Acid chlorides with azirines

Azirines react with carboxylic acid chlorides in benzene to give the Ar-benzoyl-2-chloroaziridines (133) in good yield.23,60 These aziridines are unstable and are converted in polar solvents or by heating into a mixture of the oxazole and dichloroamide (134). 

Sato et al. observed that the reaction of 2-phenyl-1-azirine with acid chlorides and anhydrides in the presence of triethylamine gives the oxazole directly.57 They have reported that azirines also react with carboxylic anhydrides to give oxazoles (136).57 Aziridine (135) is suggested as a likely intermediate in the reaction of acetic anhydride with azirine (42a), since carrying out the reaction at lower temperature and for a shorter reaction time gave a compound to which they assigned structure 135. 

The photochemical addition of 2H-azirines to the carbonyl group of aldehydes, ketones and esters is completely regiospecific (77H143). Besides the formation of the isomeric oxazolines 18 from 3 and ethyl cyanoformate, there is also formed the imidazole 19 from addition to the C = N in the expected regioselective manner. Thioesters lead to thiazolines 20, while isocyanates and ketenes produce heterocycles 21 (Scheme 4). The photocycloaddition of arylazirines with a variety of multiple bonds proceeds in high yield and provides a convenient route for the synthesis of five-membered heterocyclic rings. Some of the dipolarophiles include azodicarboxylates, acid chlorides, vinylphospho-nium salts and p-quinones. 

Reactions of Isoxazoles. The kinetics of the isoxazole azirine rearrangement (336) -> (337) and those of the isoxazole oxazole transformation (338) (339) have been determinedPalladium(II) chloride-triphenyl-phosphine catalyses the cross-coupling of 4-iodo-3,5-dimethylisoxazole with styrene to yield the trans- compound (340). 3,5-Dimethylisoxazole can be lithiated in two stages, first at the 5-methyl group and then at the 3-methyl group. Isoxazoles add hypochlorous acid to form 4-chloro-2,3-dihydro-... 

The reaction of 2 with 3-(dimethylamino)-2,2-dimethyl-2//-azirine (83) affords in 94% yield the diamide (R)-( — )-2-(2-hydroxy-2-phenylacetamido)-A, A -2-trimethylpropionamide (84). Selective acidic hydrolysis of 84 with gaseous hydrogen chloride in acetonitrile-water provides the acid 85. The hydroxyl group is protected as a THP ether and the compound is converted to the depsipeptide 86 in good yield. Cyclization of 86 occurs with gaseous hydrogen chloride in toluene at 100 °C to furnish in 88% yield cyclo[(7 )-Mns-Aib-(7 )-... 

An efficient procedure for the synthesis of isoxazoles suitable for a multi-kilogram scale is shown in Scheme 1. An imine 1 is converted into its lithium derivative 2 by the action of lithium diisopropylamide, and an ester is added, The product 3 is treated with aqueous or methanolic hydroxylamine and the resulting oxime 4 (which exists largely as the hemiacetal 4a) is dehydrated to the isoxazole 5 with concentrated sulfuric acid. <97S439>. 5-Alkoxyisoxazoles and /VTV-disubstituted 5-isoxazolamines 6 (R = OMe, NMe2 or NMePh) rearrange to the azirines 7 in the presence of iron(II) chloride <97710911>. 

---