Homogeneous Catalysis DOI: 10.1002/anie.200604472 Palladium-Catalyzed2-PyridylmethylTransferfrom2-(2-Pyridyl)- ethanolDerivativestoOrganicHalidesbyChelation-AssistedCleavage ofUnstrainedC sp 3 À C sp 3 Bonds** Takashi Niwa, Hideki Yorimitsu,* and Koichiro Oshima* Transition-metal-catalyzed cleavage of carbon–carbon bonds is not only scientifically challenging but also potentially useful in organic synthesis. [1] Among the bond-breaking reactions, the cleavage of unstrained carbon–carbon bonds ranks as one of the most difficult processes because of the lack of sufficient strain energy as a driving force. Assistance by chelation is promising for the metal-mediated cleavage of such unstrained carbon–carbon bonds. [1d,f,2] However, it is always C sp 3 ÀC sp 2 [1d,f,2b,c] or C sp 2 ÀC sp 2 [2d] bonds that are cleaved. The kinetic as well as thermodynamic stability [1a–d] of C sp 3 ÀC sp 3 bonds has resulted in little being known about their chela- tion-assisted cleavage under catalytic conditions. [3] Here we report such an example: the palladium-catalyzed reactions of aryl and alkenyl chlorides with 2-(2-pyridyl)ethanol deriva- tives that result in the substitution of the chloro moieties with a 2-pyridylmethyl group. Treatment of chlorobenzene (2a) with pyridyl alcohol 1a in the presence of cesium carbonate and a palladium catalyst in refluxing xylene provided 2-benzylpyridine (3a) in good yield (Table 1, entry 1). Avariety of aryl chlorides underwent the reaction and the presence of either an electron-with- drawing or electron-donating group on the aryl chlorides did not hinder the reaction (Table 1, entries 2–5). Aryl chloride 2f with a methyl group at the 2-position also participated in the reaction (Table 1, entry 6). It is worth noting that the reaction of 4-chlorostyrene (2g) provided the desired product 3g selectively (Table 1, entry 7), even though 2g can com- petitively undergo repetitious Mizoroki–Heck reactions which lead to oligo(4-phenylenevinylene) through self-oligo- merization. [4] The synthesis of di(2-pyridyl)methane (3h) was also successful (Table 1, entry 8). The yield of 3a was slightly lower when the reaction with 2a was performed at a lower temperature (Table 1, entry 9). Aryl bromides and iodides also underwent the pyridylmethylation (Table 1, entries 10 and 11). Triphenylphosphine functioned as well as tricyclohexyl- phosphine as the catalyst in the reaction of iodobenzene in refluxing toluene, and resulted in 3a in being formed in 80% yield (Table 1, entry 12). The choice of palladium salt is crucial. Palladium trifluoroacetate proved to be the best precursor. The use of Pd(OAc) 2 , [Pd(acac) 2 ], PdCl 2 , [PdCl 2 (CH 3 CN) 2 ], [PdCl(p-allyl)] 2 , [Pd(PPh 3 ) 4 ] (with no additional ligand), and [Pd 2 (dba) 3 ] (acac = acetylacetanoate, dba = trans ,trans-dibenzylideneacetone) resulted in signifi- cantly lower yields of 73, 33, 15, 14, 20, 26, and 73%, respectively, relative to that obtained with P(cC 6 H 11 ) 3 (Table 1, entry 11). We have no clear reason for the differ- ence. Unfortunately, the reactions of alkyl chlorides failed to yield the corresponding products, and 1a was completely recovered. The reactions of benzyl chloride and allyl chloride afforded complex mixtures. The reaction of alkenyl chloride 2i yielded 2-prenylpyr- idine (3i ) in reasonable yield [Eq. (1)]. The high efficiency of Table 1: Palladium-catalyzed 2-pyridylmethyl transfer to aryl halides 2 from alcohol 1a. [a] Entry R X 2 3 Yield [b] [%] 1 H Cl 2a 3a 88 2 4-CF 3 Cl 2b 3b 89 3 4-COOEt Cl 2c 3c 80 4 4-CN Cl 2d 3d 70 5 4-OMe Cl 2e 3e 90 6 2-Me Cl 2f 3f 79 7 4-CH 2 =CH Cl 2g 3g 81 8 2-chloropyridine 2h 3h 50 (63) 9 H Cl 2a 3a 85 [c] 10 H Br 2a-Br 3a 80 [c] 11 H I 2a-I 3a 88 [c] 12 H I 2a-I 3a 80 [c,d] [a] A mixture of 1a (0.8 mmol), 2 (1.2 equiv), Pd(OCOCF 3 ) 2 (5 mol%), P(cC 6 H 11 ) 3 (10 mol%), and Cs 2 CO 3 (1.2 equiv) was heated at reflux in xylene (0.5 m) for 1.5–10 h. [b] Yield of isolated product. The yield determined by 1 H NMR spectroscopy is given in parentheses. [c] Per- formed in refluxing toluene. [d] PPh 3 was used instead of P(cC 6 H 11 ) 3 . [*] T. Niwa, Dr. H. Yorimitsu, Prof.Dr. K. Oshima Department of Material Chemistry Graduate School of Engineering Kyoto University Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510 (Japan) Fax: (+ 81)75-383-2438 E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp oshima@orgrxn.mbox.media.kyoto-u.ac.jp [**] This work was supported by Grants-in-Aid for Scientific Research from MEXT and the JSPS. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Angewandte Chemie 2643 Angew. Chem. Int. Ed. 2007, 46, 2643–2645 # 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim