Fused Polycyclic Compounds via Cycloaddition of 4-(1′-Cyclohexenyl)-5-iodo-1,2,3-triazoles with 4-Phenyl-1,2,4-triazoline-3,5-dione: The Importance of a Sacrificial Iodide Leaving Group

Abstract

4-(1'-Cyclohexenyl)-5-iodo-1,2,3-triazole and 4-phenyl-1,2,4-triazoline-3,5-dione undergo a formal Diels-Alder reaction, which following an S(N)2' solvolysis process to displace the iodo group affords a fused polycyclic compound.

Chemoselective Modification of Vinyl DNA by Triazolinediones

“…Thesame results were obtained when using MeOH/CH 2 Cl 2 (2.5:1) and H 2 O/DMF (4:1) as solvent mixtures.I nc ontrast, when 5-vinyl-2'-deoxyuridine (VdU, 3)w as reacted with PTAD,t he acyclic reaction products 4a and 4b were obtained in 92-94 %y ields of isolated product (Scheme 2). Taken together,these results are consistent with astep-wise reaction mechanism (Figure S1 in the Supporting Information) [26] where an addition reaction gives apolarized biradical or zwitterionic intermediate that is either trapped by solvent in the case of VdU (3), or undergoes cyclization in the case of 5-vinyluracil (1). To evaluate the kinetics of VdU-PTAD addition reactions,stopped flow measurements were used to track the loss of PTAD absorbance (546 nm) upon mixing with VdU under pseudo-first-order reaction conditions.Incontrast to previous bioorthogonal chemical reactions involving terminal alkenes, [21][22][23] an exceptionally large second-order rate constant of 1.9 10 3 m À1 s À1 was observed at RT (Figure 2a).…”

Mechanism of Copper(I)-Catalyzed 5-Iodo-1,2,3-triazole Formation from Azide and Terminal Alkyne

“…21,22 The method that our group reported (Figure 1c) 19 is initialized by the reaction between an alkali metal iodide and Cu(ClO 4 ) 2 •6H 2 O, which quickly affords the CuI catalyst for the subsequent cycloaddition, and the electrophilic I 2 or I 3 − as the source of the iodo substituent. 23 This method avoids the preformation of an iodoalkyne and the direct use of the often corrosive electrophilic iodinating agents in the earlier methods, and has since been applied in producing iodotriazoles as synthetic intermediates 24 or anion receptors. 11−13 In these iodotriazoleforming reactions, 5-protio-1,2,3-triazole (protiotriazole) resulting from the more conventional copper(I)-catalyzed azide− alkyne cycloaddition is the somewhat persistent side product.…”

“…5-Iodo-1,2,3-triazoles (iodotriazoles) have found increasing utilities in multicomponent synthesis, − halogen-bonding-based anion recognition, − and radiolabeling of probes and drugs in biomedical research. , An iodotriazole can be synthesized from a copper­(I)-catalyzed cycloaddition between an organic azide with either a terminal alkyne in the presence of an electrophilic iodinating agent (Figure a–c) − or a 1-iodoalkyne (iodoalkyne, Figure d). , The method that our group reported (Figure c) is initialized by the reaction between an alkali metal iodide and Cu­(ClO 4 ) 2 ·6H 2 O, which quickly affords the CuI catalyst for the subsequent cycloaddition, and the electrophilic I 2 or I 3 – as the source of the iodo substituent . This method avoids the preformation of an iodoalkyne and the direct use of the often corrosive electrophilic iodinating agents in the earlier methods, and has since been applied in producing iodotriazoles as synthetic intermediates or anion receptors. − In these iodotriazole-forming reactions, 5-protio-1,2,3-triazole (protiotriazole) resulting from the more conventional copper­(I)-catalyzed azide–alkyne cycloaddition is the somewhat persistent side product. This mechanistic study was motivated in part by the need of increasing iodo/protio selectivity in the synthesis of iodotriazoles.…”