Pd-Catalyzed Carbonylative Cross-coupling Reactions of Chloroarene-Cr(CO)₃ Complexes

Abstract

Palladium-catalyzed carbonylative cross-methylation reactions of different chloroarene-Cr(CO)₃ complexes employing an intramolecularly stabilized dimethylindium (III) reagent have been studied. The coupling products (acetophenone derivatives) were isolated in 43-96% yield under standard reaction conditions (5 mol% PdCl₂(PPh₃)₂, 50 °C, 5 atm CO-pressure in THF). Also, carbonylative Suzuki-coupling reactions of phenylboronic acid with different chloroarene-Cr(CO)₃ complexes afforded the corresponding benzophenone derivatives in 48-78% yield under comparable conditions in the presence of potassium carbonate as a base.

Key words

arene-chromium complexes - indium(III) - palladium - catalysis - carbonylation - cross-coupling - Suzuki-coupling

References

• Selected overviews:
• 1a Schmalz H.-G. Siegel S. In Transition Metals for Organic Synthesis   Vol. 1:  Beller M. Bolm C. Wiley-VCH; Weinheim: 1998.  p.550 
• 1b Hegedus LS. Transition Metals in the Synthesis of Complex Organic Molecules   2nd ed.:  University Science Books; Sausalito: 1999.  Chap. 10.
• 1c Pape AR. Kaliappan KP. Kündig EP. Chem. Rev.  2000,  100:  2917 
• 1d Kamikawa K. Uemura M. Synlett  2000,  938 
• For some recent works, see:
• 2a Kündig EP. Ratni H. Crousse B. Bernardinelli G. J. Org. Chem.  2001,  66:  1852 
• 2b Kamikawa K. Tachibana A. Sugimoto S. Uemura M. Org. Lett.  2001,  3:  2033 
• 2c Gotov B. Schmalz H.-G. Org. Lett.  2001,  3:  1753 
• 2d Wilhelm R. Widdowson DA. J. Chem. Soc., Perkin Trans. 1  2000,  3808 
• 2e Prim D. Tranchier J.-P. Chavignon R. Rose-Munch F. Rose E. Organometallics  2001,  20:  1279 
• 2f Gotov B. Kaufmann J. Schumann H. Schmalz H.-G. Synlett  2002,  361 
• 2g Müller TJJ. Ansorge M. Aktah D. Angew. Chem.  2000,  112:  1323 
• 3 Metal-Catalyzed Cross-Coupling Reactions   Diederich F. Stang PJ. Wiley-VCH; Weinheim: 1997. 
• 4 For a review, see: Carpentier J.-F. Petit F. Mortreux A. Dufand V. Basset J.-M. Thivolle-Cazat J. J. Mol. Catal.  1993,  81:  1 
• 5 Tsuji J. Palladium Reagents and Catalysts   Wiley; Chichester: 1996.  Chap. 4. p.188 
• 6 The formation of a complexed benzophenone derivative as an(undesired) side-product of a non-carbonylative Suzuki-coupling of a haloarene-Cr(CO)₃ complex was mentioned by: Kamikawa K. Watanabe T. Uemura M. J. Org. Chem.  1996,  61:  1375 
• For recent work from this laboratory, see:
• 7a Schwarz O. Brun R. Bats JW. Schmalz H.-G. Tetrahedron Lett.  2002,  1009 
• 7b Dehmel F. Schmalz H.-G. Org. Lett.  2001,  3:  3579 
• 7c Hörstermann DP. Schmalz H.-G. Kociok-Köhn G. Tetrahedron  1999,  55:  6905 
• 7d Hoffmann O. Schmalz H.-G. Synlett  1998,  1426 
• 7e Schellhaas K. Schmalz H.-G. Bats JW. Chem.-Eur. J.  1998,  4:  57 
• 8 The direct complexation of Ar-COR by thermolysis of Cr(CO)₆ by standard techniques usually results in low yields except for the case of acetic acid catalyzed complexation in refluxing decalin: Hrnciar P. Toma S. J. Organomet. Chem.  1991,  413:  161 
• For the synthesis and full characterization of reagent 4, see:
• 9a

  Schumann, H.; Kaufmann, J.; Wassermann, B.C.; Girgsdies, F.; Jaber, N.; Blum, J. Z. Anorg. Allg. Chem., in press.

