Pyrrolopyridines nucleophilic

Gamez-Montaho et al. described an Ugi variation where the carboxylic acid was replaced with an amide [68]. The amide oxygen is nucleophilic enough to effect ring closure to oxazole intermediates 44, which then undergo aza-Diels-Alder reaction with the double bond of the allylic amine component to form oxa-bridged heterocycles 45, which can either be isolated as a separate class of compounds or converted to pyrrolopyridines 46 by treatment with TEA (Scheme 8). 

In pyrrolopyridine synthesis reactions, nitropyridines are less reactive than the corresponding nitropyridone derivatives due to the decreased aromaticity of the pyridone ring. The pyridone is more attractive for nucleophilic attack in the reaction <2002H(58)301> (see Section 10.06.5.3). 

Compound (1) reacted with selenium dioxide to afford the disubstituted selenium derivative (49). Nucleophilic attack at the pyrrolopyridine C-3 atom by diethyl selenite, generated from selenium dioxide and ethanol, afforded the product (49) in 44% yield (Equation 6). An analogous reaction was carried out using sulfur dichloride to give the thio derivative (50) (44%). Both reactions are shown in Equation (6) <92BCJ2992>. 

Four-Component Synthesis of Pyrrolopyridines If a primary amine were used as an input, the three-component reaction shown in Scheme 15.10 would produce an oxazole bearing a secondary amine. In other words, the so-produced adduct 24 would contain both a diene (oxazole) and a nucleophilic site (amine). Therefore, a dienophile bearing an electrophihc center would pair perfectly with the dual reactivity of 24. In practice, if an activated a,P-unsaturated carboxylic acid derivative were introduced after the three-component reaction, a sequence of N-acylation/intramolecular Diels-Alder reaction (IMDA) might occur to produce the four-component adducts. 

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