Enantiomer stability of atropisomeric 1,5-disubstituted 1,2,3-triazoles

Abstract

The synthesis and characterisation of axially chiral atropisomeric 1,5-disubstituted 1,2,3triazoles is reported. Molecules designed to display restricted rotation about 1,2,3-triazole N-1-aryl or 1,2,3-triazole C-5-aryl bonds were investigated by physical and computational techniques. The barrier to 1,2,3-triazole N-1-aryl rotation was found to be higher than that for 1,2,3-triazole C-5-aryl rotation, confirming axial chirality stemming from restricted rotation about an N-1-aryl bond in a 1,5-disubstituted 1,2,3-triazole to be the most suitable for the development of an axial chirality triazole-based platform.

Catalytic Enantioselective Azide–Alkyne Cycloaddition Chemistry Opens Up New Prospects for Chiral Triazole Syntheses

“…The three research groups utilized different catalytic systems to achieve the synthesis of axially chiral 1,2,3-triazoles via E-AAC reactions. It should be pointed out that prior to these reports, Dehaen et al and Fossey et al . have independently reported the construction of atropisomeric triazoles, but both of them were based on the use of nonasymmetric click reactions.…”

Stereodynamic Strategies to Induce and Enrich Chirality of Atropisomers at a Late Stage

“…A list of these scaffolds and available parameters has been compiled up to 2015 in a review by Sibi, Sivaguru, and co-workers . Here we will highlight some studies on the effects of substituents on nonbiaryl atropisomerization barriers that have been reported since 2015, including tertiary amides, diarylamines, enamides, N -phenyl lactams, triazoles, and carbolines . Additionally, an important 2017 study by Farran, Roussel, and co-workers developed a steric scale of substituents from rotational barriers on a N -( ortho -substituted aryl)­thiazoline-2-thione scaffold …”

Enantioselective Rh-Catalyzed Azide-Internal-Alkyne Cycloaddition for the Construction of Axially Chiral 1,2,3-Triazoles

“…In comparison to the well-explored racemic CuAAC, , the catalytic asymmetric version of the [3 + 2] cycloaddition of alkynes and azides is still challenging because of the linear geometry of the alkynes and azides, the complex mechanism of cycloaddition, − and no new chiral center generation from this reaction . Remarkable progress on the enantioselective CuAAC (E-CuAAc) of terminal alkynes using prochiral substrates has been achieved by Fokin, Zhou, Topczewski, Fossey, and others, especially Zhou’s elegant work for the construction of quaternary carbon central chirality (Scheme A). However, the exploration in the asymmetric [3 + 2] cycloaddition of internal alkynes and azides remained extremely rare.…”