Metal-catalyzed annulations of strained cycloalkanes Public Deposited

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  • March 21, 2019
Creator
  • Parsons, Andrew Thomas
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • I. Lewis Acid-Catalyzed (3 + 2) Annulation of Malonate-Derived Donor-Acceptor Cyclopropanes and Aldehydes An overview of the development, scope, and mechanism of the (3 + 2) annulation of malonate-derived donor-acceptor cyclopropanes and aldehydes is presented. II. Palladium(0)-Catalyzed Annulation of Dimethyl 2-Vinylcyclopropane-1,1-Dicarboxylate and Aldehydes: The Synthesis of Tetrahydrofurans through an Aldol– Allylic Etherification Sequence The synthesis of tetrahydrofurans via palladium(0)-catalyzed annulation of dimethyl 2-vinylcyclopropane-1,1-dicarboxylate and aldehydes is described. Carbon-carbon bond cleavage of the cyclopropane was achieved through ð-allylpalladium formation. Aldol reaction with an aldehyde and subsequent ring-closure provides the desired 2,5-cisdisubstituted tetrahydrofurans with high diastereoselectivity. III. Enantioselective Synthesis of Tetrahydrofurans via Dynamic Kinetic Asymmetric (3 + 2) Annulation of Racemic Cyclopropanes and Aldehydes The synthesis of enantioenriched 2,5-cis-disubstituted tetrahydrofurans was achieved through a dynamic kinetic asymmetric transformation (DyKAT) of racemic cyclopropanes. Use of a catalytic amount of 4-chloro-tert-butylpybox/MgI2 facilitated the enantioselective annulation of electron-rich donor-acceptor cyclopropanes and aldehydes. The electrondeficient 4-chloro-pybox ligand provided an increase in yield while maintaining high levels of stereoselectivity. IV. Dynamic Kinetic Asymmetric Synthesis of Pyrrolidines from Racemic Cyclopropanes and Aldimines: Reaction Development and Mechanistic Insights The use of a (pybox)MgI2 catalyst for the dynamic kinetic asymmetric synthesis of pyrrolidines from donor-acceptor cyclopropanes and aldimines is described. The choice of N-protecting group and 4-substituted-tert-butyl-pybox ligand was essential to achieving high yields and selectivities. Mechanistic investigations suggest that the reaction occurs via annulation with the (E)-aldimine dipolarophile exclusively and minimal E¯Z-isomerization occurs prior to annulation. V. Lewis Acid-Catalyzed (4 + 2) Annulation of Donor-Acceptor Cyclobutanes and Aldehydes The diastereoselective synthesis of 2,6-cis-disubstituted tetrahydropyrans via (4 + 2) annulation of D–A cyclobutanes and aldehydes is described. Sc(OTf)3 and Hf(OTf)4 catalyze the annulation with cinnamyl and aryl aldehydes. Extension of this methodology to alkyl aldehydes required the use of a bulky aluminum(III) Lewis acid. A one-pot cycloaddition/annulation cascade was achieved, providing access to tetrahydropyrans directly from an olefin, dimethyl 2-methylenemalonate, and an aldehyde.
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  • "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry."
Advisor
  • Johnson, Jeffrey
Degree granting institution
  • University of North Carolina at Chapel Hill
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  • Chapel Hill, NC
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  • Open access
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