Issue 7, 2015

Understanding the domino reaction between 3-chloroindoles and methyl coumalate yielding carbazoles. A DFT study

Abstract

The molecular mechanism of the reaction between N-methyl-3-chloroindole and methyl coumalate yielding carbazole has been studied using DFT methods at the MPWB1K/6-311G(d,p) level in toluene. This reaction is a domino process that comprises three consecutive reactions: (i) a polar Diels–Alder (P-DA) reaction between indole and methyl coumalate yielding two stereoisomeric [2 + 4] cycloadducts (CAs); (ii) the elimination of HCl from these CAs affording two stereoisomeric intermediates; and (iii) the extrusion of CO2 in these intermediates, finally yielding the carbazole. This P-DA reaction proceeds in a completely regioselective and slightly exo selective fashion. In spite of the highly polar character of this P-DA reaction, it presents a high activation enthalpy of 21.8 kcal mol−1 due to the loss of the aromatic character of the indole during the C–C bond formation. Thermodynamic calculations suggest that the P-DA reaction is the rate-determining step of this domino reaction; in addition, the initial HCl elimination in the formal [2 + 4] CAs is kinetically favoured over the extrusion of CO2. Although the P-DA reaction is kinetically and thermodynamically very unfavourable, the easier HCl and CO2 elimination from the [2 + 4] CAs together with the strong exergonic character of the CO2 extrusion makes the P-DA reaction irreversible. An ELF topological analysis of the bonding changes along the P-DA reaction supports a two-stage one-step mechanism. An analysis of the global DFT reactivity indices at the ground state of the reagents confirms the highly polar character of this P-DA reaction. Finally, the complete regioselectivity of the studied reactions can be explained using the Parr functions.

Graphical abstract: Understanding the domino reaction between 3-chloroindoles and methyl coumalate yielding carbazoles. A DFT study

Supplementary files

Article information

Article type
Paper
Submitted
04 Nov 2014
Accepted
05 Dec 2014
First published
05 Dec 2014

Org. Biomol. Chem., 2015,13, 2034-2043

Author version available

Understanding the domino reaction between 3-chloroindoles and methyl coumalate yielding carbazoles. A DFT study

L. R. Domingo, J. A. Sáez and S. R. Emamian, Org. Biomol. Chem., 2015, 13, 2034 DOI: 10.1039/C4OB02340D

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