Metal-Catalyzed Isomerization of 5-Heteroatom-Substituted Isoxazoles­ as a New Route to 2-Halo-2H-azirines

Abstract

A convenient gram-scale method for the preparation of 2-halo-2H-azirine-2-carboxylic acid esters, thioesters and amides via metal-catalyzed isomerization of 5-heteroatom-substituted 4-haloisoxazoles is developed. The formation of the esters and amides is efficiently catalyzed by Rh2(Piv)4, while FeCl2·4H2O is the catalyst of choice for the synthesis of the thioesters. In addition, rhodium catalysis is successfully applied in the synthesis of azirine-2-carboxylates from non-halogenated 5-alkoxyisoxazoles.

Stable 2-Azaallyl Salts as a Bridge between 2H-Azirines and Densely Functionalized 2H-Pyrroles

“…First of all, we wondered whether the nature of the halogen in the azirine affects the course of the reaction and the yield of compound 2a . For this purpose, fluoro-, chloro-, and iodoazirines 1a F , 1a Cl , 1a I were prepared according to known procedures and reacted with the cyanide source under the same conditions. Salt 2a was obtained in all cases, and its yield increased with increasing nucleofugality of the halogen.…”

“…Azirines 1a , b , f , h , 1c , f , l , 1d , g , 1e , 1j , 1k and phenacyl halides 5a – g , 5l , 5m , , 5i , 5j , , 5h , k , , 5′a , 5′b , 5′f , 5′j–5′l , , 5′n , , 5′o , , 5′p , are known compounds and were prepared according to the reported procedures.…”

Divergent Synthesis of Pyrazolo[1,5-a]pyridines and Imidazo[1,5-a]pyridines via Reagent-Controlled Cleavage of the C–N or C–C Azirine Bond in 2-Pyridylazirines

“…The isoxazole−azirine isomerization 6a → 1a may be carried out using Fe(II) 16 or Rh(II) catalysis. 17 Our choice fell on the second isomerization method, because it requires a catalyst loading from 100 to 500 times smaller than the iron-catalyzed version. Isoxazole was heated with Rh 2 (OAc) 4 (0.5 mol %) at 110 °C for 0.5 h and then cooled to 90 °C, and stannane 2a (1.1 equiv) was added.…”

“…Having optimized conditions for the isomerization of 3 into 4 in hand, next we tried to perform the synthesis of 4a in a one-pot fashion directly from a synthetic precursor of bromoazirine 1a , 4-bromo-5-methoxy-3-phenylisoxazole ( 6a ). The isoxazole–azirine isomerization 6a → 1a may be carried out using Fe­(II) or Rh­(II) catalysis . Our choice fell on the second isomerization method, because it requires a catalyst loading from 100 to 500 times smaller than the iron-catalyzed version.…”