C O M M U N I C A T I O N S
Table 1. Catalytic Arylation of Substrate 5 (Selected Data)
of generally more reactive C-H bonds (OCH3, SCH3, arene C-H
bonds) were detected. Also, it seems that the alkyl group must be
of sufficient steric bulk (tBu versus iPr) for the reaction to proceed.
At the same time, the arylation/alkenylation products (cf. 6, 12)
apparently already exceeded the optimal steric requirement and did
not undergo subsequent functionalization.14 Remarkably, the cy-
clized isomer 13 did in fact undergo the second arylation, albeit at
a slower rate as compared to that of 11.
Pd(OAc)2
mol %
Ph-Ph
(%)
PhOAc
(%)
silanol
yield %
TON
In summary, a new system for the catalytic arylation and
alkenylation of alkane segments has been developed. The ortho-
tert-butylaniline substrates and 2-pivaloylpyridine may be arylated
and alkenylated on the tert-butyl group, while no functionalization
occurred at more reactive C-H and other bonds. We hypothesize
that the high selectivity of this system stems from the confluence
of the directing effect of the Schiff base or pyridine moiety and
the unique reactivity properties of a phenyl-palladium acetate
species (Ph-Pd-OAc‚Ln).
PhSi(OH)Me2
Ph2Si(OH)Me
PhSi(OH)2Me
PhSi(OMe)3
2.5
2.5
2.5
2.5
33
51
20
31
13
20
8
5
<1
8
5
<1
4
12
4
<1
Table 2. Catalytic Arylation and Alkenylation of Selected
Substratesa
Acknowledgment. Funding was provided by the National
Institute of Health (NIGMS: R01 GM60326) and GlaxoSmithKline.
D.S. is a recipient of the Cottrell Scholar Award of Research Corp.,
Alfred P. Sloan Fellowship, and the Camille Dreyfus Teacher-
Scholar Award. We gratefully acknowledge Dr. Brian D. Dangel
(experimental and intellectual assistance), Dr. J. B. Schwarz
(editorial assistance), and Vitas Votier Chmelar (intellectual
contribution).
Supporting Information Available: Experimental procedures,
preparation, and spectral data for compounds 1, 4-14 (PDF). This
a Conditions: substrate (c ) 0.02 M) in DMF, silanol (2 equiv), Pd(OAc)2
(4 mol %), benzoquinone (4 mol %), Cu(OAc)2 (2 equiv), 100 °C. The
alkenylation reactions also yielded a side product (PhCHdCH)2 in 10%
yield.
References
(1) Davies, H. M. L.; Hansen, T.; Churchill, M. R. J. Am. Chem. Soc. 2000,
122, 3063-3070.
(2) (a) Miura, M.; Nomura, M. Top. Curr. Chem. 2002, 219, 211-241. (b)
Yonehara, F.; Kido, Y.; Morita, S.; Yamaguchi, M. J. Am. Chem. Soc.
2001, 123, 11310-11311.
Scheme 2. Tandem Alkenylation-Arylation of tert-Butyl Groupa
(3) (a) Kakiuchi, F.; Murai, S. In ActiVation of UnreactiVe Bonds and Organic
Synthesis; Murai, S., Ed.; Springer: Berlin, 1999; pp 47-79. (b) Jia, C.;
Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633-639.
(4) (a) Cho, J.-Y.; Tse, M. N.; Holmes, D.; Maleczka, R. E.; Smith, M. R.,
III. Science 2002, 295, 305-308. (b) Ishiyama, T.; Takagi, J.; Ishida, K.;
Miyaura, N.; Anastasi, N. R.; Hartwig, J. F. J. Am. Chem. Soc. 2002,
124, 390-391. For catalytic borylation of alkanes, see: Chen, H.; Schlecht,
S.; Semple, T. C.; Hartwig, J. F. Science 2000, 287, 1995-1997.
(5) (a) Corey, E. J.; Hertler, W. R. J. Am. Chem. Soc. 1958, 80, 2903-2904.
