Reaction of Cyclic α-Oxoketene Dithioacetals with Methylene Isocyanides: A Novel Pyrrole Annulation–Ring-Expansion Domino Process

Abstract

The title reaction provides a direct entry to a range of biologically relevant annulated pyrroles via a domino process involving a regioselective one-carbon homologation of cyclic ketones as the key step.

′′One‐Pot′′ Selective Synthesis of 3,4‐Disubstituted Pyrroles and Benzo[f]indole‐4,9‐diones from 1,3‐Indanedione, Aromatic Aldehydes and TosMIC

“…Based on the aforementioned results and literature precedence,, possible mechanism for the formation of substituted or condensed pyrrole derivatives is outlined in Scheme . The mechanism of ethyl 2‐(4‐phenyl‐1H‐pyrrole‐3‐carbonyl)benzoate ( 4 a ) involves, initial 1,4‐conjugate addition of TosMIC anion 9a to Michael acceptor 2 a followed by intramolecular cyclization of the enolate adduct A , furnishes the spiropyrrolenine anion B , which takes the proton from EtOH and further undergo facile ring cleavage by nucleophilic attack of ethoxide on carbonyl group of C yielding the ortho‐substituted ethyl ester D and subsequent elimination of toluenesulfinate anion and isomerization to yield the final product 4 a .…”

“…The formation of ethyl 2‐(4‐phenyl‐1H‐pyrrole‐3‐carbonyl)benzoate ( 4 a ) was confirmed from NMR studies (DEPT, COSY, HSQC, HMBC and 15 N HMBC) and HRMS (Supporting Information, page:15‐18). Surprisingly, the change of the solvent from EtOH to THF or 1,4‐dioxane at reflux temperature resulted in 3‐phenyl‐1H‐benzo[f]indole‐4,9‐dione ( 5 a ) 11 with moderate yields through one‐carbon‐atom ring expansion along with acyl 1,2‐migration ,. Notably, when CuI (10 mol%) was employed as catalyst and Cs 2 CO 3 (1.2 eq) as the base in 1,4‐dioxane at 80 °C, the yield of 5 a was greatly improved to 91% (entry 8).…”

“…In continuation, the extension of the van Leusen pyrrole synthesis for the formation of 2‐acylpyrroles and medium‐ring fused pyrroles by capturing the incipient imidoyl anion with a tethered carbonyl group was reported . In addition, recently Ila et al reported the base mediated reaction of cyclic oxoketene dithioacetals with methyl isocyanides for the synthesis of 3‐(methylthio)‐1H‐bezo[f]indole‐4,9‐diones at high temperature and Zhang et al has reported the silver‐catalysed reaction of TosMIC with 2‐methyleneindene‐1,3‐diones for the synthesis of bezo[f]indole‐4,9‐diones through a domino [3+2]‐ cycloaddition/ringexpansion . However, to the best of our knowledge, the synthesis of 3,4‐disubstituted pyrroles from 2‐methyleneindene‐1,3‐diones has not been documented yet.…”

“…Surprisingly, the change of the solvent from EtOH to THF or 1,4-dioxane at reflux temperature resulted in 3phenyl-1H-benzo[f]indole-4,9-dione (5 a) 11 with moderate yields through one-carbon-atom ring expansion along with acyl 1,2migration. [10,11] Notably, when CuI (10 mol%) was employed as catalyst and Cs 2 CO 3 (1.2 eq) as the base in 1,4-dioxane at 80 8C, the yield of 5 a was greatly improved to 91% (entry 8). However, the yield of 5 a was lower in the absence of the catalyst.…”

Arylsulfonylmethyl isocyanides: a novel paradigm in organic synthesis

“…In continuation, Ila and co-workers disclosed a domino process for the diversity oriented synthesis of annulated pyrroles involving a base-induced reaction of cyclic a-oxoketene dithioacetals with activated methylene isocyanides. 33 The generality and scope of this method is described in Fig. 3.…”