Synthesis of Annulated N-Containing Heterocycles via C-H Activation

Key words

palladium catalysis - pyrroles - pyrazoles - C-H activation

Significance

Starting with simple, readily prepared starting materials, a one-step, two-C-C-bond-forming approach to highly substituted six- and seven-membered annulated pyrroles and pyrazoles is described. The efficient palladium-catalyzed synthesis takes advantage of a mechanistically interesting norbornene-mediated sequential aromatic alkylation/aryl-heteroaryl coupling (Catellani-type reaction) and tolerates electron-withdrawing and electron-donating groups at 2-, 3-, and 4-positions of the iodoarenes.

Comment

In comparison with previous methods which involve multi-step syntheses of such annulated heterocycles (e.g., H.-J. Knölker, S. Agarwal Tetrahedron Lett. 2005, 46, 1173-1175; W. R. Bowman et al. Tetrahedron 2005, 61, 2689-2696), the present one-step approach is more efficient and powerful. As an expansion of the previous similar annulation with indoles (M. Lautens et al. J. Am. Chem. Soc. 2005, 127, 13148-13149), this methodology allows rapid construction of unique tricyclic skeletons which are found in natural products and bioactive compounds, such as lettowianthine and lamellarin D.