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Publication Date

2025-5

First Advisor

David Gorin

Document Type

Honors Project

Degree Name

Bachelor of Arts

Department

Chemistry

Keywords

organic synthesis, benzylation, Cham-Evans-Lam reaction

Abstract

The Chan-Evans-Lam reaction presents a powerful approach for late-stage functionalization (LSF) of complex molecules, enabling selective C-H functionalization without the need for pre-functionalized substrates. This thesis optimized the Chan-Lam C-H benzylation of 1,3,5-trimethoxybenzene (TMB) using boronic acid reagents, focusing on mild reaction conditions and high regioselectivity. Copper trifluoroacetate was utilized as the catalyst in an effort to develop a more efficient and cost-effective system compared to traditional palladium-based methods. The study also explored the use of copper sources with varying electronic properties and extended the substrate scope to include the isomers 1,2,3-TMB and 1,2,4-TMB, examining the influence of steric and electronic factors on the benzylation process. Further optimization of the reaction conditions with 123 TMB led to a crude yield of 18%. The synthesis of novel boron esters as reagents was also explored, providing an alternative to the commonly used BPin, which showed potential for enhancing reactivity and reducing side reactions. Overall, this work contributes to the development of C-H functionalization methods.

Rights

©2025 Liangnuo Zhang. 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

Comments

57 pages: illustrations, charts (some color). Includes bibliographical references (pages 45-47).

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