Total Synthesis of Communesin F

Key words

communesin F - indol-2-one - Diels–Alder cycloaddition - mercuric triflate - trimethyl aluminum

Significance

The stereochemically complex polycyclic structure of the communesins has ­attracted the interest of several researchers and led to the total syntheses of communesin A, B and F. Funk and co-worker now report an elegant and concise synthesis of the moderately cytotoxic communesin F that relies on an unusual Diels–­Alder cycloaddition of indol-2-one, a reaction ­developed by the group. Its considerable synthetic utility has previously been demonstrated in the total synthesis of perophoramidine and is now further showcased by the synthesis of communesin F in only 15 steps and an overall yield of 6.7%.

Comment

Indol-2-one B was generated from bromooxindole A and underwent smooth cyclo­addition with indole C to afford E via intermediate D. Tosylation of the amide followed by methano­lysis led to formation of aminal F. Advanced tetracyclic intermediate G was obtained in three more steps. Heck reaction of G with alcohol H, followed by a high-yielding mercuric-triflate promoted cyclization to the benzazepine gave I. Cyclization to the bridged lactam J could not be achieved under thermal conditions, but exposure to trimethyl aluminum effected the desired transformation. Synthetic communesin F was obtained after four more steps.