InCl3-catalyzed reductive coupling of aromatic carbonyl compounds in the presence of magnesium and chlorotrimethylsilane

Article abstract of DOI:10.1246/bcsj.74.1497

Reductive homocoupling of aromatic aldehydes and ketones has been achieved in tetrahydrofuran at room temperature using a catalytic amount of InCl₃ (0.005-0.1 molar amount) under nitrogen atmosphere in the presence of both chlorotrimethylsilane and magnesium metal (Mg turnings) to provide the corresponding 1,2-diols in good to moderate yields with a high diastereoselectivity.

Full text of DOI:10.1246/bcsj.74.1497

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Bull. Chem. Soc. Jpn., 74, 1497–1498 (2001) 1497
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Short Articles
Table 1. Reductive Coupling of Aromatic Aldehydesa)
InCl3-Catalyzed Reductive Coupling
ofAromatic Carbonyl Compounds in
the Presence of Magnesium and
Chlorotrimethylsilane
01
K. Mori et al.
97
98
Kenji Mori, Seiji Ohtaka, and Sakae Uemura*
Isolated
Entry Substrate Product Time/h
dl/mesoc)
SJA8
09-2673
1008
yield%b)
Department of Energy and Hydrocarbon Chemistry, Graduate
School of Engineering, Kyoto University, Sakyo-ku, Kyoto
606-8501
1
2d)
3f)
4d)
5
1a
1a
1a
1a
1b
1b
1c
1c
1d
1d
2a
2a
2a
2a
2b
2b
2c
2c
2d
2d
2
67
0
0
45
59
16
69
43
43
5
68/32
—
—
59/41
50/50
50/50
56/44
57/43
85/15
51/49
2e)
2e)
20
01
(Received March 26, 2001)
17
17
18
18
10
10
6d)
7
01
0
8d)
9
Reductive homocoupling of aromatic aldehydes and ke-
tones has been achieved in tetrahydrofuran at room tempera-
ture using a catalytic amount of InCl3 (0.005–0.1 molar
amount) under nitrogen atmosphere in the presence of both
chlorotrimethylsilane and magnesium metal (Mg turnings) to
provide the corresponding 1,2-diols in good to moderate
yields with a high diastereoselectivity.
10d)
a) Reaction conditions; 1 (5 mmol), InCl3 (0.025 mmol),
Mg (20 mmol), TMSCl (20 mmol), THF (50 mL), rt, N2. b)
The formation of 2.5 mmol of 2 corresponds to 100% yield.
c) Determined by 1H NMR. d) Without InCl3. e) No reac-
tion. f) Without TMSCl.
Quite recently, we have reported that indium(Ⅲ) chloride
and some other indium compounds worked as effective cata-
lysts in the reductive homocoupling of carbonyl compounds
and imines in the presence of aluminum (Al) and chlorosi-
lanes.1 A similar catalytic effect of InCl3 was also observed
when magnesium (Mg) was employed as a reductant in the
place of Al with a higher diastereoselectivity of the coupled
products. We report here another example of InCl3-catalyzed
organic transformation of current interest2 by comparing with
those of the Al case.
Treatment of benzaldehyde (1a) with magnesium metal (Mg
turnings, 4 mol amt.), TMSCl (4 mol amt.), and a catalytic
amount of InCl3 (5 × 10−3 mol amt.) in tetrahydrofuran (THF)
under nitrogen atmosphere at room temperature for 2 h afford-
ed 1,2-diphenyl-1,2-ethanediol (2a) in 67% yield (Table 1, en-
try 1). In this case the diastereoselectivity of 2a was slightly
higher (dl/meso = 68/32) than when using Al as a reductant
(dl/meso = 57/43). Without either InCl3 or TMSCl, the reac-
tion did not proceed for 2 h (Table 1, entries 2,3). However,
when the reaction time was elongated to 20 h, even in the ab-
sence of InCl3 the coupling reaction proceeded, though both
the product yield and diastereoselectivity were lower (entry 4).
The yield of the expected diols was somewhat low despite a
complete conversion of 1a, partly because of the formation of
a small amount of benzyl alcohol and small amounts of many
unidentified compounds. The results of application of this op-
timized condition to p-substituted benzaldehydes are shown in
Table 1. In these cases, although the reaction became slow, the
corresponding coupling product was obtained in 43–69%
yields, and especially in the case of p-methoxybenzaldehyde
(1d) the highest diastereoselectivity (dl/meso = 85/15) was
observed [50% yield (dl/meso = 59/41) in the case of Al].
Reductive coupling similarly proceeded with acetophenone
(3a) as a substrate to afford 2,3-diphenyl-2,3-butanediol (4a)
in moderate yield and high diastereoselectivity. In this case the
diastereoselectivity of 4a was also much higher (dl/meso = 82/
18) compared with the case using Al as a reductant (dl/meso =
68/32). The use of 0.1 mol amt. of InCl3 and 2 mol amt. of Mg
to 4a was revealed to give the best result. The reaction also oc-
curred even without the addition of InCl3, but a long induction
period was observed and even so the product yield was much
lower, similar to the case of Al as a reductant.1 Figure 1 shows
the relationship between the reaction time and the isolated
yield of 4a in this homocoupling in the presence and absence
of InCl3. Results of the reductive coupling of various aromatic
ketones are summarized in Table 2. Especially in the case of
p-methylacetophenone, the best product yield (98% yield) and
high diastereoselectivity (dl/meso = 82/18) were obtained
only for 4 h [72% yield (dl/meso = 65/35) for 5 h in the case
of Al].
Next, we performed the reductive coupling of other various
carbonyl compounds. Intramolecular reductive coupling of
[1,1ꢀ-biphenyl]-2,2ꢀ-dicarbaldehyde (5) occurred under the
same condition and only the trans-9,10-dihydrophenanthrene-
9,10-diol (6) was obtained in good yield (76% yield). The re-
action using Al as a reductant also gave only the trans-isomer
in 39% yield under similar conditions. Such high trans-selec-
tivity of the product from this substrate has already been ob-
served in several cases.4 In the case of aliphatic ketones such
as 1-tetralone and cyclohexanone, the corresponding 1,2-diols
were formed in low to moderate yield (< 33%), while in the
case of aliphatic aldehydes such as octanal, only the reduction
of carbonyl moiety occurred to give 1-octanol. On the other
hand, the reaction of both substrates using Al as a reductant did

