Triazolopyridines with electrophiles

As depicted in Scheme 11, ylides 39 derived from 4-methyl-[l,2,3]triazolo[l,5- ]pyridine react with Michael acceptors, which, upon nucleophilic attack at C3 and ring opening, lead to nucleophilic displacement of nitrogen. The intermediate diradical led to a mixture of compounds, including alkenes and a cyclobutane derivative when methyl acrylate was used, and the indolizine 40 with methyl propiolate as the electrophile <1998T9785>. Heating 4-methyl triazolopyridine with benzenesulfonyl chloride in acetone also confirmed decomposition via a radical pathway. 

General chemical properties of triazolopyridines, such as oxidations, reductions, reaction with electrophiles, reactions with nucleophiles, homolytic reactions, ring-opening reactions, and photochemical reactions can be found in <2002AHC(83)2>. 

Like all simple triazolopyridines, bitriazolopyridines 76 react with electrophiles to produce 2,2 -bipyridines 118 (Scheme 24). With these reactions a general route to 2,2 -bipyridines has been discovered with a variety of substituents in the 6 and 6 positions (97T8257). These compounds have use in supramolecular chemistry because of their great complexing power for metal ions and, in particular, 2,2 -disubstituted-6,6 -bipyridines are useful building blocks for oligobipyridines, which spontaneously form helical metal complexes (92T8451). 

In contrast to the ease of N-functionalization, shown in Scheme 1, the triazolopyridine nucleus is resistant to direct nuclear oxidation or electrophilic additions. Electrophilic additions will occur on aryl substituents for example, nitration of l-phenyltriazolo[4,5-c]pyridine (26) and sulfonation of 2-phenyl-2i/-triazolo[4,5-6]pyridine (28) occur exclusively in the para position of the phenyl ring <34LA(514)279, 38MI 710-01). Nuclear functionalization was observed when l-( -butyl)-5-methyl-tri-azolo[4,5-c]pyridinium iodide (30) was treated with potassium ferricyanide to afford triazolopyridin-4-one (31), as shown in Scheme 2. Similarly, the iodide (30) is converted by either phosphorus oxychloride-phosphorus pentachloride, or bromine or nitric acid to 7-substituted triazolopyridin-4-ones (32) <37LA(529)288>. 

Chiral triazolopyridines have been made by regioselective metalla-tion of triazolopyridines followed by treatment with chiral electrophiles such as R-(+)-menthyl-p-toluene-sulphinate or (—)-fenchone, giving the corresponding chiral sulphoxides as well as the chiral alcohols in very good yields, and 97% ee (07T10479) (Scheme 14). 

In the classical lithiation of triazolopyridines at —40 °C with LDA in THF, the 7-lithio derivatives 71 formed are trapped by electrophiles giving 7-substituted triazolopyridines 138a-d. When the starting material was 3-(2-pyridyl)-triazolopyridine 33,19a was formed (Scheme 32), using as electrophiles 2-pyridine carbaldehyde (98T15287), 2-cyanopyridine, and in better yield, ethyl picolinate (04T5785). 

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