A Manganese-Catalyzed Cross-Coupling Reaction

Abstract

A manganese-catalyzed cross-coupling reaction of ­heterocyclic chlorides with aryl- as well as alkylmagnesium halides has been developed. The reaction provides a variety of heterocyclic compounds under mild and practical reaction conditions using low amounts of manganese chloride as catalyst.

manganese catalysis - cross-coupling - arylation - alkylation - heterocycles - pyridine - quinoline

References and Notes

1a Diederich F. Stang PJ. Metal-Catalyzed Cross-Coupling Reactions   Wiley-VCH; Weinheim: 1998. 

1b Miyaura N. Cross-Coupling Reactions. A Practical Guide   Springer; Berlin: 2002. 

1c Knochel P. Handbook of Functionalized Organometallics   Wiley-VCH; Weinheim: 2005. 

2 Shinokubo H. Oshima K. Eur. J. Org. Chem.  2004,  2081 

3a Takahashi T. Kanno K. Modern Organonickel Chemistry   Wiley-VCH; Weinheim: 2005. 

3b Tamao K. Sumitani K. Kumada M. J. Am. Chem. Soc.  1972,  94:  4374 

3c Kiso Y. Tamao K. Kumada M. J. Organomet. Chem.  1973,  50:  C12 

3d Erdelmeier I. Gais HJ. J. Am. Chem. Soc.  1989,  111:  1125 

3e Li GY. Angew. Chem. Int. Ed.  2001,  40:  1513 ; Angew. Chem. 2001, 113, 1561

3f Li GY. Marshall WJ. Organometallics  2002,  21:  590 

3g Ackermann L. Born R. Spatz JH. Meyer D. Angew. Chem. Int. Ed.  2005,  44:  7216 ; Angew. Chem. 2005, 117, 7382

4a Littke AF. Fu GC. Angew. Chem. Int. Ed.  2002,  41:  4176 

4b Whitcombe NJ. Hii KK. Gibson SE. Tetrahedron  2001,  57:  7449 

4c Beletskaya IP. Cheprakov AV. Chem. Rev.  2000,  100:  3009 

5a Fürstner A. Leitner A. Méndez M. Krause H. J. Am. Chem. Soc.  2002,  124:  13856 

5b Quintin J. Frank X. Hocquemiller R. Figadère B. Tetrahedron Lett.  2002,  43:  3547 

5c Dohle W. Kopp F. Cahiez G. Knochel P. Synlett  2001,  1901 

5d Cahiez G. Avedissian H. Synthesis  1998,  1199 

5e Tamura M. Kochi JK. J. Am. Chem. Soc.  1971,  93:  1487 

5f Tamura M. Kochi JK. Synthesis  1971,  303 

5g Neumann SM. Kochi JK. J. Org. Chem.  1975,  40:  599 

5h Smith RS. Kochi JK. J. Org. Chem.  1976,  41:  502 

5i Kochi JK. Acc. Chem. Res.  1974,  7:  351 

6a Cahiez G. Avedissian H. Tetrahedron Lett.  1998,  39:  6159 

6b Avedissian H. Bérillon L. Cahiez G. Knochel P. Tetrahedron Lett.  1998,  39:  6163 

6c Korn T. Cahiez G. Knochel P. Synlett  2003,  1892 

Organocatalytic reductions of quinolines and imines:

7a Rueping M. Theissmann T. Antonchick AP. Synlett  2006,  1071 

7b Rueping M. Antonchick AP. Theissmann T. Angew. Chem. Int. Ed.  2006,  45:  3683 ; Angew. Chem. 2006, 118, 3765

7c Rueping M. Azap C. Sugiono E. Theissmann T. Synlett  2005,  2367 

7d Rueping M. Sugiono E. Azap C. Theissmann T. Bolte M. Org. Lett.  2005,  7:  3781 

7e Rueping M. Sugiono E. Azap C. Angew. Chem. Int. Ed.  2006,  45:  2617 ; Angew. Chem. 2006, 118, 2679

7f Rueping M. Antonchick AP. Theissmann T. Angew. Chem. Int. Ed.  2006,  45:  6751 ; Angew. Chem. 2006, 118, 6903

7g Rueping M. Azap C. Angew. Chem. Int. Ed.  2006,  45:  7832 ; Angew. Chem. 2006, 118, 7996

8 For an earlier report on functional-group-directed manganese-catalyzed cross-coupling with activated aryl chlorides, see: Cahiez G. Lepifre F. Ramiandrasoa P. Synthesis  1999,  2138 

9

For the reactions reported commercially available MnCl₂ salts were applied. MnCl₂ anhyd (Aldrich 99.999%), MnCl₂·4H₂O (Strem 99.999%) and MnCl₂ (Aldrich 98%) gave the same results in the cross-coupling reactions.

