One-Pot Synthesis of N–H-Free Pyrroles from Aldehydes and Alkynes

Abstract

The first base-mediated intermolecular cyclization of arylaldehydes and terminal arylacetylenes for the synthesis of a wide range of pyrroles in a single step has been described. The developed methodology used commercially available starting materials and tolerated a broad range of functional groups affording 2,3,5-triaryl-substituted-1Hpyrroles with good yields (up to 92% yield) under mild conditions. The possible mechanism was also discussed.

Synthesis of Indoles via Domino Reactions of 2-Methoxytoluene and Nitriles

“…28 Building upon this strategy, related approaches were developed to construct diverse functionalized heterocycles. 21,34,35 For example, a synthesis of indoles was developed from 2-fluorotoluenes and benzonitriles (Scheme 2b) 21 and a protocol to generate 2-azaaryl tetrahydroquinolines from azaaryl methyl amines by addition of the resulting carbanion to the styrene double bond, and S N Ar (Scheme 2c). 35,36 Both reaction sequences proceed via a combination of benzylic carbanions and nucleophilic aromatic substitution (S N Ar) reactions at C−F bonds.…”

2-Arylindoles: Concise Syntheses and a Privileged Scaffold for Fungicide Discovery

“…18,19 More recently, our two labs explored whether the combined advances of Mao's indole synthesis and Zhang's pesticide discovery could address these challenges in pesticide discovery. 20,21 Beginning in 2017, the Mao Representative examples include one-pot aminobenzylation of aldehyde with toluenes (Figure 3a), 22 tandem synthesis of indoles with 2-fluorotoluenes (Figure 3b), 23 and many others. 24−27 Despite the advances in highly efficient indole syntheses and their potential applications in industry, two major questions remained: first, could these 2-arylindoles be applied as agrochemicals?…”

“…For example, traditional Bischler–Möhlau synthesis and the Fischer indole synthesis need harsh reaction conditions and poisonous hydrazines. Many modern indole syntheses could improve the synthetic yield by employing transition-metal catalysts, but the limitations of these noble metals as well as the requirements on trace heavy metal residue in fine chemicals have driven the desire to develop transition-metal-free approaches with easily accessible feedstocks. , More recently, our two labs explored whether the combined advances of Mao’s indole synthesis and Zhang’s pesticide discovery could address these challenges in pesticide discovery. , Beginning in 2017, the Mao group developed a collection of Brønsted bases (MN­(SiMe 3 ) 2 , M = Li, Na, K, Cs) that mediated functionalization of weakly acidic C–H bonds. The key findings include: (1) the “mixed bases” (LiN­(SiMe 3 ) 2 /CsF, NaN­(SiMe 3 ) 2 /CsTFA) could facilitate toluene deprotonation under the assistance of alkali-metal cation–pi interaction; (2) the dual role of MN­(SiMe 3 ) 2 can promote the tandem C–N and C–C bond formations; (3) the products contain critical motifs with potential applications in medicinal chemistry.…”

BF3-promoted reactions of α-amino acetals with alkynes to 2,5-disubstituted pyrroles

“…However, metal-free processes for the synthesis of pyrroles using alkynes as two carbon synthons have been rarely realized. 10,17 On the other hand, α-amino acetals are widely used as the building blocks for the synthesis of N-heterocycles owing to their unique functionalities. 18 Recently, several kinds of azapolycyclic frameworks, such as bridged ring, potential dopamine D1 receptor ligands, and tetrahydrobenzo [c]phenanthridines, have been constructed through intramolecular double cyclization of α-amino acetals, 19 which were prepared by α-amination of aldehydes.…”

“…However, metal-free processes for the synthesis of pyrroles using alkynes as two carbon synthons have been rarely realized. 10,17…”