A New Method for Preparing Benzylzinc Reagents via Homologation of Triorganozincates

Full text of DOI:10.1021/jo971615q

8966
J . Org. Chem. 1997, 62, 8966-8967
Sch em e 1
A New Meth od for P r ep a r in g Ben zylzin c
Rea gen ts via Hom ologa tion of
Tr ior ga n ozin ca tes
Toshiro Harada,* Takayuki Kaneko,
Takayuki Fujiwara, and Akira Oku
Department of Chemistry, Kyoto Institute of Technology,
Matsugasaki, Sakyo-ku, Kyoto 606, J apan
2,5-cyclohexadienyl)metal 4 (eq 3). Coexistence of the
Received September 2, 1997
Homologation of organometallics is becoming of in-
creasing importance in organic syntheses because the
reaction allows the efficient assembly of complex molec-
ular structures through additional bond formation of the
resulting homologated organometallics.1 Organoboronate
complexes 1 and 2 (M ) B, n ) 2) bearing a leaving group
at the R-position and the γ-position with R,â-unsatura-
tion, respectively, undergo 1,2-migration of a ligand (R)
to give homologated organoboron compounds (eqs 1 and
2).2,3 Recent reports from this laboratory revealed that
negatively charged metal atom center and the potential
cationic center in 1 and 2 must be a major driving force
of the 1,2-migration. However, for 3, not only are these
two reactive centers separated by the longer aromatic
π-system but also 1,2-migration leading to cross-conju-
gated 4 would suffer from a considerable loss of aromatic
stabilization. We wish to report herein that arylzincates
3 (M ) Zn, n ) 1), generated by the reaction of
p-iodobenzyl mesylate (6) and organozincates, undergo
facile 1,2-migration even at low temperatures (<-40 °C)
to give benzylzinc 5a , which can be utilized in the
reaction with a variety of electrophiles (Scheme 1).
Treatment of mesylte 6 with Bu3ZnLi (1.2 equiv) in
THF at -85 °C and hydrolysis of the mixture after being
warmed to -40 °C afforded p-butyltoluene (7) in 61%
yield.5,6 The yield of 7 was improved to 90% by using
2.0 equiv of Bu3ZnLi under similar conditions. Genera-
tion of benzylzinc 5a (R ) Bu) under these conditions
was verified by the formation of alcohol 8 (80% yield) in
subsequent treatment of the reaction mixture with
2-phenylpropanal (1.2 equiv) at -85 °C (eq 4). Although
related organozincates 1 and 2 (M ) Zn, n ) 1), readily
generated by halogen/zinc exchange and zincation with
triorganozincates (R3ZnM′, M′ ) Li, MgX), undergo facile
1,2-migration at lower temperatures to give synthetically
versatile organozinc reagents with carbon-carbon bond
formation.4
Ate complexes 3 bearing a leaving at the remote
benzylic position would rearrange with carbon-carbon
bond formation to give benzylmetal 5 via (4-methylene-
an excess amount of Bu3ZnLi was employed in this
reaction, formation of the butylation product, 1-phenyl-
3-heptanol, was not detected, indicating the higher
reactivity of the benzyl moiety in zinc reagent 5a .7
Treatment of 6 with Bu3ZnLi (2.0 equiv) at -85 °C for
20 min and the hydrolysis of the mixture at this tem-
perature gave benzyl mesylate in 84% yield. The result
shows that the iodine/zinc exchange reaction9 proceeds
smoothly at -85 °C, giving rise to arylzincate intermedi-
ate 3 (M ) Zn, n ) 1, R ) Bu), which is stable at this
temperature. Upon warming to -40 °C, the arylzincate
may undergo 1,2-migration to give benzylzinc 5a (R )
Bu) via intermediate 4 (M ) Zn, n ) 1, R ) Bu). When
the reaction mixture was allowed to warm to rt, 5a (R )
(1) (a) Knochel, P. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 4, pp 865-
911. (b) Suzuki, M.; Yanagisawa, A.; Noyori, R. J . Am. Chem. Soc.
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Brown, H. C. Organic Synthesis via Boranes; Wiley-Interscience: New
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istry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon
Press: Oxford, 1982; Vol. 5, p 255. (e) Pelter, A.; Smith, K.; Brown,
H. C. Borane Reagents; Academic Press: London, 1988. (f) Matteson
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dran, P. V. Pure Appl. Chem. 1994, 66, 201. (h) J adhav, P. K.; Man,
H.-W. J . Am. Chem. Soc. 1997, 119, 846.
(3) For 1,2-migration of other ate complexes see: (a) Negishi, E.;
Akiyoshi, K. J . Am. Chem. Soc. 1988, 110, 646. (b) Negishi, E.;
Akiyoshi, K.; O’Connor, B.; Takagi, K.; Wu, G. J . Am. Chem. Soc. 1989,
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K. J . Am. Chem. Soc. 1989, 111, 2363. (e) Stocks, M.; Kocienski, P.;
Donald, K. K. Tetrahedron Lett. 1990, 31, 1637. (f) Knochel, P.; J eong,
N.; Rozema, M. J .; Yeh, M. C. P. J . Am. Chem. Soc. 1989, 111, 6474.
