A metal-free route to 2-aminooxazoles by taking advantage of the unique ring opening of benzoxazoles and oxadiazoles with secondary amines.

Recognizing the value of (hetero)arylamine motifs in biological and pharmaceutical sciences, chemists continue to devise novel and more practical methods for their synthesis. Buchwald–Hartwig-type amination reactions and those mediated by copper are the most powerful and reliable methods available for N arylation. However, since these procedures employ aryl halides as the starting material, the direct amination of a C H bond in heteroaromatics would be beneficial, thus avoiding additional halogenation steps to obtain halogenated derivatives. In this context, recent examples of metal-mediated C N bond formation in azoles represent important contributions to this area (Scheme 1).

[1]  Sukbok Chang,et al.  Cobalt- and manganese-catalyzed direct amination of azoles under mild reaction conditions and the mechanistic details. , 2010, Angewandte Chemie.

[2]  M. Mąkosza.  Nucleophilic substitution of hydrogen in electron-deficient arenes, a general process of great practical value. , 2010, Chemical Society reviews.

[3]  Sukbok Chang,et al.  A new combined source of "CN" from N,N-dimethylformamide and ammonia in the palladium-catalyzed cyanation of aryl C-H bonds. , 2010, Journal of the American Chemical Society.

[4]  M. Zanda,et al.  A new entry of amination reagents for heteroaromatic C-H bonds: copper-catalyzed direct amination of azoles with chloroamines at room temperature. , 2010, Journal of the American Chemical Society.

[5]  Sukbok Chang,et al.  Highly efficient and versatile pd-catalyzed direct alkynylation of both azoles and azolines. , 2010, Organic letters.

[6]  Sukbok Chang,et al.  Rhodium(NHC)-catalyzed amination of aryl bromides. , 2010, Organic letters.

[7]  Sukbok Chang,et al.  Silver-mediated direct amination of benzoxazoles: tuning the amino group source from formamides to parent amines. , 2009, Angewandte Chemie.

[8]  Sukbok Chang,et al.  Rhodium/N-heterocyclic carbene catalyzed direct intermolecular arylation of sp2 and sp3 C-H bonds with chelation assistance. , 2009, Angewandte Chemie.

[9]  S. Schreiber,et al.  Copper-Mediated Amidation of Heterocyclic and Aromatic C−H Bonds , 2009, Organic letters.

[10]  H. Furukawa,et al.  Direct amination of azoles via catalytic C-H, N-H coupling. , 2009, Organic letters.

[11]  E. De Clercq,et al.  Structure-activity relationship of new anti-hepatitis C virus agents: heterobicycle-coumarin conjugates. , 2009, Journal of medicinal chemistry.

[12]  Yuyang Jiang,et al.  Easy copper-catalyzed synthesis of primary aromatic amines by couplings aromatic boronic acids with aqueous ammonia at room temperature. , 2009, Angewandte Chemie.

[13]  J. Hartwig.  Evolution of a fourth generation catalyst for the amination and thioetherification of aryl halides. , 2008, Accounts of chemical research.

[14]  Wei Zhang,et al.  Efficient aerobic oxidative synthesis of 2-substituted benzoxazoles, benzothiazoles, and benzimidazoles catalyzed by 4-methoxy-TEMPO. , 2008, Angewandte Chemie.

[15]  Sukbok Chang,et al.  Synthesis of condensed pyrroloindoles via Pd-catalyzed intramolecular C-H bond functionalization of pyrroles. , 2008, Journal of the American Chemical Society.

[16]  Sukbok Chang,et al.  Synthetic utility of ammonium salts in a Cu-catalyzed three-component reaction as a facile coupling partner. , 2008, The Journal of organic chemistry.

[17]  Stephen L. Buchwald,et al.  Biarylphosphanliganden in der palladiumkatalysierten Aminierung , 2008 .

[18]  D. Surry,et al.  Biaryl phosphane ligands in palladium-catalyzed amination. , 2008, Angewandte Chemie.

