Endo Rules! Multigram Synthesis of a Molecular Box

Article Article scientifique Article Endo Rules! Multigram Synthesis of a Molecular Box eng 2025-07-04 author Jamagne Romain 0000-0003-0454-3435 820969 Chimie organique (groupe 9) (CHOR9) author Low-Der's Nicolas Vinh Tri 0009-0007-0533-5546 840454 Département de chimie organique (CHIOR) author Jansen Nils 0000-0001-6472-2502 416202 Chimie organique (groupe 9) (CHOR9) author Pupier Marion 812717 Département de chimie organique (CHIOR) author Herren Anaïs 939360 author Besnard Céline 0000-0001-5699-9675 682138 Administration de la section de chimie (CHIAD) author Viger-Gravel Jasmine 0000-0003-4627-7972 936045 Département de chimie organique (CHIOR) author Rickhaus Michel 0000-0002-6107-2310 416710 Département de chimie organique (CHIOR) acs.jchemed.5c00457 10.1021/acs.jchemed.5c00457 0021-9584 https://pubs.acs.org/doi/10.1021/acs.jchemed.5c00457 Thermal and photochemical cycloadditions are key reactions in second-year undergraduate organic chemistry curricula, valued for their ability to construct complex molecules from simple precursors. The experiments described herein demonstrate how a sequence of thoughtfully designed cycloadditions enables the synthesis of a complex small molecular box in a concise time frame, suitable for undergraduate teaching laboratories. Beginning with a Diels–Alder reaction, students observe the exclusive formation of an <i>endo</i>-product due to secondary orbital stabilization in the transition state. The resulting product undergoes a light-mediated [2 + 2] cycloaddition, reproducible in standard undergraduate laboratory settings without specialized equipment, to yield an open molecular box precursor. The final step─hydration by adding one water molecule─completes the molecular box’s closure. Alongside the synthesis, students analyze intriguing solvent effects in the NMR spectra, enhancing their skills in structural characterization. The methodology is scalable and robust, as demonstrated by a multigram synthesis using leftover student material. These experiments combine fundamental concepts in reaction mechanisms, stereochemistry, and structural analysis with hands-on engagement, offering students a unique opportunity to appreciate the beauty of bottom-up molecular design by constructing a complex, aesthetically intriguing molecular box. Detailed instructions for assessing student learning, a step-by-step protocol, NMR spectral analysis, and crystal structure data are provided, ensuring educational value and facile integration into undergraduate teaching. Dewey 540 Fondation Philanthropique Famille Sandoz Swiss National Science Foundation Shape-Governed Supramolecular Systems (FLATLANDER) 218367 CH Programmes 36 Département de chimie organique 141 false 1425 Groupe Rickhaus Journal of chemical education bc473a00-f241-40e8-b7d4-a46ba066325c Article (Published version) Restricted jamagne-et-al-2025-endo-rules-multi.pdf 5154891 application/pdf ab03e7c3b75ef1f90434b8000b26b68e3fe525fd18f25d49b324237fe7dac7da Vignette Public Figure 0_TOC_forWeb.jpg 94456 image/png restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie organique

Title	Published in	Year	Views	Downloads

Endo Rules! Multigram Synthesis of a Molecular Box	Journal of chemical education	2025	44	4
Catalysis with Pnictogen, Chalcogen, and Halogen Bonds	Angewandte Chemie: International Edition	2018	699	540

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Low-Der's, Nicolas Vinh Tri