Synthesizing Stilbene by Olefin Metathesis Reaction Using Guided Inquiry To Compare and Contrast Wittig and Metathesis Methodologies

Abstract

In this experiment, students are asked to conduct a catalytic cross-metathesis experiment and compare this reaction to the Wittig reaction within the confines of green chemistry. Students synthesize stilbene from styrene using Grubbs second-generation catalyst. Products can be minimally characterized by IR spectroscopy and melting point, but using 1 H NMR spectroscopy is preferred. Students find that the Wittig reaction is selective for cis-stilbene while the metathesis reaction produces >98% trans-stilbene. Students determine the cis/trans selectivity, turnover number, and maximum turnover frequency of the reaction. The experiment is conducted alongside the synthesis of stilbene using Wittig chemistry from a published procedure.

Synthesis of Stilbene and Chalcone Inhibitors of Influenza A Virus by SBA-15 Supported Hoveyda-Grubbs Metathesis

“…Irrespective to experimental conditions, the stilbene derivatives 8-14 (Scheme 2) were obtained from acceptable to high yield beside to few amounts of the unreacted substrate ( Table 1, entries 2-9). The reaction proceeded with high selectivity to afford trans-isomers as evaluated by 1 H NMR analysis (SI#2), in accordance with the known regioselectivity pattern previously reported for Hoveyda-Grubbs catalysts [45] ASIPr/SBA performed in a way similar to ASIPr alone in the self-metathesis of eugenol 1, suggesting the complete retention of the reactivity of ruthenium after the immobilization on SBA-15 ( Table 2, entry 1 versus entry 2). The presence of the OH moiety in the ortho-position of the substrate with respect to the side-chain, as in the case of compounds 4 and 5, significantly decreased the yield of the reaction (Table 2, entries 5-6 versus entries 2-4), as a consequence of the unfavorable electron-donating effect associated to the oxygen atom [46].…”

Design and Delivery of Virtual Inquiry-Based Organic Chemistry Experiments

“…There are many examples reported in this Journal of inquirybased organic experiments where students can apply core organic theory, including the aldol reaction, 3,4 nucleophilic addition to carbonyls, 5 E2 elimination, 6 electrophilic aromatic substitution, 7 the Wittig reaction, 8 and metathesis. 9,10 There are also examples where whole or partial organic laboratory courses have become inquiry-based with positive outcomes for the development of scientific skills. 11−14 At the University of Leeds, inquiry-based experiments form a core part of the level 2 synthetic chemistry laboratory course to help students transition from being able to perform expository experiments toward being able to perform research projects.…”

“…There are many examples reported in this Journal of inquiry-based organic experiments where students can apply core organic theory, including the aldol reaction, , nucleophilic addition to carbonyls, E2 elimination, electrophilic aromatic substitution, the Wittig reaction, and metathesis. , There are also examples where whole or partial organic laboratory courses have become inquiry-based with positive outcomes for the development of scientific skills. − …”

Student-Designed Green Chemistry Experiment for a Large-Enrollment, Introductory Organic Laboratory Course

“…Green chemistry approaches can improve undergraduate lab safety, minimize hazardous waste generation, and lower facility costs. Recent examples of incorporating green chemistry into teaching laboratories range in both depth and complexity: An old experiment can be replaced with a greener alternative. − There are also many exercises that ask students to use the 12 principles of green chemistry , to evaluate an experimental protocol. − For an even deeper engagement in green chemistry, there are examples wherein students compare multiple synthetic routes using green chemistry metrics for comparison. − …”