10.1021/acs.joc.8b02724.s001 Spandan Chennamadhavuni Spandan Chennamadhavuni James S. Panek James S. Panek John A. Porco John A. Porco Lauren E. Brown Lauren E. Brown Diastereodivergent Synthesis of Chiral Tetrahydropyrrolodiazepinediones via a One-Pot Intramolecular <i>aza</i>-Michael/Lactamization Sequence American Chemical Society 2018 Chiral Tetrahydropyrrolodiazepinediones esters diastereodivergent synthesis reaction conditions Herein ester substrates interplay variety base-mediated material stereochemistry propensity Diastereodivergent Synthesis acid-coupled homoallylic diastereomer isomerization chiral centers epimerization Sequence One-Pot Intramolecular aza Diastereoselectivity tandem process tetrahydropyrrolodiazepinedione scaffold cyclization event 2018-11-20 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Diastereodivergent_Synthesis_of_Chiral_Tetrahydropyrrolodiazepinediones_via_a_One-Pot_Intramolecular_i_aza_i_-Michael_Lactamization_Sequence/7427489 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.