6766
J . Org. Chem. 1998, 63, 6766-6767
Sch em e 1. P r ep a r a tion a n d Cou p lin g Rea ction of
A F a cile Syn th etic Meth od for th e
P r ep a r a tion of Ben zylic Ma n ga n ese Ha lid es
Usin g High ly Active Ma n ga n ese a n d Th eir
Cou p lin g Rea ction s
Ben zylic Ma n ga n ese Ha lid es
Seung-Hoi Kim and Reuben D. Rieke*
Department of Chemistry, University of NebraskasLincoln,
Lincoln, Nebraska 68588-0304
manganese iodide. Trace amounts (less than 1%) of homo-
coupling product was formed in this case.
The cross-coupling reaction of the benzylic manganese
halides with acid chlorides was carried out at room temper-
ature in 2 h in THF. It is worthy to note that the coupling
reaction was performed in the absence of any transition
metal catalyst (except entry 14, Table 1). An excess of acid
chloride was employed in this reaction to avoid the further
reaction of the remaining benzylic manganese halides with
the ketone formed. Both aryl and alkyl acid chlorides gave
excellent yields (Table 1). As shown in Table 1, some
functionalized benzylic manganese halides (entries 4-9, and
14, Table 1) have been obtained as well as nonfunctionalized
ones (entries 1 and 2, Table 1). From these results, it can
be inferred that the present conditions tolerate a wide range
of functional groups attached to the benzyl halides. Of
special interest is entry 8 in Table 1. Preparing organome-
tallics with molecules containing a trifluoromethyl group can
be problematic. However, 1g was readily converted to the
corresponding organomanganese reagent, and subsequent
cross-coupling proceeded in excellent yield. The oxidative
addition will tolerate an electron-withdrawing group such
as a carbomethoxy group. In contrast to all the rest of the
entries in Table 1, the manganese derivative of 1k does not
undergo cross-coupling in the absence of a catalyst. How-
ever, in the presence of CuI, product 2m readily forms. The
reason for this is not clear but may be the reduced nucleo-
philicity caused by the carbomethoxy group (entry 14, Table
1). The p-cyano derivative only leads to homocoupling under
a wide variety of solvents and reaction conditions. Interest-
ingly, treatment of Mn* with R,R′-dichloro-m-xylene and the
consecutive coupling reaction with benzoyl chloride gave a
symmetrical biaryl compound in 79% yield (entry 10, Table
1). The reason is not clear at this moment. Presumably, a
competitive reaction occurred during the following cross-
coupling reaction with benzoyl chloride. Unfortunately, in
the reaction of 1j, homo-coupling product 2l was obtained
during the oxidative addition. The benzylic manganese
halides were found to add to several other electrophiles
including aldehydes, ketones, and di-tert-butyl azodicar-
boxylate (DBAD). The results are summarized in Table 2.
Addition to aldehydes (entries 1-4 and 7, Table 2) gave the
corresponding secondary alcohols in good yields (78-93%)
even with a bulky aldehyde (entry 8, Table 2). The reaction
tolerated halides or a nitrile group in the aldehyde but not
a nitro group (entry 10, Table 2). The addition to an alkyl
ketone yielded the corresponding tertiary alcohol in good
yield (entry 5, Table 2). Coupling with acetophenone was
successful. However, yield was uncharacteristically low. Di-
tert-butyl azodicarboxylate (DBAD) was also employed as
an electrophile, and the corresponding coupling product 3i
was obtained in excellent yield (80%).
Received J une 15, 1998
Most benzylic lithium reagents have been prepared via
bond cleavage reactions1 and/or transmetalation reactions.2,3
Unfortunately, these methods are often accompanied by the
formation of complex mixtures and homo-coupling products
even at low temperature.1
Other metals which undergo oxidative addition to benzylic
halides are zinc4 and cadmium.5 Recently, an interesting
new synthetic method for benzylic zinc reagent has been
reported using triorganozincate.6
We, herein, report an alternative synthetic route for the
direct formation of nonfunctionalized and functionalized
benzylic manganese halides from highly reactive manganese
and benzylic halides.7
Treatment of the highly active manganese (Mn*)7,8 with
benzyl halides (bromide and chloride) gave high yields of
the corresponding benzylic manganese halides. The result-
ing benzylic manganese halides reacted readily with an
appropriate electrophile to give the corresponding cross-
coupled product. Significantly, the majority of these reac-
tions were carried out without a transition metal catalyst.