[19]  Sukbok Chang,et al.  Ammonium salts as an inexpensive and convenient nitrogen source in the Cu-catalyzed amination of aryl halides at room temperature. , 2008, Chemical communications.

[20]  Sukbok Chang,et al.  Palladium-catalyzed C-H functionalization of pyridine N-oxides: highly selective alkenylation and direct arylation with unactivated arenes. , 2008, Journal of the American Chemical Society.

[21]  Takashi Watanabe,et al.  Regulatory molecules for the 5-HT3 receptor ion channel gating system. , 2007, Bioorganic & medicinal chemistry.

[22]  Rafael S Sánchez,et al.  Mechanistic evidence for a ring-opening pathway in the Pd-catalyzed direct arylation of benzoxazoles. , 2007, Journal of the American Chemical Society.

[23]  R. Hili,et al.  Making carbon-nitrogen bonds in biological and chemical synthesis , 2006, Nature chemical biology.

[24]  T. Wirth.  Hypervalent iodine chemistry in synthesis: scope and new directions. , 2005, Angewandte Chemie.

[25]  T. Wirth.  Hypervalente Iodverbindungen in der Synthese: Möglichkeiten und Grenzen , 2005 .

[26]  D. Díaz,et al.  Modular synthesis of formamidines and their formation of stable organogels. , 2004, Chemical communications.

[27]  D. Ma,et al.  Mild method for Ullmann coupling reaction of amines and aryl halides. , 2003, Organic letters.

[28]  S. Ren,et al.  Dication C(R1)–N(R2)2 Synthons and their use in the Synthesis of Formamidines, Amidines, and α-Aminonitriles , 2000 .

[29]  Y. Sato,et al.  Benzoxazole derivatives as novel 5-HT3 receptor partial agonists in the gut. , 1998, Journal of medicinal chemistry.

[30]  Michael P. Winters,et al.  New N- and O-arylations with phenylboronic acids and cupric acetate , 1998 .

[31]  O. Prakash,et al.  Hypervalent iodine oxidation of phenolic schiff's bases: Synthesis of 2-arylbenzoxazoles , 1997 .

[32]  M. Mąkosza,et al.  The vicarious nucleophilic substitution of hydrogen and related reactions in nitrobenzoxazoles , 1995 .

[33]  A. G. Mikhailovskii,et al.  Synthesis and alkylation of amidines of the phenanthridine series , 1991 .

[34]  V. S. Bogdanov,et al.  Synthesis and nmr study of 7-aryl-1,2,4-triazolo-[1,5-a]-1, 3,5-triazines , 1989 .

[35]  O. Chupakhin,et al.  Cyclization of N-alkylazinium cations with bifunctional nucleophiles. 14. Reaction of quinoxalinium salts with mono- and N,N′-disubstituted amidines , 1985 .

[36]  H. L. Yale,et al.  2-amino-5-substituted 1,3,4-oxadiazoles and 5-imino-2-substituted delta-2-1,3,4-oxadiazolines. A group of novel muscle relaxants. , 1966, Journal of medicinal chemistry.

[37]  G. Giacomelli,et al.  Parallel synthesis of trisubstituted formamidines: a facile and versatile procedure. , 2009, Journal of combinatorial chemistry.

[38]  Yaseen A. Al-Soud,et al.  Synthesis, Characterization and anti-HIV and Antitumor Activities of New Coumarin Derivatives , 2008 .

[39]  S. Buchwald,et al.  Practical Palladium Catalysts for C-N and C-O Bond Formation , 2002 .

[40]  Y. Kita,et al.  Hypervalent Iodine Oxidation of p-Alkoxy- and Related Phenols: A Facile and Efficient Synthesis of p-Quinones , 1989 .

[41]  F. Babudri,et al.  Ring opening of benzothiazoles with allylic grignard reagents , 1984 .

[42]  S. Florio.  Ring opening of benzoxazoles with allylic grignard reagents: synthesis of n-diallylalkyl-o-aminophenols. , 1984 .