New strategies for the synthesis and functionalization of aliphatic amines
Trowbridge, Aaron Daniel
Gaunt, Matthew J.
University of Cambridge
Doctor of Philosophy (PhD)
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Trowbridge, A. D. (2019). New strategies for the synthesis and functionalization of aliphatic amines (Doctoral thesis). https://doi.org/10.17863/CAM.35257
The invention of catalytic processes that convert feedstock chemicals into pharmacologically-privileged amines is a landmark challenge in organic synthesis. This thesis describes the development of three novel transition-metal catalyzed processes for the synthesis of alkylamines that attempts to meet this challenge. The first Pd-catalyzed methylene β-C−H carbonylation of alkylamines to form substituted β-lactams is reported. Through the synergistic use of a Pd-catalyst and Xanpthos ligand, secondary amines underwent exclusive methylene β-C−H activation in high yields and diastereoselectivities. Subsequently, the development of a remarkably selective methylene β-C−H carbonylation of α-tertiary amines (ATAs), is detailed. This methodology enables the C−H carbonylation of methylene C−H bonds over traditionally more reactive methyl and C(sp2)−H bonds. Importantly, a range of functional groups previously incompatible with C−H technologies were tolerated in good yields. Finally, the development of a novel multicomponent synthesis of tertiary amines is described. The novel photocatalytic single-electron reduction of alkyl iminium ions furnishes -amino radicals that engage alkenes forming a new C–C bond. The reaction exhibits broad functional group tolerance and enables the synthesis of amines not readily accessible by existing methods.
C-H activation, transition-metal catalysis, amines, photocatalysis, multicomponent, alkylamines, hydroaminoalkylation, carbonylation, palladium, lactam
Herchel Smith Scholarship
This record's DOI: https://doi.org/10.17863/CAM.35257
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