(g) AchyuthaRao, S.; Rosema, M. J .; Knochel, P. J . Org. Chem. 1993,
58, 2694. (h) Miller, J . A. J . Org. Chem. 1989, 54, 998. (i) Kakiya,
H.; Inoue, R.; Shinokubo, H.; Oshima, K. Tetrahedron Lett. 1997, 38,
3275.
(5) Lithium trialkylzincates R3ZnLi were prepared by treatment of
RLi (3 equiv) with anhydrous ZnCl2 in THF at 0 °C.4b
(6) The temperature -85 °C is not critical. A similar result was
obtained at -78 °C. Authors use a Neslab Cryocool CC-100 immersion
cooler in performing low-temperature reactions.
(7) Assuming a rapid ligand transfer,8 the initially formed benzylzinc
(L ) Bu) should react reversibly with Bu3ZnLi to form the correspond-
ing benzylzincate (Zn(L) ) Zn(Bu)2Li).
(8) (a) Seitz, L. M.; Brown, T. L. J . Am. Chem. Soc. 1966, 88, 4140.
(b) Seitz, L. M.; Brown, T. L. J . Am. Chem. Soc. 1967, 89, 1602. (c)
Seitz, L. M.; Little, B. F. J . Organomet. Chem. 1969, 18, 227.
(9) Y. Kondo, N. Takezawa, C. Yamazaki, and T. Sakamoto, J . Org.
Chem. 1995, 59, 4717.
(4) (a) Harada, T.; Hara, D.; Hattori, K.; Oku, A. Tetrahedron Lett.
1988, 29, 3821-3824. (b) Harada, T.; Katsuhira, T.; Osada, A.;
Iwazaki, K.; Maejima, R.; Oku, A. J . Am. Chem. Soc. 1996, 118, 11377
and references therein.
S0022-3263(97)01615-0 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 26, 1997 8967
Ta ble 1. Gen er a tion a n d Rea ction of Ben zylzin c
Tributylzincate prepared from BuMgBr (3 equiv) and
ZnCl2 can also be used albeit with lower efficiency (Table
1, entry 3). The reaction of s-Bu3ZnLi and t-Bu3ZnLi
afforded the corresponding p-substituted benzylzinc re-
agents, which further reacted with isobutyraldehyde to
give the corresponding adducts (entries 4 and 5). The
reaction of Me3ZnLi, however, gave 4,4′-dimethylbibenzyl
as a major product but not the corresponding product
(entry 6).10 The benzylzinc reagents reacted successfully
not only with aldehydes but also with ketones, acyl
chlorides, tosyl cyanide,12,13 and chlorodimethylphenyl-
silane (entries 7-12). It should be noted that, in acyla-
tion, the formation of tert-alcohols derived from further
reaction of the benzylzinc to the product ketones was not
detected.
Rea gen tsa
Because secondary benzyl mesylates are unstable and
difficult to handle, the reaction of stable phosphate 11
was examined. The reaction with Bu3ZnLi at tempera-
tures from -85 to 0 °C gave dibutylation products 12 in
85% yield. The secondary benzylzinc reagent is more
reactive, and the formation of 12 was not completely
retarded even at -40 °C. Nevertheless, the secondary
zinc can be used in the reaction with other electrophiles
under Barbier conditions. Thus, the reaction of phos-
phate 11 and Bu3ZnLi in the presence of allyl bromide
(3 equiv) at temperatures from -85 to 0 °C afforded the
corresponding adducts 13 (74%) and 14 (65%), respec-
tively.
In summary, we have shown that arylzincates bearing
a remote leaving group at the benzylic position undergo
a facile 1,2-migration to give homologated benzylzinc
reagents. The zinc reagents reacted efficiently with a
variety of electrophiles. The overall reaction serves as a
useful one-pot method for the synthesis of p-substituted
benzene derivatives.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedure including synthesis and characterization of new com-
pounds (17 pages).
Bu) reacted with iodobutane, generated in situ by iodine/
zinc exchange, to give p-butylpentylbenzene in 57% yield.
Support for the 1,2-migration mechanism was obtained
in the reaction of m-iodobenzyl mesylate (9) with Bu3-
ZnLi at temperatures from -85 to -40 °C (eq 5).
Formation of benzyl mesylate (71%) shows the stability
of m-substituted arylzincate 10 at higher temperatures.
J O971615Q
(10) Me3ZnLi did not react with 6 at -85 °C. Owing to the lower
reactivity,11 iodine/zinc exchange and subsequent 1,2-migration took
place simultaneously at higher temperatures. The dimeric product was
most probably produced by the coupling reaction of 4-methylbenzylzinc
reagent with 4-methylbenzyl iodide, which is formed in situ by iodine/
zinc exchange of 6 with the benzylzinc reagent.
(11) Harada, T.; Katsuhira, T.; Hara, D.; Kotani, Y.; Maejima, K.;
Kaji, R.; Oku, A. J . Org. Chem. 1993, 58, 4897.
(12) It was reported that benzylzinc bromide reacts with tosyl
cyanide exclusively at the ortho position to give 2-methylbenzonitrile.13
Formation of this regioisomeric product was not observed in the present
reaction.
(13) Klement, I.; Lennick, K.; Tucker, C. E.; Knochel, P. Tetrahedron
Lett. 1993, 34, 4623.