Triethylborane-induced radical reactions with gallium hydride reagent HGaCl2

Article abstract of DOI:10.1021/ol015904j

(formula presented) Agallium hydride reagent, HGaCl₂, was found to act as a radical mediator, like tributyltin hydride. Treatment of alkyl halides with the gallium hydride reagent, generated from gallium trichloride and sodium bis(2-methoxyethoxy)aluminum hydride, provided the corresponding reduced products in excellent yields. Radical cyclization of halo acetals was also successful with not only the stoichiometric gallium reagent but also a catalytic amount of gallium trichloride combined with stoichiometric aluminum hydride as a hydride source.

Full text of DOI:10.1021/ol015904j

ORGANIC
LETTERS
2001
Vol. 3, No. 12
1853-1855
Triethylborane-Induced Radical
Reactions with Gallium Hydride Reagent
HGaCl2
Satoshi Mikami, Kazuya Fujita, Tomoaki Nakamura, Hideki Yorimitsu,
Hiroshi Shinokubo, Seijiro Matsubara, and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
oshima@fm1.kuic.kyoto-u.ac.jp
Received March 28, 2001
ABSTRACT
A gallium hydride reagent, HGaCl2, was found to act as a radical mediator, like tributyltin hydride. Treatment of alkyl halides with the gallium
hydride reagent, generated from gallium trichloride and sodium bis(2-methoxyethoxy)aluminum hydride, provided the corresponding reduced
products in excellent yields. Radical cyclization of halo acetals was also successful with not only the stoichiometric gallium reagent but also
a catalytic amount of gallium trichloride combined with stoichiometric aluminum hydride as a hydride source.
Organotin hydrides have played an extraordinarily important
role in synthetic radical chemistry because of their excellent
reactivity.1 However, organotin compounds are usually toxic2
and difficult to remove completely from the desired reaction
products. Therefore, many efforts have been made to
overcome these difficulties.3,4 Silanes5 and germanes,6 group
14 metal hydrides, are good alternatives to tributyltin hydride
and are used in organic synthesis. The phosphorus-hydrogen
bond in phosphites, phosphines, and hypophosphorous acid
is also weak, allowing these reagents to act as hydrogen atom
transfer agents and radical chain carriers.7 Very recently, we
reported the Cp2Zr(H)Cl-mediated radical reaction involving
homolytic cleavage of the zirconium-hydrogen bond.8 Here
we wish to introduce the gallium hydride reagent HGaCl2, a
group 13 metal hydride, as an efficient radical mediator.9,10
Gallium trichloride (2.0 mmol) was treated with sodium
bis(2-methoxyethoxy)aluminum hydride (Red-Al, 1.0 mmol)
(1) (a) Neumann, W. P. Synthesis 1987, 665-683. (b) Curran, D. P.;
Porter, N. A.; Giese, B. Stereochemistry of Radical Reactions; VCH
Verlagsgesellschaft mbH.: Weinheim, 1996. (c) Giese, B.; Kopping, B.;
Go¨bel, T.; Dickhaut, J.; Thoma, G.; Kulicke, K. J.; Trach, F. Org. React.
1996, 48, 301-856.
(2) Boyer, I. J. Toxicology 1989, 55, 253-298.
(3) Studies on removal of tin residues or on tin hydride-catalyzed reaction
in conjunction with a stoichiometric reductant: (a) Crich, D.; Sun, S. J.
Org. Chem. 1996, 61, 7200-7201. (b) Clive, D. L. J.; Yang, W. J. Org.
Chem. 1995, 60, 2607-2609. (c) Curran, D. P.; Chang, C.-T. J. Org. Chem.
1989, 54, 3140-3157. (d) Curran, D. P.; Hadida, S. J. Am. Chem. Soc.
1996, 118, 2531-2533. (e) Gerlach, M.; Jo¨rdens, F.; Kuhn, H.; Neumann,
W. P.; Peterseim, M. J. Org. Chem. 1991, 56, 5971-5972. (f) Hays, D. S.;
Fu, G. C. J. Org. Chem. 1996, 61, 4-5. (g) Corey, E. J.; Suggs, J. W. J.
Org. Chem. 1975, 40, 2554-2555. (h) Stork, G.; Sher, P. M. J. Am. Chem.
