New method for the preparation of an active manganese species and its use for radical cyclization reactions

Article abstract of DOI:10.1055/s-1998-1897

Reduction of Li₂MnCl₄ with magnesium in THF afforded a fairly active manganese species which readily initiated radical cyclization of 2-iodoethanal allylic acetals at room temperature. The corresponding 2-bromoethanal acetals also pr

Full text of DOI:10.1055/s-1998-1897

October 1998
SYNLETT
1075
New Method for the Preparation of an Active Manganese Species and its Use for Radical
Cyclization Reactions
Jun Tang, Hiroshi Shinokubo, and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Sakyo-ku, Yoshida, Kyoto 606-8501, Japan
Fax: +81-75-761-8846; E-mail: oshima@fm1.kuic.kyoto-u.ac.jp
Received 27 July 1998
Abstract: Reduction of Li MnCl with magnesium in THF afforded a
2
4
fairly active manganese species which readily initiated radical
cyclization of 2-iodoethanal allylic acetals at room temperature. The
corresponding 2-bromoethanal acetals also provided the same cyclized
products upon treatment with the activated manganese reagent at reflux
in THF.
Recently, we have reported that treatment of 2-iodoethanal acetals with
trialkylmanganate such as n-Bu MnMgBr afforded tetrahydrofuran
3
derivatives in good yields. The catalytic reaction proceeded smoothly, as
well as the stoichiometric reaction, and the same cyclized products were
obtained upon treatment of the acetals with butylmagnesium bromide in
the presence of a catalytic amount of manganese(II) chloride.1 Low-
valent manganese such as Mn(0) could be an active catalyst and play a
critical role in the manganese-catalyzed cyclization reaction. Here we
will to describe the preparation of low-valent manganese and its use for
radical cyclization of 2-haloethanal acetals.
The manganese reagent was obtained upon reduction of the well soluble
ate-complex Li MnCl with magnesium turnings activated by 1,2-
2
4
dibromoethane. 1,2-Dibromoethane (5.0 mmol) was added to a
2
suspension of magnesium (40 mmol) in THF (4 mL). Exothermic
reaction took place. After being stirred for another 5 min, THF and the
produced MgBr2 were removed by a syringe and the resulting
3
magnesium turnings were washed with THF (3 x 4 mL). Then, a pale
4
yellow-green solution of Li MnCl (15 mmol), derived from MnCl2
2
4
(
15 mmol) and LiCl (30 mmol), in THF (40 mL) was added to the above
magnesium turnings. The mixture was stirred for 24 h at room
temperature. The original pale yellow-green color turned dark. This
5
,6
resulting finely divided black powder was partially soluble in THF. A
clear dark supernatant solution of manganese in THF (5.0 mL, 1.8
˜
mmol) was added by a syringe to a solution of 2-iodoethanal acetal 1a
(
1.0 mmol) in THF (2.0 mL) at 25 °C under argon atmosphere. The
mixture was stirred for 6 h at 25 °C. The resulting mixture was
quenched with sat. NH Cl, extracted with ethyl acetate (3 x 10 mL), and
4
the combined organic layers were washed with NaCl solution, dried
over anhydrous Na SO , and concentrated. Silica gel column
2
4
chromatography provided a cyclized product 2a in 70% yield (Scheme
).
1
Scheme 1
The representative results of the reaction of various acetals with low-
valent manganese are shown in Table 1. This new method has some
derived from γ,γ-disubstituted allylic alcohol (1d and 1g) gave the
cyclized products having an alkenyl moiety in addition to the products
bearing an alkyl group. Thus, 4-alkyl-substituted tetrahydrofuran
derivatives were obtained principally in this new procedure. These
characteristics compared to the reaction with n-Bu MnMgBr and
3
several comments are worth noting. (1) In the case of the substrates (1a,
1
b, 1e, and 1f) which have terminal alkene or disubstituted olefins,
results show sharp contrast to those of the reaction with n-Bu MnMgBr
products having a methyl group or an alkyl group on the tetrahydrofuran
ring were obtained exclusively. In contrast, the substrates which are
3
which provides alkenyl-substituted tetrahydrofuran products

