Indium(III) chloride-sodium borohydride system: A convenient radical reagent for an alternative to tributyltin hydride system

Article abstract of DOI:10.1021/ja017537c

The indium hydride generated from NaBH₄ and InCl₃, is a promising candidate of alternative to Bu₃SnH. In particular, the catalytic performance of InCl₃ in the dehalogenation of alkyl and aryl halides, intramolecular cyclization and intermolecular coupling reaction are noteworthy. Copyright

Full text of DOI:10.1021/ja017537c

Published on Web 01/11/2002
Indium(III) Chloride-Sodium Borohydride System: A Convenient Radical
Reagent for an Alternative to Tributyltin Hydride System
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 November 14, 2001; Revised Manuscript Received December 14, 2001
Scheme 1
Among radical reducing reagents, tributyltin hydride (Bu3SnH)
is the most useful one in intermolecular radical additions using alkyl
halides and unsaturated compounds such as alkenes and alkynes
because of the high kinetic balance of the steps of dehalogenation
by tributyltin radical, addition of the resulting alkyl radical to
unsaturated bond and hydrogen donation of tributyltin hydride.1
Hence, the development of novel radical initiators such as Et3B
Scheme 2
for the generation of tributyltin radical under mild conditions has
still been an important subject.2 On the other hand, because the
toxicity of tributyltin compounds has become a serious problem,
an alternative hydride reagent has been strongly required. Although
Table 1. Indium-Catalyzed Reduction of Alkyl Halide with Mt-Ha
some promising reagents such as tris(trimethylsilyl)silane ((TMS)3-
SiH),3 cyclohexadienyl-silane,4 tri-2-furanylgermane,5 and Schwartz
reagents6 systems have been reported to promote intermolecular
addition reactions, their applicability has not extended over that of
tributyltin hydride. More convenient and useful radical reducing
systems including no tin species have to be developed.
entry
Mt-H
solvent
THF
THF
THF
THF
THF
toluene
diglyme
MeCN
MeCN
MeCN
MeCN
MeCN
yield of 2a/%
1
2
3
4
5
6
7
8
Bu3SnH
CaH2
LiH
82
trace
trace
trace
15
We have already demonstrated that an indium hydride (Cl2InH),
generated by the transmetalation between Bu3SnH and indium(III)
trichloride (InCl3), has a radical character to promote the reduction
of organic halides.7 Interestingly, even a catalytic amount of InCl3
was also effective for the dehalogenation.8 For the InCl3-catalyzed
reaction, it could be considered that in situ generated Cl2InH works
as reactive species for the reduction of organic halides. However,
we could not completely exclude the possibility that InCl3 simply
assists the radical reduction promoted by tributyltin hydride (Scheme
1 path b). To exclude the latter possibility, we have to develop
other hydride sources (Mt-H) than tin hydrides, which should have
no ability for the reduction of organic halide, but should promote
the transmetalation with InCl3 (Scheme 2). In the context of our
studies on the catalytic use of InCl3, we have found a simple, mild
and nontoxic system NaBH4/InCl3/CH3CN in which indium hydride
apparently works as a radical reducing reagent at ambient temper-
ature without any initiators in which dehalogenation, intramolecular
cyclization, and intermolecular coupling reactions have been
effected in the manner similar to the reaction using the usual Bu3-
SnH system.9
Table 1 shows the results of using various hydride sources in
the presence of a catalytic amount of InCl3 for carrying out the
reduction of 2-bromopropylbenzene (1a). Under the same conditions
as using Bu3SnH (THF solvent, rt) (entry 1), all attempts using
metal hydrides such as CaH2, LiH, and BH3-THF failed in the
reduction (entries 2-4). The use of NaBH4 afforded n-propylben-
zene (2a) in 15% yield (entry 5). In this NaBH4/InCl3 system, no
product was obtained in toluene (entry 6), whereas, the reduction
proceeded in diglyme solution to give 62% yield (entry 7).