• 9b Compound 4 had been previously described by: Maeda T. Okawara R. J. Organomet. Chem.  1972,  39:  87 
• 11a Kamikawa K. Watanabe T. Uemura M. J. Synth. Org. Chem., Jpn.  2001,  59:  1078 
• 11b Uemura M. Nishimura H. Hayashi T. J. Organomet. Chem.  1994,  473:  129 
• 12 Ishiyama T. Kizaki H. Miyaura N. Suzuki A. Tetrahedron Lett.  1993,  7595 
• 14a Federic J. Toma S. Gautheron B. J. Organomet. Chem.  1988,  338:  221 
• 14b Besancon J. Top S. Tiroflet J. Gautheron B. Disasoy Y. J. Organomet. Chem.  1975,  94:  35 
• 14c Hudecek M. Toma S. J. Organomet. Chem.  1990,  393:  115 
• 14d Mandal SK. Sarkar A. J. Org. Chem.  1998,  63:  5672 
• 14e Effenberger F. Schöllkopf K. Chem. Ber.  1985,  118:  4377 

10

Typical Experimental Procedure: The indium reagent (1 mmol, 232 mg), PdCl₂(PPh₃)₂ (5 mol%, 35 mg) and 1a (1 mmol, 249 mg) were placed in a Büchi glass-autoclave and deoxygenated THF (10 mL) was added under Ar. The apparatus was pressurized with CO (5 atm) and placed in an oil bath pre-heated to 50 °C. After stirring for 15 h, the pressure was normalized and the reaction mixture was cooled to ambient temperature, diluted with MTBE (10 mL), filtered through a short pad of silica, washed with MTBE and concentrated under reduced pressure. The residue was purified by chromatography on silica (20 g) with cyclo-hexane-MTBE = 4:1 to give 175 mg (68%) of the product 2a as an orange crystalline compound. Mp 87-88 °C (ref. [14a] 83-85 °C). ¹H NMR (250 MHz, CDCl₃): δ = 6.03 (d, 2 H), 5.62 (t, 1 H), 5.26 (t, 1 H), 2.43 (s, 3 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 230.5, 194.9, 95.5, 95.2, 94.2, 89.2, 25.2; FT-IR(neat): 1255, 1357, 1410, 1514, 1681, 1883, 1965
cm^-1.
rac -2b: Mp 58-59 °C (ref. [14a] 59-61 °C). ¹H NMR (250 MHz, CDCl₃): δ = 5.89 (d, 1 H), 5.60 (t, 1 H), 5.14 (t, 1 H), 5.02 (d, 1 H), 2.47 (s, 3 H) 2.38 (s, 3 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 231.2, 198.0, 110.8, 98.5, 96.6, 95.8, 92.2, 87.5, 28.1, 21.2; FT-IR(neat): 1244, 1681, 1877, 1961 cm^-1.
C₁₂H₁₀CrO₄; calcd: C 53.34%, H 3.73%; found: C 53.23%, H 3.74%.
rac -2c: Mp 60-62 °C. ¹H NMR (250 MHz, CDCl₃): δ = 6.24 (d, 1 H), 5.77 (t, 1 H), 5.01 (d, 1 H), 4.93 (t, 1 H), 3.84 (s, 3 H) 2.56 (s, 3 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 231.1, 195.1, 144.4, 95.5, 95.4, 89.5, 84.3, 72.4, 55.9, 31.1; FT-IR(neat): 1241, 1668, 1867, 1959 cm^-1.
C₁₂H₁₀CrO₅; calcd: C 50.36%, H 3.52%; found: C 50.56%, H 3.66%.
rac -2d: Mp 67.5-68.5 °C (ref. [14b] 70 °C). ¹H NMR (250 MHz, CDCl₃): δ = 5.74-5.78 (m, 1 H), 5.37-5.41 (m, 3 H), 3.86 (s, 3 H) 2.49 (s, 3 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 229.8, 198.0, 166.0, 109.2, 92.5, 91.1, 90.6, 90.4, 90.2, 53.2, 29.5; FT-IR(neat): 1280, 1695, 1718, 1892, 1972 cm^-1.
C₁₃H₁₀CrO₆; calcd: C 49.69%, H 3.21%; found: C 49.68%, H 3.33%.
2e: Mp 107.5-109 °C. ¹H NMR (250 MHz, CDCl₃): δ = 6.07 (d, 2 H), 5.11 (d, 2 H), 2.41 (s, 3 H) 2.27 (s, 3 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 230.8, 194.6, 111.5, 94.9, 93.8, 90.2, 25.2, 20.7; FT-IR(neat): 1258, 1681, 1876, 1961 cm^-1.
C₁₂H₁₀CrO₄; calcd: C 53.34%, H 3.73%; found: C 53.27%, H 3.79%.
2f: Mp 86-88 °C. ¹H NMR (250 MHz, CDCl₃): δ = 6.16 (d, 2 H), 5.13 (d, 2 H), 3.75 (s, 3 H) 2.39 (s, 3 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 230.5, 193.9, 144.5, 94.6, 91.2, 76.5, 55.9, 25.2; FT-IR(neat): 1255, 1679, 1880, 1962 cm^-1.
C₁₂H₁₀CrO₅; calcd: C 50.36%, H 3.52%; found: C 50.32%, H 3.61%.
2g: Mp 95-97 °C. ¹H NMR (250 MHz, CDCl₃): δ = 6.01 (d, 2 H), 5.98 (d, 2 H), 3.91 (s, 3 H) 2.45 (s, 3 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 229.5, 195.2, 165.9, 97.0, 92.3, 91.5, 91.4, 53.1, 25.4; FT-IR(neat): 1282, 1684, 1725, 1904, 1977 cm^-1.
C₁₃H10CrO₆; calcd: C 49.69%, H 3.21%; found: C 49.94%, H 3.30%.
2h: Mp 69-70 °C (ref. [14b] 71 °C). ¹H NMR (250 MHz, CDCl₃): δ = 5.47-5.51 (m, 2 H), 5.41-5.45 (m, 2 H), 2.46 (s, 6 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 229.7, 197.6, 104.8, 90.7, 90.5, 28.3; FT-IR(neat): 1252, 1679, 1897, 1970 cm^-1.
C₁₃H₁₀CrO₅; calcd: C 52.36%, H 3.38%; found: C 52.28%, H 3.54%.

