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Lookup NU author(s): Dr Paul Waddell, Dr Michael HallORCiD, Professor Mike ProbertORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Bicyclic triazolium scaffolds are widely employed in N-heterocyclic carbene (NHC) organocatalysis. Whilst the incorporation of a fused ring was initially for synthetic utility in accessing chiral, modular triazolyl scaffolds, recent results highlight the potential for impact upon reaction outcome with underpinning origins unclear. The common first step to all triazolium-catalyzed transformations is C(3)-H deprotonation to form the triazolylidene NHC. Herein, we report an analysis of the impact of size of the fused (5-, 6- and 7-membered, n=1, 2 and 3 respectively) ring on the C(3) proton transfer reactions of a series of bicyclic triazolium salts. Rate constants for the deuteroxide-catalyzed C(3)-H/D-exchange of triazolium salts, kDO, were significantly influenced by the size of the adjacent fused ring, with the kinetic acidity trend, or protofugalities, following the order: kDO (n=1) > kDO (n=2) ≈ kDO (n=3). Detailed analyses of X-ray diffraction (XRD) data for 20 triazolium salts (including 16 new structures), and of computational data for the corresponding triazolylidene NHCs, provide insight on structural effects of alteration of fused ring size. In particular, changes in internal triazolyl NCN angle and positioning of the most proximal CH2 with variation in fused ring size are proposed to explain the experimental protofugality order.
Author(s): Zhu J, Moreno I, Quinn P, Yufit DS, Song L, Young CM, Duan Z, Tyler AR, Waddell PG, Hall MJ, Probert MR, Smith AD, O'Donoghue AC
Publication type: Article
Publication status: Published
Journal: Journal of Organic Chemistry
Year: 2022
Volume: 87
Issue: 6
Pages: 4241–4253
Print publication date: 18/03/2022
Online publication date: 01/03/2022
Acceptance date: 03/02/2022
Date deposited: 16/02/2022
ISSN (print): 0022-3263
ISSN (electronic): 1520-6904
Publisher: American Chemical Society
URL: https://doi.org/10.1021/acs.joc.1c03073
DOI: 10.1021/acs.joc.1c03073
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