10

Typical Procedure: Preparation of 4-Isopropyl-2-phenylquinoline ( 3k).
A two-necked round-bottomed flask was charged under Ar with 4-chloro-2-phenylquinoline (0.2397 g, 1.00 mmol), MnCl₂ (6.3 mg, 50 µmol) and THF (5mL) and cooled to 0 °C. The Grignard reagent i-PrMgCl (1.25 mL, 1.20 M in THF, 1.50 mmol) was added slowly via a syringe and the reaction mixture was stirred at 0 °C for 4 h. The reaction mixture was quenched with sat. NH₄Cl (5 mL) and H₂O (5 mL) at 0 °C, extracted with EtOAc (3 × 25 mL), and dried over Mg(SO₄). After removal of solvents in vacuo, the crude product was purified by column chromatography (hexane-EtOAc, 50:1) to give the product as a pale yellow oil (0.1887 g, 81%). ¹H NMR (250 MHz, CDCl₃): δ = 8.12 (d, J = 8.5 Hz, 1 H, ArH), 8.10-8.02 (m, 2 H, ArH), 7.99 (d, J = 8.3 Hz, 1 H, ArH), 7.68 (s, 1 H, ArH), 7.64-7.55 (m, 1 H, ArH), 7.47-7.32 (m, 4 H, ArH), 3.68 [sept, J = 6.8 Hz, 1 H, CH(CH₃)₂], 1.35 [d, J = 6.8 Hz, 6 H, CH(CH₃)₂]. ¹³C NMR (63 MHz, CDCl₃): δ = 157.4 (C), 155.0 (C), 148.6 (C), 140.3 (C), 130.7 (CH), 129.2 (CH), 129.1 (CH), 128.8 (CH), 127.7 (CH), 126.0 (CH), 125.9 (C), 123.0 (CH), 115.0 (CH), 28.6 (CH), 23.1 (CH₃). IR (neat): ν = 3061 (m), 2865 (s), 2930 (m), 2871 (w), 1596 (s), 1551 (s), 1508 (m), 1494 (s), 1460 (m), 1445 (m), 1414 (w), 1385 (m), 1364 (w), 1347 (s), 1234 (w), 1181 (w), 1071 (w), 1029 (w), 907 (w), 879 (m), 838 (w), 792 (m), 770 (s), 694 (s) cm^-1. ESI-MS: m/z = 248 [M + H]⁺. Anal. Calcd for C₁₈H₁₇N: C, 87.41; H, 6.93; N, 5.66. Found: C, 87.59; H, 7.04; N, 5.45.
Preparation of 4-( p -Tolyl)quinoline ( 3y).
A two-necked round-bottomed flask, equipped with a reflux condenser and dropping funnel, was charged with Mg (63.2 mg, 2.60 mmol) and THF (8 mL) under Ar and a solution of p-bromotoluene (0.4276 g, 2.50 mmol) in THF (5 mL) was added dropwise (15 min). Subsequently, the reaction mixture was refluxed for 1 h and cooled to 0 °C. A solution of 4-chloroquinoline (0.1636 g, 1.00 mmol) in THF (3 mL) was added via syringe to the reaction mixture and MnCl₂ (2.5 mg, 20 µmol) was quickly added. The resulting solution was stirred at 0 °C for 2 h, quenched with sat. NH₄Cl (5 mL) and H₂O (5 mL) at 0 °C, extracted with EtOAc (3 × 25 mL), and dried over Mg(SO₄). After removal of solvents in vacuo, the crude product was purified by silica gel column chromatography (hexane-EtOAc, 5:1) to provide the product as a pale yellow oil (0.1857 g, 85%). ¹H NMR (250 MHz, CDCl₃): δ = 8.05 (d, J = 8.5 Hz, 1 H, ArH), 8.79 (d, J = 4.5 Hz, 1 H, ArH), 7.81 (d, J = 8.3 Hz, 1 H, ArH), 7.61-7.78 (m, 1 H, ArH), 7.37-7.28 (m, 1 H, ArH), 7.28-7.14 (m, 5 H, ArH), 2.31 (s, 3 H, CH₃). ¹³C NMR (63 MHz, CDCl₃): δ = 150.0 (CH), 148.8 (C), 148.5 (C), 138.4 (C), 135.1 (C), 129.9 (CH), 129.5 (CH), 129.3 (CH), 129.2 (CH), 126.9 (C), 126.5 (CH), 126.0 (CH), 121.3 (CH), 21.3 (CH₃). IR (neat): ν = 3027 (m), 2920 (m), 1614 (m), 1586 (s), 1569 (s), 1501 (s), 1459 (w), 1421 (m), 1389 (m), 1275 (w), 1112 (w), 1021 (w), 872 (w), 819 (s), 765 (s), 721 (w), 674 (m), 661 (w) cm^-1. ESI-MS: m/z = 220 [M + H]⁺. Anal. Calcd for C₁₆H₁₃N: C, 87.64; H, 5.98; N, 6.39. Found: C, 87.53; H, 6.15; N, 6.29.