Diazophosphonates: Effective Surrogates for Diazoalkanes in Pyrazole Synthesis

Ruffell, Katie; Smith, Frances R.; Green, Michael T.; Nicolle, Simon M.; Inman, Martyn; Lewis, William; Hayes, Christopher J.; Moody, Christopher J.

Abstract

Diazophosphonates, readily prepared from -ketophosphonates by oxidation of the corresponding hydrazones in batch or in flow, are useful partners in 1,3-dipolar cycloaddition reactions to alkynes to give N-H pyrazoles, including the first intramolecular examples of such a process. The phosphoryl group imbues a number of desirable properties in the diazo 1,3-dipole. The electron-withdrawing nature of the phosphoryl stabilizes the diazo compound making it easier to handle, whilst the ability of the phosphoryl group to migrate readily in a [1,5]-sigmatropic rearrangement enables its transfer from C to N to aromatize the initial cycloadduct, and hence its facile removal from the final pyrazole product. Overall, the diazophosphonate acts as a surrogate for the much less stable diazoalkane in cycloadditions, with the phosphoryl group playing a vital, but traceless, role. The cycloaddition proceeds more readily with alkynes bearing electron-withdrawing groups, and is regiospecific with unsymmetrical alkynes. The potential for use of diazophosphonates in bioorthogonal cycloadditions is demonstrated by their facile addition to strained alkynes.

Citation

Ruffell, K., Smith, F. R., Green, M. T., Nicolle, S. M., Inman, M., Lewis, W., Hayes, C. J., & Moody, C. J. (2021). Diazophosphonates: Effective Surrogates for Diazoalkanes in Pyrazole Synthesis. Chemistry - A European Journal, 27(55), 13703-13708. https://doi.org/10.1002/chem.202101788

• Journal Article Type: Article
• Acceptance Date: Jul 26, 2021
• Online Publication Date: Aug 23, 2021
• Publication Date: Oct 1, 2021
• Deposit Date: Sep 28, 2021
• Publicly Available Date: Aug 24, 2022
• Journal: Chemistry - A European Journal
• Print ISSN: 0947-6539
• Electronic ISSN: 1521-3765
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 27
• Issue: 55
• Pages: 13703-13708
• DOI: https://doi.org/10.1002/chem.202101788
• Keywords: pyrazole; diazophosphonate; dipolar cycloaddition; 1,5-sigmatropic rearrangement
• Public URL: https://nottingham-repository.worktribe.com/output/5953594
• Publisher URL: https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202101788
• Additional Information: This is the peer reviewed version of the following article: K. Ruffell, F. R. Smith, M. T. Green, S. M. Nicolle, M. Inman, W. Lewis, C. J. Hayes, C. J. Moody, Chem. Eur. J. 2021, 27, 13703, which has been published in final form at https://doi.org/10.1002/chem.202101788. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.