Triphenylcyclopentadienyl Rhodium Complexes in Catalytic C-H Annulations. Application for Synthesis of Natural Isocoumarins.

Abstract

Efficient protocols for the synthesis of triphenylcyclopentadienyl rhodium halides [(1,2,4-C5Ph3H2)RhX2]2 (1a,b: X = Cl, I) starting from 1,2,4-triphenylcyclopentadiene or the cyclooctadiene derivative (1,2,4-C5Ph3H2)Rh(cod) (2) were developed. Iodide abstraction from 1b with thallium or silver salts allowed us to prepare rhodocenium [(1,2,4-C5Ph3H2)RhCp]PF6 (3PF6) and mesitylene complex [(1,2,4-C5Ph3H2)Rh(mesitylene)](SbF6)2 (4(SbF6)2). Halides 1a,b (at 0.5 mol % loading) showed high catalytic activity in the construction of C-C, C-O, and C-N bonds via the C(sp2)-H activation approach. Their efficiency was demonstrated in the synthesis of more than 40 examples of polycyclic organic compounds (such as isocoumarins and naphthalenes, as well as isoquinolinium and dibenzo[a,f]quinolizinium salts). The protocols developed tolerate a wide range of functional groups. In particular, they were successfully used for the atom- and step-economical synthesis of hydroxy-substituted isocoumarins, including the natural product oospalactone 7fe. The 6- or 8-hydroxy-substituted isocoumarins showed moderate antiproliferative activity against several human cell lines in vitro.