Synthesis of Structurally Diverse 3-, 4-, 5-, and 6-Membered Heterocycles from Diisopropyl Iminomalonates and SoftC-Nucleophiles

• DOI: 10.1021/acs.joc.9b00681
• Publication Date: 2019-04-22T22:47:58Z
• Authors: Padmanabha V. Kat...; Urmibhusan Bhakta; Surached Siriwongsup; Doo-Hyun Kwon; Lawrence B. Alemany; Muhammed Yousufuddin; Daniel H. Ess; László Kürti
• Keywords: Carbanion; Nucleophilic Addition

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- N-aryl-substituted diisopropyl iminomalonates wide range soft anionic C-nucleophiles without using any catalyst or additive. Fully substituted aziridines were obtained in single step when enolates α-bromo esters employed as nucleophiles. Enantiomerically enriched azetidines, γ-lactones, tetrahydroquinolines via two-step catalytic asymmetric reduction cyclization sequence from ketone enolate-derived adducts. Finally, highly γ-lactams prepared one pot adducts acetonitrile-derived carbanions. Overall, this work clearly demonstrates utility versatile building blocks practical scalable synthesis structurally diverse heterocycles.