1498 Bull. Chem. Soc. Jpn., 74, No. 8 (2001)
© 2001 The Chemical Society of Japan
closed that using a catalytic amount of InCl3 (0.05 mol amt.)
and an equimolar amount of zinc (Zn) as a reductant, the corre-
sponding 1,2-diamine was obtained in 92% yield (dl/meso =
51/49). The result that the reaction in the absence of InCl3 af-
forded the product in 40% yield (dl/meso = 51/49) indicated a
remarkable catalytic effect of InCl3 also in this case. It is
worth noting here, however, that the combination of Zn and
InCl3 is not suitable for reductive homocoupling of either alde-
hydes or ketones.
Experimental
General. 1H and 13C NMR spectra were measured on JEOL
EX-400, JNM-AL300, and JEOL GSX270 spectrometers for solu-
tions in CDCl3 with Me4Si as an internal standard. Analytical thin
layer chromatographies (TLC) were performed with Merck silica
gel 60 F-254 plates. Column chromatographies were performed
with Merck silica gel 60.
InCl3 was purchased from Aldrich and used without further pu-
rification. Magnesium metal (Mg turnings) was purchased from
Nacalai Tesque and used without further purification. TMSCl and
THF were distilled before use. All carbonyl compounds were
commercial products and were used without further purification.
All of imines were prepared by the condensation of carbonyl com-
pounds and amines. The structures of 1,2-diols (2a–d, 4a–c, 4e,
4f) and 1,2-diamines were determined by comparison of the spec-
tral data with those of the authentic samples reported.1 The com-
pounds 4d,4 4g,5 and 63 are known.
Fig. 1. Yield of 4a in the Coupling of Acetophenone (3a) in
the Presence (ꢀ) and Absence (ꢁ) of InCl3. Reaction con-
ditions; 3a (1 mmol), InCl3 (0.1 mmol), Mg (2 mmol),
TMSCl (4 mmol), THF (10 mL), rt, N2.
Table 2. Reductive Coupling of Aromatic Ketonesa)
Typical Procedure for InCl3-Catalyzed Reductive Coupling
Reaction of Benzaldehyde (1a). To a mixture of InCl3 (5.5 mg,
0.025 mmol), magnesium (0.486 g, 20 mmol), chlorotrimethylsi-
lane (2.5 mL, 20 mmol), and THF (40 mL) in a 200 mL two
necked round-bottom flask was added 1a (0.53 g, 5 mmol) in THF
(10 mL) at room temperature under N2. The mixture was kept at
room temperature with magnetic stirring for 2 h, during which pe-
riod the white turbid solution turned grey with a slight dissolution
of Mg. Without InCl3, such change was not observed and the re-
action mixture remained colorless for 2–10 h. Diethyl ether (100
mL) and aqueous HCl (1.2 mol L−1, 50 mL) were added to the re-
sulting mixture and then the organic layer was separated, washed
with saturated aqueous NaHCO3 (50 mL × 3), dried over Na2SO4,
and concentrated. The residue was purified by column chroma-
tography on silica gel (eluent, hexane/ethyl acetate) to give 1,2-
diphenyl-1,2-ethanediol 2a (359 mg, 1.68 mmol, 67% yield; dl/
meso = 68/32) and a complex mixture containing benzyl alcohol
and many unidentified compounds (67 mg).
Isolated
Entry Substrate Product Time/h
dl/mesoc)
yield%b)
1
3a
3a
3b
3c
3c
3d
3e
3f
4a
4a
4b
4c
4c
4d
4e
4f
18
18
24
4
60
12
43
98
0
41
64
49
37
82/18
55/45
76/24
82/18
—
—
70/30
—
2d)
3
4
5d)
6
4
24
24
24
24
7
8
9
3g
4g
81/19
a) Reaction conditions; 3 (1 mmol), InCl3 (0.1 mmol), Mg
(2 mmol), TMSCl (4 mmol), THF (10 mL), rt, N2. b) The
formation of 0.5 mmol of 4 corresponds to 100% yield. c)
1
Determined by H NMR. d) Without InCl3. e) The ratio
could not be determined because of the overlapping of
References
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1
S. Ohtaka, K. Mori, and S. Uemura, Heteroatom Chem.,
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2
For recent reviews of the application of indium compounds
not proceed. α,β-Unsaturated carbonyl compounds such as
trans-cinnamaldehyde yielded the corresponding 1,2-diols in
14% yield [27% yield (dl/meso = 60/40) in the case of Al].
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such as N-benzylideneaniline to the corresponding 1,2-di-
amine occurred (71% yield, dl/meso = 45/55) by using Al and
a catalytic amount of InCl3 (0.03 mol amt.) [0% yield without
InCl3], such a compound was not obtained in the case of Mg
because of the facile decomposition of the substrate to the
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3
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5