(b) Buchschacher, P.; Kalvoda, J.; Arigoni, D.; Jeger, O. J. Am. Chem.
Soc. 1958, 80, 2905-2906. (c) Barton, D. H. R.; Beaton, J. M. J. Am.
Chem. Soc. 1961, 83, 4083-4089. (d) Breslow, R.; Baldwin, S.; Flechtner,
T.; Kalicky, P.; Liu, S.; Washburn, W. J. Am. Chem. Soc. 1973, 95, 3251-
3262. (e) Corey, E. J.; Felix, A. M. J. Am. Chem. Soc. 1965, 87, 2518-
2519. (f) Taber, D. F.; Stribia, S.-E. Chem.-Eur. J. 1998, 4, 990-992.
(6) Johnson, J. A.; Li, N.; Sames, D. J. Am. Chem. Soc. 2002, 124, 6900-
6903.
a Conditions: (a) Pd(OAc)2 (4 mol %), benzoquinone (4 mol %),
Cu(OAc)2 (2 equiv), DMF, 100 °C, 66%. (b) MeSO3H, CH2Cl2, 52%. (c)
Pd(OAc)2 (8 mol %), benzoquinone (8 mol %), Cu(OAc)2 (2 equiv), DMF,
100 °C, 45% of 14 (4:1 ratio of diastereomers). Configuration of the major
isomer has not been determined. R ) o-MeSC6H4.
(7) Dangel, B. D.; Godula, K.; Youn, S. W.; Sezen, B.; Sames, D. J. Am.
Chem. Soc. 2002, 124, 11856-11857.
(8) (a) Dieck, H. A.; Heck, R. F. J. Org. Chem. 1975, 40, 1083-1090. (b)
Moreno-Man˜as, M.; Pe´rez, M.; Pleixats, R. J. Org. Chem. 1996, 61, 2346-
2351.
(9) Hirabayashi, K.; Ando, J.; Kawashima, J.; Nishihara, Y.; Mori, A.; Hiyama,
T. Bull. Chem. Soc. Jpn. 2000, 73, 1409-1417.
(10) Denmark, S. E.; Sweis, R. F. J. Am. Chem. Soc. 2001, 123, 6439-6440.
(11) For intramolecular functionalization of a tert-butyl group, see: (a) Dyker,
G. Angew. Chem., Int. Ed. Engl. 1994, 33, 103-105. (b) Laaziri, H.;
Bromm, L. O.; Lhermitte, F.; Gschwind, R. M.; Knochel, P. J. Am. Chem.
Soc. 1999, 121, 6940-6941.
ation at the t-butyl group. However, the Schiff base derived from
ortho-i-propylaniline yielded no desired material, biphenyl (22%)
being the major detected product (Supporting Information).
A concise synthesis of compound 14, depicted in Scheme 2,
demonstrated the synthetic power of the new methodology, and
simultaneously revealed both the remarkable selectivity as well as
the limitations of this system. Substrate 11 was converted to
complex product 14 in three steps via catalytic alkenylation of 11,
Friedel-Crafts cyclization, and finally catalytic arylation. Thus,
tandem alkenylation-arylation of the tert-butyl group provided a
product of considerable complexity via a novel bond construction
strategy. It is of note that no products originating from the activation
(12) Formation of putative intermediate 3 (and ultimately product 4) may occur
via an alternative route wherein the cyclopalladation takes place first,
followed by transmetalation (the order of steps 1 and 2 is reversed, Figure
2). This was ruled out as the corresponding palladacycle acetate (not
shown) did not afford the product under reaction conditions.
(13) In addition to the desired products and biphenyl, there were no other
products formed. The starting material was recovered to yield a satisfactory
mass balance (∼90%).
(14) It is also conceivable that the double bond or phenyl ring of the product
coordinates to the metal, thus preventing subsequent functionalization.
JA027891Q
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J. AM. CHEM. SOC. VOL. 124, NO. 45, 2002 13373