Indium hydride: A novel radical initiator in the reduction of organic halides with tributyltin hydride

Article abstract of DOI:10.1016/S0040-4039(01)00816-4

Dichloroindium hydride (Cl₂InH), which was generated in situ by transmetallation between tributyltin hydride and indium trichloride, acted as a novel radical initiator for the reduction of organic halides with tributyltin hydride. The reaction was revealed to proceed through a radical process under non-oxygen conditions at room temperature, and to be applicable to intramolecular radical cyclizations.

Full text of DOI:10.1016/S0040-4039(01)00816-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4661–4663
Indium hydride: a novel radical initiator in the reduction of
organic halides with tributyltin hydride
Katsuyuki Inoue, Akemi Sawada, Ikuya Shibata and Akio Baba*
Department of Molecular Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-Oka, Suita,
Osaka 565-0871, Japan
Received 11 April 2001; revised 8 May 2001; accepted 11 May 2001
Abstract—Dichloroindium hydride (Cl2InH), which was generated in situ by transmetallation between tributyltin hydride and
indium trichloride, acted as a novel radical initiator for the reduction of organic halides with tributyltin hydride. The reaction was
revealed to proceed through a radical process under non-oxygen conditions at room temperature, and to be applicable to
intramolecular radical cyclizations. © 2001 Elsevier Science Ltd. All rights reserved.
Radical reactions with tributyltin hydride (Bu3SnH),
which are initiated under mild conditions, have become
a valuable method for stereoselective carbonꢀcarbon
bond formation.1 The development of a novel radical
initiator is still an important subject, though some
versatile reagents such as Et3B and Et2Zn have been
widely used at low temperature.2 We wish to report
here a convenient initiator, indium trichloride (InCl3),
which is stable against air and acts at user-friendly
room temperature. We have recently demonstrated that
dichloroindium hydride generated by transmetallation
between Bu3SnH and InCl3 facilely reduced alkyl bro-
mides in a radical manner.3 In the context of further
study on the radical reaction, InCl3 was found to be a
new type of effective initiator for the reduction of
organic halides with Bu3SnH.
pressed the formation of toluene, a radical process is
plausibly included in this reduction. The yield decreased
to 35% in the reaction at 0°C, and no reduction pro-
ceeded at −78°C. Use of metal halides of other group-
13 elements, such as AlCl3 and BF3·OEt2 instead of
InCl3, was less effective (entries 4 and 5). Employment
of such solvents as MeCN, CH2Cl2 and hexane resulted
in considerably low yields (entries 6–8). We determined
that the use of 0.1 equiv. of indium trichloride with 1.0
equiv. of Bu3SnH in THF at room temperature (entry
1) was optimal, and these conditions were consequently
applied to all other substrates in this study.4
Table 1. Effects of InCl3 on the reduction of benzyl bro-
mide with Bu3SnHa
catalyst
Bu3SnH
The conditions for carrying out the reduction were
optimized by using benzyl bromide (1a) with tributyltin
hydride (Bu3SnH) and indium trichloride (InCl3) as
outlined in Table 1. All treatments were done using a
dry and degassed solvent in a dark room in order to
avoid the influence of light and oxygen. In the absence
of InCl3, no reduction took place (entry 3). In both
cases of using a catalytic amount and an equimolar
amount of InCl3, effective reduction proceeded at room
temperature in THF to give toluene in 75 and 86%
yields, respectively (entries 1 and 2). Because the addi-
tion of a radical scavenger, galvinoxyl, completely sup-
Me
Br
solvent, rt, 2 h
1a
2a
Entry
Catalyst (mol%)
Solvent
Yield of 2a/%
1
2
3
4
5
6
7
8
InCl3 (10)
InCl3 (100)
None
AlCl3 (10)
BF3·OEt (10)
InCl3 (10)
InCl3 (10)
InCl3 (10)
THF
THF
THF
THF
75 (0)b
86 (0)b
0
28
22
27
39
THF
MeCN
CH2Cl2
Hexane
Keywords: indium and compounds; transmetallation; catalysis; radi-
cals and radical reactions.
* Corresponding author. Tel.: +81-6-6879-7386; fax: +81-6-6879-7387;
e-mail: baba@ap.chem.eng.osaka-u.ac.jp
43
a Bu3SnH 1 mmol, 1 1 mmol, THF 2 mL.
b 1 mol% of galvinoxyl was added.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00816-4

