Synthesis of a new chiral cyclic o-hydroxynaphthylphosphonodiamide and its application as ligand catalyst in asymmetric silylcyanation of aromatic aldehydes

Article abstract of DOI:10.1055/s-2004-829075

A new chiral cyclic o-hydroxynaphthylphosphonodiamide (+)-2 was synthesized starting from (+)-cis-1,2,2-trimethylcyclopentane-1,3-diamine. The absolute configuration of phosphorus atom was determined as S by X-ray diffraction analysis. Excellent enantiose

Full text of DOI:10.1055/s-2004-829075

LETTER
1521
Synthesis of a New Chiral Cyclic o-Hydroxynaphthylphosphonodiamide and
its Application as Ligand Catalyst in Asymmetric Silylcyanation of Aromatic
Aldehydes
S
K
ynthesis of
a
N
ew
e
Chiral Cyclic
o-
H
H
ydroxynaphthylp
e
hosphonod
,
iamide Zhenghong Zhou,* Lixin Wang, Kangying Li, Guofeng Zhao, Qilin Zhou, Chuchi Tang
State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. China
Fax +86(22)23503438; E-mail: z.h.zhou@nankai.edu.cn
Received 24 March 2004
droxyl group or an amino group bearing at least a N-H
bond which is favorable to coordinate conveniently with
the metal atom in Lewis acid. Thus the moiety of the co-
Abstract: A new chiral cyclic o-hydroxynaphthylphosphonodi-
amide (+)-2 was synthesized starting from (+)-cis-1,2,2-trimethyl-
cyclopentane-1,3-diamine. The absolute configuration of phos-
phorus atom was determined as S by X-ray diffraction analysis. ordinated metal atom should work as a Lewis acid center
Excellent enantioselectivity (up to 98.3% ee) was achieved in asym- (LA). Moreover, if a phosphoryl group (P=O) is existed at
metric silylcyanation of aromatic aldehydes using a chiral titanium an appropriate position in the ligand molecule, the un-
complex prepared in situ from Ti(Oi-Pr) and (+)-2 as the catalyst.
4
shared electron pair on oxygen atom should act as a Lewis
Key words: chiral phosphonodiamide, asymmetric silylcyanation, base (LB). In the catalyst, it contains both a Lewis acid
catalysis, enantioselectivity, aromatic aldehyde
center and a Lewis base center, namely, LALB catalyst. It
is a new type of chiral bifunctional catalyst.5b Based on
these findings, recently, a new cyclic o-hydroxynaphthyl-
Optically active cyanohydrins are important intermediates phosphonodiamide (1) was synthesized starting from (–)-
in organic synthesis for the synthesis of a variety of valu- a-phenylethylamine and employed in the asymmetric si-
able classes of chiral compounds, such as a-amino acids, lylcyanation of aromatic aldehydes in the presence of
a-hydroxyl carboxylic acids, b-amino alcohols, vicinal di- Ti(Oi-Pr) by our research group. The corresponding cy-
4
ols, a-hydroxyketones, etc. Many efficient approaches anohydrins were obtained in high chemical yields with
6
have been reported for obtaining them by biochemical and good to excellent enantiomeric excesses up to 90%. In or-
1
chemical methods. In the latter, the most important one der to further improve the enantioselectivity of this type of
was the asymmetric silylcyanation of aldehydes with tri- cyclophosphonodiamides, in this paper, we will report the
methylsilylcyanide catalyzed by a Lewis acid, such as synthesis of a new cyclic o-hydroxynaphthylphosphono-
Ti(Oi-Pr) , TiCl , AlCl , SmCl , etc. in the presence of a diamide (2) containing a phosphorus stereocenter starting
4
4
3
3
chiral ligand. In this reaction, a wide range of chiral from (+)-cis-1,2,2-trimethylcyclopentane-1,3-diamine (3)
2
3
ligands have been elaborated, such as Schiff bases, diols,
and its application in asymmetric silylcyanation of aro-
4
5
diamides, phosphorus compounds, etc. As shown in lit- matic aldehydes (Figure 1, Scheme 1).
erature, most of the effective chiral ligands have a free hy-
Ph
N
Ph
O
O
BuLi
N
OH
O
P
N
P
OP(O)Cl2
B:
N
i) PhCHO
ii) NaBH4
Ph
Ph
(+)-(S)-2
NH2
NH2
+)-(S)-3
NHCH2Ph
NHCH2Ph
(-)-(R)-5
(
(+)-4
Ph
N
O
BuLi
No desired product
was obtained
P
N
O
Ph
(+)-(S)-5
Scheme 1
SYNLETT 2004, No. 9, pp 1521–1524
2
2.
0
7.
2
0
0
4
Advanced online publication: 29.06.2004
DOI: 10.1055/s-2004-829075; Art ID: U08304ST
©
Georg Thieme Verlag Stuttgart · New York

