Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

Abstract

A reliable method for the synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexanes through the 1,3-dipolar cycloaddition (1,3-DC) reactions of cyclopropenes to the stable azomethine ylide – protonated form of Ruhemann's purple (PRP) has been developed. Both 3-substituted and 3,3-disubstituted cyclopropenes reacted with PRP, affording the corresponding bis-spirocyclic 3-azabicyclo[3.1.0]hexane cycloadducts in moderate to good yields with high diastereofacial selectivity. Moreover, several unstable 1,2-disubstituted cyclopropenes were successfully trapped by the stable 1,3-dipole under mild conditions. The mechanism of the cycloaddition reactions of cyclopropenes with PRP has been thoroughly studied using density functional theory (DFT) methods at the M11/cc-pVDZ level of theory. The cycloaddition reactions have been found to be HOMOcyclopropene–LUMOylide controlled while the transition-state energies for the reaction of 3-methyl-3-phenylcyclopropene with PRP are fully consistent with the experimentally observed stereoselectivity.

11H-Benzo[4,5]imidazo[1,2-a]indol-11-one as a New Precursor of Azomethine Ylides: 1,3-Dipolar Cycloaddition Reactions with Cyclopropenes and Maleimides

“… Our previous studies on 1,3-dipolar cycloaddition of azomethine ylides to cyclopropenes [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. …”

“…In previous studies bys our research group, cyclopropenes were widely used as dipolarophiles in 1,3-dipolar cycloaddition reactions with azomethine ylides generated from the corresponding ketones and α -amino acids ( Scheme 1 ). We used derivatives of isatin [ 22 ], alloxan [ 23 ], ninhydrin [ 24 , 25 , 26 , 27 ], 11 H -indeno[1,2- b ]quinoxalin-11-one [ 28 ], and tryptanthrin [ 29 ] as the ketone components. The products of these reactions were pharmacologically interesting spiro-fused 3-azabicyclo[3.1.0]hexanes and pyrrolizines, some of which were identified as exhibiting in vitro antitumor activity [ 30 , 31 ].…”