A Catalytic System Consisting of Vanadium, Chlorosilane, and Aluminum Metal in the Stereoselective Pinacol Coupling Reaction of Benzaldehyde Derivatives

Full text of DOI:10.1021/jo990902m

J . Org. Chem. 1999, 64, 7665-7667
7665
benzaldehyde (1a ) with a vanadium catalyst (5 mol %)
in the presence of Me3SiCl and several metals. The
results for the reductive coupling of 1a by using several
co-reductants such as Mg, Mn, Zn, and Al are sum-
marized in Table 1.
A Ca ta lytic System Con sistin g of
Va n a d iu m , Ch lor osila n e, a n d Alu m in u m
Meta l in th e Ster eoselective P in a col
Cou p lin g Rea ction of Ben za ld eh yd e
Der iva tives
The use of Mg as a co-reductant for the catalytic
coupling of 1a was not effective for the stereoselective
coupling, because the reaction was accompanied by the
formation of stilbene as a byproduct (ca. 10% yield, entry
1). However, Mn provided 2a in improved yield and with
similar diastereoselectivity (entry 2). The use of a VCl3-
Zn reagent, which is known to attain high stereoselec-
tivity in the stoichiometric reductive coupling of aliphatic
aldehydes,10 improved the stereoselectivity (entry 3).
Although the use of Al powder gave stilbene as a
byproduct (ca. 10% yield), the highly dl-selective forma-
tion of the diol 2a was observed in this system (entry 4).
In the hope of improving the diastereoselectivity of the
reaction, the influence of vanadium catalysts on this
reductive coupling was studied. Cp2VCl2, which was an
effective catalyst for the reductive coupling of secondary
aliphatic aldehydes, indicated low yield and selectivity
in the coupling of 1a using Al powder and Me3SiCl (entry
5). However, the oxovanadium VOCl3, which is widely
accepted as a one-electron oxidant, was found to catalyze
a highly selective pinacol coupling of 1a in the presence
of Al powder and Me3SiCl (entry 6). This result suggests
that an active low-valent vanadium species may be
generated in situ through reduction of the oxovanadium-
(V) with Al. The diastereoselectivity was improved under
the optimized conditions, and this system was success-
fully applied to a variety of aromatic aldehydes to produce
the corresponding 1,2-diols in good yields with excellent
selectivity, as summarized in Table 2.
Toshikazu Hirao,* Bunpei Hatano, Yuka Imamoto, and
Akiya Ogawa
Department of Applied Chemistry, Faculty of Engineering,
Osaka University, Yamada-oka, Suita,
Osaka 565-0871, J apan
Received J une 2, 1999
In tr od u ction
Recently, the development of catalytic reactions for
stoichiometric electron-transfer processes has attracted
increasing attention because of the synthetic ease and
efficiency of the process. This concept has been demon-
strated in the pinacol coupling of ketones catalyzed by
catalytic Cp2TiCl2/RMgBr1 or electrochemical coupling
using catalytic SmCl3.2 The silylation system is another
catalytic method of reductive carbonyl coupling,3 which
was developed by Fu¨rstner’s group4 and our group5
independently to demonstrate the catalytic McMurry
coupling and pinacol coupling reactions, respectively.
Quite recently, high diastereoselectivity has been achieved
in the pinacol coupling using a catalytic low-valent early
transition metal system.5c-e,6-9 Our system consisting of
catalytic Cp2VCl2/R3SiCl/Zn has been revealed to work
in the diastereoselective pinacol coupling reaction of
aliphatic aldehydes and aromatic aldimines, giving the
corresponding vicinal diols and diamines with excellent
dl- and meso-selectivity, respectively.5c,e However, this
catalytic system does not exhibit enough stereoselectivity
in the case of aromatic aldehydes. The stereoselectivity
of the product depends on the individual components of
the system and their cooperation. The stereochemical
outcome of the coupling products is determined by the
stereochemistry of the possible transition states. From
these points of view, a vanadium (or titanium) catalyst
and chlorosilane are considered to play a key role. It is
also important how the catalyst is reduced with a
co-reductant. The choice of co-reductants is expected to
affect the reaction course, which prompted us to inves-
tigate the influence of the co-reductant on the stereose-
lectivity. We herein report a combination of a vanadium
catalyst and an aluminum co-reductant in the presence
of a chlorosilane that effects the selective reductive
coupling of aromatic aldehydes and aldimines (eq 1).
Purification of Me3SiCl is very important in these
reductive coupling reactions. The use of undistilled
Me3SiCl lowered the diastereoselectivity of 2a (dl/meso
) 85/15). The benzaldehydes bearing p-methyl and
(3) Nomura, R.; Matsuno, T.; Endo, T. J . Am. Chem. Soc. 1996, 118,
11666.
