Stereocontrolled Sequence-Defined Oligotriazoles through Metal-Free Elongation Strategies

Abstract

The functionality of biomacromolecules has stimulated the development of stereocontrolled biomimetic oligomers for diverse functional applications. Here we report the synthesis of one novel sequence-defined oligotriazole architecture with excellent stereoregularity from 1,2,3-triazole-based chiral monomers. The facile introduction of broad side chains into this skeleton is enabled by the easy preparation of these building blocks from the efficient reaction of one L-prolinol-derived azide with various internal 1thioalkynes under mild iridium-catalyzed azide−alkyne cycloaddition (IrAAC) conditions. Assembly of them into desired oligomers could be achieved through metal-free iterative sequential or exponential growth strategies, the efficiency of which was demonstrated by the construction of three stereocontrolled oligotriazoles bearing different chain lengths and side groups. The structure and monodispersity of these oligomers were well characterized by 1 H NMR, SEC, MS, and tandem MS/MS analysis, and their stereoregularity was identified by circular dichroism.

Iridium-Catalyzed Synthesis of Chiral 1,2,3-Triazoles Units and Precise Construction of Stereocontrolled Oligomers

“…For instance, the phenyl group was introduced by the reaction of phenylacetylene, and the reaction of disulfide with propargyl alcohol afforded the thioalkyne involving a hydroxyl group for the post-introduction of benzyl or tetraphenylethanyl groups. In parallel, the chiral organic azide 2 was prepared from commercially available N-Boc-L-prolinol (>99.9% ee) through a simple two-step synthetic protocol, which was well demonstrated in our previous research [29]. Gram-scale coupling of it with different functionalized thioalkynes under the mild and simple IrAAC condition was easily achieved, affording fully substituted triazole motifs 3 in good to excellent yields.…”

“…L-Proline is the only proteinogenic secondary amino acid, the distinctive cyclic structure of which endows its polymer with exceptional conformational rigidity [27,28]. By using one organic azide derived from L-prolinol, we realized the synthesis of chiral fully substituted triazole building blocks and their precise assembly into stereocontrolled sequence-defined oligotriazoles [29]. However, functional variations in the side chain of these oligomers are limited to some extent.…”

Internally Functionalized Dendrimers Based on Fully Substituted 1,2,3‐Triazoles

“…In this context, we envisaged the exploitation of these triazole skeletons as interior functionality carries, which could be actualized through the reaction of azides with functionalized internal alkynes in a straightforward fashion. [ 28 ] Hence, as a continuation of our research on the assembly of 1,4,5‐trisubstituted triazole units into uniform macromolecules, [ 29–33 ] here we report their potency in the construction of internally functionalized dendrimers. By using synthetic protocols established on IrAAC—one highly desirable chemical tool for the exclusively regioselective creation of fully substituted triazoles from 1‐thioalkynes, [ 34,35 ] different dendritic structures with heterofunctionality distributed at sequence‐controlled layers were smoothly obtained through divergent or convergent growth approaches ( Scheme ).…”

Unsymmetrical Growth Synthesis of Nontraditional Dendrimers

“…In recent years, the annulation of internal alkynes with azides has been realized under different catalytic systems . One emblematic example is the mild iridium-catalyzed transformation of 1-thioalkynes into fully substituted triazoles with absolute regioselectivity (IrAAC), − the uniqueness and high efficiency of which inspired us to envision motifs with two thioalkynyl substructures in serving as effective linear ABB-type building blocks (Scheme C). IrAAC reaction of these alkyne units with diverse organic azides are expected to generate various linear multifunctionalized triazole dimers.…”