The Cascade Reactions of Substituted Indigos and the Development of Indigo Oligomers

In a continuation to better understand cascade reactions of indigo 1 and generate new heterocycles, a series of electron-rich and electron-deficient indigos were targeted to evaluate the effects of electronics upon the outcome. The synthesis of methoxy-, bromo- and phenyl-substituted indigos 120, 124, 145 – 147, 149 and 164 was achieved in modest to good yields (22 – 58%) in one step according to the Baeyer-Drewson synthesis. Access to 5,5'- and 6,6'-dinitroindigos 148 and 150 was achieved through the hydrolysis of 3-acetoxy-5-nitroindole 154 and the Baeyer-Drewson synthesis, respectively, though an additional Boc-protection and deprotection was required to purify these derivatives. The isolation of novel N,N',O,O'-tetraBoc-5,5'- and 6,6'-dinitroindigos 157 and 170 as minor by-products (1%) in these syntheses required a 2 e- reduction, suggesting the electron-deficient nature of the dinitroindigos 148 and 150 may enable reductive processes to occur with greater ease than electron-rich derivatives, though further investigations are required to identify the reducing agent in these reactions. The propargylation of 5,5'-dibromoindigo 146 with propargyl bromide 47 yielded a new oxazinodiindolone 176 in 10% yield, which was proposed to be a mechanistic intermediate toward the synthesis of a similar oxazinobiindolone observed previously. Attempted cascade reactions of 5,5'-dimethoxyindigo 145 and 5,5'-dinitroindigo 148 with propargyl bromide 47 and propargyl chloride 189 led to extensive decomposition with no isolable cascade products, suggesting the substituted indigos are more susceptible to degradation in the propargylation cascade reactions.