1
522
K. He et al.
LETTER
H
tion. However, it is gratifying that ligand (+)-(S)-2 was
very stable and could be readily recovered and reused
without loss of its catalytic activity and asymmetric induc-
tion ability. It was found that a 4:1 molar ratio of ligand to
Ph
Me
OH
N
O
P
N
Ti(Oi-Pr) resulted in better enantioselectivity, whereas
4
Me
the use of one equivalent of ligand (+)-(S)-2 per Ti(Oi-
Ph
1
H
Pr) led to higher chemical yield (entries 1, 5 and entries
4
6
, 9). Buono reported that the introduction of i-PrOH as an
Figure 1
additive has a dramatic influence on the enantioselectivity
5
d
2
i
in asymmetric silylcyanation. However, only a little in-
crease in selectivity was observed in our research (entries
1
Dibenzylation of (+)-3 derived from D-camphor led to
N,N′-dibenzyl-1,2,2-trimethylcyclopentane-1,3-diamine
, 4 and entries 6, 11). The reaction temperature was also
(
4). The cyclization of the latter with O-1-naphthyl phos-
found to be an essential factor to the reaction. The reaction
at 20 °C generally led to better results than that carried out
at 0 °C. An increase in reaction temperature resulted in a
detrimental effect to the reaction due to the instability of
the adduct silyl ether. The nature of the substrate aromatic
aldehyde has a dramatic influence on the catalytic effect.
Generally, the enantioselectivity of aldehyde substituted
with electron donating group (methyl and methoxy) on the
benzene ring was better than that of electron withdrawing
group (chloro and nitro) substituted one. Moreover, the
enantioselectivity was also affected by the position of the
substituent on the benzene ring. When methoxy substitut-
ed benaldehyde was employed as the substrate, it was
found that the enantioselectivity falls in the order: o>m>p
phorodichloridate afforded O-naphthyl phosphorodiami-
date (5). A pair of diastereomers of 5 was obtained via
column chromatography. A subsequent P-O to P-C rear-
rangement upon treatment of (–)-5 with n-BuLi resulted in
the formation of cyclic (+)-o-hydroxynaphthylphos-
phonodiamide (2). The corresponding rearrangement
product of (+)-5 was not obtained under the same condi-
tions. The absolute configuration of the phosphorus atom
in (+)-5 was determined as S via X-diffraction analysis.7
Thus the absolute configuration of the phosphorus atom in
(
–)-5 should be R. At the same time, crystallographic
study shown that the absolute configuration of the phos-
8
phorus atom in (+)-2 was S. Therefore, the rearrange-
ment from (–)-5 to (+)-2 proceeded with total retention of
configuration at the phosphorus atom.
(
entries 6, 14 and 12). This finding indicates that not only
the electrical effect but also the position of the subtituent
or steric effect) had a decisive role on the enantioselectiv-
The catalytic effect of the titanium complex formed in situ
(
from (+)-(S)-2 and Ti(Oi-Pr) in asymmetric silylcyana-
4
ity of the reaction.
tion of aromatic aldehydes was investigated. The experi-
mental results were listed in Table 1.
In conclusion, a new chiral cyclic o-hydroxynaphthyl-
phosphonodiamide (+)-2 was synthesized and the abso-
lute configuration of phosphorus atom was determined by
the X-ray diffraction analysis. Excellent results (up to
Usually, the silylcyanation reaction was best conducted in
methylene chloride. We firstly examined the influence of
the amount of ligand used on the enantioselectivity of the
reaction. It was found that a variation of decrease in yield
and enantiomeric excesses value was observed depending
on the substrate employed with the reducing of the
amount of (+)-(S)-2 from 40 mol% to 20 mol%. As to the
substrate o-methoxybenzaldehyde whose ee value was
9
8.3% ee) were achieved in the asymmetric silylcyanation
of aromatic aldehydes using (+)-2 as the ligand catalyst in
10
the presence of Ti(Oi-Pr) . Investigations on further ex-
4
tending the range of substrates and application of this
compound for other asymmetric reaction are continuing in
our laboratory.
9
8% and 97%, respectively, only a very slight change in
yield and enantioslectivity was observed (entries 6 and 7).
While for some substrates, such as p-methoxybenzalde-
hyde, m-methoxybenzaldehyde and a-naphthyl aldehyde,
Acknowledgment
We are grateful to the National Natural Science Foundation of
this change led to an obvious decrease in enantioselectiv- China (No. 20272025) and the Ph. D. Programs of Ministry of
ity (entries 12 and 13, 14 and 15, 18 and 19). Further re- Education of China for generous financial support for our programs.
ducing the amount of (+)-(S)-2 to 10 mol% resulted in
remarkable decrease both in yield and enantioselectivity
References
(
entry 8). These results showed that the change from the
(
1) (a) North, M. Tetrahedron: Asymmetry 2003, 14, 147.
b) Schmidt, M.; Herve, S.; Klempier, N.; Griengl, H.
ligand 1 to (+)-(S)-2 led to a significant improvement in
the enantioselectivity. Under the same condition, the use
of 40 mol% of ligand 1 led to only 90% ee for the substrate
o-methoxybenzaldehyde. Although a slight high ligand
loading (20–40 mol%) was required for the silylcyana-
(
Tetrahedron 1996, 52, 7833. (c) Effenberger, F. Angew.
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Synlett 2004, No. 9, 1521–1524 © Thieme Stuttgart · New York

