SYNTHETIC STUDIES ON APHIDICOLANE AND STEMODANE DITERPENES .5. A FACILE FORMAL TOTAL SYNTHESIS OF (+ -)-APHIDICOLIN VIA A LEWIS ACID-MEDIATED STEREOSELECTIVE SPIROANNELATION/

Formal total synthesis of (+/-)-aphidicolin (1) was achieved via a Lew is acid-mediated stereoselective spiroannelation reaction as a key ste p. The bisbenzyl acetal (2) was synthesized from the readily available dimethyl acetal (4). Treatment of 2 with trimethylsilyl trifluorometh anesulfonate (TMSOTf) afforded a 69:31 mixture of the spirocyclic enon es (9 and 10) in excellent yield. The tricyclic ketal-ketone (3) corre sponding to the B/C/D rings of 1 was easily generated from the enone ( 9) by intramolecular alkylation and catalytic hydrogenation as princip al steps. The A-ring construction was performed by a procedure similar to one used previously. Barbier reaction of 14, followed by oxidative rearrangement, stereoselective 1,4-addition of a methyl group, and su bsequent intramolecular aldol-condensation afforded the tetracyclic en one (18), which has already been transformed into (+/-)-aphidicolin (1 ).