13

Typical Experimental Procedure: Phenylboronic acid (2 mmol, 244 mg), potassium carbonate (828 mg, 6 mmol), PdCl₂(PPh₃)₂ (5 mol%, 35 mg) and 1a (1 mmol, 249 mg) were placed in a Büchi glass-autoclave and deoxygenated THF (10 mL) was added under Ar. The apparatus was set under CO-pressure (5 atm) and placed in an oil bath pre-heated to 50 °C. After stirring for 15 h, the pressure was normalized and the reaction mixture was cooled to ambient temperature, diluted with MTBE (10 mL), filtered through a short pad of silica, washed with MTBE and concentrated under reduced pressure. The residue was purified by chromatography on silica (20 g) with cyclohexane-MTBE = 4:1 to give 210 mg (66%) of the product 3a as an orange crystalline compound. Mp 91-93 °C (ref. [14c] 92-93 °C). ¹H NMR (250 MHz, C₆D₆): δ = 6.97-7.59 (m, 5 H); 5.48 (d, 2 H), 4.53 (t, 1 H), 4.24 (t, 1 H); ¹³C NMR (62.5 MHz, C₆D₆): δ = 231.3, 193.0, 137.0, 132.1, 128.8, 128.6, 96.8, 95.6, 94.3, 89.7; FT-IR(neat): 1267, 1366, 1408, 1514, 1650, 1881, 1964 cm^-1.
rac -3b: Mp 64-66 °C. ¹H NMR (250 MHz, CDCl₃): δ = 7.43-7.88 (m, 5 H), 5.51-5.62 (m, 2 H), 5.10-5.15 (m, 2 H), 2.23 (s, 3 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 231.5, 193.8, 137.0, 133.5, 129.6, 128.7, 109.2, 104.8, 95.9, 94.7, 91.0, 86.6, 20.0; FT-IR(neat): 1263, 1652, 1879, 1962 cm^-1.
C₁₇H₁₂CrO₄; calcd: C 61.45%, H 3.64%; found: C 61.31%, H 3.60%.
rac -3c: Mp 127-128 °C (ref. [14d] 115 °C). ¹H NMR (250 MHz, CDCl₃): δ = 7.40-7.87 (m, 5 H), 5.86 (d, 1 H), 5.67 (t, 1 H), 5.06 (d, 1 H), 4.90 (t, 1 H), 3.63 (s, 3 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 231.5, 191.5, 141.6, 137.3, 133.2, 129.4, 128.3, 96.6, 96.4, 94.4, 83.0, 72.0, 55.9; FT-IR(neat): 1280, 1668, 1879, 1962 cm^-1.
C₁₇H₁₂CrO₅; calcd: C 58.63%, H 3.47%; found: C 58.57%, H 3.55%.
3e: Mp 115-117 °C (ref. [14e] 118-120 °C). ¹H NMR (250 MHz, CDCl₃): δ = 7.44-7.74 (m, 5 H), 6.05 (d, 2 H), 5.15 (d, 2 H), 2.28 (s, 3 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 230.8, 193.4, 136.7, 132.2, 128.5, 128.5, 111.0, 96.4, 94.2, 90.5, 20.7; FT-IR(neat): 1268, 1651, 1883, 1962 cm^-1.
C₁₇H₁₂CrO₄; calcd: C 61.45%, H 3.64%; found: C 61.15%, H 3.69%.
3f: Mp 78-80 °C (ref. [14e] 136-138 °C). ¹H NMR (250 MHz, CDCl₃): δ = 7.43-7.71 (m, 5 H), 6.17 (d, 2 H), 5.16 (d, 2 H), 3.75 (s, 3 H); ¹³C NMR (62.5 MHz, CDCl₃): δ = 230.5, 192.8, 144.2, 136.7, 132.1, 128.5, 128.4, 96.2, 91.4, 76.5, 55.9; FT-IR(neat): 1254, 1651, 1888, 1962 cm^-1.
C₁₇H₁₂CrO₅; calcd: C 58.63%, H 3.47%; found: C 58.53%, H 3.54%.