# Base-Mediated Synthesis of Imidazole-Fused 1,4-Benzoxazepines via 7-exo-dig Cyclizations: Propargyl Group Transformation

## TL;DR

This paper presents a new method for synthesizing imidazole-fused 1,4-benzoxazepines using base-mediated cyclization and propargyl group transformations.

## Contribution

The study introduces a novel base-mediated 1,3-H shift to convert exocyclic to endocyclic products and explains unexpected isomer formation via DFT calculations.

## Key findings

- Disubstituted alkyne substrates smoothly produce exocyclic E/Z configured products.
- Terminal alkynes lead to isomeric products with altered structures due to O-to-N-propargyl transfer reactions.
- Base-mediated 1,3-H shift effectively converts exocyclic to endocyclic products.

## Abstract

Herein, we describe the synthesis of a series of imidazole-fused
1,4-benzoxazepines using 7-exo-dig cyclizations.
Two sets of substrates, one containing disubstituted alkyne functional
groups and the other featuring terminal alkynes, were synthesized
by using O-propargylation, Sonogashira cross-coupling,
and condensation reactions between aldehydes and o-diaminobenzene. While the disubstituted substrates yielded exocyclic E/Z configured cyclization products smoothly,
the reactions involving terminal alkynes resulted in the formation
of isomeric products with altered skeletal structures, in addition
to the expected 7-exo-dig cyclization products. Density
functional theory (DFT) calculations were used to clarify the mechanisms
underlying the formation of these products. It is suggested that these
unexpected products are formed through a series of intermolecular O-to-N-propargyl transfer reactions, followed
by 7-exo-dig cyclization, in accordance with Baldwin’s
rules. Furthermore, this study extensively demonstrates the conversion
of exocyclic products to endocyclic products through a base-mediated
1,3-H shift.