Padmanabha V Kattamuri1, Urmibhusan Bhakta1, Surached Siriwongsup1, Doo-Hyun Kwon2, Lawrence B Alemany1,3, Muhammed Yousufuddin4, Daniel H Ess2, László Kürti1. 1. Department of Chemistry , Rice University, BioScience Research Collaborative , Houston , Texas 77005 , United States. 2. Department of Chemistry and Biochemistry , Brigham Young University , Provo , Utah 84602 , United States. 3. Shared Equipment Authority , Rice University , 6100 Main Street , Houston , Texas 77005 , United States. 4. Life and Health Sciences Department , University of North Texas at Dallas , Dallas , Texas 75241 , United States.
Abstract
Herein, we present a general synthetic strategy for the preparation of 3-, 4-, 5-, and 6-membered heterocyclic unnatural amino acid derivatives by exploiting facile Mannich-type reactions between readily available N-alkyl- and N-aryl-substituted diisopropyl iminomalonates and a wide range of soft anionic C-nucleophiles without using any catalyst or additive. Fully substituted aziridines were obtained in a single step when enolates of α-bromo esters were employed as nucleophiles. Enantiomerically enriched azetidines, γ-lactones, and tetrahydroquinolines were obtained via a two-step catalytic asymmetric reduction and cyclization sequence from ketone enolate-derived adducts. Finally, highly substituted γ-lactams were prepared in one pot from adducts obtained using acetonitrile-derived carbanions. Overall, this work clearly demonstrates the utility of iminomalonates as highly versatile building blocks for the practical and scalable synthesis of structurally diverse heterocycles.
Herein, we present a general synthetic strategy for the preparation of 3-, 4-, 5-, and 6n class="Chemical">-membered heterocyclic unnatural amino acid derivatives by exploiting facile Mannich-type reactions between readily available N-alkyl- and N-aryl-substituted diisopropyl iminomalonatesand a wide range of soft anionic C-nucleophiles without using any catalyst or additive. Fully substituted aziridines were obtained in a single step when enolates of α-bromo esters were employed as nucleophiles. Enantiomerically enriched azetidines, γ-lactones, andtetrahydroquinolines were obtained via a two-step catalytic asymmetric reduction and cyclization sequence from ketone enolate-derived adducts. Finally, highly substituted γ-lactams were prepared in one pot from adducts obtained using acetonitrile-derived carbanions. Overall, this work clearly demonstrates the utility of iminomalonates as highly versatile building blocks for the practical and scalable synthesis of structurally diverse heterocycles.
Authors: Andrea Stevenazzi; Mattia Marchini; Giovanni Sandrone; Barbara Vergani; Maria Lattanzio Journal: Bioorg Med Chem Lett Date: 2014-10-13 Impact factor: 2.823