N-Heterocyclic NCN-Pincer Palladium Complexes: A Source for General, Highly Efficient Catalysts in Heck, Suzuki, and Sonogashira Coupling Reactions

Abstract

Readily available NCN-pincer palladium complexes comprising two pyrazole units as the source of both N-donor atoms are successfully employed as catalysts in a range of C-C bond-forming reactions. Good to excellent results are obtained in all cases regardless of the electronic nature of the substrates, along with more convenient procedures and comparatively much lower catalysts loadings in Suzuki and Sonogashira couplings. This paper presents the first report of a Sonogashira coupling reaction by means of a NCN catalyst.

palladacycles - catalysis - pincer complexes - cross-coupling

References

1 For a review, see: Metal-Catalyzed Cross-Coupling Reactions   2nd ed.:  De Meijere A. Diederich F. Wiley-VCH; Weinheim: 2004. 

See, for example:

2a DeVasher RB. Moore LR. Shaughnessy KH. J. Org. Chem.  2004,  69:  7919 

2b Braunstein P. J. Organomet. Chem.  2004,  689:  3953 

2c Van de Weghe P. Lett. Org. Chem.  2005,  2:  113 

3a Hernández S. SanMartin R. Tellitu I. Domínguez E. Org. Lett.  2003,  5:  1095 

3b Churruca F. SanMartin R. Tellitu I. Domínguez E. Eur. J. Org. Chem.  2005,  2481 

For a review on the use of pincer complexes, see:

4a Singleton JT. Tetrahedron  2003,  59:  1837 

4b See also: Beletskaya IP. Cheprakov AV. J. Organomet. Chem.  2004,  689:  4055 

The synthesis and properties of several NCN-pincer palladium complexes have been described in:

4c Rietveld MHP. Grove DM. van Koten G. New J. Chem.  1997,  21:  751 

4d Dijkstra HP. Slagt MQ. McDonald A. Kruithof CA. Kreiter R. Mills AM. Lutz M. Spek AL. Klopper W. van Klink GPM. van Koten G. Eur. J. Inorg. Chem.  2003,  830 

4e Slagt MQ. van Zwieten DAP. Moerkerk AJCM. Gebbink RJMK. van Koten G. Coord. Chem. Rev.  2004,  248:  2275 

4f Takenaka K. Minakawa M. Uozomi Y. J. Am. Chem. Soc.  2005,  127:  12273 

There is discussion about the real role of pincer complexes in palladium-catalyzed reactions, as their decomposition to generate Pd(0) in several Heck reaction conditions is well documented. See, for example:

4g Sommer WJ. Yu K. Sears JS. Ji Y. Zheng X. Davis RJ. Sherill CD. Jones CW. Weck M. Organometallics  2005,  24:  4351 

4h Olsson D. Nilsson P. El Masnaouy M. Wendt OF. Dalton Trans.  2005,  1924 

4i Bergbreiter DE. Osburn PL. Frels JD. Adv. Synth. Catal.  2005,  347:  172 

5a Najera C. Gil-Moltó J. Karlström S. Falvello LR. Org. Lett.  2003,  5:  1451 

5b Iyer S. Jayanthi A. Synlett  2003,  1125 

5c Wang A.-E. Xie J.-H. Wang L.-X. Zhou Q.-L. Tetrahedron  2005,  61:  259 

6a CNC: Loch JA. Albrecht M. Peris E. Mata J. Faller J. Crabtree RH. Organometallics  2002,  21:  700 

6b PCP: Lee HM. Zeng JY. Hu C.-H. Lee M.-T. Inorg. Chem.  2004,  43:  6822 

6c SCS: Zim D. Grubber AS. Ebeling G. Dupont J. Monteiro AL. Org. Lett.  2000,  2:  2881 

The application of such NCN-palladacycles in Heck coupling is restricted to the following reports:

7a Magill AM. McGuiness DS. Cavell KJ. Britovsek GJP. Gibson VC. White AJP. Williams DJ. White AM. J. Organomet. Chem.  2001,  617-618:  546 

