Cu(I)-Catalyzed cycloaddition of constrained azido-alkynes: access to 12- to 17-membered monomeric triazolophanes incorporating furanoside rings

The intramolecular click reaction using ‘carbocontiguous’ precursors

“…However, with smaller potential ring sizes, the 1,5- or exo cycloadducts can result despite the employment of the copper/ascorbate reaction system. 3 Consistent with mechanistic studies, we find that in the products 6a-d , the endo or 1,4-disposed regioisomers resulted from the cycloaddition. Routine 400 or 700 MHz 1 H NMR data recorded with products 6a-d reveal that the lone triazole proton, although obscured by two phenyl groups of the oxazole and one of the phenylsulfonyl group, firmly reside in the δ7.2-7.6 region.…”

“…To examine the regiochemistry, or endo vs exo disposition of the intramolecular click cycloaddition reaction, NOESY experiments at 700MHz (CDCl 3 ) were performed with products 6a-d . 3 The NOESY experiments revealed that in all four example, overlap of the triazole ring proton and the geminal protons of the ring methylene that is α- to the N1 of the triazole. Interestingly, close examination of the NOESY spectrum of the smallest ring product 6a revealed additional overlap between the triazole ring proton and the geminal protons of the methylene positioned in between the triazole group and the phenylsulfonylmethyl group.…”

“…Surprisingly, NOESY experiments conducted on isolated product 8 revealed no overlap between the exo -disposed triazole ring proton and the protons of the major ring of 8 . 3 …”

“…The endo or exo products arising from cycloaddition of the azide to the alkyne defines the overall ring size and provides a ring whereby the endo product possesses one more carbon in the chain than the exo -derived product. 3 Moreover, the newly-formed 1,2,3-triazole ring which is common to either cyclic polypeptide or most recently, even cyclic carbohydrate ‘click’ analogues, may act in additional capacity as a basic, hydrogen bond acceptor or π–stacking site. 4 We describe herein an intramolecular click reaction in which the azide-alkyne precursor are the reacting components in a contiguous carbon chain thereby yielding two new rings.…”

Peptide Cyclization and Cyclodimerization by CuI-Mediated Azide−Alkyne Cycloaddition

“…Recently the copper(I)-mediated azide-alkyne cycloaddition (CuAAC) reaction has been employed as a means of orthogonal modification15 and cyclization of peptides, 16-18 glycopeptides,19 polymers,20 and dendrimers 21,22. In the context of peptides, this “click reaction”23-25 methodology offers two important advantages.…”