(4) (a) Fu¨rstner, A.; Hupperts, A. J . Am. Chem. Soc. 1995, 117, 4468.
(b) Fu¨rstner, A.; Shi, N. J . Am. Chem. Soc. 1996, 118, 2533. (c)
Fu¨rstner, A.; Shi, N. J . Am. Chem. Soc. 1996, 118, 12349.
(5) (a) Hirao, T.; Hasegawa, T.; Muguruma, Y.; Ikeda, I. Abstracts
for 6 th International Conference on New Aspects of Organic Chemistry,
1994; p 175. (b) Hirao, T.; Hasegawa, T.; Muguruma, Y.; Ikeda, I. J .
Org. Chem. 1996, 61, 366. (c) Hirao, T.; Asahara, M.; Muguruma, Y.;
Ogawa, A. J . Org. Chem. 1998, 63, 2812. (d) Hirao, T.; Hatano, B.;
Asahara, M.; Muguruma, Y.; Ogawa, A. Tetrahedron Lett. 1998, 39,
5247. (e) Hatano, B.; Ogawa, A.; Hirao, T. J . Org. Chem. 1998, 63,
9421. (f) Hirao, T. Synlett 1999, 2, 175.
(6) (a) Gansa¨uer, A. Chem. Commun. 1997, 457. (b) Gansa¨uer, A.
Synlett 1997, 363. (c) Gansa¨uer, A.; Bauer, D. J . Org. Chem. 1998, 63,
2070.
(7) Lipski, T. A.; Hilfiker, M. A.; Nelson, S. G. J . Org. Chem. 1997,
62, 4566.
(8) Liao, P.; Huang, Y.; Zhang, Y. Synth. Commun. 1997, 27, 1487.
(9) Yamamoto, Y.; Hattori, R.; Itoh, K. Chem. Commun. 1999, 825.
(10) Pedersen’s group and Cinquini’s group reported that [V2Cl3-
(THF)6]2[Zn2Cl6] prepared in situ from VCl3(THF)3 and Zn powder was
effective for the stoichiometric reductive coupling of aldehydes: (a)
Kang, M.; Park, J .; Pedersen, S. F. Synlett 1997, 41. (b) Konradi, A.;
Kemp, S.; Pedersen, S. F. J . Am. Chem. Soc. 1994, 116, 1316. (c)
Konradi, A. W.; Pedersen, S. F. J . Org. Chem. 1992, 57, 28. (d) Raw,
A. S.; Pedersen, S. F. J . Org. Chem. 1991, 56, 830. (e) Freudenberger,
J . H.; Konradi, A. W.; Pedersen, S. F. J . Am. Chem. Soc. 1989, 111,
8014. (f) Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Giaroni,
P. J . Org. Chem. 1991, 57, 782. (g) Kammermeier, B.; Beck, G.; J acobi,
D.; J endralla, H. Angew. Chem., Int. Ed. Engl. 1994, 33, 685.
Resu lts a n d Discu ssion
To construct an efficient reduction system using a
vanadium catalyst, we first examined the reduction of
(1) Zhang, Y.; Liu, T. Synth. Commun. 1988, 18, 2173.
(2) Le´onard, E.; Dun˜ach, E.; Pe´richon, J . J . Chem. Soc., Chem.
Commun. 1989, 276.
10.1021/jo990902m CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/14/1999

7666 J . Org. Chem., Vol. 64, No. 20, 1999
Notes
Ta ble 1. Va n a d iu m -Ca ta lyzed P in a col Cou p lin g of 1a a
Ta ble 3. Red u ctive Cou p lin g of 3 by Ca ta lytic Cp 2VCl2/
P h Me2SiCl/Al/Im id a zole System a
2a
4
entry
cat. V
VCl3
VCl3
VCl3
VCl3
Cp2VCl2
VOCl3
M
yield, %b
dl/mesob
62/38c
68/32
79/21
84/16c
60/40
90/10d
entry
Ar
R′
allyl
allyl
allyl
allyl
3
cat. V yield, %b dl/mesoc
1
2
3
4
5
6
Mg
Mn
Zn
Al
Al
Al
66
83
76
56
50
70
1d,e C6H5
3a VOCl3
3a VOCl3
3a Cp2VCl2
3a Cp2VCl2
3b Cp2VCl2
3c Cp2VCl2
tracef
tracef
30
86
62
72
quant
71
2e
3e
4
5
6
C6H5
C6H5
C6H5
p-MeC6H4 allyl
p-ClC6H4 allyl
13/87
13/87
11/89
25/75
45/55
23/77
a
Reaction conditions: 3.3 mmol of 1a , 5 mol % of cat. V, 6.6
mmol of Me3SiCl, 6.6 mmol of M, 10 mL of THF, rt, Ar, 24 h.
b Determined by 1H NMR. c Stilbene was obtained in ca. 10% yield.
