3)2C6H3
PA 18, R = 2,3,4,5,6-F5C6
PA 19, R = 2-naphthyl
O
OP
O
OH
R
R
R
R
PA 20, R = CF3PA 21, R = SF5PA 22, R = PhPA 23, R = 2,4,6-(Me)3C6H2
20
N
Ts
H2N O
Me+
Me
HN
N
Ts
PA 2 (10 mol%)Hantzsch ester
5Å MS, 24-96 h40-50 Cbenzene 90% yield
93% ee
MacMillan, D.W.C. et al. J. Am. Chem. Soc. 2006, 128, 84.
O
OP
O
OH
SiPh3
SiPh3
PA 2
General BINOL-PA
21
selective formethyl versus ethyl ketones
Si-face
= H
Si-face blocked= Me
Si-face exposed
ON
OR
N
EtO2C
Me Me
CO2Et
H
H H
+ OHN
OR
PA 2 (10 mol%)
5Å MS, 40 Cbenzene
R = Me, 82% yield, 97% eeR = Et, 27% yield, 79% ee
MacMillan, D.W.C. et al. J. Am. Chem. Soc. 2006, 128, 84.
General BINOL-PA
22Ackermann, L. et al. Synlett 2008, 995.; Akiyama, T. Angew. Chem. Int. Ed. 2008, 47, 4016.
General BINOL-PA
BnHNPh Ph
PA (20 mol%)
1,4-dioxane130 C, 20 h
N
Bn
Me
Ph
Ph
N
Ph
Ph
BnH P
O
O
O
O
H
*
transition state:
R1
NO2
NH
R2
NO2
HN
R2R1
PA 2 (10 mol%)
3 Å MS, -35 °Cbenzene/DCE 1:1
14 examples57-99% yield
88-94% ee
N
H
R1
N
PO
O
O
O
*
O
O
H
transition state:
PA 2 95% yieldPA 20 (S)-17% ee
23Gong, L.-Z. et al. J. Am. Chem. Soc. 2006, 128, 14802.; Gong, L.-Z. et al. Angew. Chem. Int. Ed. 2010, 49, 6378.
R1 CHO
+
H2N NH2
X
Me OR2
O O
X = O, S
NH NH
CO2R2
X
Me R1[H8]-PA 10 (10 mol%)
CH2Cl2, rt, 4d
24 examples40-86% yield
88-97% ee
Ar CHO
+H2N NH2
S
Me OEt
O O
Ar = 4-NO2C6H4
NH NH
CO2R2
S
Me Ar
NH NH
CO2R2
S
Me Ar
(S), 95%, 96% ee
(R), 94%, 85% ee
PA 2 (10 mol%)
toluene, 50 C, 4d
[H8]-PA 10 (10 mol%)
CH2Cl2, rt, 4d
R
O
O
R
PO
OH
PA 2, R = SiPh3PA 10, R = Ph
General BINOL-PA
24Gong, L.-Z. et al. J. Am. Chem. Soc. 2009, 131, 15301.
Ph
OP
O
O O
Ph
H
H
N
N
H
S
ArO
HMe
CO2Et
O
O
Ph
Ph
P
O
O H
HN
N
S
Ar
O Me
CO2Et
H
H
Ia, Ar = 4-NO2C6H4
IIa, Ar = 4-NO2C6H4
SiPh3
OP
O
O O
SiPh3
H
H
N
N
R'
S
ArO
H
R1
O
O
SiPh3
SiPh3
P
O
O H
HN
N
S
Ar
O R2
R1
H
R'
Ib, Ar = 4-NO2C6H4 R' = H, Me
IIb, Ar = 4-NO2C6H4R' = H, Me
R2
General BINOL-PA
25Luo, S. et al. Chem. Eur. J. 2012, 18, 799.
