Convergent synthesis of trifunctional molecules by three sequential azido-type-selective cycloadditions

Abstract

A facile strategy for the synthesis of trifunctional molecules involving three sequential selective triazole-forming reactions is proposed. This method exploits three kinds of mechanistically different azido-type-selective cycloadditions. Three different azidophiles could be efficiently connected to a triazido platform molecule with three types of azido groups in a consecutive manner, which rendered a practical trifunctional molecule readily available.

Site-Selective Conversion of Azido Groups at Carbonyl α-Positions to Diazo Groups in Diazido and Triazido Compounds

“…To date, site-selective conjugation strategies using heterocycles and polyalkyne compounds have been developed. − In contrast, difficulties remain with compounds containing multiple azido groups (multiple azido compounds) in site-selective reactions, especially among alkyl azido moieties (Scheme a) . Since multiple azido compounds are easily accessible, ,, such as by late-stage global S N 2 azidation, and have a high reactivity with a sufficient molecular stability, they offer promising platforms toward the development of multifunctional element-block materials, such as advanced imaging probes and high-performance polymers, by the integration of various functional units . Hence, the recent growth of interest in the site-selective manipulations of multiple azido groups in one molecule, such as conjugation, ,, reduction, protection, and desymmetrization reactions, demands further exploration.…”

Sequential conjugation methods based on triazole formation and related reactions using azides

“…In 2018, we found three types of selectivities in triazole formation, namely SPAAC, Ru-catalyzed azide-alkyne cycloaddition (RuAAC), 19 and base-catalyzed triazole formation with 1,3-dicarbonyl compounds, 42c by competitive experiments using an equimolar mixture of 2,6-diisopropylphenyl azide, phenyl azide, and benzyl azide. 49 On the basis of these findings, we succeeded in a consecutive tris(triazole) synthesis using triazide platform 127 (Fig. 19).…”

Selectivity in multiple multicomponent reactions: types and synthetic applications

“…However, if in analogous experiments several reactants of a kind, displaying different reactivities, are used, their relative nucleophilicities/electrophilicities [7] may lead, in principle, to biased mixtures. At the same time, this innate selectivity is not straightforward, as the most reactive combination would promote a fast first MCR, and likely the following MCR processes may also involve this same set [8]. Experimental findings showing complex mixtures, although far from statistical product ratios, are the usual outcome of MMCRs involving several reactants of one kind.…”