Vanadium-catalyzed stereoselective cyclodimerization of arylidene malononitrile in the presence of chlorosilane and zinc

Article abstract of DOI:10.1016/S0040-4039(00)01540-9

A catalytic cyclodimerization of arylidene malononitriles proceeded diastereoselectively with reversible redox between vanadium and zinc in the presence of chlorotrimethylsilane. The reductive coupling reaction strongly depended on the co-reductant, addit

Full text of DOI:10.1016/S0040-4039(00)01540-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8517–8521
Vanadium-catalyzed stereoselective cyclodimerization of
arylidene malononitrile in the presence of chlorosilane and
zinc
Longhu Zhou and Toshikazu Hirao*
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Yamada-oka, Suita,
Osaka 565-0871, Japan
Received 26 July 2000; revised 6 September 2000; accepted 8 September 2000
Abstract
A catalytic cyclodimerization of arylidene malononitriles proceeded diastereoselectively with reversible
redox between vanadium and zinc in the presence of chlorotrimethylsilane. The reductive coupling
reaction strongly depended on the co-reductant, additive, solvent, and substrate. © 2000 Elsevier Science
Ltd. All rights reserved.
Keywords: vanadium catalyst; diastereoselective cyclization; one-electron reduction; silylating reagent; co-reductant.
Catalytic reactions for the stoichiometric electron transfer process has attracted increasing
attention due to the synthetic utility and efficiency of the process. This concept has been
1
demonstrated in the pinacol coupling reaction catalyzed by cat. Cp TiCl /RMgBr and electro-
2
2
2
chemical coupling using cat. SmCl . Recently, a catalytic reductive coupling procedure has been
3
3
4
developed independently by F u¨ rstner’s group and our group by using a combination of an
early transition metal catalyst, a chlorosilane and a zerovalent metal as a co-reductant. Our
system has been revealed to work in the diastereoselective pinacol coupling reactions of
aldehydes and aldimines, giving the corresponding vicinal diols and diamines with excellent dl-
and meso-selectivity, respectively. In order to extend the versatility of our catalytic system, we
herein report that a combination of cat. Cp VCl /Me SiCl/Zn effects the diastereoselective
2
2
3
cyclodimerization of arylidene malononitriles.
Treatment of benzylidene malononitrile (1a) with a catalytic amount of Cp VCl , Me SiCl,
2
2
3
and zinc powder led to the formation of the cyclodimerization compound 2a via one-electron
reductive coupling followed by cyclization (Eq. (1)). To construct an efficient reduction system,
the effect of vanadium catalysts, metallic co-reductants, and silylating reagents was investigated
as shown in Table 1.
*
Corresponding author. Fax: +81 6 6879 7415; e-mail: hirao@ap.chem.eng.osaka-u.ac.jp
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01540-9

8518
(1)
Table 1
a
Cyclodimerization of 1a with cat. Cp VCl in the presence of additive
2
2
b
c
Entry
Cp VCl2
Metal
MeSi Cl
Isolated yield (%)
trans:cis
2
3
1
2
3
4
5
6
7
8
9
+
+
+
−
−
+
+
+
+
+
+
−
+
−
+
−
+
+
+
+
+
+
0
0
38
25
0
79
81
62
Zn
Zn
Zn
Zn
Al
Mn
In
Mg
Sm
88:12
74:26
83:17
71:29
77:23
54:46
66
Mixture
Mixture
1
1
0
1
a
Reaction conditions: 1a (1 mmol), Cp VCl (5 mol%), metal (2 mmol), Me SiCl (2 mmol), DMF (5 mL), Ar, rt,
2
2
3
3
h.
b
Distilled Me SiCl was used.
Determined by H NMR.
3
c
1
When 1a was stirred in DMF with a catalytic or even stoichiometric amount of Cp VCl at
2
2
room temperature for 24 h, no reaction took place (entry 1). Although a combination of cat.
Cp VCl and Me SiCl did not effect the reduction of 1a (entry 2), the use of cat. Cp VCl and
2
2
3
2
2
zinc powder gave the cyclization product 2a in 38% yield (entry 3). The attempted reduction of
5
1
a using a Zn/Me SiCl system only resulted in low yields and moderate stereoselectivity (entry
3
4
). Since no reaction took place with zinc powder alone (entry 5), the active reductive species is
likely to be a low-valent vanadium species formed in situ by the reduction of Cp VCl with zinc.
2
2
The fact that the addition of Me SiCl to the Cp VCl ꢀZn system successfully improved the yield
3
2
2
of 2a with good stereoselectivity (entry 6) clearly indicates that efficient cyclodimerization of 1a
requires a combination of cat. Cp VCl , Me SiCl, and Zn. Although the use of Al as a
2
2
3
co-reductant raised the yield of 2a, the diastereoselectivity decreased (entry 7). The employment
of In and Mn gave only low yields and poor stereoselectivity (entries 8 and 9). Moreover, an
attempted reaction of 1a using Mg (entry 10) or Sm (entry 11) as a co-reductant only gave rise
to a complex mixture.
Since the cat. Cp VCl /Me SiCl/Zn system was revealed to be the best combination for the
2
2
3
cyclodimerization of 1a, the influence of the silyl compound, solvent, and temperature was
examined (Table 2). Surprisingly, the reaction of 1a provided poor yields and no diastereoselec-
tivity by switching the solvent from DMF to THF (entry 1). When DME was used in place of
THF or DMF, the reductive cyclization reaction proceeded very slowly without any diastereosel-
ection (entry 2). Use of toluene and dichloromethane gave only a trace amount of the desired

