Abstract
The retro-Cope elimination reaction between dimethylhydroxylamine (DMHA) and various cyclic alkynes has been quantum chemically explored using DFT at ZORA-BP86/TZ2P. The purpose of this study is to understand the role of the following three unique activation modes on the overall reactivity, that is (i) additional cycloalkyne predistortion via fused cycles, (ii) exocyclic heteroatom substitution on the cycloalkyne, and (iii) endocyclic heteroatom substitution on the cycloalkyne. Trends in reactivity are analyzed and explained by using the activation strain model (ASM) of chemical reactivity. Based on our newly formulated design principles, we constructed a priori a suite of novel bioorthogonal reagents that are highly reactive towards the retro-Cope elimination reaction with DMHA. Our findings offer valuable insights into the design principles for highly reactive bioorthogonal reagents in chemical synthesis.
| Original language | English |
|---|---|
| Number of pages | 14 |
| Journal | Chemical Science |
| DOIs | |
| Publication status | E-pub ahead of print - 27 Aug 2024 |
Bibliographical note
Publisher Copyright:© 2024 The Royal Society of Chemistry.
Funding
This work was supported by the Netherlands Organization for Scientific Research (NWO) and the Fondazione Cassa di Risparmio di Padova e Rovigo (CARIPARO). This work was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative.
| Funders | Funder number |
|---|---|
| Nederlandse Organisatie voor Wetenschappelijk Onderzoek | |
| Fondazione Cassa di Risparmio di Padova e Rovigo | |
| CARIPARO |