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Issue 43, 2017
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Mechanistic investigation on N → Cα → O relay via non-Brook rearrangement: reaction conditions promote synthesis of furo[3,2-c]pyridinones

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Abstract

A comprehensive density functional theory investigation was employed to disclose the effect of reaction conditions on the mechanism and effective anion relay sequence of a NaH promoted non-Brook rearrangement of benzaldehyde and 1-cinnamoylcyclopropanecarboxamides. Two main mechanisms were explored under four different reaction conditions: Na+-assisted and nH2O-Na+, 2H2O-DMSO-Na+, and Na+-DMSO co-assisted, and the difference relies on the reaction sequence between the concerted ring-opening and recyclization and electrophilic addition. Being different from previous reports, a cooperative participation of water, solvent DMSO and counterion Na+ is revealed in the preferential mechanism. The preferred scenario undergoes five major steps: deprotonation, aza-Michael addition, electrophilic addition, NaOH elimination and a concerted ring-opening and recyclization step. The rate-determining step is the concerted ring-opening and recyclization process with an energy barrier of 30.2 kcal mol−1. We found that the effective anion relay of a non-Brook rearrangement order is N → Cα → O rather than the previously proposed aza-oxy-carbanion. Meanwhile, a mixed type of ARC chemistry through a novel non-Brook rearrangement was disclosed. Moreover, the non-covalent interactions between substrate and reactant extensively affect the anion relay process by hydrogen-bonding (O–H⋯O and C–H⋯O) and electrostatic (Na+⋯O) interactions. Thus, our results provide insightful clues to the mechanism of the reaction condition catalyzed non-Brook rearrangement reaction.

Graphical abstract: Mechanistic investigation on N → Cα → O relay via non-Brook rearrangement: reaction conditions promote synthesis of furo[3,2-c]pyridinones

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Publication details

The article was received on 21 Aug 2017, accepted on 11 Oct 2017 and first published on 11 Oct 2017


Article type: Paper
DOI: 10.1039/C7OB02081C
Citation: Org. Biomol. Chem., 2017,15, 9127-9138
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    Mechanistic investigation on N → Cα → O relay via non-Brook rearrangement: reaction conditions promote synthesis of furo[3,2-c]pyridinones

    L. Zhu, H. Yuan and J. Zhang, Org. Biomol. Chem., 2017, 15, 9127
    DOI: 10.1039/C7OB02081C

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