Two-Step Synthesis of 2,3-Dihydropyrroles via a Formal 5-endo Cycloisomerization of Ugi 4-CR/Propargyl Adducts

Abstract

A practical two-step synthesis of 2,3-dihydropyrroles from Ugi 4-CR/propargyl adducts is presented. The protocol includes a base-mediated formation of an allenamide functional group and an in situ metal-free formal 5-endo cycloisomerization that occurs in a highly regioselective manner at the allenamide C-γ.

Allenamides: A Powerful and Versatile Building Block in Organic Synthesis

“…Miranda 87 reported a two-step operation to access 2,3-dihydropyrroles 306 involving a base-promoted cyclization of allenamide intermediates 305 (Scheme 83). A Ugi four-component reaction (Ugi 4-CR) 88 was conducted with In(III) catalyst to afford propargyl amide 304 .…”

A Convenient Synthesis of 1,2‐Disubstituted‐cis‐3,4‐Dihydroxypyrrolidines via an Ugi‐Four‐Component‐Reaction/Cycloisomerization/Dihydroxylation Protocol

“…[47] Thus, propargylamine (11), ethyl glyoxalate (12; 50 % in toluene; 1.2 equiv. [47] Thus, propargylamine (11), ethyl glyoxalate (12; 50 % in toluene; 1.2 equiv.…”

“…First, the synthesis of Ugi model compound 15a was carried out in 45 % yield through a modification of a procedure reported by Miranda and coworkers. [47] Thus, propargylamine (11), ethyl glyoxalate (12; 50 % in toluene; 1.2 equiv. ), benzoic acid (13), and tert-butyl isocyanide (14) were heated in 2,2,2-trifluoroethanol (0.3 M) in the presence of InCl 3 (2 mol-%) under microwave irradiation (MW; 70°C, 2 h; Table 1).…”

Transition-metal free highly selective aerobic oxidation of hindered 2-alkylindoles

“…2, B). 23 Zhang et al have established an intramolecular nucleophilic aromatic substitution reaction (Fig. 2, C) under basic conditions.…”