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Publication Date

2022-05-09

First Advisor

David Gorin

Document Type

Honors Project

Degree Name

Bachelor of Arts

Department

Biochemistry

Keywords

cyclopropylation, copper-catalyzed, chemistry, alcohol, alkylation, oxidation

Abstract

Cyclopropanes possess unique physical qualities due to their strained conformation, making them a structure of interest in drug development efforts. Researchers have found that the installation of these three-membered rings in drug candidates allowed for greater metabolic stability and solubility. Cyclopropyl ether moieties have also been found to improve drug efficacy, but these structures are a relatively challenging target to synthesize. Current methods to synthesize these ethers either require specific functional groups or utilize a multi-step synthesis. A Chan-Lam oxidative cross-coupling method using an aliphatic alcohol to synthesize these ethers would involve a one-step synthesis with mild reaction conditions. However, examples of Chan-Lam alkylation reactions are limited and no examples of Chan-Lam cyclopropylation of aliphatic alcohols currently exist. Based on previous work in the Gorin Lab involving Chan-Lam O-methylation, this project aimed to develop conditions for Chan-Lam O-cyclopropylation of aliphatic alcohols. This reaction would react an aliphatic alcohol with cyclopropylboronic acid, using a copper catalyst to oxidatively cross-couple the two nucleophiles. After screening multiple reaction conditions, we developed a set of conditions that proved successful in cyclopropylation of phenethyl alcohol. We found that the addition of a base was necessary to ensure cyclopropyl ether formation. The cyclopropyl ether product of phenethyl alcohol was characterized using gas chromatography mass spectrometry (GC/MS), proton NMR, and carbon NMR. Preliminary results also suggested that this set of conditions may have synthesized the cyclopropyl ether product of 2-cyclohexylethanol, but further studies are required to make this conclusion. Future work would involve optimizing the reaction conditions and expanding the substrate scope to encompass a variety of aliphatic alcohols.

Rights

©2022 Miranda Wu. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.

Language

English

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