7
8
C6H5
C6H5
isopropyl 3d Cp2VCl2
n-hexyl 3e Cp2VCl2
d
a
Reaction temperature was 50 °C.
Reaction conditions: 2.0 mmol. of 3, 5 mol % of cat. V, 4.0
mmol of PhMe2SiCl, 4.0 mmol of Al, 3.0 mmol of imidazole, 10
Ta ble 2. P in a col Cou p lin g of 1 by Ca ta lytic VOCl3/
Me3SiCl/Al System a
mL of DMF, rt, Ar, 24 h. b Isolated yield. c Determined by 1H NMR.
Me3SiCl was used instead of PhMe2SiCl. e In the absence of
d
imidazole. f 1a was obtained in 50% yield.
produced with moderate to good diastereoselectivity
(entries 5 and 6). However, the selectivity was lowered
by a change of the substituent on nitrogen from the allyl
group to an isopropyl or n-hexyl group (entries 7 and 8).
The diastereoselectivity strongly depends on the sub-
stituent on nitrogen.
In conclusion, it has been demonstrated that the
reductive coupling of benzaldehydes could be catalyzed
effectively by a vanadium complex in the presence of a
chlorosilane and a co-reductant. The best result was
obtained by use of Al as a co-reductant. An addition of
imidazole to this system improved the yields of coupling
of benzaldimines. The difference in the stereoselectivity
might be explained by the difference in their intermedi-
ates.12
a
Reaction conditions: 3.3 mmol of 1a , 5 mol % of cat. V, 6.6
mmol of Me3SiCl, 6.6 mmol of Al, 10 mL of DME, 50 °C, Ar, 24 h.
Isolated yield. c Determined by 1H NMR. Reaction time was
b
d
48 h.
p-chloro groups (1b and 1c) were converted to the corre-
sponding diols 2b and 2c, respectively, with excellent
diastereoselectivity (entries 2 and 3), whereas 1d with a
strong electron-releasing substituent was reduced very
slowly. Although 31% of 1d was recovered after reaction
for 48 h, the diol 2d was produced in a moderate yield
with excellent selectivity (entry 4). In contrast, the polym-
erization product was obtained in the case of p-cyanoben-
zaldehyde. The benzaldehyde 1f11 bearing an olefinic
moiety also coupled diastereoselectively in a good yield,
without formation of any cyclization product (entry 6).
Moreover, Al powder could successfully be employed
as a co-reductant in the vanadium-catalyzed reductive
coupling of benzaldimines (3), as illustrated in Table 3.
Attempted reduction of 3a under the reduction conditions
mentioned above afforded a trace amount of products
along with 50% of 1a , which was formed by hydrolysis
of the starting 3a under the reaction conditions (entries
1 and 2). In comparison, Cp2VCl2 showed moderate
catalytic activity in the presence of PhMe2SiCl/Al in DMF
(entry 3). It is noteworthy that the addition of imidazole
to this system markedly improved the yield of 4a (entry
4). Similarly, as observed in the reductive coupling of
benzaldimines by use of a system of catalytic vanadium
compound/chlorosilane/Zn,5e,12 the present system of cata-
lytic Cp2VCl2/PhMe2SiCl/imidazole/Al also indicated meso-
selectivity, and furthermore, the yields were improved
successfully. Starting from p-methyl- and p-chloroben-
zaldimines (3b and 3c), the corresponding diamines were
Exp er im en ta l Section
Gen er a l P r oced u r e for Red u ctive Cou p lin g Rea ction of
Ben za ld eh yd e Der iva tives (1). To a mixture of Al (178 mg,
6.6 mmol, Kanto Chemical Co., Inc.) in DME (9.5 mL) was added
a solution (0.5 mL) of VOCl3 (0.331 mL, 3.3 mmol) in DME (10
mL) at room temperature under argon. The reaction mixture
was heated at 50 °C, and the color of the solution changed from
brown to red purple. Distilled Me3SiCl (0.838 mL, 6.6 mmol) was
added to the reaction mixture, and the color changed from red
purple to light blue. The benzaldehyde 1 (3.3 mmol) was added
to the mixture, and the color again changed from light blue to
brown. The mixture was kept at 50 °C with magnetic stirring
for 24 h. After the mixture cooled to room temperature, ether
(10 mL) and aqueous HCl (1.5 M, 10 mL) were added to the
resulting mixture, and two liquid layers were separated. The
organic layer was washed with saturated aqueous NaHCO3 (10
(12) The stereoselectivity for the formation of diols and diamines is
described in ref 5d; a cyclic intermediate is suggested to favor the
formation of the dl-isomer. On the other hand, an acyclic intermediate
is proposed to give meso-selectivity. Although the role of a co-reductant
requires further detailed mechanistic experiment, it may affect the
transition state.
