by the availability of benzylic halides, which are not always
stable and easy to handle and, hence, not suitable for the
production of large numbers of molecules in a combinatorial
way.3
Scheme 2. Synthetic Strategy toward Diarylmethanes through
Sequential Pd-Catalyzed Cross-Coupling Reactions
We envisioned that a mixed gem-dimetalmethane
(MCH2M′)4,5 would be a suitable coupling platform for a
general and straightforward synthesis of diarylmethanes if
selective arylation at each of the carbon-metal bonds could
be realized using Pd-catalyzed cross-coupling chemistry
(Scheme 1).6 However, to our knowledge, such a straight-
forward strategy has not been reported for the preparation
of diarylmethanes.
During our recent program using a dimethyl(2-pyridyl)-
silyl (2-PyMe2Si) group as a removable directing group,7-9
we developed several 2-PyMe2Si-based mixed gem-dimetal-
methanes such as silylmethyllithium,10 silylmethylmagne-
sium,11 and silylmethylstannane.12 We envisaged that 2-PyMe2-
SiCH2SnBu3 (1) should be particularly suitable as a platform
for diarylmethane synthesis because of its practical advan-
tages: (i) stable to air and moisture,13 (ii) storable, and (iii)
easy to prepare (two steps from 2-bromopyridine) in a large
scale (>10 g).12 In this communication, we report the use
of 1 as an excellent mixed gem-dimetalmethane for the
preparation of diarylmethanes through sequentially integrated
Pd-catalyzed cross-coupling reactions with aryl iodides
(Scheme 2). Advantageous features of our strategy are that
(i) because of the reactivity difference of two carbon-metal
bonds (C-Sn vs C-Si), selective and stepwise arylations
should be possible, and (ii) because both of the aryl groups
of diarylmethane structure stem from readily available aryl
iodides (more than 20 000 aryl iodides are commercially
available), the synthesis becomes sufficiently diversity-
oriented (Scheme 2).14
Although it has been well-known that silylmethylstannanes
are unreactive15 toward cross-coupling reaction (Migita-
Kosugi-Stille coupling),16 we have established that a (2-
pyridyl)silylmethylstannane such as 1 undergoes Pd-cata-
lyzed cross-coupling reaction with aryl iodide 2 (step 1 in
Scheme 2) presumably due to the pyridyl-to-palladium
coordination effect in the transmetalation step.12 Therefore,
the second cross-coupling reaction (Hiyama coupling, step
2 in Scheme 2)17 is the initial focal point of our campaign
toward diarylmethane synthesis.
Although we have already reported that the cross-coupling
reactions of alkenyl(2-pyridyl)silanes with aryl iodides are
efficiently catalyzed by PdCl2(PhCN)2/TBAF18 system,7b we
had several concerns in our mind prior to the investigation
described herein. (i) If we are conducting the second cross-
coupling (cross-coupling using benzylic silanes) under the
mechanism similar to that used for alkenyl(2-pyridyl)silanes
(cross-coupling proceeds through the intermediacy of silanol
with quantitative removal of pyridyl group from silicon), the
protonation of benzylic group must be slower than the
transmetalation and the protonation of pyridyl group. Oth-
erwise, it will end up in exclusive protodesilylation. (ii)
Judging from the paucity in the literature, a benzylic group
might be more difficult to transfer from silicon to palladium
(and then to coupling product) than other common transfer
groups such as aryl, alkenyl, alkynyl, and allyl groups.19 (iii)
If the above-mentioned concerns were found to be the case,
alternative activation of the ArCH2-SiMe2Py bond must be
developed.
(3) For an excellent approach toward a diarylmethane library: Vanier,
C.; Lorge´, F.; Wagner, A.; Mioskowski, C. Angew. Chem., Int. Ed. 2000,
39, 1679.
(4) For excellent reviews on gem-dimetalmethane: (a) Marek, I.;
Normant, J. F. Chem. ReV. 1996, 96, 3241. (b) Normant, J. F. Acc. Chem.
Res. 2001, 34, 640.
(5) For selected examples: (a) Knochel, P. J. Am. Chem. Soc. 1990,
112, 7431. (b) Zheng, B.; Srebnik, M. J. Org. Chem. 1995, 60, 486. (c)
Nakamura, M.; Hara, K.; Hatakeyama, T.; Nakamura, E. Org. Lett. 2001,
3, 3137. (d) Matsubara, S.; Oshima, K.; Utimoto, K. J. Organomet. Chem.
2001, 617-618, 39. (e) Shimizu, M.; Kurahashi, T.; Hiyama, T. J. Synth.
Org. Chem. Jpn. 2001, 59, 1062.
(6) Metal-Catalyzed Cross-coupling Reactions; Diederich, F., Stang, P.