The environmental advantages are obvious.9
The oxidative addition of Mn* to benzyl halides was
completed at room temperature in 20 min in THF (Scheme
1). Small amounts (3-9%) of homo-coupling product of
benzyl halide were observed. This problem was improved
by using more highly active manganese10 prepared from
(1) (a) Screttas, C. G.; Micha-Screttas, M. J . Org. Chem. 1979, 44, 713.
(b) Still, W. C. J . Am. Chem. Soc. 1978, 100, 1481. (c) Parham, W. E.; J ones,
L. D.; Sayed, Y. A. J . Org. Chem. 1976, 41, 1184. (d) Gilman, H.; McNinch,
H. A. J . Org. Chem. 1961, 26, 3723.
(2) (a) Clarembeau, M.; Krief, A. Tetrahedron Lett. 1985, 26, 1093. (b)
Seyferth, D.; Suzuki, R.; Murphy, C. J .; Sabet, C. R. J . Organomet. Chem.
1964, 431. (c) Gilman, H.; Rosenberg, S. D. J . Org. Chem. 1959, 24, 3.
(3) (a) van den Anker, T. R.; Harvey, S.; Raston, C. L. J . Organomet.
Chem. 1995, 502, 35. (b) Bernardon, C. J . Organomet. Chem. 1989, 367,
11. (c) Harvey, S.; J unk, P. C.; Raston, C. L.; Salem, G. J . Org. Chem. 1988,
53, 3, 3134. (d) Gallagher, M. J .; Harvey, S.; Raston, C. L.; Sue, R. E. J .
Chem. Soc., Chem. Commun. 1988, 289. (e) Harvey, S.; Raston, C. L. J .
Chem. Soc., Chem. Commun. 1988, 652. (f) Itsuno, S.; Darling, G. D.; Sto¨ver,
H. D. H.; Fre´chet, J . M. J . J . Org. Chem. 1987, 52, 4644. (g) Raston, C. L.;
Salem, G. J . Chem. Soc., Chem. Commun. 1984, 1702.
(4) (a) Betzemeier, B.; Knochel, P. Angew. Chem., Int. Ed. Engl. 1997,
36, 2623. (b) Rottla¨nder, M.; Knochel, P. Synlett, 1997, 1084. (c) Klement,
I.; Lennick, K.; Tucker, C. E.; Knochel, P. Tetrahedron Lett. 1993, 34, 4623.
(d) Chia, W.-L.; Shiao, M.-J . Tetrahedron Lett. 1991, 32, 2033. (e) Shing,
T.-L.; Chia, W.-L.; Shiao, M.-J . Chau, T.-Y. Synthesis 1991, 849. (f) Chen,
H. G.; Hoechstetter, C.; Knochel, P. Tetrahedron Lett. 1989, 30, 4795. (g)
Berk, S. C.; Knochel, P.; Yeh, M. C. P. J . Org. Chem. 1988, 53, 5789.
(5) Burkhardt, E. R.; Rieke, R. D. J . Org. Chem. 1985, 50, 416.
(6) Harada, T.; Kaneko, T.; Fujiwara, T.; Oku, A. J . Org. Chem. 1997,
62, 8966.
(7) (a) An attempt for the preparation of benzylic manganese reagent
has been carried out using manganese powder, resulting in the formation
of homocoupling product (89%), see: Hiyama, T.; Sawahata, M.; Obayashi,
M. Chem. Lett. 1983, 1237. (b) Use of manganese for the preparation of
allylic manganese reagent, see: Hiyama, T.; Obayashi, M.; Nakamura, A.
Organometallics 1982, 1, 1249.
Benzylic manganese halides were also found to undergo
palladium-catalyzed cross-coupling reactions with aryl
iodides.4a As shown in Scheme 2, the corresponding coupling
(8) Typical procedure for the preparation of Mn*, see: Rieke, R. D.; Kim,
S.-H.; Wu. X. J . Org. Chem. 1997, 62, 6921.
(9) For use of nontoxic manganese in chromium-catalyzed reaction, see:
(a) Fu¨rstner, A.; Shi, N. J . Am. Chem. Soc. 1996, 118, 2533. (b) Fu¨rstner,
A.; Shi, N. J . Am. Chem. Soc. 1996, 118, 12349.
(10) Different reactivity of Mn* depending on manganese halide, see:
Kim, S.-H.; Rieke, R. D. Synth. Commun. 1998, 28, 1065.
(11) Goswami, S.; Mahapatra, A. K. Tetrahedron Lett. 1998, 39, 1981.
S0022-3263(98)01136-0 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/17/1998