Nitrobutadienes as powerful benzannulating agents: An unprecedented easy access to rare nitroindoles

Sequential Annulations to Interesting Novel Pyrrolo[3,2-c]carbazoles

“…( a ) Reduction of the nitro group in 6a to obtain 11a , a possible precursor for new polyheterocyclic targets. ; ( b ) the same reducing agent proves less efficient in the reduction of nitro groups in a 4,7-diaryl-5,6-dinitroindole reported in ref [21]. …”

“…We started our research applying to the model substrate 4a (Ar = p -Tol) the same reaction conditions previously applied [21] to diene 3 (2 mol equiv of pyrrole, TFE, 50 °C). Here again, 24 h were necessary to observe, by TLC, the complete disappearance of 4a ; the analysis of the chromatographed final reaction mixture highlighted the formation of three different indole derivatives ( 6a – 8a , Scheme 2), 6a being by far the prevalent one (Table 1, entry 1).…”

“…Beside to the interest in obtaining merely the corresponding amino derivatives, we intend in the future, to investigate their possible utilization to obtain different polyheterocyclic systems (Scheme 5) involving the nucleophilic primary amino group in further reactions. A preliminary test on the model substrate 6a showed the expected reduction to occur smoothly in satisfactory yield ( 11a : 61% of isolated compound; Scheme 5a) and in a reasonable reaction time (overnight), in conditions (SnCl 2 ·2H 2 O, EtOH 60 °C, under Ar) [26] that were not as efficient when previously tried on diaryldinitroindoles (from [21]; Scheme 5b): an encouraging result in the above mentioned perspective of widening the scope of the reduction of 6 towards the synthesis of new N -heterocycles.…”

“…It should be said that the practical interest of such benzannulation processes was somehow diminished by their modest selectivity, leading in every case to mixtures of compounds. Interestingly enough, when we applied the same procedure on pyrrole [21] with the 2,3-dinitrobutadienes 3 , the method’s outcomes were more gratifying from both the mechanistic and the synthetic point of view, thanks to the unexpected interception of a key intermediate ( 5 , Scheme 1, part b ), that allowed a definitely better selectivity to the whole process: actually, from the isolated 5 , suitable procedures were optimized to generate either mononitro- or dinitro-indoles substituted in positions that are not easily accessible, for instance, by means of S E Ar reactions.…”

Synthesis of functionalized indoles via cascade benzannulation strategies: a decade's overview

“…In 2019, Petrillo, Tavani and co-workers unveiled the synthesis of rare nitroindoles through benzannulation of pyrrole with dinitrobutadienes (Scheme 31). 41 According to the mechanistic hypothesis, the formation of nitroindoles 217–219 could be rationalized via a common intermediate 216 , which might have been generated through two different reaction pathways. In the first pathway, the formation of intermediate 213 might have occurred via a not fully-concerted [4 + 2] cycloaddition between pyrrole and dinitrobutadiene 211 followed by dehydrogenation.…”