Document Type
Article
Department or Administrative Unit
Chemistry
Publication Date
1-23-2023
Abstract
Functionalized 1,3-dienes are ubiquitous structural motifs in biologically pertinent molecules. They are frequently employed as precursors for a broad range of chemical transformations, including Diels-Alder reactions. The stereoselective construction of highly decorated 1,3-dienes therefore represents an important research objective. Medicinal chemists are becoming increasingly interested in synthetic methodologies that not only achieve expedient construction and peripheral editing of heterocycles, but also seek to modify their core framework in order to achieve skeletal remodeling. In a succinct manifestation of this 'scaffold hopping' concept, we herein describe a cascade reaction, which converts thiomorpholinone-tethered alkenoic acids to 1,1-disubstituted amino-1,3-dienes. This domino process involves esterification of the acid, base-assisted ring-opening, and concomitant 1,2-migration of the alpha-amino alkenyl group. Several control experiments have revealed that the alkenyl substituent is necessary for deconstruction to occur. Inherently more activated N-aryl-substituted thiomorpholinone acids react significantly faster than their less activated N-alkyl congeners.
Recommended Citation
Farah, A. O., Garcia, J., Borg, C., & Beng, T. K. (2023). Serendipitous synthesis of cross-conjugated dienes by cascade deconstructive esterification of thiomorpholinone-tethered alkenoic acids. RSC Advances, 13(5), 3181–3185. https://doi.org/10.1039/D2RA07916J
Journal
RSC Advances
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License
Rights
© 2023 The Author(s).
Comments
This article was originally published open access in RSC Advances. The full-text article from the publisher can be found here.