Regiospecific Synthesis of 7‐Hydroxyindoles from Pyrroles by Anionic Benzannulation

Abstract

Anionic annulation of appropriate 2,3‐disubstituted pyrroles with Michael acceptors provides an expedient route to densely substituted 7‐hydroxyindoles. Intrinsic to the methodology, the resulting substituents are disposed in a fully regiocontrolled manner. The methodology is applicable to the synthesis of 7‐hydroxybenzofurans. None of the indoles/benzofurans or pyrrole synthons synthesized in this study have hitherto been reported.

Brønsted Acid‐Promoted Cascade Alkylation/Cyclization of Pyrroles with N,N‐Dimethylaminomethyleneglutaconic Acid Dinitrile: A Concise Route to Cyclopenta[b]pyrroles

“…Brønsted or Lewis acid‐promoted Friedel–Crafts cyclization has been considered as a powerful method to prepare heterocyclic compounds 10. A pyrrole ring can thus be used as the “template”‐like structure to establish another ring onto it for the construction of polycyclic compounds,11 in which annulation of pre‐functionalized alkynes or olefins to a pyrrole core is usually involved. After screening of the relevant known synthetic methods, we reasoned that a diene might be utilized to replace the pre‐functionalized alkynes or olefins for the same purpose.…”

“…[10] Ap yrrole ring can thusb eu sed as the "template"-like structure to establish another ring onto it for the construction of polycyclic compounds, [11] in which annulation of prefunctionalized alkynes or olefins to ap yrrole core is usuallyi nvolved. After screening of the relevant known synthetic methods, we reasonedt hat ad iene might be utilized to replace the pre-functionalized alkyneso ro lefins for the same purpose.T he polarized diene, N,N-dimethylaminomethyleneglutaconic acid dinitrile, [12] which is structurally endowedw ith an electron-donating NMe 2 moiety andt wo electronwithdrawing cyano groups attacheda ti ts two C=C bonds,h as been useda saC 3 building block to synthesize carbocyclic compounds.…”

“…To our delight, a1 :1 molar ratio reactiono ccurred in the presence of 50 mol% p-TsOH·H 2 Oa st he promoter in dichloromethane at ambient temperature,f orming the target product 3a in 32% yield with excellent diastereoselectivity (dr > 20:1) ( Among the tested solvents (dichloromethane,1 ,2-dichloroethane,a cetonitrile, toluene andT HF), bothd ichloromethane and1 ,2-dichloroethane were found to provide suitabler eactionm edia, in contrast, the reaction hardly proceeded in THF (Table 1, entries 5a nd [8][9][10][11]. Elevating the reactiont emperature to 40-60 8 8C loweredt he formation of 3a (Table 1, entries 12 and 13).…”

Recent Progress in Transition‐Metal‐Free, Base‐Mediated Benzannulation Reactions for the Synthesis of a Diverse Range of Aromatic and Heteroaromatic Compounds

“…Mal′s group reported an anionic annulation reaction for the synthesis of 7‐hydroxyindoles with complete regioselectivity in the presence of LHMDS as a base in THF from −78 °C to room temperature (Scheme ) . [(Phenylsulfonyl)methyl]pyrrole 111 attacked alkynes 112 as Michael acceptors to furnish aromatized indoles 113 in good‐to‐excellent yields.…”

Sulfonyl Azoles in the Synthesis of 3-Functionalized Azole Derivatives

“…Recently, dimethyl 1,3‐dimethyl‐2,5‐pyrroledicarboxylate has been converted into the corresponding 3‐phenylsulfonylmethyl derivative by exploiting the same procedure as that described for N ‐Boc‐3‐methylindole in Scheme 103. The sulfonyl pyrrole was obtained in 70% yield and employed in the preparation of 7‐hydroxyindoles by an anionic benzannulation with electron‐poor alkenes and alkynes.…”