Reductive coupling of aromatic dialkyl acetals using the combination of zinc and chlorotrimethylsilane in the presence of potassium carbonate

Article abstract of DOI:10.1246/cl.2007.1418

The treatment of aromatic acetals with zinc and chlorosilane in the presence of potassium carbonate in toluene brought about facile and effective reductive coupling to give the corresponding coupling products. Copyright

Full text of DOI:10.1246/cl.2007.1418

1418
Chemistry Letters Vol.36, No.12 (2007)
Reductive Coupling of Aromatic Dialkyl Acetals Using the Combination of Zinc and
Chlorotrimethylsilane in the Presence of Potassium Carbonate
Bunpei Hatano,Ã Keita Nagahashi, and Shigeki Habaue
Department of Chemistry and Chemical Engineering, Faculty of Engineering, Yamagata University,
4-3-16 Jonan, Yonezawa 992-8510
(Received August 13, 2007; CL-070861; E-mail: hatano@yz.yamagata-u.ac.jp)
The treatment of aromatic acetals with zinc and chlorosilane
in the presence of potassium carbonate in toluene brought about
facile and effective reductive coupling to give the corresponding
coupling products.
OMe
OMe
M/chlorosilane/additive
Toluene/rt/5 h
Ph
OMe
Ph
1a
(1)
Ph
Ph
OMe
+
Ph
OMe
2a
Vicinal diol and diamine structures are often present in nat-
ural products and biologically active molecules, and have been
successfully used as chiral ligands in asymmetric synthesis. A
number of synthetic methods have been developed for access
to the vicinal structures. Among them, the reductive coupling
of carbonyl compounds (C=O and C=N) has some advantage
in terms of simplicity of the process, and a number of reductants
have been developed.1 However, there are only several reports
for sp3 carbon such as acetal, which are a readily available com-
pound and are widely used as a protecting group for carbonyl
compounds in organic synthesis,2 using either TiCl4–LiAlH4,3a
[V2Cl3(THF)6]2[Zn2Cl6],3b Al–PbBr2,3c Ti–TMSCl,3d SmI2–
TFA,3e or TiI4–Zn.3f We now report a reductive coupling of
aromatic dialkyl acetals using the combination of zinc and
chlorosilane in the presence of potassium carbonate. The reduc-
tive coupling of aromatic dialkyl acetals 1 using these low cost
reagents proceeded, giving the corresponding coupling product 2
in good yield.
At first, we demonstrated the reductive coupling of 1a using
reductant, chlorosilane, and additive in toluene. The results are
summarized in eq 1 and Table 1. When 1a was treated with zinc
and chlorotrimethylsilane, the coupling product 2a was obtained
in 76% yield (dl/meso = 56/44) along with olefin 3a formed
via pinacol rearrangement of 2a under acidic conditions
(Entry 1).4,5 To control the pinacol rearrangement, the influence
of base on the reductive coupling was studied. The addition of
potassium carbonate and sodium carbonate improved the selec-
tivity and yield of coupling products, giving 2a as a single prod-
uct in 98 and 86% yields, respectively (Entries 2 and 3). On the
other hand, the addition of potassium bicarbonate, potassium
acetate, triethylamine, 1,8-diazabicyclo[5,4,0]-7-undecene, and
pyridine impeded the reductive coupling of 1a, giving un-
changed 1a along with the deprotected benzaldehyde (Entries
4–8). These results suggest that the addition of carbonate ion
is useful to control the pinacol rearrangement of 2a without dis-
turbing the reductive coupling of 1a.6 In this reductive coupling,
the amounts of zinc are important: the use of 0.5 or 1.0 mol
equiv. amounts of zinc against 1a resulted in the low yield of
2a (Entries 9 and 10). We also found that zinc was essential
for the reductive coupling of 1a. Though it is reported that mag-
nesium, aluminum, and manganese, were effective for reductive
coupling of benzaldehyde as reductant or co-reductant in the
presence of chlorotrimethylsilane,7 these reductants cannot work
at all (Entries 11–13). Furthermore, the use of copper and sama-
3a
Table 1. Reductive coupling of 1a in the presence of
chlorosilanea
Yield /%b
Reductant Chloro-
(M)/mmol
Entry
Additive
dl/mesoc
silane
2a
3a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Zn (6.0) Me3SiCl none
Zn (6.0) Me3SiCl K2CO3
Zn (6.0) Me3SiCl Na2CO3
Zn (6.0) Me3SiCl KHCO3
Zn (6.0) Me3SiCl CH3COOK
Zn (6.0) Me3SiCl Et3N
Zn (6.0) Me3SiCl DBU
Zn (6.0) Me3SiCl Pyridine
Zn (1.5) Me3SiCl K2CO3
Zn (3.0) Me3SiCl K2CO3
Mg (6.0) Me3SiCl K2CO3
76
98
86
0
0
0
0
0
26
59
0
4
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
56/44
51/49
49/51
—
—
—
—
—
50/50
49/51
—
Al (6.0)
Me3SiCl K2CO3
0
0
—
—
—
—
Mn (6.0) Me3SiCl K2CO3
Cu (6.0) Me3SiCl K2CO3
Sm (6.0) Me3SiCl K2CO3
Zn (6.0) Et3SiCl
Zn (6.0) Me2SiCl2 K2CO3
Zn (6.0) SiCl4 K2CO3
Trace
0d
0
K2CO3
—
44
53
Trace 55/45
23 91/9
aReaction conditions: 1a (3.0 mmol), reductant, chlorosilane (6.0
mmol), additive (8.0 mmol), rt, 5 h, under N2. bIsolated yield.