Soc. 1986, 108, 303-304.
O.; Jaszberenyi, J. C. Tetrahedron Lett. 1990, 31, 4681-4684. (g) Lesage,
M.; Simoes, J. A. M.; Griller, D. J. Org. Chem. 1990, 55, 5413-5414. (h)
Yamazaki, O.; Togo, H.; Matsubayashi, S.; Yokoyama, M. Tetrahedron
1999, 55, 3735-3747. (i) Yamazaki, O.; Togo, H.; Nogami, G.; Yokoyama,
M. Bull. Chem. Soc. Jpn. 1997, 70, 2519-2523.
(6) (a) Pike, P.; Hershberger, S.; Hershberger, J. Tetrahedron Lett. 1985,
26, 6289-6290. (b) Pike, P.; Hershberger, S.; Hershberger, J. Tetrahedron
1988, 44, 6295-6304. (c) Gupta, V.; Kahne, D. Tetrahedron Lett. 1993,
34, 591-594. (d) Chatgilialoglu, C.; Ballestri, M. Organometallics 1995,
14, 5017-5018. (e) Nakamura, T.; Yorimitsu, H.; Shinokubo, H.; Oshima,
K. Synlett 1999, 1415-1416. (f) Nakamura, T.; Yorimitsu, H.; Shinokubo,
H.; Oshima, K. Bull. Chem. Soc. Jpn. 2001, 74, 747-752.
(4) Review on radical chemistry without tin: Bagulay, P. A.; Walton, J.
C. Angew. Chem., Int. Ed. 1998, 37, 3072-3082.
(5) (a) Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188-194. (b)
Chatgilialoglu, C.; Guerrini, A.; Seconi, G. Synlett 1990, 219-220. (c)
Chatgilialoglu, C.; Guerrini, A.; Lucarini, M. J. Org. Chem. 1992, 57, 3405-
3409. (d) Cole, S. J.; Kirwan, J. N.; Roberts, B. P.; Willis, C. R. J. Chem.
Soc., Perkin Trans. 1 1991, 103-112. (e) Barton, D. H. R.; Jang, D. O.;
Jaszberenyi, J. C. Synlett 1991, 435-438. (f) Barton, D. H. R.; Jang, D.
(7) (a) Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. C. J. Org. Chem.
1993, 58, 6838-6842. (b) Jang, D. O.; Song, S. H. Tetrahedron Lett. 2000,
41, 247-249. (c) Yorimitsu, H.; Shinokubo, H.; Oshima, K. Bull. Chem.
Soc. Jpn. 2001, 74, 225-235 and references therein.
(8) Fujita, K.; Nakamura, T.; Yorimitsu, H.; Oshima, K. J. Am. Chem.
Soc. 2001, 123, 3137-3138.
10.1021/ol015904j CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/16/2001

in THF at 0 °C for 30 min to prepare dichlorogallane.11,12
1-Iodododecane (1.0 mmol) and triethylborane (0.20 mmol)
as an initiator13 were sequentially added, and the whole
mixture was stirred for 4 h. Dodecane was obtained in 92%
yield after usual workup and purification. Various halides
were examined (Table 1).
We then turned our attention to the radical cyclization of
halo acetals.14 Substrates shown in Table 2 underwent 5-exo
Table 2. Radical Cyclization of Halo Acetals
Table 1. Radical Reduction of Various Halides with Gallium
Hydridea
entry
R-X
time/h
yield/%
1
2
3
4
5
6
7
8
1-iodododecane
1-bromododecane
1-bromododecane
2-bromododecane
1-bromoadamantane
c-C12H23OC(dS)SMe
3-bromopropyl benzoate
4-iodobutyrophenone
4
5
5
5
5
6
5
9
92
1
X
R1
R2
R3
R4
R5
2
yield/%a
88b
81b,c
81b,c
78b
84
1a
1b
1c
1d
1e
1f
1g
1h
1i
I
Br
I
Br
I
Br
I
Br
I
Br
(CH2)3
H
H
H
H
Me
Me
n-Pr
n-Pr
H
Me 2a
Me 2a
87 (70/30)b
82 (71/29)c
85 (84/16)b
80 (84/16)c
85 (57/43)b
80 (56/44)c
97 (84/16)b
79 (84/16)c
99 (50/50)b
94 (52/48)c
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)3
H
H
H
H
H
H
H
H
2c
2c
2e
2e
2g
2g
2i
88b
80
n-Pen
n-Pen
H
H
n-Bu
H
H
H
H
n-Pr
n-Pr
H
a Halide (1.0 mmol), GaCl3 (2.0 mmol), Red-Al (1.0 mmol), triethylbo-
rane (0.20 mmol), and THF (3 mL) were used. b 1.0 mmol of Et3B was
employed. c Diisobutylaluminum hydride (2.0 mmol) was used instead of
Red-Al (1.0 mmol).
