Facile Multicomponent Synthesis of Oxazolidinones from Primary Amines and Cesium (Hydrogen)Carbonate

Abstract

A facile multicomponent, catalyst-free oxazolidinone synthesis from primary aliphatic or aromatic amines, dibromoethane (DBE), and the usage of either cesium carbonate or cesium hydrogencarbonate as the simultaneous base and C1 source is reported. The applicability of this technically simple reaction was demonstrated by a broad scope with generally high yields, enabling concise late-stage functionalization of amino groups into N-substituted oxazolidinones. The proposed operating reaction mechanism consists of a first-step nucleophilic substitution reaction between DBE and the primary amine, followed by the formation of a carbamate or carbonate intermediate and subsequent cyclization. Additional versatility of the herein-developed protocol has been showcased in a medicinal chemistry approach by the generation of an oxazolidinone-modified dipeptidyl peptidase 8 (DPP8) inhibitor.

C1 functionalization of imidazo heterocycles via carbon dioxide fixation

“…Carbonate salts as C 1 feedstocks instead of carbon dioxide have rarely been applied to the synthesis of oxazolidinones and especially to the case of oxazinanones. 56–59 Very interestingly, when we employed a salicyl aldehyde as our oxo-component in the GBB-3CR, we noticed that just treatment with NaHCO 3 in the absence of any metal-catalyst or metal-additive afforded the carbamates 3k–s in high yields (Scheme 3).…”

Graphene Oxide Membrane Reactor for Electrochemical Deuteration Reactions

“…Substituted C–H bonds with heavier C–D bonds are in great demand in the pharmaceutical industry because drug molecules with C–D bonds exhibit improved stability against metabolic cleavage. Hydrogen–deuterium (H–D) substitution has received considerable attention since the U.S. Food and Drug Administration confirmed in 2017 the use of a deuterated drug, deuterobenazine (Austedo), for treating chorea associated with Huntington’s disease and tardive dyskinesia. − Deuterium-labeled alkynes, − alkenes, , alkanes, , amines, , and ketones are valuable in the biotechnology, pharmaceutical, and medical chemistry industries . Therefore, there is an urgent need to innovate new routes to produce various deuterium-labeled compounds with excellent efficiency.…”