Key Points - C-Symmetrical Ligands are privileged.

johnnepaleseElectronics - Devices

Oct 10, 2013 (3 years and 11 months ago)

151 views

Lecture 3: C
2

Symmetrical
Ligands
Introduction
Key Points - C
2
-Symmetrical
Ligands
are
privileged.
H. B; Dang, T-P.
J.Chem. Soc. Chem. Commun.
1971
, 481.
Born in 1930
Graduated from
Sorbonee
and
Ecole Nationale Superieure
de
Chimie
de Paris 1954.
PhD 1960 under Dr. Jacques
DIOP
(
Kagan
, 1971)
Dr. Henri
Kagan
O
O
P
P
h
2
P
P
h
2

Of the thousands of
chiral ligands
prepared so far, a

relatively
small number of structural classes stand out because of their
broad applicability. These

privileged
ligands
,

as they

may be
called, allow

high levels of
enantiocontrol
in many different
metal-catalyzed reactions. A survey of their structures reveals
that, at first

sight, a surprisingly large number of them possess
C
2

symmetry.

Lecture 3: C
2

Symmetrical
Ligands
P
P
Why
C
2
-Symmetry?


The symmetry axis reduces the # of competing
diastereomeric
reaction pathways


Enables a straightforward analysis of substrate-
catalyst interaction


Simplifies mechanistic and structural studies

Quadrant I and III or II and IV are equivalent
M
X
X
I
I
I
I
I
I
I
V
b
a
c
k
b
o
n
e
c
h
i
r
a
l
i
t
y
M
X
X
I
I
I
I
I
I
I
V
C
o
o
r
d
i
n
a
t
i
n
g

a
t
o
m
c
h
i
r
a
l
i
t
y
L
L
Lecture 3: C
2

Symmetrical
Ligands
H
O
O
E
t
O
H
H
O
O
E
t
O
H
O
E
t
O
H
O
E
t
O
H
O
O
O
H
H
O
H
H
O
O
O
T
s
H
O
T
s
H
O
O
P
P
h
2
H
P
P
h
2
H
O
O
D
I
O
P
L
(
+
)
-
t
a
r
t
a
r
i
c

a
c
i
d
Synthesis of DIOP (1971)
Key

design elements for C
2

symmetric
ligands


Easy to modify

Rigid
chiral
pocket

Stereogenic centers are positioned

in close
proximity to the coordination site

Bind to metals strongly
Synthesis of

BINAP (
1976)

J. Org.
Chem
.
1986
,
51
, 629.
Aldrich

1g

~$ 90.00
Aldrich
1g

~$ 110.00
B
r
B
r
1
.

M
g
2
.

A
r
2
P
O
C
l
T
H
F
-
t
o
l
u
e
n
e
P
P
O
O
A
r
2
A
r
2
A
r

=

P
h
A
r

=

p
-
C
H
3
C
6
H
4
A
r

=

p
-
t
-
C
4
H
9
C
6
H
4
P
P
A
r
2
A
r
2
P
P
A
r
2
A
r
2
(
R
)
-
B
I
N
A
P
(
S
)
-
B
I
N
A
P
1
.

c
a
m
p
h
o
r
s
u
l
f
o
n
i
c

a
c
i
d




o
r

2
,
3
-
O
-
d
i
b
e
n
z
o
y
l
t
a
r
t
a
r
i
c

a
c
i
d
2
.

f
r
a
c
t
i
o
n
a
l

r
e
c
r
y
s
t
a
l
l
i
z
a
t
i
o
n
3
.

S
i
H
C
l
3
,

E
t
3
N
Lecture 3: C
2

Symmetrical
Ligands
Synthesis of
Salen
(1990)
For the synthesis, see:
Larrow
, F.; Jacobsen, E. N.
Organic Syntheses.
2004
,
10
, 96. For a recent review,
see:
Katsuki
,

T.
Synlett
2003
, 281.
Aldrich

1g

~$ 30.00
Synthesis of TADDOL (1983)
H
O
O
M
e
O
H
H
O
O
M
e
O
H
O
M
e
O
H
O
M
e
O
H
O
O
R
1
R
2
O
H
H
O
H
H
O
O
R
1
L
(
+
)
-
t
a
r
t
a
r
i
c

a
c
i
d
A
r
A
r
A
r
A
r
A
r
M
g

B
r
N
M
e
2
O
H
N
M
e
2
O
H
O
O
R
1
R
2
P
h
H
P
h
H
O
O
R
1
R
2
P
h
M
g

B
r
O
O
R
M
g

B
r
O
H
H
O
H
H
O
O
R
1
R
2
P
h
A
r
P
h
A
r
R
1
O
R
2
Review, see:
Seebach
, D.; Beck, A. K.;
Heckel
, A.
Angew.
Chem
. Int. Ed.
2001
,
40
, 92

