Organocatalyzed CO₂ Trapping Using Alkynyl Indoles

Abstract

The first organocatalyzed trapping of CO2 through C-C and C-O bond formation is reported. Alkynyl indoles together with catalytic amounts of an organic base and five equivalents of CO2 resulted in the formation new heterocyclic structures. These tricyclic indole-containing products were successfully prepared under mild reaction conditions from aromatic, heteroaromatic, and aliphatic alkynyl indoles with complete regioselectivity. Further investigations suggest that C-C bond formation is the initial intermolecular step, followed by lactone-forming C-O bond formation.

Coupling Reactions of Alkynyl Indoles and CO2 by Bicyclic Guanidine: Origin of Catalytic Activity?

“…For computational efficiency, substrate 1 a (Scheme ) was used to investigate the three possible activation modes in Scheme . It is noteworthy that Skrydstrup and co‐workers reported the use of 3 equivalents of TBD to generate significant levels of 1 a at a lower temperature (70 °C) than the optimal temperature (100 °C) . This change was made to avoid the decomposition of 1 a at 100 °C.…”

“…Based on the correlation between the catalytic activity and basicity properties of amines/guanidines in the reactions of CO 2 with propargylamines, the authors concluded that the basicity of the catalyst, rather than the formation of the CO 2 adduct, was responsible for the catalytic activity. This interesting finding raised obvious questions pertaining to the source of the catalytic activity in the CO 2 coupling reaction reported by Skrydstrup's group …”

“…Various organic compounds, such as guanidine, can form stable adducts with CO 2 , as exemplified by the crystal structure of the zwitterionic adduct of the bicyclic guanidine 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD) with CO 2 (TBD‐CO 2 ), which was reported by Villiers et al . Skrydstrup and co‐workers recently reported the elegant use of TBD as an organocatalyst for the coupling of alkynyl indoles with CO 2 (Scheme ) . Notably, this work allowed for the synthesis of several biologically important indoles using CO 2 as a readily available and inexpensive C1 source.…”

“…With this in mind, we envisaged that density functional theory (DFT) calculations could be used to elucidate the mechanism of this useful guanidine‐catalyzed CO 2 transformation. In this study, we investigated the intriguing catalytic mechanism of CO 2 trapping by alkynyl indoles in the presence of a guanidine base catalyst . We considered three plausible activation modes for the CO 2 trapping mechanism of alkynyl indoles (Scheme ).…”

Direct Carboxylation of C(sp3)-H and C(sp2)-H Bonds with CO2 by Transition-Metal-Catalyzed and Base-Mediated Reactions

“…A TBD base was used by Skyrdrup to catalyze a carboxylation/cyclization reaction applied to 2-alkynyl indoles (127) with aromatic or aliphatic substituents at the alkyne unit (Scheme 53) to produce selectively the new heterocyclic structures 128 [128]. Aromatic 2-alkynyl indoles (R 2 = aryl, Scheme 53) (0.20 mmol) were reacted in the presence of 0.3 eq.…”