LETTER
Synthesis of a New Chiral Cyclic o-Hydroxynaphthylphosphonodiamide
1523
Table 1 Asymmetric Silylcyanation of Aromatic Aldehydes Catalyzed by (+)-(S)-2/Ti(Oi-Pr)4
O
i
OSiMe3
OH
*
(
+)-(S)-2/Ti(OPr)4
H+
+
Me3SiCN
*
Ar
H
CH2Cl2
Ar
CN
Ar
CN
a
c
Entry
Ar
(+)-(S)-2
mol%)
Ti(Oi-Pr)4
(mol%)
i-PrOH
(mol%)
Reaction temp. Yield (%)
(∞ C)
[a]D
(c 1, CHCl3)
Ee (%)
(
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
40
20
40
40
40
40
20
10
40
40
40
40
20
40
20
40
20
40
20
40
40
40
10
5
20
10
20
/
20
20
0
84
74
90
90
96
87
78
69
91
78
86
64
50
78
73
75
74
66
55
81
71
73
+23.8
+19.6
+15.1
+12.5
+22.2
+26.8
+26.4
+14.4
+24.5
+25.0
+24.8
+25.5
+15.4
+34.6
+10.6
+32.5
+30.5
+55.0
+37.3
+40.0
+22.5
+5.5
53 (54.2)b
44
10
10
40
10
5
34
20
20
20
20
20
20
0
28
20
20
10
5
47
2-MeOC H
98 (98.3)b
6
4
4
4
4
4
4
4
4
4
4
2-MeOC H
97
6
2-MeOC H
2.5
40
10
10
10
5
53
6
2-MeOC H
20
20
/
90
6
1
1
1
1
1
1
1
1
1
1
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
2-MeOC H
92
6
2-MeOC H
20
20
20
20
20
20
20
20
20
20
20
20
91
6
4-MeOC H
20
10
20
10
20
10
20
10
20
20
20
54
6
4-MeOC H
32
6
3-MeOC H
10
5
84
6
3-MeOC H
26
6
2-MeC H4
10
5
78
6
2-MeC H4
72 (70.0)b
84
6
a-Naphthyl
a-Naphthyl
10
5
57
4-MeC H4
10
10
10
78
6
4-ClC H4
55
6
4-NO C H
4
35
2
6
a
b
c
Isolated yield.
Determined by HPLC analysis of silyl ether on a chiralcel OD column.
20
1a
20
Determined by comparison of specific rotation values: Ar = Ph, [a] +45 (c 1, CHCl ) in ref. ; Ar = 2-MeOC H , [a] –21.0 (c 1.25,
D
3
6
4
D
1
a
20
1a
20
CHCl ) with 77% ee in ref. ; Ar = 4-MeOC H , [a] +45.5 (c 1, CHCl ) with 95% ee in ref. ; Ar = 3-MeOC H , [a] –40.8 (c 1.25, CHCl3)
3
6
20
4
D
3
6
4
20
D
1
a
9
with 99% ee in ref. ; Ar = 2-MeC H , [a] +21.3 (c 1.03, CHCl ) with 61% ee in ref. ; Ar = a-Naphthyl, [a] +48.0 (c 1.325, CHCl ) with
6
4
20
D
3
D
3
9
9
20
7
3% ee in ref. ; Ar = 4-MeC H , [a] +47.4 (c 1.822, CHCl ) with 92% ee in ref. ; Ar = 4-ClC H , [a] +27.2 (c 1.487, CHCl ) with 66%
6 4 D 3 6 4 D 3
9 20 9
ee in ref. ; Ar = 4-NO C H , [a] +4.6 (c 1.417, CHCl ) with 29% ee in ref.
2
6
4
D
3
(
2) (a) Feng, X. M.; Gong, L. Z.; Hu, W. H.; Li, M.; Mi, A. Q.;
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1
Synlett 2004, No. 9, 1521–1524 © Thieme Stuttgart · New York

