Thermally Induced Tandem Cycloaddition of 2-Alkyl-3-phenylcyclopropenones to 6-Aryl-1,5-diazabicyclo[3.1.0]hexanes

Abstract

Thermolysis of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes in the presence of 2-alkyl-3-phenylcyclopropenones gives fused polycyclic systems of the 4a,7b-diazacyclopenta[cd]inden-7-one series as a result of addition of two cyclopropenone molecules and extrusion of CO molecule. The first step of the process is characterized by 100% regioselectivity, leading to the adduct with vicinal arrangement of the aryl groups, while the regioselectivity of the second step is likely to be determined by spatial interactions between substituents in the cyclopropenone molecule and trimethylene bridge of the diazabicyclohexane. Steric hindrances in the second step could eliminate formation of stable products.Cyclopropenones are known to react with a large number of organic compounds having a C=N bond, e.g., imines, diimines, amidines, guanidines, etc., to give mono-and polycyclic structures which may be regarded as formal [2 + 3]-cycloaddition products at the C-C(O) bond of the three-membered ring [1,2]. Cycloaddition at the double carbon-carbon bond of cyclopropenones occurs more rarely; it is typical of nitrogen-containing 1,3-dipoles such as ylides and azomethine imines [2,3]. Here, the initially formed fused system consisting of three-and five-membered rings undergoes expansion to six-membered ring [4]. As a result, stable zwitterionic cyclic structure may be obtained provided that appropriate stabilizing substituents are present [5].We recently showed that thermolysis of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes in the presence of diphenylcyclopropenone leads to formation of fused tricyclic systems, 4a,7b-diazacyclopenta[cd]inden-7-ones as a result of unusual successive cycloadditions of two cyclopropenone molecules [6]. It was presumed that in the first step diphenylcyclopropenone adds to unstable azomethine imine which is generated by thermally induced opening of the diaziridine fragment in 6-arylsubstituted diazabicyclohexanes [7-9]; the subsequent ring expansion gives azomethine ylide which is stabilized via addition of the second diphenylcyclopropenone molecule and extrusion of one carbon(II) oxide molecule.In the present work we studied the regio-and stereoselectivity and the role of electronic and steric factors in the reactions of unsymmetrically substituted cyclopropenones, 2-methyl-3-phenyl-cyclopropenone (Ia) and 2-isopropyl-3-phenylcyclopropenone (Ib), with 6-aryl-1,5-diazabicyclo[3.1.0]hexanes IIa-IIe. In keeping with the mechanism proposed previously, formation of four regioisomeric adducts A-D might be expected and their relative configuration should be analogous to the configuration of adducts with diphenylcyclopropenone [6].

Heterocycles from cyclopropenones

“…122 2-Benzyl-3-isopropylquinoxaline (140) was synthesized via reacting 2-isopropyl-3-phenylcycloprop-2-en-1-one (1z) with benzene-1,2-diamine (139) in diethyl ether for 8 h and in the presence of 1H-pyrazole as a catalyst (Scheme 86). 124 Aly's group reacted 1b with hydrazinecarbothioamides 138ac in MeOH. 125 The reaction yielded substituted triazolopyridazines 150a-d.…”

“…Molchanov et al have developed on the synthesis of pyridazines 149a , b during refluxing a mixture of 6-aryl-3,3-dimethyl-1,5-diazabicyclo[3.1.0]hexanes 148a , b with 2-methyl-3-phenylcycloprop-2-enone ( 1j ) in p -xylene for 20 min (Scheme 89). 124…”

Recent developments of cyclopropene chemistry

“…[146][147][148] For example, the formal dipolar cycloaddition of a twofold excess of diphenylcyclopropenone with azomethine ylides afforded tricyclic hetero compounds in good yields. 149,150 Aly and co-workers have reported [3+3] cycloaddition reactions of 2,3-diphenylcyclopropenone 215 with thiosemicarbazides, 151 N-imidoylthioureas 152 and N-oxide 153 compounds for the synthesis of N-heterocyclic compounds. Recently, they reported the [3+2] cycloaddition of 2,3-diphenylcyclopropenone 215 with arylmethylidene-N-phenylhydrazinecarbothioamides 216 for the synthesis of pyrrolo[2,1-b]-1,3,4-oxadiazoles 219.…”