Pyrrole Chemistry. XV. The Chemistry of Some 3,4-Disubstituted Pyrroles

The syntheses of a variety of 3,4-disubstituted pyrroles including the antimitotic agent Verrucarin E are described. 3,4-Pyrroledicarboxylic esters were prepared through a Diels–Alder reaction. Partial hydrolysis of the diesters gave the 4-ester-3-acids which were modified to achieve the synthesis of a variety of unsymmetrically 3,4-disubstituted pyrroles. Raney nickel reduction of a thiolester gave hydroxymethyl under conditions which left acyl or carbalkoxy substituents unaffected. Pyrrole reactions involving carbanionic reagents are complicated by 1-proton abstraction. Therefore, when necessary, the nitrogen was protected by an N-benzyloxymethyl substituent which can be cleaved to the N-hydroxymethyl derivative by aluminum chloride or by hydrogenolysis. Subsequent treatment with benzyltrimethylammonium hydroxide gave back the pyrrole.