Comparison of the reactivity between 2- and 3-nitropyrroles in cycloaddition reactions. A simple indole synthesis

Why Do Five-Membered Heterocyclic Compounds Sometimes Not Participate in Polar Diels–Alder Reactions?

“…Single FHCs can participate as diene components in DA reactions toward electrophilically activated π systems, due to their electron-rich nature, but do not readily participate as dienophilic components, demanding a chemical and/or physical activation for such a reaction. However, the presence of strong electron-withdrawing groups such as the nitro one activates FHCs electrophilically participating in DA reactions as the dienophilic component …”

Formal [4+2] Reaction between 1,3‐Diynes and Pyrroles: Gold(I)‐Catalyzed Indole Synthesis by Double Hydroarylation

“…2 According to the classification system proposed by Taber et al.,2a the majority of the traditional synthetic approaches to indoles are based on the construction of the pyrrole ring on an existing benzene ring (Figure 1, Types 1–7). In contrast, very few indole syntheses have been reported to proceed by a [4+2]‐type reaction (classified as Type 8),3 including the hetero‐Diels–Alder (DA) reaction of N ‐methylpyrroles (Scheme a)4 and the thermal DA reaction of N ‐tosylpyrroles (Scheme b) 5. The application of these reactions, however, has been limited because of their requirement for highly activated substrates, such as dicyanopyridazine, Danishefsky’s diene, and nitrated pyrroles.…”

“…In contrast, very few indole syntheses have been reported to proceed by a [4+2]-type reaction (classified as Type 8), [3] including the hetero-Diels-Alder (DA) reaction of N-methylpyrroles (Scheme 1 a) [4] and the thermal DA reaction of N-tosylpyrroles (Scheme 1 b). [5] The application of these reactions, however, has been limited because of their requirement for highly activated substrates, such as dicyanopyridazine, Danishefsky's diene, and nitrated pyrroles. A related transformation involving the Ru-catalyzed annulation of pyrroles has been developed, but this process requires pent-1-en-4-yn-3-ol derivatives as the C4 synthon (Scheme 1 c).…”

Indole synthesis: a review and proposed classification

“…Pedro Mancini of the Universidad Nacional de Litoral showed 112 that nitropyrroles, such as 252 (Scheme 96) were effective Diels–Alder dienophiles. Regiocontrol was poor with isoprene, whereas addition to the more activated diene 253 proceeded to give the 5-hydroxyindole 254 with complete regiocontrol.…”