Oxidative [3+2]Cycloaddition of Alkynylphosphonates with Heterocyclic N-Imines: Synthesis of Pyrazolo[1,5-a]Pyridine-3-phosphonates

Abstract

A series of pyrazolo[1,5-a]pyridine-3-ylphosphonates were prepared with moderate to good yields by the oxidative [3+2]cycloaddition of 2-subtituted ethynylphosphonates with in situ generated pyridinium-N-imines and their annulated analogs. 2-Aliphatic and 2-Ph acetylenes demonstrate low activity, and the corresponding pyrazolopyridines were achieved with a moderate yield in the presence of 10 mol% Fe(NO3)3·9H2O. At the same time, tetraethyl ethynylbisphosphonate, diethyl 2-TMS- and 2-OPh-ethynylphosphonates possess much greater reactivity and the corresponding pyrazolo[1,5-a]pyridines, and their annulated derivatives were obtained with good to excellent yields without any catalyst. 2-Halogenated ethynylphosphonates also readily reacted with pyridinium-N-imines, forming complex mixtures containing poor amounts of 2-halogenated pyrazolopyridines.

Simple and green synthesis of 3‐acyl‐pyrazolo[1,5‐a]pyridines: [3+2] through cycloaddition of N‐aminopyridines on enaminones

“…This is one of the reasons why effective synthetic strategies have emerged over the past decade for constructing this skeleton (Scheme 1) [3]. The most common approach is regioselective cycloaddition [3+2] of 1‐aminopyridin‐1‐ium 1a [4] with activated alkenes [5] or alkynes [6] in presence of basis and/or oxidant. Adimurthy's group developed a methodology based on NMP/O 2 (Scheme 1A) [7].…”

Copper-Catalyzed Asymmetric Dearomative [3+2] Cycloaddition of Nitroheteroarenes with Azomethines

“…The privileged skeletons with multiple contiguous stereogenic centers are widely encountered in natural alkaloids and synthetic compounds with important biological profiles [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. As shown in Figure 1 , the dispiro–butyrolactone–pyrrolidine-fused oxindole derivative A exhibits significant anticancer activity [ 8 ].…”

One-Pot Phosphonylation of Heteroaromatic Lithium Reagents: The Scope and Limitations of Its Use for the Synthesis of Heteroaromatic Phosphonates

“…Finally, the formation of lithium derivatives or Grignard reagents using aryl halides as substrates may be also employed [ 2 , 6 , 7 ]. In the past decade, interesting methods of nontypical specific procedures for the synthesis of heteroaromatic phosphonates have been studied and elaborated [ 12 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”