7b Díez-Barra E. Guerra J. Hornillos V. Merino S. Tejeda J. Organometallics  2003,  22:  4610 

7c Jung IG. Son SU. Park KH. Chung K.-C. Lee JW. Chung YK. Organometallics  2003,  22:  4715 

7d We found only two reports that use the above-mentioned heterocyclic NCN-pincers in the Suzuki reaction: Gupta AK. Rim CY. Oh CH. Synlett  2004,  2227 ; see also ref. 7a

8 Hartshorn CM. Steel PJ. Organometallics  1998,  17:  3487 . In our case, overall yield of complexes 2a-b starting from commercially available 1,3-bis(bromomethyl)-1-methylbenzoate (3) was 90-95%

9 Abe T, Matsunaga H, Mihira A, Sato C, Ushirogochi H, Sato K, Takasaki T, Venkatesan AM, and Mansour TS. inventors; U.S. Patent  US2004132708.  ; Chem. Abstr. 2004, 141, 106320

10 Liu P. Chen Y. Deng J. Tu Y. Synthesis  2001,  2078 

11

2a: white powder, mp >300 °C (EtOAc). FTIR (neat film): 1714, 1592, 1510, 1412 cm^-1. ¹H NMR (500 MHz, DMSO): δ = 3.83 (3 H, s, CH₃), 5.55 (4 H, s, CH₂), 6.46 (2 H, dd, J = 2.0, 1.6 Hz, H-4′), 7.70 (2 H, s, H2, H-6), 7.92 (2 H, d, J = 1.6 Hz, H-5′), 8.14 (2 H, d, J = 2.1 Hz, H-3′). ¹³C NMR (63 MHz, DMSO): δ = 52.1 (CH₃), 56.7 (CH₂), 106.6 (C-4′), 125.9 (C-2, C-6), 126.4 (C-1), 133.1 (C-5′), 137.2 (C-3, C-5), 143.2 (C-3′), 150.7 (C-4), 166.2 (CO). Anal. calcd for C₁₆H₁₅ClN₄O₂Pd: C, 43.96; H, 3.46; N, 12.82. Found: C, 43.93; H, 3.48; N, 12.83.
2b: white powder, mp >300 °C (EtOAc). FTIR (neat film): 1702, 1590, 1549, 1425 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 2.34 (6 H, s, C5′-CH₃), 2.61 (6 H, s, C3′-CH₃), 3.87 (3 H, s, COOCH₃), 4.95 (2 H, d, J 14.1 Hz, CHaHb), 5.66 (2 H, d, J = 14.1 Hz, CHaHb), 5.82 (2 H, s, H-4′), 7.58 (2H, s, H-2, H-6). ¹³C NMR (63 MHz, CDCl₃): δ = 11.7 (C-5′CH₃), 15.5 (C-3′CH₃), 52.0 (COOCH₃), 54.1 (CH₂), 107.1 (C-4′), 125.5 (C-2, C-6), 126.3 (C-1), 137.3 (C-3, C-5), 140.4 (C-5′), 152.5 (C-3′), 154.6 (C-4), 166.8 (CO). Anal. calcd for C₂₀H₂₃ClN₄O₂Pd: C, 48.70; H, 4.70; N, 11.36. Found: C, 48.74; H, 4.67; N, 11.35.

12

General procedure: A dry 5-mL round-bottom flask was charged with aryl bromide (1 mmol), alkene (1.5 mmol), catalyst 2 (0.001 mmol Pd), and anhyd DMF (1 mL). The mixture was stirred at 140 °C under argon for 18 h. After cooling, H₂O (10 mL) was added, and the aqueous layer was extracted with EtOAc (3 × 10 mL). The combined organic extracts were dried over anhyd Na₂SO₄ and evaporated in vacuo. The residue was dissolved in CDCl₃ and analyzed by ¹H NMR and ¹³C NMR spectroscopy [bis(ethylene glycol) dimethyl ether as an internal standard]; the identity of every product was confirmed by comparison with spectroscopic data in the literature.