138.
O
H
H
O
H
H
O
O
M
e
M
e
O
H
H
O
H
H
O
O
M
e
M
e
O
H
O
H
O
O
M
e
M
e
P
Aldrich
100 mg ~$ 240.00
Aldrich
1g

~$ 115.00
Aldrich
1g

~$ 250.00
N
H
2
N
H
2
+
H
O
2
C
O
H
C
O
2
H
O
H
H
2
O
,

H
O
A
c
9
0

º
C

t
o

5

º
C
N
H
3
N
H
3

O
2
C
O
H
O
2
C
O
H
O
H
t
-
B
u
+
N
N
N
N
1
.

H
O
A
c
,

1
3
0

º
C
2
.

H
2
S
O
4
O
H
t
-
B
u
t
-
B
u
O
A
t
-
B
u
N
H
3
N
H
3

O
2
C
O
H
O
2
H
2
C
O
H
A
,

K
2
C
O
3
H
2
O
,

E
t
O
H
,

8
0

º
C
N
N
O
H
H
O
Jacobsen &
Katsuki
independently disclosed the
use of

chiral salen ligands
.
Lecture 3: C
2

Symmetrical
Ligands
Synthesis of

semicorrin ligand
(
Pfaltz
1990)
Pfaltz
, A.

Acc.
Chem
.
Res
.
1993
,
26
, 339

345.
N
H
O
H
O
2
C
M
e
O
H
,

H
+
r
e
f
l
u
x

E
t
3
O
B
F
4
N
O
E
t
M
e
O
2
C
N
M
e
O
2
C
N
C
C
H
2
C
O
2
-
t
B
u
1
0
0

º
C
N
H
M
e
O
2
C
C
F
3
C
O
2
H
C
N
N
H
M
e
O
2
C
C
O
2
-
t
B
u
N
C
C
N
H
N
C
O
2
M
e
C
F
3
C
O
2
H
C
l
C
H
2
C
H
2
C
l
P
h
N
2
C
H
C
O
2
E
t
1

m
o
l

%

c
a
t
a
l
y
s
t
C
l
C
H
2
C
H
2
C
l
P
h
C
O
2
E
t
9
2
%

e
e
H
2
N
R
O
H
N
O
C
l
O
C
l
2
.


S
O
C
l
2
3
.

N
a
O
H
,

E
t
O
H
1
.
N
N
O
O
N
R
R
Synthesis of

PyBOX Ligand
(
Nishiyama
1989)
Nishiyama
, H. et al.,
Organometallics
1989
,
8
, 846

848.

M
e
O
M
e
O
H
1
.


4

m
o
l

%

c
a
t
2
.


P
h
2
S
i
H
2





A
g
B
F
4
3
.

H
+
/
H
2
O
9
4
%

e
e
Lecture 3: C
2

Symmetrical
Ligands
Synthesis of

bisoxazoline
(BOX)
ligand
(1991)
Attractive because they are easy to access from
commercially available amino acids.
N
O
R
N
O
R
H
2
N
R
O
H
M
e
O
O
1
.
O
M
e
O
2
.


S
O
C
l
2
3
.

N
a
O
H
,

E
t
O
H
N
O
R
N
O
R
H
2
N
R
O
H
C
l
O
O
C
l
E
t
3
N
N
H
R
N
H
O
O
O
H
O
H
R
M
e
M
e
T
s
C
l
D
M
A
P
Lowenthal
, R.,

