Synthesis of 5‐Substituted 1,2,3‐Triazolyl‐4‐phosphonate through Cross‐Coupling Reactions of 5‐Iodo‐1,2,3‐triazolyl‐4‐phosphonate

Abstract

Two methods for the preparation of 5-iodo-1,2,3-triazolyl-4-phosphonate were explored. This compound was then functionalized by Suzuki and Stille cross-coupling reaction to obtain 5-aryl-, 5-heteroaryl- or 5-alkenyl-1,2,3-triazolyl-4-phosphonates

Multicomponent Synthesis of Potentially Biologically Active Heterocycles Containing a Phosphonate or a Phosphine Oxide Moiety

“…85,86 By the click reaction of benzyl azide and ethyl ethynylphosphonate, 1,2,3-triazolyl-4-phosphonate and 1,2,3-triazolyl-5-phosphonate were synthesized without catalyst in toluene at reflux temperature. 87 In two cases, triazoles containing bisphosphonate unit were obtained by the 1,3-dipolar cycloaddition of organic azides and propargyl-substituted bisphosphonates at room temperature after long reaction times (24-68 h). 88,89 In one case, the reaction was carried out in the presence of copper iodide (CuI) as a catalyst and N,N-diisopropylethylamine Scheme 11.…”

Synthesis of (1,2,3-triazol-4-yl)methyl Phosphinates and (1,2,3-Triazol-4-yl)methyl Phosphates by Copper-Catalyzed Azide-Alkyne Cycloaddition

“…The most convenient synthetic method for the preparation of 1,4-disubstituted 1 H -1,2,3-triazoles is the Cu(I)-catalyzed 1,3-dipolar (Huisgen) cycloaddition of azides with alkynes (CuAAC) (the “click reaction”), which was developed by Meldal and Sharpless [14,15]. The 1,2,3-Triazolyl phosphonates may be synthesized by the reaction of azides with phosphorus-containing acetylenes [12,13,16,17,18,19,20] or by the cycloaddition of azides incorporating a phosphonate moiety with alkynes [21,22,23,24]. In this paper, reports of the former method will be presented in detail.…”

“…The 1,3-dipolar cycloaddition of benzyl azide and ethyl ethynylphosphonate ( 1 ) was carried out in the absence of any catalyst at reflux temperature in toluene (Scheme 1) [16]. The reaction was not selective, two regioisomers, 1,2,3-triazolyl-4-phosphonate ( 2a ) and 1,2,3-triazolyl-5-phosphonate ( 2b ) were formed.…”

5-Iodo-1H-1,2,3-triazoles as Versatile Building Blocks

“…Abarbri and co-workers reported the synthesis of diethyl (5-iodotriazol-4-yl)phosphonates 25 and their modification through the C5-I position using the Suzuki and Stille coupling to give triazoles 26 and 27, respectively (Scheme 8). 90 For these substrates only the Pd 2 (dba) 3 /K 3 PO 4 catalytic system was efficient in avoiding reductive deiodination in the Suzuki coupling, while the use of either Pd(PPh 3 ) 4 or PdCl 2 (PPh 3 ) 4 even in the presence of non-amine base (K 3 PO 4 ) gave the 5-H-triazole as the main reaction product. The use of Pd 2 (dba) 3 under mild heating (50 °C) worked well in the Stille reaction providing various (5-vinyltriazolyl)-and (5-heteroaryltriazolyl)phosphonates 27 in moderate to high yields.…”