Abstract
The palladium-catalyzed ureidation reaction of 2-chloropyridines can be regioselectively performed in good yield, with both aryl and aliphatic ureas, using xantphos as the ligand, Pd(OAc)2 as the source of palladium, NaOt -Bu/H2 O or NaOH/H2 O as the base, and dioxane as the solvent
Key words
palladium - catalysis - cross-coupling - pyridines - ureidation
References
1a Dahl BH, Christophersen P, Engsig MT, Karsdal MA, and Foged NT. inventors; PCT Int. Appl. WO, 2004022529.
1b Taylor CP, Price C, and Weber ML. inventors; US Patent, 6133299.
1c Michael RP.
Scandra JL.
Charles PT.
Fred MH.
David LM.
J. Med. Chem.
1990,
33:
54
1d Henrie RN. inventors; PCT Int. Appl., WO 8702665.
2a Honma T.
Hayashi K.
Aoyama T.
Hashimoto N.
Machida T.
Fukasawa K.
Iwama T.
Ikeura C.
Ikuta M.
Suzuki-Takashashi I.
Iwasawa Y.
Hayama T.
Nishimura S.
Morishima H.
J. Med. Chem.
2001,
44:
4515
2b Honma T.
Yoshizumi T.
Hashimoto N.
Hayashi K.
Kawanishi N.
Fukasawa K.
Takai T.
Ikeura C.
Ikuta M.
Suzuki-Takashashi I.
Hayama T.
Nishimura S.
Morishima H.
J. Med. Chem.
2001,
44:
4628
3 Chieng C.-H.
Leung M.-K.
Su J.-K.
Li G.-H.
Liu Y.-H.
Wang Y.
J. Org. Chem.
2004,
69:
1866
4 Yabuuchi K.
Marfo-Owusu E.
Kato T.
Org. Biomol. Chem.
2003,
1:
3464
5a Ling G.
Chen J.
Lu S.
J. Chem. Res., Synop.
2003,
442
5b Chen J.
Ling G.
Lu S.
Tetrahedron
2003,
59:
8251 ; and references cited therein
6 Gabriele B.
Salerno G.
Mancuso R.
Costa M.
J. Org. Chem.
2004,
69:
4741 ; and references cited therein
7a Hartwig JF.
Angew. Chem. Int. Ed.
1998,
37:
2046
7b Wolfe JP.
Wagaw S.
Marcoux JF.
Buchwald SL.
Acc. Chem. Res.
1998,
31:
805
8 Yin J.
Buchwald SL.
J. Am. Chem. Soc.
2002,
124:
6043
9 Rivas FM.
Giessert AJ.
Diver ST.
J. Org. Chem.
2002,
67:
1708
10 Hartwig JF.
Kawatsura M.
Hauck SI.
Shaughnessy KHM.
Alcaraz-Roman L.
J. Org. Chem.
1999,
64:
5575
11 Shakespeare WC.
Tetrahedron Lett.
1999,
40:
2035
12 Bolm C.
Hildebrand JP.
J. Org. Chem.
2000,
65:
168
13a Artamkina GA.
Sergeev AG.
Beletskaya IP.
Tetrahedron Lett.
2001,
42:
4381
13b Artamkina GA.
Sergeev AG.
Beletskaya IP.
Zh. Org. Khim.
2002,
38:
563
14 Sergeev AG.
Artamkina GA.
Beletskaya IP.
Tetrahedron Lett.
2003,
44:
4719
15 Ferraccioli R.
Carenzi D.
Synthesis
2003,
1383
16a Arterburn JB.
Corona C.
Rao KV.
Carlson KE.
Katzenellenbogen JA.
J. Org. Chem.
2003,
68:
7063
16b Urgaonkar S.
Nagarajan M.
Verkade JG.
Org. Lett.
2003,
5:
815
16c Maes BUW.
Loones KTJ.
Lemière GLF.
Dommisse RA.
Synlett
2003,
1822
16d Viciu MS.
Kelly RA.
Stevens D.
Naud F.
Studer M.
Nolan S.
Org. Lett.
2003,
5:
1479
16e Burton G.
Cao P.
Li G.
Rivero R.
Org. Lett.
2003,
5:
4373
16f Huang X.
Anderson KW.
Zim D.
Jiang L.
Klapars A.
Buchwald SL.
J. Am. Chem. Soc.
2003,
125:
6653
16g Urgaonkar S.
