Regioselective free radical cyclization: a general method for the synthesis of the spiro[4.4]nonane system of fredericamycin A

Introduction of a halogen atom at the middle carbon atom of cyclic 1,3-diketones is described. A convenient approach for constructing the spiro[4.4]nonane system of fredericamycin A has been demonstrated by halogen transfer during radical cyclization followed by reductive elimination of the halogen atom. The configuration of the bromo compound 6b was confirmed by X-ray crystal structure analysis

Synthesis of (±) Fredericamycin A

The synthesis of Fredericamycin A (1) has been achieved by subjecting the 1,3-dione (14) to an unusual 5-trigonal radical cyclization followed by reductive elimination of the halogen in 15 and subsequent demethylation