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DOI: 10.1055/s-2006-955745
Pyrroles and Pyrazoles by a C-N Coupling-Hydroamination Sequence
Contributor(s):Victor Snieckus, Todd MacklinMassachusetts Institute of Technology, Cambridge, USA
Domino Cu-Catalyzed C-N Coupling/Hydroamination: A Highly Efficient Synthesis of Nitrogen Heterocycles
Angew. Chem. Int. Ed. 2006, 45: 7079-7082
Publication History
Publication Date:
15 December 2006 (online)
Key words
pyrroles - pyrazoles - copper catalysis - C-N coupling - hydroamination
Significance
Reported is an elegant Cu-catalyzed amidation/hydroamidation of haloenynes with tert-butyl carbamate or bis(Boc)hydrazine affording, after TFA-induced deprotection/tautomerization, highly substituted pyrroles and pyrazoles in good to excellent yields. N,N′-Dimethylethylenediamine (20 mol%) was found to be the most effective ligand for the conversion. Intermediary amidation products were isolated, thus validating the proposed sequence of C-N coupling followed by hydroamidation.
Comment
Are copper salts on the verge of a renaissance? Recently, long after the Ullmann reaction, Cu-catalyzed processes have become increasingly competitive with popular Pd catalysis for C-C, C-heteroatom (N, O, P, S, Se) to C-H and C-metal bond forming reactions (see first review below). The current method efficiently extends Cu catalysis by amalgamating well-developed C-N coupling (see second review below) with recent amidation chemistry (L. Ackermann Org. Lett. 2005, 7, 439-442). The scope of this reaction offers highly functionalized disubstituted and trisubstituted pyrroles and pyrazoles bearing alkene, ester, silyl ether, and alkyl halide handles for further potential synthetic manipulation.
Reviews
I. P. Beletskaya, A. V. Cheprakov Coord. Chem. Rev. 2004, 248, 2337-2364; L. Jiang, S. L. Buchwald In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; F. Diederich, A. de Meijere, Eds.; Wiley-VCH: Weinheim, 2004, 699-760.