This Is AuburnElectronic Theses and Dissertations

Regio- and Enantioselective Synthesis of N-alkyl 1,2- and 1,6-dihydropyridines through Rhodium-Catalyzed Nucleophilic Dearomatization




Robinson, Donovan

Type of Degree

PhD Dissertation


Chemistry and Biochemistry

Restriction Status


Restriction Type

Auburn University Users

Date Available



Nonaromatic nitrogen heterocycles, particularly the ones containing one or multiple stereogenic centers, are common structural motifs in bioactive natural products and continue to be challenging synthetic targets. The dihydropyridine motif is an attractive intermediate in the synthesis of such heterocycles. Prior syntheses of such molecules usually involve linear syntheses or highly specialized starting materials. Dihydropyridines can be converted to other (partially) saturated nitrogen heterocycles such as tetrahydropyridines and piperidines through hydrogenation and functionalization reactions. Here, we discuss the synthesis of 1,6- and 1,4 dihydropyridines as synthetic intermediates to small molecule synthesis. First, we investigated boronic acids as nucleophiles due to their commercial availability and functional group tolerance. We have reported the formation of 1,6-dihydropyridines containing fully substituted stereogenic centers using phenyl and alkenyl boronic acids with a variety of functional groups including alkenes, free alcohols, ethers, amides, esters, halides, and heterocycles. Next, we explored the use of boronic acid pinacol esters (Bpins) as nucleophiles due to their higher stability, which enabled us to increase the yield of heterocycle addition, as well as expand the scope of N-heteroarene starting materials. We were also able to employ our strategy to complete an enantioselective total synthesis of the natural product nuphar indolizidine. Finally, we are currently developing the regioselective addition of boronic acids and their pinacol esters to N-alkyl pyridinium salts. We found that different ligands bound to the metal provide different selectivity, particularly to the C-2 electrophilic site on the heteroarenium salt.