Abstract
Heteroaryl amines are efficiently coupled (in two hours) to aryl halides with catalytic Pd2 (dba)3 and Xantphos to provide the corresponding biaryl amines under microwave and standard thermal conditions. The use of organic-soluble sodium phenolate (NaOPh) as the stoichiometric base promotes facile coupling of a variety of substrates in excellent yields.
Key words
palladium-catalyzed - sodium phenolate - C-N bond-forming - biaryl amine - heteroaryl amine
References and Notes
1a Okushima H, Narimatsu A, Kobayashi M, Furuya R, and Kitada Y. inventors; US 4 661 484.
1b Blancafort P.
Serradell MN.
Castañer J.
Thorpe P.
Drugs Future
1983,
8:
223
1c Kim KS, Kimball SD, Cai Z.-W, Rawlins DB, Misra RN, Poss MA, Webster KR, Hunt JT, and Han W.-C. inventors; US 6 262 096B1.
1d Rackur G, and Hoffman I. inventors; US 4 302 468.
1e Castañer J.
Prous J.
Drugs Future
1986,
11:
465
2 Yang J.-S.
Lin Y.-H.
Yang C.-S.
Org. Lett.
2002,
4:
777
3 Yin J.
Zhao MM.
Huffman MA.
McNamara JM.
Org. Lett.
2002,
4:
3481
4 Usui S.
Suzuki T.
Hattori Y.
Etoh K.
Fujieda H.
Nishizuka M.
Imagawa M.
Nakagawa H.
Kohda K.
Miyata N.
Bioorg. Med. Chem. Lett.
2005,
15:
1547
5 Byth KF.
Culshaw JD.
Green S.
Oakes SE.
Thomas AP.
Bioorg. Med. Chem. Lett.
2004,
14:
2245
6 Tundel RE.
Anderson KW.
Buchwald SL.
J. Org. Chem.
2006,
71:
430
7 Anderson KW.
Tundel RE.
Ikawa T.
Altman RA.
Buchwald SL.
Angew. Chem.
2006,
45:
6523
8 At the time of this manuscript’s preparation, a search via ACD and ACX failed to find any commercially available arylnonaflates.
9a Wolfe JP.
Buchwald SL.
Tetrahedron Lett.
1997,
38:
6359
9b Ali MH.
Buchwald SL.
J. Org. Chem.
2001,
66:
2560
9c Wolfe JP.
Buchwald SL.
J. Org. Chem.
2000,
65:
1144
9d Wolfe JP.
Tomori H.
Sadighi JP.
Yin J.
Buchwald SL.
J. Org. Chem.
2000,
65:
1158
9e Jensen TA.
Liang X.
Tanner D.
Skaerbaek N.
J. Org. Chem.
2004,
69:
4936
10a Hartwig JF.
Kawatsura M.
Hauck SI.
Shaughnessy KH.
Alcazar-Roman LM.
J. Org. Chem.
1999,
64:
5575
10b Miyaura N.
Yamada K.
Suginome H.
Suzuki A.
J. Am. Chem. Soc.
1985,
107:
972
10c Komatsu A, Akutagawa S, and Someya T. inventors; U 3859374. For the use of NaOPh in isoprene dimerization, see:
tert -butylphenoxide, NaOt -Bu, and NaOCEt3 , see:
11a Shekhar S.
Hartwig JF.
Organometallics
2007,
26:
340
11b Alcazar-Roman LM.
Hartwig JF.
J. Am. Chem. Soc.
2001,
123:
12905
12 All microwave reactions were conducted in a 2-5 mL Biotage Microwave Vial Kit with sealable cap (code no. 351521) using a magnetic stirbar. Microwave heating was performed with a single-mode cavity Emrys SmithCreator.
13
General Procedure for Compounds Shown in Table 3
2 (dba)3 (12.6 mg, 0.0137 mmol, 2.5 mol% of Pd), and Xantphos (19.1 mg, 0.0330 mmol, 3.0 mol%) followed by degassed 1,4-dioxane (6.50 mL). The mixture was stirred while degassing with argon for 1 min. The heteroaryl amine (1.21 mmol) was added last, the vial was immediately capped and sealed, then heated at 80 °C for 2 h. After cooling to r.t., the mixture was diluted with EtOAc (400 mL), washed with 1 N aq NaOH (3 × 100 mL) and brine (100 mL), dried over anhyd Na2 SO4 , filtered, and the solvent removed under vacuum. The resulting residue was purified over silica gel (12 g, hexanes-EtOAc) and the product was freeze-dried from MeCN-H2 O to provide the pure product.
14a Mann G.
Incarvito C.
Rheingold AL.
Hartwig JF.
J. Am. Chem. Soc.
1999,
121:
3224
14b Kataoka N.
Shelby Q.
Stambuli JP.
Hartwig JF.
J. Org. Chem.
2002,
67:
5553
14c Aranyos A.
Old DW.
Kiyomori A.
Wolfe JP.
Sadighi JP.
Buchwald SL.
J. Am. Chem. Soc.
1999,
121:
4369