R1
R1
OMe
O
O
R2
+
(S)-PA-18 (2 mol%)InBr3 (1 mol%)
4Å MSCH2Cl2, -70 C O
R1
MeO2C
R2H
R1 11 examples85-99% yield
53-99% ee
O
Me
MeO2C
PhH
MeO
Bn
MeO2C
PhH
Bn
4-Cl
91%, 95% ee 99%, 99% ee
O
OP
O
OH
R
RPA 18
R = 2,3,4,5,6-F5C6
General BINOL-PA
26Luo, S. et al. Chem. Eur. J. 2012, 18, 799.
F
F
F
F
F
FF
FF
F
O
O
PO
O
H
In
Br
O
OPh
Oa
b
c
- Accessible space- Favorable pi-interaction
- Less accessible- Unfavorable pi-interaction
O
OO
Ph
1-
4-
2-
3- - 1- and 3-positions space less demanding
- 2- and 4-positions sterically unfavored
General BINOL-PA Stereocontrol
Regioselectivity control/Sunbstitution bias
27
O
OP
O
OH
RR
R
R
RR
O
OP
O
OH
R2R1
R1
R1
R1R2
O
OP
O
OH
RR
R
R
RR
X
X
PA 24, R = Me
PA 25, R = iPr
PA 26, R1 = Me, R2 = OMe
PA 27, R1 = iPr, R2 = tBu
PA 28, R1 = iPr, R2 = 4-tBuC6H4
PA 29, R1 = iPr, R2 = 9-anthracenyl
PA 30, R = iPr, X = I
PA 31, R = iPr, X = NO2
PA 32, R = iPr, X = Si(iPr)3
PA 33, R = iPr, X = C8H17
General BINOL-PA
28
N
OMe
(S)-PA 25 (1 mol%)
N
CO2EtEtO2C
H H
H
toluene, 35 C, 71 h
N HH
98% yield93% ee
XH
RX
Br
R
(S)-PA 25 (10 mol%)NBS
CH2Cl2, 0 C, 18 h 25 examples45-96% yield
21-90 eeX = O, NsN, or TrisylN
List.B. et al. Angew. Chem. Int. Ed. 2005, 44, 7424.; Shi.Y. et al. Org. Lett. 2011, 13, 6350.
General BINOL-PA
29Shi.Y. et al. Org. Lett. 2011, 13, 6350.
General BINOL-PA
O
OP
O
O
iPr
iPr
iPr
iPr
iPr
iPr
H
HN
R'
R
O N O
BrNR' R
Br
favored
A
O
OP
O
O
iPr
iPr
iPr
iPr
iPr
iPr
H
H
Br
disfavored
O N O
N
R'
R
B
NR' R
Br
Proposed transition state model for bromoaminocy-clization of cis--amino-alkenes.
30
R1
NH2
O
R2
N
R2
R2
hvPA 25 (1 mol%)
H *Bchiral ion pair
NH
R2*dihydropyridinetoluene, 55 C
R1
hvPA 25 dihydropyridine
17 examples52-84% yield
84-96% eeO
OP
O
OH
iPriPr
iPr
iPr
iPriPr
PA 25
Rueping, M. et al. Chem. Commun. 2013, 49, 7953.
General BINOL-PA
31
O
OP
O
OH
iPriPr
iPr
iPr
iPriPr
C8H17
C8H17
PA 33
General BINOL-PA
32Toste, F. D. et al. Science 2011, 334, 1681.
ONH
OR
PA 33 (5 mol%)Selectfluor (1.25 equiv)
Proton Sponge (1.1 equiv)
C6H5F, -20 C, 24 h ON
O RF
X
NH
OR
X = C, O
PA 33 (5 mol%)Selectfluor (1.25 equiv)
Na2CO3 (1.1 equiv)
C6H5F/hexane (1:1)23 C, 24 h
X
N
O
FR
9 examples67-96% yield9:1-20:1 d.r.79-97% ee
4 examples70-87% yield
>20:1 d.r.92-96% ee
ON
O
F
96%, >20:1 d.r.96% ee
N
O
F
Br
87%, >20:1 d.r.93% ee
General BINOL-PA
33Toste, F. D. et al. Science 2011, 334, 1681.
