Radical Reduction of Organic Halides
Aiming at a more practical method for radical reduction of
haloalkanes, PMHS was selected as a stoichiometric hydride
source. In the reduction of 1a-Br with PMHS at 70 °C, GaCl3
showed higher activity than InCl3 and In(OAc)3 (eq 7). Use of
1,2-dimethoxyethane (DME) as solvent remarkably improved
the reaction efficiency. The reaction at room temperature
resulted in a poor yield of 2a (DME, rt, 24 h, 10% yield).
Raising the reaction temperature (90 °C) with an increased
amount of PMHS (3 equiv) shortened the reaction time, and
the introduction of dry air (15 mL per 1 mmol of 1a-Br) also
accelerated the reduction. Under the optimized conditions, the
reduction of 1a-Br was completed within 1 h to give 2a in a
quantitative yield (eq 8). Even with 5 mol % GaCl3, the yield
of 2a reached 90%.
2,6-lutidine and dry air. In addition, we have found that GaCl3
is an effective catalyst of radical reduction with PMHS, an
inexpensive hydrosilane. The present study has also disclosed
that air plays an important role probably as radical initiator in
these radical reductions using indium and gallium hydride
species. In summary, we have developed new catalytic systems
valuable for tin-free radical reactions.14 Application of the In-
(OAc)3-PhSiH3 system to intermolecular radical addition of
haloalkanes to electron-deficient alkenes is now under investiga-
tion, and the results will be reported in due course.
Experimental Section
General Procedure for In(OAc)3-Catalyzed Reduction of
Organic Halides with PhSiH3 in THF (Method A, Entry 1 in
Table 1). Under a nitrogen atmosphere (2 L balloon), 1-bromo-3-
phenylpropane (1a-Br, 99 mg, 0.50 mmol) and PhSiH3 (54 mg,
0.50 mmol) were added to a stirred suspension of In(OAc)3 (15
mg, 0.050 mmol) in THF (0.5 mL). The mixture was warmed to
70 °C and stirred for 24 h. Saturated aqueous NaHCO3 (0.5 mL)
was added to the stirred reaction mixture at room temperature. The
mixture was diluted with t-BuOMe and dried over Na2SO4. The
dried solution was subjected to GC analysis using an internal
standard (undecane) to determine the yield of the product, propy-
lbenzene (2a, 94%); otherwise, it was evaporated and purified by
silica gel column chromatography (hexane) to demonstrate the
identity and purity of the product.
General Procedure for Et3B-Initiated, In(OAc)3-Catalyzed
Reduction of Organic Halides with PhSiH3 (Methods B and C,
Entry 1 in Table 1). Under a nitrogen atmosphere (2 L balloon),
1-bromo-3-phenylpropane (1a-Br, 99 mg, 0.50 mmol), PhSiH3 (54
mg, 0.50 mmol), Et3B (1.0 M in hexane, 0.10 mmol), and dry air
(5 mL) were successively added to a stirred suspension of In(OAc)3
(29 mg, 0.10 mmol) in THF (0.5 mL) at 30 °C (Method B). After
being stirred for 24 h, the mixture was subjected to the same workup
as performed in Method A. The yield of the product 2a was
determined by GC analysis (91%). In Method C, EtOH (1.0 mL)
was used instead of THF.
General Procedure for In(OAc)3-Catalyzed Reduction of
Organic Halides with PhSiH3 in EtOH Containing 2,6-Lutidine
(Method D, Entry 3 in Table 2). Under a nitrogen atmosphere (2
L balloon), 1-iodododecane (148 mg, 0.50 mmol), PhSiH3 (54 mg,
0.50 mmol), dry air (5 mL), and 2,6-lutidine (27 mg, 0.25 mmol)
were successively added to a stirred suspension of In(OAc)3 (29
mg, 0.10 mmol) in ethanol (1.0 mL) at room temperature. After
being stirred for 1.5 h, the mixture was subjected to the same
workup as performed in Method A. The yield of the product,
dodecane (2b), was determined by GC analysis (87%). Purification
of the crude product by silica gel column chromatography (hexane)
was performed to demonstrate the identity and purity of the product.
The GaCl3-PMHS system was efficient in the reduction of
non-functionalized bromo- and iodoalkanes but not in the
reduction of chloroalkanes (eq 8). Bromoalkanes 1g-Br and 1i-
Br, bearing an ether moiety, were reduced in good yield. In
contrast, the reduction of 1h-Br and 1j-Br, bearing a hydroxy
or carbonyl group, caused the destruction of these functionalities.
The GaCl3-catalyzed reduction of 1a-Br with PMHS did not
occur in the presence of galvinoxyl. This observation and the
rate-accelerating effect of air imply that the reduction proceeds
via a radical chain process mediated by a gallium hydride
species,5,13 although the detailed mechanism is not clear.
Conclusion
We have demonstrated that indium and gallium salts can
catalyze the dehalogenation of organic halides with hydrosilanes.
The In(OAc)3-PhSiH3 reduction system is applicable to various
bromo- and iodoalkanes. A plausible mechanism for this
reduction involves radical reduction of haloalkanes with indium
hydride species catalytically generated by transmetalation of
PhSiH3. Similar indium-catalyzed systems using NaBH4, Bu3-
SnH, hydrosilanes, and DIBAL-H as terminal reductants have
been reported by other research groups.4,5a We have succeeded
in catalytic radical reduction using PhSiH3, a mild and less toxic
reducing agent. The In(OAc)3-PhSiH3 system enables an ef-
ficient reduction of both simple and functionalized iodoalkanes
in EtOH, a environmentally friendly solvent, with the aid of
General Procedure for GaCl3-Catalyzed Reduction of Or-
ganic Halides with PMHS in DME (eq 8). In a glove box filled
with argon, GaCl3 (18 mg, 0.10 mmol) was introduced into a
reaction flask, which was brought out from the box and connected
with an argon balloon (2 L). DME (1.0 mL), 1-bromo-3-phenyl-
propane (1a-Br, 199 mg, 1.00 mmol), PMHS (180 mg, 3.00 mmol
of Si-H), and dry air (15 mL) were added to the flask. The stirred
mixture was warmed to 90 °C. After being stirred for 1 h, the
resultant mixture was cooled to room temperature and subjected
to the same workup as performed in Method A. The yield of the
product 2a was determined by GC analysis (99%). Purification of
the crude product by silica gel column chromatography (hexane)
was performed to demonstrate the identity and purity of the product.
(13) It is known that HGaCl2 can be prepared from GaCl3 and Me3SiH
by transmetalation. Ohshita, J.; Schmidbaur, H. J. Organomet. Chem. 1993,
453, 7.
(14) (a) Radicals in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.;
Wiley-VCH: Weinheim, 2001. (b) Baguley, P. A.; Walton, J. C. Angew.
Chem., Int. Ed. 1998, 37, 3073.
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