# Straightforward Access to Polyfunctionalized δ-Lactams via Domino Aza–Michael/Thia–Michael/Aldol Sequence

## TL;DR

This paper introduces a new chemical method to efficiently create complex molecules called δ-lactams using a sequence of reactions.

## Contribution

A new domino reaction sequence is introduced for synthesizing polyfunctionalized δ-lactams with mild conditions and good yields.

## Key findings

- The method uses N-alkoxyacrylamides and α,β-unsaturated carbonyls to form δ-lactams efficiently.
- The reaction is compatible with various thiophenol derivatives and uses a one-pot process.
- Acrylamides act as both nucleophiles and electrophiles in a single reaction flask.

## Abstract

Domino reactions are powerful tools for the straightforward synthesis of complex molecules with a particular emphasis on functionalized azacycles. We report a contribution in this field, implemented via a new thia–Michael/aldol sequence between readily accessible N-alkoxyacrylamides and α,β-unsaturated carbonyls, for access to polysubstituted δ-lactams with acceptable-to-good yields and good selectivity. This method, initially developed in a two-component approach and characterized by the mildness of its reaction conditions, was shown to be compatible with various thiophenol derivatives and to employ a simple pre-thiasilylation step in a one-pot process. This further extension to the monotype aza–Michael/thia–Michael/aldol sequence establishes a proof-of-concept that acrylamides can react as both 1,3-bis-nucleophiles and 1,4-electrophiles in a single flask operation.