n-Bu
n-Bu
n-Bu
H
n-Pen
n-Pen
1j
H
2i
a Isolated yield. Diastereomer ratios are in parentheses. b 0.20 mmol of
Et3B was used. c 1.0 mmol of Et3B was used.
Alkyl bromides were also reduced to the corresponding
hydrocarbons in excellent yields, although a larger amount
of triethylborane (1.0 mmol) was necessary. Without Red-
Al and gallium trichloride, reduction of 1-bromododecane
in the presence of triethylborane in THF resulted in recovery
of the starting material. A combination of gallium trichloride
and an equimolar amount of diisobutylaluminum hydride was
also effective, forming the gallium hydride reagent (entries
3 and 4). Unfortunately, alkyl chloride and aryl iodide
remained almost unchanged. Radical deoxygenation via
dithiocarbonate was successful (entry 6). Interestingly, reduc-
tion of the ketone did not take place at all under the reaction
conditions (entry 8). However, reduction of a benzylic
bromide, 4-bromobenzyl bromide, resulted in recovery of
the starting material (89%).
reductive cyclization smoothly by the action of the gallium
hydride reagent in the presence of triethylborane.
The reaction of 1a did not proceed in the absence of
triethylborane. 2,2,6,6-Tetramethylpiperidine-N-oxyl com-
pletely inhibited the reaction. The reaction of halo acetals
1a, 1c, and 1e with tributyltin hydride, a representative
method for radical cyclization, under similar reaction condi-
tions provided the corresponding products 2a, 2c, and 2e,
respectively, in moderate yields with the same diastereo-
selctivities as in the reaction with HGaCl2 (2a, 60% (69/
31), 2c, 63% (86/14), 2e, 46% (52/48)). These results support
a radical mechanism for the present reaction. It is worth
noting that the reaction proceeded less efficiently when
monochlorogallane (H2GaCl), which can be prepared by
mixing GaCl3 and Red-Al in 1:1 ratio, was used. For
example, the reaction of 1g provided 2g in 74% yield.
Furthermore, treatment of 1f with H2GaCl (1.5 mmol) yielded
a complex mixture. Red-Al itself worked far less efficiently
compared with HGaCl2. Treatment of 1c and 1e with Red-
Al in the presence of triethylborane provided 2c and 2e in
23% and <1% yields, respectively. The starting materials
1c (57%) and 1e (74%) were recovered.
(9) Baba’s group orally presented the reduction of halide with indium
hydride species, derived from indium trichloride and tributyltin hydride:
Inoue, K.; Sawada, A.; Shibata, I.; Baba, A. The 78th Annual Meeting of
the Chemical Society of Japan, March, 28-31, 2000, 4F230.
(10) The reaction of dichlorogallane with ethyl halides has been reported,
although the reaction was concluded to proceed via σ-bond metathesis: (a)
Csa´kva´ri, B.; Jenei, S.; Knausz, D.; Meszticzky, A. Acta Chim. Acad. Sci.
Hung. 1969, 59, 225-227. (b) Meszticzky, A.; Knausz, D.; Csa´kva´ri, B.;
Emmer, J. Acta Chim. Acad. Sci. Hung. 1976, 89, 203-208.
(11) Examples of gallium hydride reagents, especially LiGaH4, used for
reduction of various functional groups such as carbonyl groups and
halides: (a) Schmidba, H.; Findeiss, W.; Gast, E. Angew. Chem., Int. Ed.
Engl. 1965, 4, 152. (b) Choi, J. H.; Yun, J. H.; Hwang, B. K.; Baek, D. J.
