Sequential generation and utilization of radical and anionic species with a novel manganese-lead reducing agent. Three-component coupling reactions of alkyl iodides, electron-deficient olefins, and carbonyl compounds

Full text of DOI:10.1021/jo9617530

7990
J . Org. Chem. 1996, 61, 7990-7991
Sch em e 1
Sequ en tia l Gen er a tion a n d Utiliza tion of
Ra d ica l a n d An ion ic Sp ecies w ith a Novel
Ma n ga n ese-Lea d Red u cin g Agen t.
Th r ee-Com p on en t Cou p lin g Rea ction s of
Alk yl Iod id es, Electr on -Deficien t Olefin s,
a n d Ca r bon yl Com p ou n d s
Kazuhiko Takai,* Takashi Ueda, Norihiko Ikeda, and
Toshio Moriwake
Department of Applied Chemistry, Faculty of Engineering,
Okayama University, Tsushima, Okayama 700, J apan
manganese oxide on its surface. Recently, it was found
that such metal oxide is effectively removed by treatment
with Me3SiCl;7,8 and moreover, the manganese metal is
especially activated by addition of a catalytic amount of
PbCl2.7 Treatment of alkyl iodide 1 with the activated
manganese metal afforded four compounds, which sug-
gests the formation of an alkyl radical by reduction of
the iodide with the manganese system (eq 1).
Received September 12, 1996
Carbanion and radical chemistry represent integral
parts of organic synthesis. However, the reactivities of
the two intermediates are sometimes complementary,
and so sequential utilization of the two offers great
potential for constructing more complex molecules
(Scheme 1).1,2
Alkyl radicals are usually prepared either by chain
methods, the homolytic cleavage of covalent bonds, or by
nonchain methods based on redox reactions.1 One of the
latter accesses radicals by reduction of alkyl halides (R-
X) with reducing agents; however, the method is not so
popular as further reduction of the initial radicals (R•)
leading to alkyl anions (R-) normally proceeds faster than
the first radical formation under the reduction condi-
tions.3 Although intramolecular radical cyclization before
anionic reactions has been observed in several cases,2a,3
there are few examples of the intermolecular version due
to the above restriction.4,5 Two requirements exist for a
suitable reducing agent to connect the two reactions: (1)
The initial radial (R•) is not easily reduced to R- and has
a sufficient lifetime to undergo an intermolecular reac-
tion. (2) The final radical (R′•) is easily subjected by one-
electron reduction to R′-. Therefore, the desired reduc-
tant should be weak enough to be able to discriminate
between the two radicals R• and R′•. With these consid-
erations in mind, here, a novel manganese-lead reducing
agent was utilized, and the above concept was realized
as a three-component coupling reaction.
Intermolecular 1,4-addition to an R,â-unsaturated ester
in a protic solvent was achieved in an excellent yield
under mild conditions (eq 2).9 It is likely, therefore, that
the second one-electron reduction leading to an alkyl-
manganese compound is slower than the first reduction
with this manganese system.
When the reaction was conducted in an aprotic solvent,
the produced anionic species could be trapped with a
carbonyl compound under mild conditions (eq 3).10 Al-
though the role of PbCl2 is unclear, addition of a catalytic
amount of the salt was essential for reducing the alkyl
iodide.
Manganese powder6 is less reactive toward organic
compounds than zinc powder due to a tight layer of
(1) For some reviews of representative examples of serial processes
with different intermediates, see: Padwa, A.; Weingarten, M. D. Chem.
Rev. 1996, 96, 223. Malacria, M. Chem. Rev. 1996, 96, 289; Snider,
B. B. Chem. Rev. 1996, 96, 339.
(2) For some representative examples, see: (a) Cr: Takai, K.;
Nitta, K.; Fujimura, O.; Utimoto, K. J . Org. Chem. 1989, 54, 4732. (b)
Sm: Molander, G. A.; Kenny, C. J . Org. Chem. 1991, 56, 1439.
Molander, G. A.; McKie, J . A. J . Org. Chem. 1995, 60, 872; Curran, D.
P.; Totleben, M. J . J . Am. Chem. Soc. 1992, 114, 6050. Curran, D. P.;
Fevig, T. L.; J asperse, C. P.; Totleben, M. J . Synlett 1992,
943. Molander, G. A.; Harris, C. R. Chem. Rev. 1996, 96, 307. (c) Zn:
Bronk, B. S.; Lippard, S. J .; Danheiser, R. L. Organometallics 1993,
12, 3340.
The results of three-component coupling of alkyl io-
dides, electron-deficient olefins, and carbonyl compounds
are shown in Table 1. Both 3 mol of an alkyl iodide and
a carbonyl compound were used per mole of an olefin.
(3) (a) Nugent, W. A.; RajanBabu, T. V. J . Am. Chem. Soc. 1988,
110, 8561. (b) Curran, D. P.; Fevig, T. L.; Totleben, M. J . Synlett 1990,
773.
(4) For intermolecular carbon-carbon bond formation with radicals
followed by one-electron reduction and protonation, see: Petrier, C.;
Dupuy, C.; Luche, J . L. Tetrahedron Lett. 1986, 27, 3149. RajanBabu,
T. V.; Nugent, W. A. J . Am. Chem. Soc. 1989, 111, 4525.
(5) For Et3B-initiated three-component coupling reactions via boron
enolate, see: Nozaki, K.; Oshima, K.; Utimoto, K. Bull. Chem. Soc.
J pn. 1991, 64, 403.
(6) (a) Hiyama, T.; Sawahata, M.; Obayashi, M. Chem. Lett. 1983,
1237; Nippon Kagaku Kaishi, 1984, 1022. (b) Cahiez, G.; Chavant,
P.-Y. Tetrahedron Lett. 1989, 30, 7373. (c) Fu¨rstner, A.; Shi, N. J .
