Deprotonation of Benzoxazole and Oxazole Using Lithium Magnesates

Abstract

The first deprotonations of oxazole and benzoxazole using lithium magnesates are described. The reactions occurred in tetrahydrofuran at room temperature using 1/3 equiv of lithium tributylmagnesate. As 2-lithiooxazole and 2-lithiobenzoxazole, lithium tri(2-oxazolyl)magnesate and lithium tri(2-benzoxazolyl)magnesate very rapidly and completely isomerized to the more stable 2-(isocyano)enolate and 2-(isocyano)phenolate type structures, respectively, a result shown by NMR analysis. The isolation of 2-substituted oxazoles and benzoxazoles in medium to good yields after electrophilic trapping was interpreted in two ways: (1) the equilibration between the open and closed structures is faster than the trapping of the open isomers, and the closed isomers are more reactive than the open ones, or (2) the open isomers react with electrophiles in a intramolecular Passerini type reaction. The nonreactivity of the 2-(isocyano)enolate type structure toward anisaldehyde in the absence of lithium bromide makes the intramolecular Passerini type reaction more plausible.

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

“…The C2-magnesation of oxazole was first performed with lithium tributylmagnesate at room temperature, and rapid evolution of the C2-magnesated oxazole to a ring-open isonitrile tautomer was evidenced by 1 H NMR spectroscopy analysis [35]. Nevertheless, subsequent cross-coupling reactions under palladium catalysis were successfully achieved.…”

Deprotonierende Metallierungen mit 'at‐Verbindungen: Synergie, Synthese und Strukturaufbau

“…Deprotonierungen gelangen auch, wenn acidere Substrate wie Fluor- [34] und Chlorpyridine [35] Die Reaktionen von Thiophenen [37] und Furanen [38] Reaktionen der Oxazole 29 und 30 (Schema 10) mit Lithiummagnesiaten wurden ausführlich untersucht, wobei insbesondere analysiert wurde, welche Spezies nach dem Deprotonierungsschritt in der Lösung vorliegen. [39] Die 2-Lithiooxazole, die durch Reaktion von Alkyllithiumreagentien mit den Heterocyclen entstehen, werden in Form der bei Raumtemperatur vorherrschenden, offenen Lithium-2-(isocyan)enolate stabilisiert. [40] Oxazol (29) Die im voranstehenden Abschnitt beschriebenen Ergebnisse gaben somit erste Hinweise darauf, dass gemischte Lithium-Magnesium-Basen über ein großes Anwendungspotenzial in der organischen Synthese verfügen.…”

Transition metals in organic synthesis: Highlights for the year 2005

“…Palladiumcatalyzed coupling of lithium tri(2-oxazolyl)magnesate and tri(2-benzoxazolyl)magnesates with arylhalides [102]. A palladium-catalyzed alkyl Grignard-alkenyl triflate coupling was used in a synthesis of 15-deoxy-16-(m-tolyl)-17,18,19,20-tetranorisocarbacyclin [103].…”