Nonconcerted Cycloaddition of 2H-Azirines to Acylketenes: A Route to N-Bridgehead Heterocycles

Abstract

Reactions of acylketenes, generated from diazo diketones, with 2-unsubstituted and 2-monosubstituted 3-aryl-2H-azirines lead to 1:1 or 2:1 adducts, which are derivatives of 5-oxa-1-azabicyclo[4.1.0]hept-3-ene or 5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene. According to DFT B3LYP/6-31G(d) computations, the formation of (4+2)-monoadducts proceeds via a stepwise non-pericyclic mechanism. Reaction with methanol transforms quantitatively both 1:1 and 2:1 adducts into 1,4-oxazepine derivatives.

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

“…The formation of compounds 3 proceeds in the same way as for similar compounds obtained by reaction of azirines with acylketenes from diazo compounds (Scheme 2) [22]. According to the calculation at the DFT B3LYP/6-31G(d) level with PCM solvation model for benzene (Fig.…”

“…2 H -Azirines can react with ketenes both with cleavage and preservation of the three-membered ring [22–26]. It was found that acylketenes, which are generated in situ from diazo ketones, undergo cycloaddition with 3-mono- and 2,3-disubstituted-2 H -azirines to afford 2:1 or 1:1 adducts: 5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene or 5-oxa-1-azabicyclo[4.1.0]hept-3-ene derivatives.…”

“…It was found that acylketenes, which are generated in situ from diazo ketones, undergo cycloaddition with 3-mono- and 2,3-disubstituted-2 H -azirines to afford 2:1 or 1:1 adducts: 5,7-dioxa-1-azabicyclo[4.4.1]undeca-3,8-diene or 5-oxa-1-azabicyclo[4.1.0]hept-3-ene derivatives. From the results of DFT B3LYP/6-31G(d) computations a step-wise mechanism appears likely for the formation of [4 + 2]-monoadducts [22]. The main limitation for the synthetic application of the reaction is the nonselective mode of the Wolff rearrangement of the unsymmetrical diazo compounds.…”

“…The main limitation for the synthetic application of the reaction is the nonselective mode of the Wolff rearrangement of the unsymmetrical diazo compounds. This generates a mixture of isomeric oxoketenes [27–29] and, as a result, a complex mixture of products is formed [22]. Moreover not all diazo compounds give oxoketenes easily [27–29].…”

3.19 The Wolff Rearrangement

“…91 The quenching of ketenes can also be performed by 2H-azirines whereas the resulting zwitterion proceeds to the formation of (4 þ 2) monoadducts through a stepwise nonpericyclic mechanism. 92 In the context of organic synthesis, the entrapment of ketenes derived from the Wolff rearrangement with amines has been explored in the preparation of amides in good yields (68-92%) using microwaves to promote the ketene formation, 33 as well as amide formation of a ketose derivative employing silver salts as rearrangement promoter, 93 or in the modification of ferrocene derivatives. 94 A photolabile end functionalized monomethyl poly(ethylene glycol) containing a terminal a-diazo ketone moiety was used to monofunctionalize lysozyme and ribonuclease.…”