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

ABSTRACT: A modular and diastereodivergent synthesis of tetrahydro-1 H-pyrrolo[1,2 d]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.

SUBMITTER: Chennamadhavuni S

PROVIDER: S-EPMC7203762 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Chennamadhavuni Spandan S Panek James S JS Porco John A JA Brown Lauren E LE

The Journal of organic chemistry 20181205 24

A modular and diastereodivergent synthesis of tetrahydro-1 H-pyrrolo[1,2 d]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 diastereom ...[more]

PMID: 30458107

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