Dipolar cycloadditions 1.2.4- oxadiazoles from

In another elegant approach (Scheme 18), a synthesis of 5-alkenyl-substituted 1,2,4-oxadiazoles relies upon a selenoxide. -elimination at the 5-a-carbon of the selenium resin-supported 1,2,4-oxadiazole 152. Access to compound 152 was achieved in two steps from the supported oxadiazole 150, which underwent deprotonation and alkylation at the 5-a-carbon to give the a-alkylated selenium resin 151. 1,3-Dipolar cycloaddition then gave the selenium resin-supported 1,2,4-oxadiazole 152 <2005JC0726>. 

The use of a PEG-supported imine 326 allows the imine to be the supported component (Scheme 55). 1,3-Dipolar cycloaddition then proceeds smoothly to give the supported 4,5-dihydro-l,2,4-oxadiazoles 327, which were cleaved easily from the polymer with methoxide to give the 4,5-dihydro-l,2,4-oxadiazoles 328 <2003SL1064>. 

Dipolar cycloaddition of diazomethane to aldehydes can successfully be used for the preparation of tetrahy-drooxadiazole derivatives. Photochemical interconversion of 3-acylamino-l,2,5-oxadiazole derivatives leads to 1,3,4-oxadiazoles, though the method suffers from lack of selectivity. Many reports concentrate only on the synthesis and applications of new 1,3,4-oxadiazoles substituted with a wide variety of groups without introducing much of new chemistry. 

Dipolar cycloaddition of nitrile oxide at the C=N bond of indole imino esters 130, followed by elimination of the alcohol moity gives oxadiazole derivatives 131 (Scheme 1.26) (298). Reaction of N-arylbenzamidines with arenenitrile N-oxides (generated in situ from oximoyl chlorides) produce unstable 5-amino-4,5-dihydro-1,2,4-oxadiazoles which, on aqueous acidic treatment hydrolyze to open-chain N-benzoyloxy-N -arylareneamidines (299). 

Unlike the mesoionic 1,2,3-oxadiazoles (see Chapter 5.03), mesoionic 1,2,3,4-oxatriazoles 5 and 6 do not undergo 1,3-dipolar cycloaddition reactions. Azides formed by loss of carbon dioxide from anhydro-5-hydroxy-l,2,3,4-oxatria-zolium hydroxides 4, on prolonged heating with lithium chloride, may be trapped by cycloaddition to an alkyne < 1996CHEC-II(4)679>. 

The action of 1,3,4-oxadiazoles on bicyclic alkenes under high pressure leads to multiply bridged products, e.g., 172 from norbornene 169 and 2,5-bis(trifluoromethyl)-l,3,4-oxadiazole. It is suggested that the reaction involves a Diels-Alder addition to give 170, followed by loss of nitrogen to give 171 and, finally, a 1,3-dipolar cycloaddition (Scheme 10) <97SL196>. 

Sodium hydrogen carbonate 3-Bromo-l,2,4-oxadiazoles from nitriles 1,3-Dipolar cycloaddition with bromonitrile oxide... 

Dipolar cycloadditions of nitrile oxides to the various unsaturated alditol derivatives 92 led to pairs of isoxazolidine regio-isomers, e.g. 93 and 94, each as predominantly one stereoisomer (Scheme 16). The isoxazole 95 was the major product from addition of bromoformonitrile oxide to the nitro-alkene. The nitrile moiety of D-mannononitrile pentabenzoate was transformed into either a 3-substituted 5-methyl-1,2,4-oxadiazole moiety (with NH2OH then AC2O) or a 5-substituted 2-methyl-1,3,4-oxadiazole moiety (with NH4N3 then AC2O, Py) cf. Vol.24, p.l35. The synthesis of 2-(alditol-l-yl) substituted 2-aza-3,7-dioxabicy-clo[3.3.0]octanes by intramolecular dipolar cyclization of 2-0-d y -aldehydo-sugar nitrones is covered in Chapter 24. 

The energetic 1,3,4-oxadiazole (22) is synthesized from the reaction of the tetrazole (20) with oxalyl chloride. In this reaction the tetrazole (20) undergoes a reverse cycloaddition with the expulsion of nitrogen and the formation of the 1,3-dipolar diazoalkane (21) which reacts with the carbonyl groups of oxalyl chloride to form the 1,3,4-oxadiazole rings. 

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