Cyclization upon quinolines. Synthesis of calothrixin

Preliminary work with model selenoester 54 revealed that the hexabutyldistannane protocol, previously used in the phenyl and pyridine series, now gave poor yields of cyclized products. However, treatment of 54 under reductive TTMSS conditions in the presence of AIBN as the initiator led to the calothrixin-related pentacycle 55 in 65% yield. This compound, which incorporated the 2-cyano-2-propyl moiety of the initiator, was converted into A -methylcalothiixin 56 by treatment with potassium hydroxide in methanol, through a process involving a gramine-type nucleophilic substitution and the oxidation of the resulting carbinol by air. 

Formation of pentacycle 55 was consistent with the radical addition-quinoline rearomatization-overoxidation sequence depicted below. Thus, the initially formed acyl radical L undergoes regioselective cyclization upon the 4-position of the quinoline ring to give the azacyclohexadienyl radical M, which is probably oxidized by hydrogen abstraction at the hands of the initiator AIBN 04AGE95 . A new hydrogen abstraction at the doubly 

Interestingly, the above homolytic sequence could be promoted in the sole presence of AIBN acting as the oxidant, accomplishing the initial homolysis of the C-Se bond under simple irradiation. Hence, treatment of selenoester 54 with excess AIBN under irradiation led to a mixture of pentacycles 55 and 56, from which A -methylcalothrixin 56 could be isolated in 75% yield after basic treatment. 

The reductive cyclization protocol was then applied to a suitably A-protected radical precursor to allow further access to the alkaloid calothrixin B. Satisfactorily, 2-indolylacyl radicals derived from A-(methoxymethyl) selenoester 57 underwent cyclization under TTMSS-AIBN conditions with an even higher efficiency than their A-methyl counterparts. The reaction nevertheless followed a different course as, after the radical addition and quinoline rearomatization, pentacyclic phenol 58, a fully aromatic tautomeric form of ketone P, was isolated in 90% yield. The same phenol 58 was isolated although in lower yields (50-70%) using either stannane-AIBN or AIBN-irradiation protocols. 

In contrast with the above A-methyl series, overoxidation of phenol 58, which would now be the most favored tautomeric form, probably because of the establishment of a hydrogen bond between the hydroxy and methoxy group, did not take place under the reaction conditions. From the synthetic standpoint, this was not a serious limitation since it could be 

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