Synthesis of α,β-unsaturated carboxylic acids by phosphonium ylide- mediated CO 2 activation Amy Lowry, Peter A. Byrne; Gerard P. McGlacken University College Cork, Ireland Carbon dioxide utilisation continues to capture the attention of chemists due to its ever-increasing levels and the negative effects of global warming. [1-2] CO 2 is an inexpensive and environmentally friendly C 1 building block, which can used in the synthesis of value-added chemicals. However, CO 2 has inherently low reactivity and therefore requires activation prior to conversion into synthetically useful products. [3] Many medicinally-important compounds and natural products contain the elements of CO 2 within their structure, including carboxylic acids, enoates, and carbamates. [4] In particular, α,β–unsaturated carboxyl compounds are typically accessed by metal-catalysed transformations or condensation reactions, which often require hydrolysis of the ester product to furnish the corresponding acid, adding an additional synthetic step.
In contrast, herein we report a telescoped process that not only achieves CO 2 activation, but exploits a novel application of the Wittig reaction, enabling direct installation of the carboxyl group by two successive carbon- carbon bond forming events. In this protocol, CO 2 is activated by reaction with a phosphonium ylide, generating a carboxyl-containing phosphonium salt ( 1 ). Deprotonation of adduct 1 generates a novel entity, carboxylate ylide 2 , which has been demonstrated to undergo a Wittig reaction with a range of aldehydes furnishing the corresponding α,β-unsaturated carboxylic acids, with facile separation from phosphine oxide. This three-step telescoped process enables incorporation of CO 2 at atmospheric pressure and also grants access to the α,β–unsaturated carboxylic acid structural motif via a novel phosphonium ylide in a Wittig reaction. References 1. See NASA website: https://climate.nasa.gov/causes/. 2. IPCC, 2014: Climate Change 2014: Synthesis Report, available at: https://www.ipcc.ch/report/ar5/syr/. 3. Curr. Opin. Green Sustain. Chem. 2017, 7, 31-38. 4. For examples of many widely used carboxyl-ontaining pharmaceuticals, see https://njardarson.lab.arizona.edu/content/top- pharmaceuticals-poster.
P60
© The Author(s), 2022
Made with FlippingBook Learn more on our blog