General BINOL-PA
PO
O
O
O2 *
Na
N
N
Cl
N
N
Cl
PO
O
O
O
*
N
N
Cl
PO
O
O
OP
O
O
O
O
*
N
N
Cl
2BF4
F
PO
O
OH
O*
N
O
F
Ar NH
ArO
F
Na2CO3
Selectfluor(insoluble)
2 NaBF4
chiral ion pair
anti-fluorocyclization
BF4
NaHCO3
NaBF4
*
34
Miscellaneous Chiral PA
Me
Me
O
O
Ar
PO
OH
PA 34, Ar = 2,4-(CF3)2C6H3PA 35, Ar = 9-anthracenyl
Ar
R
R
O
OP
O
OH
PA 36, R = HPA 37, R = Ph
O
OP
O
OH
Me
PA 38
O
OP
O
OH
N
NN
N
NN
Ad
AdC8H17
C8H17
PA 39
O
OP
O
O
R
R
PA 40, R = 9-anthracenyl
HN
O
OP
O
O
Ar
Ar
NH
H
CF3
F3C
F3C
CF3PA 41
Ar = 2,4,6-C6H2(iPr)3
35
MeO2C CO2Me
N R1
H H
R2
N
H
R2
R1
CO2MeCO2Me
H
PA 34 (10 mol%)
R3 R3
*
R1 = Me or Ph
toluene, 70-110 C5-64 h
11 examples45-100% yield
70-97% ee
MeO2C CO2Me
N Ph
Me H
Me
N
Me
CO2MeCO2Me
Yb(OTf)3 (10 mol%)
R3 R3
> 98% ee
toluene, rt, 4h
98%, 85% ee
MePh
Me
Me
O
OP
O
OH
F3C CF3
F3C CF3
PA 34
Akiyama, T. et al. J. Am.Chem.Soc. 2011, 133, 6166.
Miscellaneous Chiral PA
36Akiyama, T. et al. J. Am.Chem.Soc. 2011, 133, 6166.
Miscellaneous Chiral PA
R
R
OO
P
O O
H
R
R
O
OR
O
OR
N
H
H
stericrepulsion
stericrepulsion
ORO
OR
O
H
N
HH
PO
O
O
O
*
NH
H
O
O OR
OR
R
R
R
R
O O
P
OO
H
side view
Re-faceattack
N
Ph
Ph
CO2R
CO2R
(S)
H was preferentiallytransferred
37Toste, F. D. et al. J. Am.Chem.Soc. 2013, 135, 14044.
O
OP
O
OH
N
NN
N
NN
Ad
AdC8H17
C8H17
PA 39
Miscellaneous Chiral PA
N
NH
O
R2R1
N
NHAc
O BF4PA 39 (5 mol%)
Na3PO4 (2.4 equiv)p-xylene, rt, 48 h
N
N
O
R2R1
*
18 examples38-93% yield
60-94% ee
38Toste, F. D. et al. J. Am.Chem.Soc. 2013, 135, 14044.
Miscellaneous Chiral PA
PO
O
O
O
*
PO
O
O
O*
PO
O
O
O*
+[O]
[O]-H
N
H Nuc N
H Nuc
N
H Nuc
chiral ionpair
*
POH
O
O
O*
Base
H[O] X
X
Proposed chiral phosphate-catalyzed CDC
39
O
OP
O
O
Ar
Ar
NH
H
CF3
F3C
F3C
CF3PA 41
Ar = 2,4,6-C6H2(iPr)3
Miscellaneous Chiral PA
40List, B. et al. Angew. Chem. Int. Ed. 2008, 47, 1119.