1
076
LETTERS
SYNLETT
exclusively in the case of the substrates which have disubstituted or
trisubstituted alkenic moieties. We are tempted to assume that a
hydrogen abstraction of the intermediary carbon radical is a major step
butylmagnesium bromide (1.0 M THF solution, 2 mL, 2 mmol) in the
*
presence of Mn(0) (0.4 mL of a clear dark supernatant, 0.15 mmol)
˜
gave 7 which was identical with a sample prepared by the reaction of 1a
*
in the reaction with Mn(0) , whereas recombination with n-BuMn(I)
with n-BuMgBr in the presence of a catalytic amount of MnCl . The
2
followed by β-elimination of Mn–H producing an alkenyl substituent
result might support our reaction mechanism which has been suggested
in a previous paper (Scheme 4).
1
becomes the main route in the reaction with n-Bu MnMgBr. (2) The
3
*
bromo acetals (1b and 1d, X=Br) reacted with Mn(0) smoothly and as
well as the iodoocetals and provided comparable yields of the desired
tetrahydrofuran derivatives, although the reaction of bromo acetals
required heating of the reaction mixture at reflux in THF. (3) Acetylenic
triple bonds were equally effective as carbon-carbon double bonds for
trapping the radical intramolecularly. Quenching the reaction mixture
Scheme 4
with D O afforded a mixture of deuterated alkene (2c-d) and 2c (2c-d:2c
2
=
35:65). (4) The allylic ether 1f and allylic amine 1h provided the
This metallic manganese, prepared according to the methodology
described above, exhibits appropriate reduction potential to investigate
its use as a co-reductant with other metals. The scope and the limitation
of its mediated radical cyclization will soon be reported.
tetrahydrofuran or pyrrolidine derivative in better yield (62% or 60%)
compared to the reaction with n-Bu MnMgBr which afforded the
3
desired product in only 35% or 7%, respectively, and the starting allylic
alcohol or allylic amine was obtained as the main product. The latter
compound could be formed via E2 elimination by the attack of the ate
complex (probably a butyl anion) on iodine.
Acknowledgment: This work was supported by Grant-in Aid for
Scientific Research (No. 09450341) from the Ministry of Education,
Science, Sports and Culture, Government of Japan. We are grateful to
Professor Kazuhiko Takai at Okayama University for helpful discussion.
We are tempted to assume the following reaction mechanism. Single
*
electron transfer from Mn(0) to 2-iodoethanal acetals would give an
anion radical which provides radical 3 after departure of iodide. 5-Exo
mode cyclization could afford a carbon radical 4 which abstracts
7
hydrogen from the solvent THF (Scheme 2).
References and Notes
1
2
3
Inoue, R.; Nakao, J.; Shinokubo, H.; Oshima, K. Bull. Chem. Soc.
Jpn., 1997, 70, 2039.
Metal granules 1–3 mm; Purchased from Mitsuwa’s pure
chemicals.
The blank test without manganese species was performed as
follows. The supernatant liquid containing magnesium species in
THF (5 mL) was added to the flask containing 1d (X=I) (1.0
mmol) in THF (2 mL). No reaction was observed after 24 h from
which 90% of the starting material was recovered unchanged.
4
5
Cahiez, G.; Alami, M. Tetrahedron, 1989, 45, 4163.
Scheme 2
We are tempted to assume the manganese species to be an active
*
*
metallic manganese (Mn(0) ). Several reductive procedures have
The reagent Mn(0) also reacts with the most reactive substrates such as
allylic bromides or α-bromoesters at 25 °C. In contrast, simple
secondary iodides such as 2-iodotridecane was recovered unchanged
upon treatment with Mn(0) at 25 °C for 12 h. The cyclization of N,N-
been reported for the preparation of active manganese from
8
manganese(II) halides. LiAlH : Hiyama, T.; Obayashi, M.;
4
*
Nakamura, A. Organometallics, 1982, 1, 1249; Li-naphthalene:
Kim, S.–H.; Hanson, M. V.; Rieke, R. D. Tetrahedron Lett., 1996,
*
diallyl-2-iodoaniline with Mn(0) was not so effective as 2-iodoethanal
3
7, 2197; C K: Fürstner, A.; Brunner, H. Tetrahedron Lett., 1996,
8
acetals 1. For instance, treatment of 2-iodoaniline 5 (1.0 mmol) with
*
37, 7009.
Mn(0) (1.8 mmol) in THF at reflux for 6 h afforded an indoline
derivative 6 in only 45% yield along with reduced N,N-diallylaniline
6
Treatment of 1b (X=I) with commercially available manganese
powder (Kanto Chemical Co. Inc) at 25 °C for 36 h resulted in a
complete recovery of the starting material. Several procedures for
activation of Mn metal have been reported: Hiyama, T.; Sawahata,
M.; Obayashi, M. Chem. Lett., 1983, 1237; Cahiez, G.; Chavant,
P. Y. Tetrahedron Lett., 1989, 30, 7373; Takai, K.; Ueda, T.;
Hayashi, T.; Moriwake, T. Tetrahedron Lett., 1996, 37, 7049.
(15%) (Scheme 3).
7
8
THF is a H-donor in radical reaction (k ≈ 104 s–1). Newcomb, M.;
Curran, D. P. Acc. Chem. Res., 1988, 21, 206.
Scheme 3
Three-component coupling reactions of alkyl iodides, electronic
deficient olefins, and carbonyl compounds with manganese-lead
reducing reagent have been reported. Takai, K.; Ueda, T.; Ikeda,
N.; Moriwake, T. J. Org. Chem., 1996, 61, 7990.
*
Finally, Mn(0) -catalyzed reaction of acetals
1 was examined.
Treatment of a solution of 1a (1.0 mmol) in THF (5 mL) with