4662
K. Inoue et al. / Tetrahedron Letters 42 (2001) 4661–4663
alkyl bromides, 1b and 1c were reduced at room tem-
perature to the corresponding alkanes in 83 and 91%
yields, respectively (entries 1 and 2). A tertiary bromide,
1-bromoadamantane (1d), was also reacted effectively
(79% yield, entry 3). No reduction of alkyl chloride 1h
proceeded at all (entry 7). Aryl and vinyl bromides 1e
and 1f, however, were scarcely reduced under similar
conditions (entries 4 and 5). In contrast, aryl iodide 1g
was facilely reduced (entry 6). Survival of the carbonyl
moieties under the reduction conditions is an important
aspect of this procedure, and halogenated ketones 1i
and 1j gave the corresponding ketones in good yields
(entries 8 and 9), since moderate reduction of ketones
with indium hydride has been reported.3 In the case of
reduction of 1-bromododecane (1b), the introduction of
oxygen, by bubbling, completely suppressed the forma-
tion of dodecane, and the vigorous removal of oxygen,
increased the yield of dodecane to 90%. Thus, this
indium system needs neither heating nor oxygen, and so
it is compensatory for the conventional AIBN of Et3B
system.
Table 2 shows the results of reduction of representative
alkyl, alkenyl and aryl halides. Primary and secondary
Table 2. InCl3-promoted reduction of various halidesa
Entry
1
R-X
Yield of R-H/ %
83
Time/ h
2.0
1-bromododecane
1b
1c
1d
1e
1f
2
3
4
5
6
7
2.0
2.0
2.5
2.5
2.5
2.5
91
79
0
2-bromododecane
Br
PhBr
Br
12
63
0
Ph
PhI
1g
1h
Ph
Cl
O
8b
9b
5.0
5.0
90
61
1i
1j
Ph
Br
A plausible mechanistic pathway of the reduction is
illustrated in Scheme 1. At first, transmetallation
between Bu3SnH and InCl3 forms an indium hydride,
the facile generation of which has been already con-
firmed.3 Next, decomposition of the hydride allows
formation of an indium radical, which then reacts with
organic bromide to accomplish the catalytic cycle as
illustrated. In the cycle, the indium radical is regener-
ated, and Bu3SnH acts as only a resource for indium
hydride. Another possibility is that Bu3SnH directly
reduces organic bromides, and indium hydride acts only
as a radical initiator.5 Although the exact radical spe-
cies is unclear as yet, a catalytic amount of InCl3 proves
to act as an effective radical initiator under mild
conditions.
O
I
a InCl3 0.1 mmol, Bu3SnH 1 mmol, RX 1 mmol, THF 2mL, rt.
b Bu3SnH (3 mmol) was used.
Next, we attempted some representative cyclizations for
a radical prove of this procedure (Table 3). A primary
alkyl bromide such as 3-(2-bromo-1,1-diphenylethoxy)-
propene (3a) underwent cyclization to give 4-methyl-
2,2-diphenyl tetrahydrofuran (4a) in 94% yield. The
Scheme 1. Plausible catalytic cycle.
Table 3. Radical cyclizationa
Products (Yield/ %)
R-X
Entry
Conditions
Br
rt, 5 h
rt, 2.5 h
rt, 5 h
1
3a
3b
3c
Ph
Ph
Ph
O
O
Ph
4a (94%)
Br
2
3
+
O
O
I
O
O
O
O
4b (70%)
4b' (7%)
O
O
4c (54%)
a InCl3 0.1 mmol, Bu3SnH 1.6 mmol, RX 1 mmol, THF 2mL.