OHCR OHC
R
OPA 41 (10 mol%)
tBuOOH (1.1 equiv)
dioxane or MTBE0-35 C, 24-72 h
18 examples60-95% yield
up to 99:1 d.r.76-96% ee
Mechanism for epoxidation:
R2N RR2N R
R2N R
PO
O
O
O*
OOtBu
PO
O
O
O*
H
* O*
*
PO
O
O
O*
tBuOOH
OHCO
OHCMe
OMe
OHCO
76%, >99:1 d.r.96% ee
83%, 94% ee 75%, 90% ee
Miscellaneous Chiral PA
41
Multiple Chiral Axis Containing PA
O
OO
OO
P
HOO PO
OH
O
OP
N
Ar
Ar
PO
O
OHO
Ar
Ar
RR
RO
O
O
P OHO
PO
OH
O
R
R
R
PA 42 PA 43, Ar = 2,4,6-Et3C6H2
PA44, Ar = iPr
OO
P
OHO
OR RO
PA 45, R = alkyl
42Gong, L.-Z. et al. J. Am.Chem.Soc. 2008, 130, 5652.
R1
O
H H2N
R2
R3CO2R4
CO2R4
+ +
NH
CO2R4
R4O2C
R1
R2
R3
PA 42 (10 mol%)
CH2Cl2, rt, 3Å MS24-96 h
23 examples70-97% yield
76-99% ee
transition state:
N
H
CO2EtR2
R1 CO2Et
R4O2C CO2R4
PO
O
O
O*
HP
O
O
O
O
*
H
NH
CO2MeMeO2C
CO2Et
CO2Et NH
CO2MeMeO2C
Ph
CO2Et
Br
NH
CO2BuBuO2C
Ph
CO2Et
NO2
93%, 91% ee 93%, 97% ee 77%, 81% ee
Multiple Chiral Axis Containing PA
43
O
OP
N
Ar
Ar
PO
O
OHO
Ar
Ar
PA 43, Ar = 2,4,6-Et3C6H2
O OH
n = 0, 1, 2
O O
nn
(S)-PA 43 (1 mol%)
MTBE, 35 C, 24 h
OO
H
PO
O
OO
*transition state:
O O OO O O
77%, 96% ee 78%, 92% ee 62%, 92% ee
6 examples62-88% yield
91-97% ee
List, B. et al. Nature 2012, 483, 315.
Multiple Chiral Axis Containing PA
44
R1
NHCbz
+CHOR2
NH
CHO
R2
Cbz
R1
PA 44 (2.5 mol%)
4Å MStoluene, -80 C
11 examples48-92% yield
95-99% ee
RR
RO
O
O
P OO
PO
OO
R
R
R
PA44 Ar = iPr
R1
NH Cbz
R2
O
H
H
transition state:
NHCbz
CHONH
Cbz
Me
CHO
NHCbz
Me
CHO
Bn
79%, 99% ee 90%, 98% ee 48%, 98% ee
H
Terada, M. et al. J. Am.Chem.Soc. 2011, 133, 19294.
Multiple Chiral Axis Containing PA
45
N-Phosphoramide Catalysts
O
OP
O
NH
R1
R1
R2
NPA 1, R1 = SiPh3, R2 = Tf
NPA 2, R1 = 1-pyrenyl, R2 = Tf
NPA 3, R1 = 9-anthracenyl, R2 = Tf
NPA 4, R1 = 9-phenanthryl, R2 = Tf
NPA 5, R1 = 9-anthracenyl, R2 = Ts
O
OP
O
NH
Tf
NPA 6, R = HNPA 7, R = OMeNPA 8, R = NO2
R
R
O
OP
O
NH
R2R1
R1
R1
R1R2
Tf
NPA 9, R1 = iPr, R2 = iPr
NPA 10, R1 = iPr, R2 = Ad
O
OP
O
NH
Ar
Ar
P
O
CF3
CF3
NPA 11
Ar = 2,4,6-iPrC6H2
46
N-Phosphoramide Catalysts
Yamamoto, H. et al. J. Am.Chem.Soc. 2006, 128, 9626.