cDetermined by 1H NMR of crude 2a. dComplex mixture was ob-
tained.
rium did not improve the yield and selectivity (Entries 14 and
15). This reductive coupling of 1a using zinc in the presence
of potassium carbonate was affected by the substituent bearing
silyl chloride. The use of chlorotriethylsilane instead of chloro-
trimethylsilane did not work the reductive coupling at all
(Entry 16). Furthermore, dichloro- and tetrachlorosilane affected
the yield and the selectivity: the product 2a was obtained in
moderate yield along with a trace amount of 3a in the treatment
with dichlorodimethylsilane, and the use of tetrachlorosilane
showed the diastereoselectivity of 2a (dl/meso = 91/9), though
the product-selectivity was not observed (Entries 17 and 18).8
This reductive coupling using zinc and chlorotrimethylsi-
lane in the presence of potassium carbonate was useful for other
derivatives 1 and the results are summarized in eq 2 and Table 2.9
The reductive coupling of ethyl (1b) and isopropyl (1c) deriva-
Copyright ꢀ 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.12 (2007)
1419
R1
R3O
R2
transfer from the zinc. Then, the dimerization of 4 leads to the
coupling product 2.
In conclusion, we found that the reductive coupling of
aromatic acetals and ketals proceeded using the combination
of zinc and chlorosilane in the presence of potassium carbonate,
efficiently. Further detailed applications are now in progress.
R2
Zn/TMSCl/K2CO3
Toluene
R2
OR3
(2)
R1 OR3
OR3
R1
1
2
a
Table 2. Reductive coupling of 1 using Zn/TMSCl/K2CO3
R1
1
R2
R3
Yield of 2/%b
dl/mesoc
References and Notes
1b
1c
1d
1e
1f
1g
1h
1i
Ph
Ph
Ph
H
H
H
H
H
H
H
H
H
Et
i-Pr
c-Hexyl
Me
Me
Me
Me
Me
Me
Me
81
88
48
92
79
58
13d
53/47
49/51
50/50
50/50
50/50
46/54
51/49
—
1
2
3
Recent review, see: A. Chatterjee, N. N. Joshi, Tetrahedron
2006, 62, 12137.
Protective Group in Organic Synthesis, ed. by T. W. Greene,
P. G. M. Wuts, John Wiley & Sons, Inc. New, York, 1999.
a) H. Ishikawa, T. Mukaiyama, Bull. Chem. Soc. Jpn. 1978,
51, 2059. b) P. M. Takahara, J. H. Freudenberger, A. W.
Konradi, S. F. Pedersen, Tetrahedron Lett. 1989, 30, 7177.
c) H. Dhimane, H. Tanaka, S. Torii, Bull. Soc. Chim. Fr.
p-MeC6H4
p-ClC6H4
o-BrC6H4
p-CNC6H4
p-MeOC6H4
1-Naphthyl
Ph
Complex mixture
64
64
0
Complex mixture
1j
1k
1l
49/51
52/48
—
Me
H
Me
1990, 127, 283. d) A. Furstner, A. Hupperts, J. Am. Chem.
¨
Ph(CH2)2
Ph(CH2)2
Me
Me
Soc. 1995, 117, 4468. e) A. Studer, D. P. Curran, Synlett
1996, 255. f) N. Yoshimura, T. Mukaiyama, Chem. Lett.
2001, 1334.
1m
—
aReaction conditions: 1 (3.0 mmol), zinc (6.0 mmol), chlorotri-
methylsilane (6.0 mmol), K2CO3 (8.0 mmol), rt, 5–24 h, under
N2. bIsolated yield. Determined by 1H NMR of crude 2. dTetra-
chlorosilane was used instead of chlorotrimethylsilane.
4
Reductive coupling of carbonyl compounds based on the
combination of zinc and chlorosilane, see: a) A. Chatterjee,
T. H. Bennur, N. N. Joshi, J. Org. Chem. 2003, 68, 5668.
b) Y. Yamamoto, R. Hattori, T. Miwa, Y. Nakagai, T. Kubota,
C. Yamamoto, Y. Okamoto, K. Itoh, J. Org. Chem. 2001, 66,
3865. c) Y. Yamamoto, R. Hattori, K. Itoh, Chem. Commun.