Am. Chem. Soc. 1996, 118, 2533.
(7) Takai, K.; Ueda, T.; Hayashi, T.; Moriwake, T. Tetrahedron Lett.
1996, 37, 7049.
(8) Takai, K.; Kakiuchi, T.; Utimoto, K. J . Org. Chem. 1994, 59,
2671. See also: Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J . J .
Org. Chem. 1988, 53, 2390. J hingan, A. K.; Maier, W. F. J . Org. Chem.
1987, 52, 1161. Fu¨rstner, A.; Hupperts, A. J . Am. Chem. Soc. 1995,
117, 4468. See also ref 6c.
(9) (a) Luche, J . L.; Allavena, C. Tetrahedron Lett. 1988, 29, 5369.
(b) Blanchard, P.; Da Silva, A. D.; El Kortbi, M. S.; Fourrey, J .-L.;
Robert-Ge´ro, M. J . Org. Chem. 1993, 58, 6517.
(10) Addition of Et2AlCl or anhydrous hydrochloric acid in place of
Me3SiCl was also effective in promoting the reaction.
(11) Shono, T.; Nishiguchi, I.; Sasaki, M. J . Am. Chem. Soc. 1978,
100, 4314.
(12) Hulce, M.; Chapdellaine, M. J . In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford,
1991; Vol. 4, p 237.
S0022-3263(96)01753-7 CCC: $12.00 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 23, 1996 7991
Ta ble 1. Th r ee-Com p on en t Cou p lin g of Alk yl Iod id es, Electr on -Deficien t Olefin s, a n d Ca r bon yl Com p ou n d sa
run
R1
R2
H
R3
H
W
R4
R5
time (h)
yieldb (%)
diastereomer ratioc
1
2
3
4
5
6
7
8
9
i-Pr
CN
-(CH2)5-
0.5
0.5
1
0.5
0.5
1
6
0.5
6
86
Ph
H
H
96
57/43
68/32
Et
85d,e
83
H
H
CO2Me
-(CH2)5-
Ph
Et
H
H
H
H
H
81
41/59f
51/49f
g
52/48
55/45
77d,e
68e
67
Me
H
H
H
H
H
Me
H
H
H
CN
CN
CN
CO2Me
CN
Ph
Ph
Ph
n-Pr
t-Bu
67e
61e
86
10
11
-(CH2)5-
4
0.5
Ph
H
59/41
a
Reaction was conducted on a 2.0 mmol scale. An alkyl iodide (3.0 mol), a carbonyl compound (3.0 mol), Mn (6.0 mol), PbCl2 (0.06
mol), and Me3SiCl (0.10 mol) were used per mol of an electron-deficient olefin. Isolated yields. c Diastereomer ratios were determined
b
by isolation, GLPC, or NMR. An aldehyde (1.2 mol) was used per mol of an electron-deficient olefin. e PbCl2 (0.3 mol) was used per mol
d
of an olefin. f anti/ syn ratio. Mixture of four isomers of undetermined structures.
g
Sch em e 2
The reaction proceeded with primary, secondary, and
tertiary alkyl iodides, but in the case of primary iodide,
the amount of PbCl2 was increased from 1 to 5 mol % of
manganese to accelerate the process (Table 1, runs 9 and
10). Both acrylonitrile and acrylic esters could be
employed as activated olefins, while the reaction with an
alkyl vinyl ketone gave a complex mixture. A substituent
at the â-position of the electron-deficient olefin decreased
the reactivity of the olefin, and the reaction also required
5 mol % of PbCl2 (Table 1, run 7). Ketones and aldehydes
could be used as the third component, and the diaste-
reoselectivity of the anionic addition was approximately
1:1 ∼ 2:1 ratio.
Sch em e 3
In 1978, Shono and Nishiguchi reported a similar
three-component coupling of alkyl iodides, R,â-unsatur-
ated nitriles (or esters), and carbonyl compounds using
zinc metal,11 but the mechanism of such coupling reac-
tions with metal is still uncertain.
When 7-iodo-2-methyl-2-octene was used as an alkyl
iodide, intramolecular radical cyclization occurred before
intermolecular addition to acrylonitrile (eq 4). A three-
component coupling product without the cyclization,
however, was not detected.
3). The reduction rate of an alkyl radical to an alkyl
anion is slower than 1,4-addition of the radical to an
activated olefin. However, one-electron transfer to the
resulting radical having an electron-withdrawing group
proceeds faster than addition to a different unsaturated
bond. Sequential generation and utilization of radical
and anionic species, therefore, are the essential factors
in the coupling reaction of iodoalkanes, R,â-unsaturated
nitriles (or esters), and ketones (or aldehydes), and the
protocol itself can provide a new access to similar coup-
ling products that are difficult to obtain with organocu-
prates in one-pot reactions due to their complex nature.12
Hydroxynitrile 6 was obtained in 50% yield in the case
of 4-iodo-1-butene (eq 5), although no coupling product
was obtained from further cyclization. The results sug-
gests that the second one-electron reduction of radical 7
to a nitrile anion 8 proceeds very quickly (Scheme 2).
Ack n ow led gm en t. Financial support from the Ciba-
Geigy Foundation (J apan) for the Promotion of Science
and the Ministry of Education, Science and Culture of
J apan is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: General procedure
and spectroscopic and analytical data of all compounds in
Table 1 and compounds 5 and 6 (7 pages).
Consequently, the three-component coupling is real-
ized by a subtle balance of the reaction rates (Scheme
J O9617530