Open AccessThe Role of the Fused Ring in Bicyclic Triazolium Organocatalysts: Kinetic, X-ray, and DFT Insights
Author(s) -
Jiayun Zhu,
Inmaculada Moreno,
Peter J. Quinn,
Dmitry S. Yufit,
Lijuan Song,
Claire M. Young,
Zhuan Duan,
Andrew Tyler,
Paul G. Waddell,
Michael J. Hall,
Michael R. Probert,
Andrew D. Smith,
AnnMarie C. O’Donoghue
Publication year - 2022
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.1c03073
Subject(s) - bicyclic molecule , ring size , deprotonation , ring (chemistry) , carbene , chemistry , catalysis , organocatalysis , kinetic resolution , stereochemistry , computational chemistry , crystallography , organic chemistry , enantioselective synthesis , ion
Bicyclic triazolium scaffolds are widely employed in N -heterocyclic carbene (NHC) organocatalysis. While 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 the 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, k DO , were significantly influenced by the size of the adjacent fused ring, with the kinetic acidity trend, or protofugalities, following the order k DO ( n = 1) > k DO ( n = 2) ≈ k DO ( 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 CH 2 with variation in fused ring size are proposed to influence the experimental protofugality order.