The range of assays performed was based on the following reports, basically replacing the employed catalysts by palladacycles 2, see:

13a Alo BI. Kandil A. Patil PA. Sharp MJ. Siddiqui MA. Snieckus V. Josephy PD. J. Org. Chem.  1991,  56:  3763 

13b Müller W. Lowe DA. Neijt H. Urwyler S. Herrling PL. Blaser D. Seebach D. Helv. Chim. Acta  1992,  75:  855 

13c Coleman RS. Grant EB. Tetrahedron Lett.  1993,  34:  2225 

13d Shieh W.-C. Carlson JA. J. Org. Chem.  1992,  57:  379 

13e Wallow TI. Novak BM. J. Org. Chem.  1994,  59:  5034 

13f Marck G. Villiger A. Buchecker R. Tetrahedron Lett.  1994,  35:  3277 

13g Watanabe T. Miyaura N. Suzuki A. Synlett  1992,  207 

13h Kelly TR. García A. Lang F. Walsh JJ. Bhaskar KV. Boyd MR. Götz R. Keller PA. Walter R. Bringmann G. Tetrahedron Lett.  1994,  35:  7621 

14 Similar reaction conditions employing a silica-supported tetradentate NHC catalyst were performed by: Zhao Y. Zhou Y. Ma D. Liu J. Li L. Zhang TY. Zhang H. Org. Biomol. Chem.  2003,  1:  1643 

15

General procedure: A 5-mL round-bottom flask was charged with ArBr (1 mmol), ArB(OH)₂ (1.5 mmol), catalyst 2 (0.001 mmol Pd), K₂CO₃ (2 mmol), and H₂O (1 mL). The mixture was stirred at 100 °C in air for 2 h. After cooling, Na₂CO₃ (5 mL of 10% solution in water) was added, and the aqueous layer was extracted with CH₂Cl₂ (2 × 5 mL). The combined organic extracts were dried over anhyd Na₂SO₄ and evaporated in vacuo. The residue was dissolved in CDCl₃ and analyzed by ¹H NMR spectroscopy [using bis(ethylene glycol) dimethyl ether as an internal standard]; the identity of every product was confirmed by comparison with spectroscopic data in the literature.

NCN-, PCP-, CNC-, and NCP-pincer complexes have been used as catalysts in Suzuki coupling reactions, TON values varying from 20 to 177500, see:

16a Bedford RB. Draper SM. Scully PN. Welch SL. New J. Chem.  2000,  24:  745 

16b Steel PG. Teasdale CWT. Tetrahedron Lett.  2004,  45:  8977 

16c Rosa GR. Ebeling G. Dupont J. Monteiro AL. Synthesis  2003,  2894 

16d Vicente J. Abad J.-A. López-Serrano J. Jones PG. Nájera C. Botella-Segura L. Organometallics  2005,  24:  5044 ; see also ref. 6a, 6b, 7a, and 7d

17

A 5-mL round-bottom flask was charged with ArI (1 mmol), alkyne (1.5 mmol), catalyst 2 (0.001 mmol Pd), and pyrrolidine (2 mL). The mixture was stirred at 100 °C in air for 6 h. After cooling, the solvent was evaporated in vacuo. The residue was dissolved in CDCl₃ and analyzed by ¹H NMR spectroscopy [using bis(ethylene glycol) dimethyl ether as an internal standard]; the identity of every product was confirmed by comparison with spectroscopic data in the literature.

18

The highest value (80,000) was achieved by reaction of 4-chlorobenzene and 1-octyne in the presence of catalyst 2b (Table [3] , entry 14). When 0.01 mol% Pd was employed, 100% conversion and 80% yield for the corresponding 1-phenyloctyne were obtained; TOF = 4444.

To the best of our knowledge, three examples of Sonogashira coupling reactions catalyzed by palladium pincer complexes have been reported so far, exhibiting TON values of 20-100, see:

19a Eberhard MR. Wang Z. Jensen CM. Chem. Commun.  2002,  818 

19b Mas-Marzá E. Segarra AM. Claver C. Perisb E. Fernández E. Tetrahedron Lett.  2003,  44:  6595 ; see also ref. 6a