K. Inoue et al. / Tetrahedron Letters 42 (2001) 4661–4663
4663
reaction of a secondary alkyl bromide such as 2-allyl-
oxy-3-bromo tetrahydropyran (3b) gave 3-methylhexa-
hydro furo[2,3-b]pyran (4b and 4b%) in 77% yield with
high anti-selectivity (anti:syn=10:1). 3-Methyl-2,3-
dihydrobenzofuran (4c) was also obtained from 1-allyl-
oxy-2-iodobenzene (3c) in 54% yield. In all cases,
no by-products such as non-cyclized dehalogenated
alkenes were detected at all.
153–171; (e) Renaud, P.; Gerster, M. Angew. Chem., Int.
Ed. Engl. 1998, 37, 2562–2579; (f) Ghosh, A. K.;
Mathivanan, P.; Cappiello, J. Tetrahedron: Asymmetry
1998, 9, 1–45; (g) Sibi, M. P.; Ji, J. G.; Wu, J. H.; Gurtler,
S.; Porter, N. A. J. Am. Chem. Soc. 1996, 118, 9200–9201.
2. (a) Bu3SnH–Et3B: Miura, K.; Ichinose, Y.; Nozaki, K.;
Fugami, K.; Oshima, K.; Utimoto, K. Bull. Chem. Soc.
Jpn. 1989, 62, 143–147; (b) Bu3SnH–9BBN: Perchyonok,
V. T.; Schiesser, C. H. Tetrahedron Lett. 1998, 39, 5437–
5438; (c) Bu3SnH–CuCl: Ooi, T.; Doda, K.; Sakai, D.;
Maruoka, K. Tetrahedron Lett. 1999, 40, 2133–2136; (d)
Bu3SnH–ZnEt2: Ryu, I.; Araki, F.; Minakata, S.;
Komatsu, M. Tetrahedron Lett. 1998, 39, 6335–6336.
3. Miyai, T.; Inoue, K.; Yasuda, M.; Shibata, I.; Baba, A.
Tetrahedron Lett. 1998, 39, 1929–1932.
In conclusion, InCl3 could be employed as a novel
radical initiator in the reduction with Bu3SnH under
mild conditions.
Acknowledgements
4. In a representative case, under nitrogen in a dark condi-
tion, a mixture of InCl3 (0.1 mmol) and Bu3SnH (1.0
mmol) in dry THF (2 mL) was stirred at −78°C for 5 min
to generate dichloroindium hydride (Cl2InH). After being
warmed up to rt for 5 min, to the solution was added 1a
(1.0 mmol), and the resulting mixture was stirred for 2 h.
Aqueous ammonium fluoride was added to remove tri-
butyltin halides. After filtration, the reaction mixture was
extracted with ether (2×50 mL). The combined organic
layer was dried over Mg2SO4 and concentrated to give 2a
(86%).
This work was financially supported by a Grant-in-Aid
for Scientific Research from the Ministry of Education,
Science and Culture, and JSPS Research Fellowships
for Young Scientists.
References
1. (a) Iserloh, H.; Curran, D. P.; Kanemasa, S. Tetrahedron:
Asymmetry 1999, 10, 2417–2428; (b) Curran, D. P.; Porter,
N. A.; Giese, B. Stereochemistry of Radical Reactions;
VCH: Weinheim, 1995; (c) Smadja, W. Synlett 1994, 1–27;
(d) Sibi, M. P.; Porter, N. A. Acc. Chem. Res. 1999, 32,
5. A representative mechanism for the direct reduction by
Bu3SnH: Menapace, L. W.; Kuivila, H. G. J. Am. Chem.
Soc. 1964, 86, 3047–3051.
.