(11) Stang, J . P.; Hanack, M.; Subramanian, R. L. Synthesis 1982,
85.

Notes
J . Org. Chem., Vol. 64, No. 20, 1999 7667
mL), water (10 mL × 2), and brine (10 mL), dried over Na2SO4,
and concentrated. The residue was purified by column chroma-
tography on silica gel (25 g; eluent, hexane/ethyl acetate ) 50:
0, 48:2, 46:4, 44:6, 42:8, 40:10, 35:15, 30:20, 25:25, each × 50
mL), giving 2.
The registry numbers are as follows. (R*,R*)-1,2-Bisphenyl-
1,2-ethanediol (2a ): 655-48-1; (R*,R*)-1,2-bis(4′-methylphenyl)-
1,2-ethanediol (2b): 66749-58-4; (R*,R*)-1,2-bis(4′-chlorophenyl)-
1,2-ethanediol(2c): 116262-76-1;(R*,R*)-1,2-bis(4′-methoxyphenyl)-
1,2-ethanediol (2d ): 39090-28-3; (R*,R*)-1,2-bis(3′-chlorophenyl)-
1,2-ethanediol (2e): 188839-74-9.
for 24 h. Chloroform (10 mL) and aqueous HCl (1.5 M, 10 mL)
were added to the resulting mixture, and two liquid layers were
separated. The organic layer was washed with saturated aque-
ous NaHCO3 (10 mL), water (10 mL × 2), and brine (10 mL),
dried over Na2SO4, and concentrated. The residue was purified
by column chromatography on silica gel (25 g; eluent, hexane/
ethyl acetate ) 50:0, 48:2, 46:4, 44:6, 42:8, 40:10, 35:15, 30:20,
25:25, each × 50 mL), giving 4.
The registry numbers are as follows. (R,S)-N,N′-Diallyl-1,2-
diphenyl-1,2-ethanediamine (4a ): 219517-92-7; (R,S)-N,N′-di-
allyl-1,2-di(4-methylphenyl)-1,2-ethanediamine (4b): 219517-93-
8; (R,S)-N,N′-diallyl-1,2-di(4-chlorophenyl)-1,2-ethanediamine
(4c): 219517-94-9; (R,S)-N,N′-di(1-methylethyl)-1,2-diphenyl-1,2-
ethanediamine (4d ): 55079-98-6; (R,S)-N,N′-dihexyl-1,2-diphen-
yl-1,2-ethanediamine (4e): 60509-69-5.
(R*,R*)-1,2-Bis(2′-a llylp h en yl)-1,2-eth a n ed iol (2f). Mp 57
°C; IR (neat) 3304, 1032, 1002, 761 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 7.51-6.86 (m, 10 H), 5.64-5.44 (m, 2 H), 4.91-4.69
(m, 4 H), 2.94 (m, 2 H), 2.83 (dd, 2 H, J ) 16.2, 6.6 Hz), 2.61
(dd, 2 H, J ) 16.2, 6.0 Hz); 13C NMR (75 MHz, CDCl3) δ 138.1
(C), 137.7 (C), 137.0 (CH), 129.4 (CH), 127.8 (CH), 127.5 (CH),
126.4 (CH), 115.6 (CH2), 74.5 (CH), 36.1 (CH2); MS (EI) m/z 296
(M+), 148. Anal. Calcd for C20H22O2: C, 81.60; H, 7.53. Found:
C, 81,50; H, 7.43.
Gen er a l P r oced u r e for Red u ctive Cou p lin g Rea ction of
Ald im in e Der iva tives (3). To a mixture of Cp2VCl2 (25 mg,
0.1 mmol), Al (108 mg, 4.0 mmol), and imidazole (204 mg, 3.0
mmol) in DMF (10 mL) was added PhMe2SiCl (683 mg, 4.0
mmol) at room temperature under argon. After the mixture
stirred for 1 h, 3 (2.0 mmol) was added to the mixture. The
mixture was kept at room temperature with magnetic stirring
Ack n ow led gm en t. This research was supported in
part by a Grant-in-Aid for Scientific Research on Prior-
ity Areas from the Ministry of Education, Science and
Culture, J apan. Thanks are due to the Instrumental
Analysis Center, Faculty of Engineering, Osaka Uni-
versity for assistance in obtaining mass spectra on a
J EOL J MS-DX303 instrument.
J O990902M