Triphenylcyclopentadienyl Rhodium Complexes in Catalytic C–H Annulations. Application for Synthesis of Natural Isocoumarins
Vladimir B. Kharitonov, Dmitry V. Muratov, Yulia V. Nelyubina, Ilya A. Shutkov, Alexey A. Nazarov, Dmitry A. Loginov
Abstract
Efficient protocols for the synthesis of triphenylcyclopentadienyl rhodium halides [(1,2,4-C 5 Ph 3 H 2 )RhX 2 ] 2 ( 1a, b: X = Cl, I) starting from 1,2,4-triphenylcyclopentadiene or the cyclooctadiene derivative (1,2,4-C 5 Ph 3 H 2 )Rh(cod) ( 2 ) were developed. Iodide abstraction from 1b with thallium or silver salts allowed us to prepare rhodocenium [(1,2,4-C 5 Ph 3 H 2 )RhCp]PF 6 ( 3 PF 6 ) and mesitylene complex [(1,2,4-C 5 Ph 3 H 2 )Rh(mesitylene)](SbF 6 ) 2 ( 4 (SbF 6 ) 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(sp 2 )–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 .