Bull. Korean Chem. Soc. 1997, 18, 541-542. (c) Kim, J. S.; Choi, J. H.;
Kim, H. D.; Yun, J. H.; Joo, C. Y.; Baek, D. J. Bull. Korean Chem. Soc.
1999, 20, 237-240. Review on gallium hydrides: (d) Barron, A. R.;
MacInnes, A. N. In Encyclopedia of Inorganic Chemistry; King, R. B.,
Ed.; John Wiley & Sons: Chichester, 1994; Vol. 3, p 1249.
(12) The gallium species, described as a monomeric form in the present
text, would exist as a certain dimeric or polymeric form: Duke, B. J.;
Hamilton, T. P.; Schaefer, H. F, III. Inorg. Chem. 1991, 30, 4225-4229
and references therein.
Gallium trichloride is not cheap. It is of importance to
reduce the amount of GaCl3 employed for the reaction. Thus,
the catalytic reaction was examined. The cyclization of 1a
was performed by slow addition (2 h) of Red-Al (1.5 mmol)
to a solution of 1a (1.0 mmol), GaCl3 (0.20 mmol), and Et3B
(1.0 mmol) in THF (Table 3). The mixture was stirred for
(13) (a) Nozaki, K.; Oshima, K.; Utimoto, K. J. Am. Chem. Soc. 1987,
109, 2547-2548. (b) Oshima, K.; Utimoto, K. J. Synth. Org. Chem. Jpn.
1989, 47, 40-52. (c) Yorimitsu, H.; Oshima, K. In Radicals in Organic
Synthesis; Renaud, P., Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001;
Vol. 1, Chapter 1.2.
(14) (a) Ueno, Y.; Chino, K.; Watanabe, M.; Moriya, O.; Okawara, M.
J. Am. Chem. Soc. 1982, 104, 5564-5566. (b) Stork, G.; Mook, R., Jr.;
Biller, S. A.; Rychnovsky, S. D. J. Am. Chem. Soc. 1983, 105, 3741-
3742.
1854
Org. Lett., Vol. 3, No. 12, 2001

Scheme 1
Table 3. Radical Cyclization with a Catalytic Amount of
Gallium Trichloride
substrate
time/ha
product
yield/%b
1a
1c
1e
2 + 1
2 + 8
2 + 4
2a
2c
2e
79 (70/30)
64 (88/12)
95 (59/41)
a Red-Al was added slowly over 2 h, and the resulting mixture was stirred
additionally for the indicated time. b Isolated yield. Diastereomer ratios are
in parentheses.
an additional 1 h to yield 2a in 79% yield. Slow addition
was essential for the success of the catalytic reaction.
Exposure of GaCl3 to excess Red-Al at one time resulted in
poor conversion (2a, 10%; 1a, 65% recovered). Gallane
(GaH3) would be unstable under these reaction conditions.11c
In summary, we have revealed that the gallium hydride
reagent, HGaCl2, works well as a chain carrier in place of
tributyltin hydride. Removal of residual gallium compound
is easy and no special technique is necessary.
We are tempted to assume the catalytic mechanism as
shown in Scheme 1, in analogy with the reaction with
tributyltin hydride. An ethyl radical, generated from Et3B
by the action of a trace amount of oxygen, would abstract
hydrogen homolytically from HGaCl2 to give divalent
gallium radical •GaCl2.15 Halogen abstraction by •GaCl2 from
substrate 1a, for example, affords GaCl2I and radical 3. Ring
closure followed by hydride donation from HGaCl2 to the
Acknowledgment. Financial support by Grant-in-Aid for
Scientific Research (Nos. 09450341 and 10208208) from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy, Government of Japan, is acknowledged. H.Y. and T.N.
thank the JSPS for financial support.
•
radical 4 provides the product 2a and regenerates GaCl2.
GaCl2I, formed in the propagation step, is transformed into
HGaCl2 by the action of aluminum hydride, and the gallium
hydride works again as a hydride source for the carbon-
centered radical.
Supporting Information Available: Detailed experi-
mental procedures and characterization data of 2a-2i. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(15) Gallium-centered radical anion was reported: Brand, J. C.; Roberts,
B. P. J. Chem. Soc., Chem. Commun. 1984, 109-110.
OL015904J
Org. Lett., Vol. 3, No. 12, 2001
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