8519
Table 2
a
The influence of silyl compound, solvent, and temperature on the cyclodimerization of 1a
b
Entry
Silyl compound
Solvent
Time (h)
Isolated yield (%)
trans:cis
1
2
3
4
5
6
7
Me SiCl
THF
DME
Toluene
24
72
3
3
3
45
47
Trace
Trace
77
49:51
49:51
3
Me SiCl
3
Me SiCl
3
Me SiCl
CH Cl2
3
2
c
Me SiCl
DMF
DMF
DMF
87:13
83:17
71:29
3
PhMe SiCl
3
3
78
61
2
Ph MeSiCl
2
a
Reaction conditions: 1a (1 mmol), Cp VCl (5 mol%), Zn (2 mmol), R SiCl (2 mmol), solvent (5 mL), Ar, rt, 3
2
2
3
h.
b
c
1
Determined by H NMR.
Reaction temperature, −30°C.
product (entries 3 and 4). The cyclization reaction at −30°C improved the diastereoselectivity up
to 87:13 with 77% yield (entry 5). When PhMe SiCl was employed as a silylating reagent, good
2
yields and diastereoselectivity could be attained (entry 6). The more sterically hindered Ph MeSiCl
2
may be expected to induce higher diastereoselectivity, which resulted in moderate yields with
moderate stereoselectivity (entry 7).
Optimized reaction conditions were employed in the cyclodimerization of arylidene malono-
nitriles (Eq. (2), Table 3). Cyclodimerization of 1 induced by the cat. Cp VCl /Me SiCl/Zn system
2
2
3
in DMF afforded the desired product 2 successfully. The cyclization product 2b was obtained in
good yields with moderate diasteroselectivity (entry 2). In particular, excellent trans selectivity was
observed with 1c and 1d bearing a p-bromo or p-chloro group (entries 3 and 4). In the case of
1
e bearing an o-substituent, the diastereoselectivity considerably decreased (entry 5). Similar
results were observed with the substrates 1f and 1g (entries 6 and 7). These findings indicate that
(2)
Table 3
a
Cat. Cp VCl /Me SiCl/Zn induced cyclodimerization of 1
2
2
3
b
Entry
1
Ar
2
Isolated yield (%)
trans:cis
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
C H5
p-CH OC H
p-BrC H4
p-ClC H4
o-ClC H4
m-ClC H4
o-BrC H4
2a
2b
2c
2d
2e
2f
79
70
74
83
78
64
72
83:17
75:25
89:11
90:10
63:37
59:41
57:43
6
3
6
4
6
6
6
6
1g
2g
6
a
Reaction conditions: 1 (1 mmol), Cp VCl (5 mol%), Zn (2 mmol), Me SiCl (2 mmol), DMF (5 mL), Ar, rt, 3 h.
Determined by H NMR.
2
2
3
b
1

8520
the diastereoselectivity also strongly depends on the electronic and steric effects of the sub-
stituent on the benzene ring at the one-electron reduction or coupling step. The cyclodimeriza-
tion of 1 has also been reported to be achieved by using a stoichiometric reductant such as
6
TiCl , TiCl ꢀZn, SmI , and Sm/Me SiCl/H O. Similar stereoselectivity is observed by using
3
4
2
3
2
TiCl as a reductant. For example, the reaction of 1a with stoichiometric TiCl at room
3
3
6
a
temperature results in trans:cis=87:13.
The structure and relative configuration of 2 were readily confirmed by the spectroscopic data
and X-ray analysis. The X-ray diffraction study on a single crystal of the major isomer of 2c
supports the trans-isomer (Fig. 1).
Figure 1. ORTEP diagram of the major isomer of 2c
Treatment of 1a with cat. VCl /PhMe SiCl/Zn under similar conditions afforded the silyl-sub-
2
2
7
stituted cyclization product 3a in 24% yield with excellent diastereoselectivity (98:2) along with
the product 2a (58%, 80:20, Eq. (3)). The compound 3a was converted to 2a on treatment with
silica gel overnight. When the reaction time was prolonged to 18 h, only 2a was formed,
indicating that the silyl compound 3a is involved as an initial product in the reductive
cyclization.
(3)

8521
Acknowledgements
The use of the facilities of the Analytical Center, Faculty of Engineering, Osaka University is
acknowledged. This work was partly supported by a Grant-in-Aid for Scientific Research on
Priority Areas from the Ministry of Education, Science and Culture. We thank the Japan
Society for the Promotion of Science (JSPS) for postdoctoral fellowships to L.Z.
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1
7
. 3a: H NMR (300 MHz, CDCl ) l 0.54 (s, SiCH ), 0.68 (s, SiCH ), 0.69 (s, SiCH ), 0.71 (s, SiCH ), 3.43 (d,
3
3
3
3
3
13
J=10.8 Hz, CH), 4.49 (d, J=10.8 Hz, CH), 6.71ꢀ7.81 (m, ArH); C NMR (75 MHz, CDCl ) l 0.39, 1.04, 2.48,
3
2
1
5
.59, 49.61, 51.89, 62.87, 111.32, 113.21, 114.64, 116.72, 127.75, 127.89, 127.97, 128.05, 128.40, 128.62, 128.86,
28.91, 129.57, 130.18, 130.38, 134.54, 134.66, 135.19, 135.27, 135.77, 156.49; MS (70 eV) m/z (relative intensity)
+
+
78 (M , 15), 563 (17), 462 (13), 448 (36), 424 (24), 289 (17), 263 (41), 135 (100); exact mass M 578.2328 (calcd
for C H N Si 578.2322) (1.0 ppm).
36
34
4
2
.