Date of Award

Spring 5-11-2023

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Abstract

Alkenes as masked functional groups have been a hallmark of organic chemistry and have been utilized to diversify natural products and medicinal targets. Disubstitutions have been a challenge for researchers as the reactions that are implemented most are not selective for the face that they attack. Investigations into electrophilic cyclization looked to overcome this phenomenon by introducing a known chiral center α to an amine where a protecting group, sulfonamide, is added to increase the torsional and allylic strain in the molecules. X-ray crystal structures and NMR techniques prove that the strain does affect the diastereoselectivity of the reaction through a half chair intermediate.

Knowledge that the allylic strain of the sulfonamide affects the substituent α to the moiety lead investigations to understanding the reactivity of the nitrogen bound to the protecting group. The N-sulfonyliminium ion is less explored due to the lack of electron density residing in the protected nitrogen. Pictet-Spengler cyclizations were thoroughly scouted for Lewis acids that would coordinate to an aldehyde, enabling the sulfonamide to attack the electrophilic carbonyl and initiate a cyclization. These findings led to investigations of intramolecular Aza-Prins reactions that must invoke the N-sulfonyliminium ion to cyclize.

Determining that the sulfonamide affected the diastereotopicity of molecules, the Pummerer reaction was employed to form new trisubstituted piperidine rings. Dependent on the sulfoxide reactivity to initiate the reaction, the Pummerer cyclization has been looked over due to the lack of reactivity of unsubstituted alkenes. Research, herein, does an expansive initiator screen and identifies Lewis acids to propose a mechanism for inducing cyclization.

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