Abiko
, A.,
Masamune
,

S.
Tetrahedron
Lett
.
1990
,
31
, 6005

6008.
Helmchen
, G.,
Krotz
, A.,
Ganz
, K. T., Hansen, D.
Synlett
1991
, 257

259.
Muller, D.,
Umbricht
, G., Weber, B.,
Pfaltz
, A.

Helv
.
Chim
.
Acta
,
1991
,
74
, 232

240.
Evans, D. A.;
Woerpel
, K. A.;
Hinman
, M. M.;
Faul
, M. M.
J.
Am.
Chem
. Soc.
1991
,
113
, 726

728.
Corey, E. J.; Imai, N., Zhang, H. Y.
J. Am.
Chem
. Soc.
1991
,
113
, 728

729.
Hall, J.;
Lehn
, J. M.;
DeCian
, A., Fischer, J.
Helv
.
Chim
.
Acta
.
1991
,
74
, 1

6.
Onishi
, M.
Isagawa
, K.
Inorg
.
Chim
.
Acta
.
1991
,
179
,
155

156.
Yang, R. Y.; Chen. Y. H.; Dai, L. X.

Acta
.
Chim
. Sin.
1991
,
49
, 1038

1040.
Aldrich
1g

~$ 125.00
Aldrich
1g

~$ 480.00
Aldrich
1g

~$ 250.00
BOX
ligands
were reported independently by
these research groups in 1990

1991.
N
O
R
N
O
R
M
e
M
e
Most widely used
Diels

Alder
Mukaiyama Aldol
Conjugate Addition
Cyclopropanation
Aziridination
N
O
N
O
M
e
M
e
N
O
B
n
N
O
B
n
N
O
P
h
N
O
P
h
Lecture 3: C
2

Symmetrical
Ligands
Synthesis of

Trost ligand
(1992)
H
N
N
H
O
O
P
P
h
2
P
h
2
P
Aldrich
1g

~$ 250.00
Review, see:
Trost
, B. M.; Crawley, M. L.
Chem
. Rev.
2003
,
103
,

2921

2943.
Chiral diamines
and amino alcohols are widely utilized as
building blocks

for
chiral ligands
.
N
H
2
H
2
N
N
H
2
H
2
N
O
N
N
H
N
F
F
F
F
F
N
N
H
N
H
S
N
O
H
O
t
-
B
u
t
-
B
u
N
H
2
M
e
O
H
N
M
e
O
H
M
e
M
e
M
e
N
N
S
i
C
l
B
r
B
r
P
H
2
N
M
e
Lecture 3: C
2

Symmetrical
Ligands
Synthesis of

phosphoric acids (2004),
Independently by Akiyama and Terada
For original publications, see: (a) Akiyama, T.;
Itoh
, J.; Yokota, K.;
Fuchibe
, K.
Angew
.
Chem
.
Int
. Ed.
2004
, 43
, 1566. (b)
Uraguchi
, D.; Terada, M.
J. Am.
Chem
. Soc.
2004
,
126
, 5356.
For the synthesis of TRIP, see:
Klussmann
, M.; Hoffmann, S.;
Wakchaure
, V.; Goddard, R.; List, B.

Synlett

2010
,
14
, 2189.
O
O
P
O
O
H
i
-
P
r
i
-
P
r
i
-
P
r
i
-
P
r
i
-
P
r
i
-
P
r
TRIP
O
M
e
O
M
e
i
-
P
r
i
-
P
r
i
-
P
r
i
-
P
r
i
-
P
r
i
-
P
r
O
H
O
H
K
2
C
O
3
,

M
e
I
a
c
e
t
o
n
e
,

2
4

h
r
e
f
l
u
x
,

9
6
%
O
M
e
O
M
e
O
M
e
O
M
e
B
r
B
r
n
-
B
u
L
i
,

T
M
E
D
A
B
r
2
,

E
t
2
O
,

2
4

h

7
8

º
C
,

t
o

r
t
,

5
4
%
B
r
M
g
,

C
2
H
4
B
r

(
c
a
t
)
E
t
2
O
,

2
4

h
,

r
e
f
l
u
x
M
g
B
r
1
0

m
o
l

%
N
i
(
P
P
h
3
)
2
C
l
2

E
t
2
O
,

6

h
,

r
e
f
l
u
x
B
B
r
3
,

C
H
2
C
l
2
2
4

h
,

r
t
,

4
5
%

(
2

s
t
e
p
s
)
O
H
O
H
i
-
P
r
i
-
P
r
i
-
P
r
i
-
P
r
i
-
P
r
i
-
P
r
P
O
C
l
3
,

p
y
r
i
d
i
n
e
1
4
h
,

r
e
f
l
u
x
H
2
O
,

3
h
,

r
e
f
l
u
x
H
C
l
/
C
H
2
C
l
2
,

9
9
%
Aldrich
100 mg ~$ 260.00
Aldrich
10 g ~$ 375.00