Angewandte
Chemie
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Although not yet investigated in detail, a-arylations of
ethyl cyanoacetate also occurred with substantially lower
catalyst loading than with our standard condition of 2 mol%
of [Pd2(dba)3]. As shown in entry 2 of Table 3, the reaction of
ethyl cyanoacetate with chlorobenzene occurred in 91% yield
with 1 mol% of palladium precursor at 908C.
In summary, we have described a solution to the long-
standing challenge of developing a general method for the
direct a-arylation of nitriles with aryl chlorides. With the
catalytic system generated from palladium and commercially
available 1b, it is now possible to effect direct a-arylation of a
wide variety of nitriles with a broad range of aryl chlorides.
[7] Aldrich and Fluka for 1a, 1b, 1c; Strem for 1b.
[8] For a recent review, see J. G. Verkade, Top. Curr. Chem. 2003,
233, 1 – 44.
[9] For discussions of the electronic structure of tris(alkylamino)-
phosphanes, see: a) A. H. Cowley, M. Lattman, P. M. Stricklen,
J. G. Verkade, Inorg. Chem. 1982, 21, 543 – 549; b) K. G. Molloy,
J. L. Petersen, J. Am. Chem. Soc. 1995, 117, 7696 – 7710; c) S. K.
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Received: May 22, 2003 [Z51954]
[10] An X-ray structural study of 1c showed that the bonding
environment around the PN3 nitrogen center is rather planar, the
sum of angles being 354.9, 356.6, and 357.58: A. E. Wroblewski,
J. Pinkas, J. G. Verkade, Main Group Chem. 1995, 1, 69 – 79.
[11] S. Urgaonkar, M. Nagarajan, J. G. Verkade, Tetrahedron Lett.
2002, 43, 8921 – 8924.
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[13] General experimental: A dried Schlenk flask equipped with a
magnetic stirring bar was charged with Pd(OAc)2 or [Pd2(dba)3]
(0.02–0.04 mmol) and KO-tBu (2.0 mmol) or NaN(SiMe3)2
(1.4 mmol) inside a nitrogen-filled glove box. The flask was
capped with a rubber septum and removed from the glove box.
Toluene or dioxane (2 mL), 1b (0.04–0.08 mmol in toluene or
dioxane (0.5–0.7 mL)) and aryl halide (1.0 mmol) were then
added successively. After stirring for 20 min at room temper-
ature, a nitrile (1.1 or 1.2 mmol) was added and the reaction
mixture was stirred under the conditions indicated in Tables 1–3.
The mixture was then quenched by addition of aqueous 1n HCl
and extracted with diethyl ether. The isolated organic phase was
dried over Na2SO4, filtered, concentrated in vacuo, and purified
by column chromatography on silica gel eluting with ethl
acetate/hexane or dichloromethane/hexane.
[14] Control experiments showed that either in the absence of a Pd
source or in the absence of proazaphosphatrane, no reaction was
observed.
[15] After screening a variety of bases (i.e., Na3PO4, K3PO4, Na2CO3,
Cs2CO3, NaH, NaN(SiMe3)2, KO-tBu, and NaO-tBu), we found
that NaN(SiMe3)2 gave the best results. In the presence of a
weaker base, such as Na3PO4, K3PO4, Na2CO3 or Cs2CO3, no
reaction was observed.
[16] A 1:2 palladium-to-ligand ratio gave faster reaction rates and
better product yields than a 1:1 ratio.
[17] a) C. Cativiela, M. D. Diaz-de-Villegas, J. A. Galvez, J. Org.
Chem. 1994, 59, 2497 – 2505; b) S. Abele, D. Seebach, Eur. J. Org.
Chem. 2000, 1 – 15; c) H. Brunner, P. Schmidt, Eur. J. Org. Chem.
2000, 2119 – 2133.
Keywords: a-arylation · homogeneous catalysis · nitriles ·
P ligands · palladium
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