Furthermore, MeCN was found to be the choice of solvents
examined, giving the yield of 78% which is comparable with the
Bu3SnH system (entry 8). Of course, this reaction also proceeded
with an equimolar amount of InCl3 (entry 9). InCl3 particularly
BH3-THF
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
0
62
78 (0)f
81 (0)f
5
9b
10c
11d
12e
0
90
a InCl3 0.1 mmol, Mt-H 1 mmol, 1a 1 mmol, solvent 2 mL. b 1.0 mmol
of InCl3 was used. c Without InCl3. d AlCl3 was used instead of InCl3. e 1.5
mmol of NaBH4 was used. f 0.1 mmol of p-DNB was added.
played an important role because little reduction took place in the
absence of InCl3 (entry 10). Use of another group-13 element such
as AlCl3 was not effective at all (entry 11). These results indicate
that indium hydride generated by transmetalation between InCl3
and NaBH4 acts as a reducing reagent. When a little excess (1.5
equiv) of NaBH4 was used, the yield increased to 90% (entry 12).
It can be proved that a radical process is involved in this reduction
because the addition of a radical scavenger, p-dinitrobenzene (p-
DNB) completely suppressed the formation of 2a. In contrast to
Bu3SnH, NaBH4 has no radical reactivity;10,11 therefore, it could
be concluded that indium hydride acts as a radical reducing reagent.
Thus, novel reducing system NaBH4/InCl3 could be found here to
undergo the radical reduction of alkyl halides under very mild
conditions such as ambient temperature.12
Table 2 shows the results of reduction of representative alkyl
and aryl halides with this novel system. Secondary and primary
alkyl bromides, 1a and 1b were reduced at room temperature to
the corresponding alkanes in 90 and 95% yields, respectively
(entries 1 and 2). A tertiary bromide, 1-bromoadamantane (1c), was
readily reduced (83% yield, entry 3). Alkyl iodide 1d was also
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906 VOL. 124, NO. 6, 2002 J. AM. CHEM. SOC.
10.1021/ja017537c CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Table 2. InCl3-Promoted Reduction of Various Halidesa
(kH ) 1.0 × 109 M-1 s-1) was determined by the radical clock
experiments using 3a.13 This value is very similar to that of the
rate constant for Bu3SnH determined at 25 °C (kH ) 8.4 × 108
M-1 s-1).14
In conclusion, we found that the indium hydride generated from
NaBH4 and InCl3, is a promising candidate of an alternative to Bu3-
SnH. In particular, the catalytic performance of InCl3 in the
dehalogenation is noteworthy. The reducing system has several
advantages in terms of convenience, economical reagents, mild
conditions, and particularly both InCl3 and NaBH4 are stable and
readily available in comparison to the reported alternatives.
a InCl3 0.1 mmol, NaBH4 1.5 mmol, RX 1 mmol, MeCN 2 mL, rt, 2 h.
b InCl3 0.1 mmol, NaBH4 1 mmol, RX 1 mmol, MeCN 2 mL, rt, 2 h.
reduced to the corresponding alkane in 93% yield (entry 4). Alkyl
chloride 1e and aryl bromide 1f were both hardly reduced under
similar conditions (entries 5 and 6).
Next, we attempted some representative cyclizations and inter-
molecular addition reactions as a radical prove of this procedure.
Aryl iodide such as 1-allyloxy-2-iodobenzene (3a) underwent
cyclization to give 3-methyl-2,3-dihydrobenzofuran (4a) in 62%
yield (eq 1).
Acknowledgment. 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.
Supporting Information Available: Experimental details and
characterization data (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
References
(1) Reviews: (a) Pereyre, M.; Quintard, J.-P.; Rahm, A. Tin in Organic
Synthesis; Butterworth: London, 1987. (b) RajanBavu T. V. In Encyclo-
pedia of Reagents for Organic Synthesis; Paquette, L., Ed.; Willey: New
York, 1995; Vol. 7; pp 5016-5023.