J., Eds.; Wiley-VCH: New York, 1998.
(7) (a) Itami, K.; Mitsudo, K.; Kamei, T.; Koike, T.; Nokami, T.; Yoshida,
J. J. Am. Chem. Soc. 2000, 122, 12013. (b) Itami, K.; Nokami, T.; Yoshida,
J. J. Am. Chem. Soc. 2001, 123, 5600. (c) Itami, K.; Koike, T.; Yoshida, J.
J. Am. Chem. Soc. 2001, 123, 6957. (d) Itami, K.; Nokami, T.; Ishimura,
Y.; Mitsudo, K.; Kamei, T.; Yoshida, J. J. Am. Chem. Soc. 2001, 123, 11577.
(e) Itami, K.; Mitsudo, K.; Nokami, T.; Kamei, T.; Koike, T.; Yoshida, J.
J. Organomet. Chem. 2002, 653, 105. (f) Itami, K.; Mitsudo, K.; Yoshida,
J. Angew. Chem., Int. Ed., in press.
(8) 2-PyMe2Si group can also be used as a phase tag for acid/base
extraction. Yoshida, J.; Itami, K. J. Synth. Org. Chem. Jpn. 2001, 59, 1086.
(9) For the use of a removable directing group in metal-catalyzed
reactions, see: (a) Evans, D. A.; Fu, G. C.; Hoveyda, A. H. J. Am. Chem.
Soc. 1988, 110, 6917. (b) Breit, B. Eur. J. Org. Chem. 1998, 1123. (c) Jun,
C. H.; Lee, H. J. Am. Chem. Soc. 1999, 121, 880. (d) Buezo, N. D.; de la
Rosa, J. C.; Priego, J.; Alonso, I.; Carretero, J. C. Chem. Eur. J. 2001, 7,
3890. (e) Ko, S.; Na, Y.; Chang, S. J. Am. Chem. Soc. 2002, 124, 750.
(10) (a) Itami, K.; Kamei, T.; Mitsudo, K.; Nokami, T.; Yoshida, J. J.
Org. Chem. 2001, 66, 3970. (b) Itami, K.; Nokami, T.; Yoshida, J.
Tetrahedron 2001, 57, 5045.
(14) Schreiber, S. L. Science 2000, 287, 1964.
(15) Echavarren, A. M.; Stille, J. K. J. Am. Chem. Soc. 1987, 109, 5478.
For an exception: Vedejs, E.; Haight, A. R.; Moss, W. O. J. Am. Chem.
Soc. 1992, 114, 6556.
(16) Mitchell, T. N. in ref 6, Chapter 4.
(17) For early works: (a) Yoshida, J.; Tamao, K.; Yamamoto, H.; Kakui,
T.; Uchida, T.; Kumada, M. Organometallics 1982, 1, 542. (b) Hatanaka,
Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918. (c) Tamao, K.; Kobayashi,
K.; Ito, Y. Tetrahedron Lett. 1989, 30, 6051. For reviews: (d) Hatanaka,
Y.; Hiyama, T. Synlett 1991, 845. (e) Hiyama, T. in ref 6, Chapter 10. (f)
Hiyama, T.; Shirakawa, E. Top. Curr. Chem. 2002, 219, 61. For selected
recent examples: (g) Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999,
121, 5821. (h) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 1684.
(i) Hirabayashi, K.; Mori, A.; Kawashima, J.; Suguro, M.; Nishihara, Y.;
Hiyama, T. J. Org. Chem. 2000, 65, 5342. (j) Lee, H. M.; Nolan, S. P.
Org. Lett. 2000, 2, 2053. (k) ref 7b. (l) Denmark, S. E.; Sweis, R. F. J. Am.
Chem. Soc. 2001, 123, 6439. (m) Hosoi, K.; Nozaki, K.; Hiyama, T. Chem.
Lett. 2002, 138. (n) Denmark, S. E.; Sweis, R. F. Acc. Chem. Res. 2002,
35, 835.
(11) Itami, K.; Mitsudo, K.; Yoshida, J. Angew. Chem., Int. Ed. 2001,
40, 2337.
(12) Itami, K.; Kamei, T.; Yoshida, J. J. Am. Chem. Soc. 2001, 123,
8773.
(13) No detectable decomposition of 1 has been observed after extended
(>1 month) exposure to air.
(18) Abbreviations: TBAF ) tetrabutylammonium fluoride. TASF )
tris(diethylamino)sulfonium difluorotrimethylsilicate.
(19) In the literature, there is only one specific example of benzylic group
transfer from silicon in a cross-coupling reaction. Hatanaka, Y.; Hiyama,
T. J. Am. Chem. Soc. 1990, 112, 7793.
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