Diastereodivergent Synthesis of Chiral Tetrahydropyrrolodiazepinediones via a One-Pot Intramolecular <i>aza</i>-Michael/Lactamization Sequence

A modular and diastereodivergent synthesis of tetrahydro-1<i>H</i>-pyrrolo­[1,2<i>d</i>]­diazepine-(2,5)-diones is presented. The tetrahydropyrrolodiazepinedione scaffold is obtained via a base-mediated three-step isomerization/tandem cyclization of amino acid-coupled homoallylic amino esters. Diastereoselectivity of the process is mediated by the interplay of a kinetic cyclization event and a propensity for thermodynamic epimerization at two labile chiral centers, giving rise to two distinct major diastereomers dependent on starting material stereochemistry and reaction conditions selected. Herein, we present a synthetic and computational study for this tandem process on a variety of amino ester substrates.