(2) Bu3SnH-initiator systems. Bu3SnH-Et3B: (a) Miura, K.; Ichinose, Y.;
Nozaki, K.; Fugami, K.; Oshima, K.; Utimoto, K. Bull. Chem. Soc. Jpn.
1989, 62, 143-147. Bu3SnH-9BBN: (b) Perchyonok, V. T.; Schiesser,
C. H. Tetrahedron Lett. 1998, 39, 5437-5438. Bu3SnH-CuCl: (c) Ooi,
T.; Doda, K.; Sakai, D.; Maruoka, K. Tetrahedron Lett. 1999, 40, 2133-
2136. Bu3SnH-ZnEt2: (d) Ryu, I.; Araki, F.; Minakata, S.; Komatsu, M.
Tetrahedron Lett. 1998, 39, 6335-6336.
The reaction of alkyl bromide such as 3-(2-bromo-1-phenylethoxy)-
propene (3b) gave 4-methyl-2-phenyl tetrahydrofuran (4b) in 50%
yield (cis:trans ) 15:85) (eq 2).
(3) Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188-194.
(4) Studer, A.; Amrein, S. Angew. Chem., Int. Ed. 2000, 39, 3080-3082.
(5) Nakamura, T.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. Synlett 1999,
1415-1416 and references therein.
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(8) Inoue, K.; Sawada, A.; Shibata, I.; Baba, A. Tetrahedron Lett. 2001, 42,
4661-4663.
Intermolecular radical addition could be also accomplished with a
InCl3-catalyst loading of 10 mol %. For example, iodobenzene or
cyclohexyl iodide added to electron-deficient olefins, effectively
(eqs 3 and 4).
(9) Quite recently Oshima’s group reported the dehalogenation and the
intramolecular cyclization of halo acetals by gallium hydride reagent
induced by triethylborane, where in the application to catalytic use of
gallium(III) chloride Red-Al was slowly added over 2 h as a hydride
source. Mikami, S.; Fujioka, K.; Nakamura, T.; Yorimitsu H.; Shinokubo,
Y.; Matsubara, S.; Oshima, K. Org. Lett. 2001, 3, 1853-1855.
(10) Banfi, L.; Narisano, E.; Riva, R. In Encyclopedia of Reagents for Organic
Synthesis; Paquette, L., Ed.; Willey: New York, 1995; Vol. 7; pp 4522-
4528.
(11) 2-Bromopropylbenzene (1a) was scarcely reduced (6%) with NaBH4 (1
equiv) and AIBN (0.1 equiv) in diglyme at reflux.
(12) Although the mechanism of initiation is unclear as yet, it is considered
that the In-H bond is cleaved homolytically to generate indium radical
(Cl2In•). Alternative possibility is that indium(I) chloride or In(0) metal
generated by reduction of indium(III) trichloride with NaBH4 act as a
radical reducing reagent. However, when the reaction 1a of using InCl or
In metal instead of InCl3 were performed under the conditions noted in
Table 1, product 2a was scarcely obtained (5% and 1%, respectively).
(13) The experimental details are provided in the Supporting Information. For
the radical clocks studies, Newcomb, N. In Radicals in Organic Synthesis;
Renaud, P., Sibi, M. P., Eds; Willey-VCH: New York, 2001; Vol. 1; pp
317-336.
An electron-rich olefin was also applicable to the coupling reaction
(eq 5).
These results proved that indium hydride becomes an efficient
alternative to tributyltin hydride as a radical chain carrier. The rate
constant for the reaction of aryl radical with Cl2InH at 25 °C
(14) Recently, the similar rate constant for the reaction with Bu3SnH was
reported by Carden et al. (7.8 × 108 M-1 s-1). Garden, S. J.; Avila, D.
V.; Beckwith, A. L. J.; Bowry, V. W.; Ingold, K. U.; Lusztyk, J. J. Org.
Chem. 1996, 61, 805-809.
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