1
524
K. He et al.
LETTER
(
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aromatic aldehydes:
3
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(
2
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To a solution of (+)-(S)-2 (0.275 g, 0.54 mmol) in 5 mL of
methylene chloride was added Ti(OPr-i) (37.2 mL, 0.13
4
(
(
mmol) under a nitrogen atmosphere at 20 °C and resulting
mixture was stirred for 1 h at the same temperature. Then
iso-propanol (15.6 mL, 0.26 mmol), 2 mL of methylene
chloride, benzaldehyde (0.142 g, 1.34 mmol) and
1
5) (a) Kanai, M.; Hamashima, Y.; Shibasaki, M. Tetrahedron
Lett. 2000, 41, 2405. (b) Hamashima, Y.; Sawada, D.;
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trimethylsilyl cyanide (200 mL, 16 mmol) were added to it
and the whole stirred for 24 h at the same temperature. After
determination of the enantiomeric excess value of the
cyanohydrin trimethylsilylether by chiral HPLC, the mixture
was poured into a mixture of 1 N HCl (30 mL) and ethyl
acetate (40 mL) and stirred vigorously for 6 h. The organic
layer was separated and the aqueous layer was extracted with
ethyl acetate (2 × 20 mL). The combined organic phase was
washed with brine and dried over anhydrous magnesium
sulfate. After removal of solvent the residue was purified by
thin layer chromatography on silica gel to afford 150 mg
2
641. (c) Hamashida, Y.; Sawada, D.; Kanai, M.; Shibasaki,
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(
Natur. Univ. Nankai 2002, 35, 6. (f) Yang, W. B.; Fang, J.
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(
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4, 3937.
2
0
1
(84% yield) of the corresponding cyanohydrin. [a] +23.8
D
1
(
7) He, K.; Zhou, Z. H.; Zhao, G. F.; Wang, H. G.; Tang, C. C.
Chem. J. Chin. Univ. 2003, 24(11), 1997.
(c 1, CHCl ), H NMR (d, CHCl ): 3.51 (s, 1H, OH), 5.48 (d,
3
3
1H, CH), 7.43–7.49 (m, 5H, 5 H ).
arom
(
8) He, K.; Zhou, Z. H.; Zhao, G. F.; Tang, C. C. Main Group
Metal Chem. 2004, 27, in press.
Spectroscopic data for all prepared compounds are available
from the authors.
Synlett 2004, No. 9, 1521–1524 © Thieme Stuttgart · New York