Taming 3-Oxetanyllithium Using Continuous Flow Technology
Philipp Natho, Marco Colella, Michael Andresini, Leonardo Degennaro, Renzo Luisi
Abstract
The oxetane ring has evolved as a useful bioisostere for dimethyl and carbonyl groups for the improvement of physiochemical properties of drug candidates. Herein, we report the generation and utilization of highly unstable 3-oxetanyllithium as a hitherto unexplored nucleophile leveraging flash technology. A range of different electrophiles are suitable reaction partners in this protocol, and we demonstrate the utility of this protocol in late-stage pharmaceutical analogue synthesis.
Topics & Concepts
OxetaneChemistryElectrophileCombinatorial chemistryBioisostereNucleophileRing (chemistry)Protocol (science)Organic chemistryChemical synthesisCatalysisBiochemistryIn vitroMedicineAlternative medicinePathologyInnovative Microfluidic and Catalytic Techniques InnovationChemical Synthesis and AnalysisCatalytic Cross-Coupling Reactions