Et
O
RMe
OSi
Me
R
Et
O
SiO
+(S)-NPA 9 (5 mol%)
toluene, -78 C, 12h
Si = TBS, TIPS
8 examples35-99% yield
82-92% ee
O
Et
SiO
R
Me
PO
O
N
O
Tf*
H
transition state:
Me
Me
Et
O
TBSO
Me
Me
Et
O
TIPSO
Me
Bn
Et
O
TIPSO
43%, 92% ee 95%, 92% ee 99%, 85% ee
47
N-Phosphoramide Catalysts
Kim, S. et al. Tetrahedron Lett. 2009, 50, 3345.
Ph
N
Ar H
Ph
NH
Ar R*
NPA 9 (30 mol%)RI (5 equiv)
TTMSSH (3 equiv)
Et3B/O2toluene, -40 C, 24 h
9 examples31-77% yield
73-84% ee
N
HAr1
PO
O
N
O
Tf*
H Ar2
transition state:
R
Ph
NH
Ph Et
Ph
NH
Ph tBu
Ph
NH
Et
MeO
56 %, 83% ee 36 %, 80% ee 77 %, 73% ee
48
N-Phosphoramide Catalysts
List, B. et al. Angew. Chem. Int. Ed. 2010, 49, 9749.
OH
O
NH2R1
O
NH
O
R2
R1
(S)-NPA 11 (10 mol%)R2CHO (8 equiv)
5Å MStoluene, 50 C, 96 h
21 examples50-97% yield
51-97% ee
Proposed interaction of N-phosphinyl catalyst:
O
OP
O
NP
CF3
O
CF3
N
O
H R
OH
re
12
49
N-Thiophosphoramide Catalysts
O
OP
S
NH
Ar
Ar
N
NTA 1Ar = 3,5-CF3C6H3
O
OP
S
NH
Ar
Ar
Tf
NTA 2
Ar = 2,4,6-(iPr)3C6H2
NTA 3
Ar = 4-tBu-2,6-(iPr)2C6H2
50
N-Thiophosphoramide Catalysts
Yamamoto, H. et al. J. Am.Chem.Soc. 2008, 130, 9246.
OTMS
R
O
R(S)-NTA 3 (5 mol%)PhOH (1.1 equiv)
tolunene, rt
n n12 examples95-97% yield
54-90% ee
OMe
OCl
O
96%, 94% ee 95%, 84% ee 99%, 88% ee
51
Spiro PA
R
R
O
O PO
OH
O
O PO
OH
O
O PO
OH
R
R
R
R
R
R
R
R
R
R
O
O PO
NH
R
R
R
R
R
R
Tf
PA 1, R = 9-anthracenylPA 2, R = 2-naphthyl SPA 3, R = CF3
NPA 4, R = iPr N-SPA 1, R = iPr
Resolving agents / Promoters of rhodium catalyst / Organocatalysts
Brøsted acidic site / Lewis basic site
Functional-group-modified for steric / acidity / solubility
Summary
52
R
O
O
R
PO
X H
Brønsted acidorganocatalysis
R
O
O
R
PX
O
M+
Lewis acidmetal catalysis
mono-dual-
bifunctional-activation
Mechanisms studies are still required for further progress.
Low catalyst loadings.
To grow the ability and scope of these catalysts.
Combined with other catalysis such as metals or light activation.
Looking Forward
53
Prof. Huang
Jiean Chen
All members here
Thanks for your attention!
Acknowledgment
54
[H8]-PA 10
55Located transition state structures with distance parameters in angstroms and relative energies in enthalpy and free Energy in parentheses.
PA 2
56Located transition state structures with distance parameters in angstroms and relative energies in enthalpy and free Energy in parentheses.
NTA 3
57
HA + PhOH [PhOH2][A]
oxonium ion pair
O
R
TMSO
R
TMS
H[A]
O
RH
+ HA
a [aH][A]
[PhOH2][A]
Ph OH Ph OTMS
b
intermediary chiral ion pair HA: Chiral Brønsted Acid
or HA
Yamamoto, H. et al. J. Am.Chem.Soc. 2008, 130, 9246.
Proposed mechanism of Brønsted acid catalyzed asymmetric protonations of silyl enol ethers
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