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O
O
R
1
R
1
R
1
R
1
R
1
R
1
O
Li
R
2
Li
N
O
O
O
O
N
O
O
O
O
ether
O
O
ether
N
N
R
1
R
1
O
HO
O
R
1
R
1
R
1
R
1
HO
O
R
2
25a
R
1
= Me, R
2
= H (51%)
25b
R
1
= -(CH
2
)
5
-, R
2
= H (74%)
26a
R
1
= Me, R
2
= Me (54%)
26b
R
1
= -(CH
2
)
5
-, R
2
= Me (78%)
27a
R
1
= Me (57%)
27b
R
1
= -(CH
2
)
5
- (64%)
24a
R
1
= Me
24b
R
1
= -(CH
2
)
5
-
Scheme 13.8
Synthesis of pyridyl- and quinolyl-alcohols
25-27.
follows (i) chirality is provided by the fructopyranose and glucofuranose deriva-
tives (Figure 13.2), (ii) all of them are pyridyl alcohols with a tertiary alcohol func-
tion (iii) chelates with different ring size with the metal can be formed (
19
versus
20, 21
), (iv) the pyridyl unit can be modified by introducing substituents at posi-
tion 6 (
19c, 20c
) or quinoline may be used instead of pyridine (
21
and
27
), and
(v) tetradentate ligands
22
and
23
are dimers of
19a,b
and
20a,
respectively
(Scheme 13.7).
The synthesis of these ligands is summarized in Schemes 13.7 and 13.8. They
were obtained by the addition of different organolithium compounds to ketones
18a,b
and
24
derived from fructopyranose and glucofuranose. The starting materi-
als
18a,b
and
24
can be obtained in one and two steps, from fructose (by reaction
with acetone/H
+
) and glucose (by reaction with acetone/H
+
and oxidation with
PCC), respectively. Ligands
22a,b
were prepared by homocoupling of bromopyri-
dines
19d,e,
catalyzed by nickel. Ligand
23
was prepared in 32% overall yield from
6,6
-bipyridine by lithiation and addition to
18a
to give
20d,
and a
second lithiation and addition to
18a.
Similarly, ligands
25
and
26
were prepared
from ketones
24
by addition of the corresponding organolithium pyridyl and qui-
nolyl derivatives.
Table 13.2 shows the results obtained with ligands
19-23
and
25-27
in the addi-
tion of ZnEt
2
to benzaldehyde. From these results, it can be deduced that, in the
family of ligands
19-23,
ligands
20
and
21
(entries 4-8), which form a six-
membered chelate ring, provide higher yields and enantioselectivities than ligands
19
(entries 1-3), which form a five-membered chelate ring. This tendency was also
observed for ligands
22a
and
23
(entries 9, 11), which have similar structure but
contain different backbone length. The different behavior of these ligands was
explained by conformational analysis of their ethylzinc amino-alkoxide complex
formed
in situ.
It is not easy to explain the lower ee value obtained for ligand
22b
and the fact
that the sense of asymmetric induction is opposite to that of all of the other ligands.
Based on related work [16], it is proposed that the
C
2
symmetric bipyridyl alcohols
22
and
23
may act as bidentate ligands.
′
-dimethyl-2,2
′
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