Xu J.-H.
Verkade JG.
J. Org. Chem.
2003,
68:
8416
16h Viciu MS.
Kissling RM.
Stevens ED.
Nolan SP.
Org. Lett.
2002,
4:
2229
16i Grasa GA.
Viciu MS.
Huang J.
Nolan SP.
J. Org. Chem.
2001,
66:
7729
16j Huang X.
Buchwald SL.
Org. Lett.
2001,
3:
3417
16k Harris MC.
Buchwald SL.
J. Org. Chem.
2000,
65:
5327
16l Stauffer SR.
Lee S.
Stambuli JP.
Hauck SI.
Hartwig JF.
Org. Lett.
2000,
2:
1423
16m Wagaw S.
Buchwald SL.
J. Org. Chem.
1996,
61:
7240
17 Abad A, Agulló C, Cuñat AC, Jiménez R, Navarro I, and Vilanova C. inventors; ES Patent, Appl. 200201347.
18 A preliminary account of this work was presented at the XXIX Reunión Bienal de la Real Sociedad Española de Química, July 7-11, 2003, Madrid, Spain (abstr. no. S1P1001).
19 Argabright PA.
Phillips BL.
J. Heterocycl. Chem.
1970,
7:
999
20 Takuzo H.
Chem. Pharm. Bull.
1981,
29:
3706
21 Other minor side-products observed with long reaction times were pyridin-2-ylamine and N ,N ′-dipyridin-2-yl urea, probably originating, as shown by independent control experiments, from disproportionation of the initially formed pyridin-2-yl urea 3a .
22 Yin J.
Zhao MM.
Huffman MA.
McNamara JM.
Org. Lett.
2002,
4:
3481
23 Arterburn JB.
Rao KV.
Ramdas R.
Dible BR.
Org. Lett.
2001,
3:
1351
24 Prashad M.
Mak XY.
Liu Y.
Repic O.
J. Org. Chem.
2003,
68:
1163
25 In fact, reaction of 3-chloropyridine with aniline [Pd(OAc)2 (3 mol%), xantphos (6 mol%), NaOt -Bu (1.4 equiv), H2 O (1.4 equiv), dioxane, 100 °C, 19 h] gave a 66% yield of N -phenyl-N ′(pyridin-3-yl)amine(7b ).
26 Appropriate experimental controls showed that nearly 70-80% of the urea 3c was transformed into a mixture of disproportionated products, mainly aniline, diphenylurea and 4-aminopyridine, when treated under the coupling reaction conditions (as in entry 6 of Table
[1
27 See ref.
[7a
28 Joncker THM.
Maes BUW.
Lemière GLF.
Dommisse R.
Tetrahedron
2001,
57:
7027
29 Danuta R.
Spectrosc. Lett.
1993,
26:
227
30 ScorŢanu E.
Hitruc EG.
Caraculacu AA.
Eur. Polym. J.
2003,
39:
1051
31a Cava MP.
Bhattacharyya NK.
J. Org. Chem.
1958,
23:
1287
31b Mougin F.
Mougin O.
Trecourt F.
Godard A.
Queguiner G.
Tetrahedron Lett.
1996,
37:
6696
32 Ife RJ.
Catchpole KW.
Durant GJ.
Ganellin CR.
Harvey CA.
Meeson ML.
Ewen DAA.
Parson ME.
Slingsby BP.
Theobald CJ.
Eur. J. Med. Chem.
1989,
24:
249
33 Kranenburg M.
van der Burgt YEM.
Kamer PCJ.
van Leeuwen PWNM.
Organometallics
1995,
14:
3081
34 Chen J.
Lu S.
Appl. Catal., A
2004,
261:
199
35 Chien C.-H.
Leung M.-K.
Su J.-K.
Li G.-H.
Liu Y.-H.
Wang Y.
J. Org. Chem.
2004,
69:
1866
36 Meigh J.-P.
Álvarez M.
Joule JA.
J. Chem. Soc., Perkin Trans. 1
2001,
2012
37 Takeda M, Inage M, Wada HI, Tamaki H, and Ochiai T. inventors; Eur Patent, 268229.
38a Günther H.
NMR Spectroscopy, An Introduction
John Wiley and Sons;
New York:
1980.
Chap V.
p.160-170
38b g NMR computer program was also used: Budzelaar PHM.
g NMR Computer Program
Cherwell Scientific Publishing;
Oxford UK:
2000.
