Chennamadhavuni, SpandanPanek, James S.Porco, John A.Brown, Lauren E.2020-01-302020-01-302018-12-21Spandan Chennamadhavuni, James S Panek, John A Porco, Lauren E Brown. 2018. "Diastereodivergent Synthesis of Chiral Tetrahydropyrrolodiazepinediones via a One-Pot Intramolecular aza-Michael/Lactamization Sequence." JOURNAL OF ORGANIC CHEMISTRY, Volume 83, Issue 24, pp. 15449 - 15462 (14). https://doi.org/10.1021/acs.joc.8b027240022-3263https://hdl.handle.net/2144/39203A modular and diastereodivergent synthesis of tetrahydro-1H-pyrrolo[1,2d]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.p. 15449 - 15462en-USScience & technologyPhysical sciencesChemistry, organicChemistryDynamic thermodynamic resolutionTransannular cyclizationsCyclodimerizationEquilirationDiversityChemistry techniques, syntheticCyclizationKineticsLactamsModels, molecularMolecular conformationPyrrolesStereoisomerismThermodynamicsMedicinal and biomolecular chemistryOrganic chemistryInorganic chemistryOrganic chemistryArticle10.1021/acs.joc.8b02724420465