1999, 825. d) B. Hatano, A. Ogawa, T. Hirao, J. Org. Chem.
c
tives proceeded smoothly, giving the corresponding coupling
products 2b and 2c in good yields. In the cyclohexyl group
(1d), the reductive coupling also took place to give the corre-
sponding coupling product 2d in moderate yield. It is interesting
to note that the substituent alkoxy group on 1 did not much in-
fluence the reductive coupling as compared with the substituent
on chlorosilane. In the case of p-methyl (1e), p-chloro (1f), and
o-bromo (1g) acetals, the reductive coupling products were
obtained in moderate to good yields. The derivative having p-
cyano (1h) coupled with great difficulty under the usual reaction
conditions; the use of tetrachlorosilane led to the corresponding
product 2h in low yield. In the case of 1i, only a complex mixture
was obtained. In 1-naphthyl acetal 1j and aromatic ketal 1k, the
similar treatment led to the corresponding coupling products 2j
and 2k. In the case of aliphatic acetal 1l and ketal 1m, however,
the reaction did not proceed or gave only a complex mixture.
1998, 63, 9421. e) A. Gansauer, M. Moschioni, D. Bauer,
¨
Eur. J. Org. Chem. 1998, 1923. f) T. Hirao, B. Hatano, M.
Asahara, Y. Muguruma, A. Ogawa, Tetrahedron Lett. 1998,
39, 5247. g) T. Hirao, M. Asahara, Y. Muguruma, A. Ogawa,
J. Org. Chem. 1998, 63, 2812. h) T. A. Lipski, M. A. Hilfiker,
S. G. Nelson, J. Org. Chem. 1997, 62, 4566. i) A. Gansauer,
¨
¨
Synlett 1997, 363. j) A. Gansauer, Chem. Commun. 1997,
457. k) T. Hirao, T. Hasegawa, Y. Muguruma, I. Ikeda,
J. Org. Chem. 1996, 61, 366. l) J. H. So, M. K. Park, P.
Boudjouk, J. Org. Chem. 1988, 53, 5871. m) A. K. Banerjee,
M. C. S. Decarrasco, C. S. V. Frydrychhouge, W. B.
Motherwell, J. Chem. Soc., Chem. Commun. 1986, 1803.
The general procedure for the reductive coupling of 1 and
the physical data of 1 and 2 are available as Supporting
Information on the CSJ Journal Web site, http://www.csj.
jp/journals/chem-lett/index.html.
5
6
R1
OR2
OR2
TMSCl
Zn
Ar
activate
one-electron
transfer
The transformation into 3a from 2a was observed in the ab-
sence of potassium carbonate: when 2a (100 mg, 413 mmol,
dl/meso = 50/50) was treated with zinc (54.0 mg, 826 mmol)
and chlorotrimethylsilane (105 mL, 826 mmol) in 1,2-dichloro-
ethane (5 mL) for 24 h at room temperature, 3a was obtained
in 10% yield (8.4 mg, 40 mmol) along with unchanged 2a
(60% recovery, 60.0 mg, 248 mmol, dl/meso = 70/30). In
1
R1
R2O
R1
Ar
OR2
Ar
Ar
OR2
R1
dimerization
4
2
Scheme 1.
1
toluene, a trace amount of 3a was detected by H NMR.
It is generally accepted that the reductive coupling of acetals
proceeds via a radical process as well as in the case of reductive
coupling of carbonyl compounds. Although the detailed pathway
is not clear in the present reductive coupling using zinc and
chlorotrimethylsilane in the presence of potassium carbonate,
the reductive coupling of 1 seems to be triggered by the activa-
tion of 1 (Scheme 1). The chlorotrimethylsilane serves as not
only a trapping reagent of the eliminated alkoxy group but also
a Lewis acid,10 generating an active species of 1, which affords
the corresponding ꢀ-aryl-ꢀ-alkoxy-radical 4 by one-electron
7
8
References are cited in Ref. 1.
In the treatment of 1a with zinc and tetrachlorosilane for 1 h
instead of 5 h, 2a (dl/meso = 72/28) was obtained in 18%
yield along with 3a (5% yield).
Acetals were prepared according to literatures, see: a) D. P.
Roelofsen, H. van Bekkum, Synthesis 2002, 419. b) R.
Gopinath, S. J. Haque, B. K. Patel, J. Org. Chem. 2002, 67,
5842.
9
10 a) Y. Zhu, Y. Pan, S. Huang, Heterocycles 2005, 65, 133. b)
Y. Zhu, Y. Pan, S. Huang, Synth. Commun. 2005, 34, 3167.
Published on the web (Advance View) November 3, 2007; doi:10.1246/cl.2007.1418