Synthesis of 2,Dialkylpyrrolidines from γ-Ketooximes Derived from Isoxazolines
Poster Number
31
College
College of Arts and Sciences
Department
Chemistry, Physics, Geology, & the Environment
Faculty Mentor
Dr. Aaron M. Hartel
Abstract
γ-Ketooximes and their cyclic tautomers are versatile synthetic precursors to a variety of important compound classes, including pyrroles, pyrrolidines and γ-diketones. We are currently interested in transforming these valuable intermediates into 2,5-dialkylpyrrolidines, some of which occur naturally in the venoms of various species of Solenopsis ants. Related piperidine alkaloids from other Solenopsis species have been shown to have significant antiangiogenesis activity and have been investigated as a potential treatment for cancer.The overall synthetic strategy involves the 1,3-dipolar cycloaddition of a nitrile oxide with an α,β-unsaturated ketone to give an acylisoxazoline. This intermediate is then treated with a silyllithium reagent, triggering a ring-opening Brook rearrangement via chemistry previously developed in our laboratory. Excess silyllithium reagent then cleaves the resulting silyl enol ether giving the γ-ketooxime upon workup. Selective reduction of the oxime would then initiate an intramolecular reductive amination to give the target pyrrolidine.The current focus of the project is the determination of conditions appropriate for the final oxime reduction and reductive amination sequence. Various catalytic hydrogenation conditions have been explored using oximes prepared from cyclopentanone and cyclohexanone as inexpensive and readily available models of the γ-ketooximes. The successful reduction conditions were then applied to mixtures of oximes and ketones to determine if intermolecular reductive amination would also occur under the same conditions.
Start Date
22-4-2016 2:15 PM
End Date
22-4-2016 4:15 PM
Synthesis of 2,Dialkylpyrrolidines from γ-Ketooximes Derived from Isoxazolines
Richardson Ballroom
γ-Ketooximes and their cyclic tautomers are versatile synthetic precursors to a variety of important compound classes, including pyrroles, pyrrolidines and γ-diketones. We are currently interested in transforming these valuable intermediates into 2,5-dialkylpyrrolidines, some of which occur naturally in the venoms of various species of Solenopsis ants. Related piperidine alkaloids from other Solenopsis species have been shown to have significant antiangiogenesis activity and have been investigated as a potential treatment for cancer.The overall synthetic strategy involves the 1,3-dipolar cycloaddition of a nitrile oxide with an α,β-unsaturated ketone to give an acylisoxazoline. This intermediate is then treated with a silyllithium reagent, triggering a ring-opening Brook rearrangement via chemistry previously developed in our laboratory. Excess silyllithium reagent then cleaves the resulting silyl enol ether giving the γ-ketooxime upon workup. Selective reduction of the oxime would then initiate an intramolecular reductive amination to give the target pyrrolidine.The current focus of the project is the determination of conditions appropriate for the final oxime reduction and reductive amination sequence. Various catalytic hydrogenation conditions have been explored using oximes prepared from cyclopentanone and cyclohexanone as inexpensive and readily available models of the γ-ketooximes. The successful reduction conditions were then applied to mixtures of oximes and ketones to determine if intermolecular reductive amination would also occur under the same conditions.
