Unusual Transformations of Cyclic Allenes with an Enamine Moiety into Complex Frameworks

Abstract

The thermolysis reactions of benzoazacyclodecatrienes under microwave irradiation conditions in toluene at 150 °C afforded complex azabenzo[a]cyclopropa[cd]azulene and (epiminomethano)cyclopenta[a]indene frameworks. Cyclopropanes were established as intermediates of the ultimate thermolysis products.

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“…Compounds 12 , 15 , 17 , 18 , 27 , and 28 have already been described; their analytical and spectroscopic data agreed with those reported.…”

“…The methylation of the 29 with MeI in Et 2 O at 100 °C gave the ammonium salt 41 in good yield. Compounds 28 – 41 were formed as single diastereoisomers with cis stereochemistry at the rings’ junctions C3a, C8a, and C8 (see general structure I in Figure ), as confirmed by 1 H NMR spectra and X-ray crystal structure of 28 , and tested as racemates.…”

“…The cyclic allene 11 , containing an intracyclic enamine fragment, was converted into complex frameworks to N -bridged cyclopenta­[ a ]­indene 26 and cyclopropa­[ cd ]­azulene 27 under microwave assisted heating of its toluene solution at 150 °C . Using a higher temperature of 180 °C in the thermal transformations of axially chiral allenes 12 – 25 , only the N -bridged cyclopenta­[ a ]­indenes 28 – 40 were obtained.…”

“…More recently Voskressensky et al developed an original and efficient synthesis of allene 3-benzazecines incorporating an enamine fragment in α-position to the allene system (see Scheme , compounds 11 – 25 ). , Some of them proved to be noncytotoxic, highly potent inhibitors of P-glycoprotein efflux pumps and in vitro reversers of multidrug resistance (MDR) in cancer cells . Interestingly, under microwave irradiation conditions in toluene at 150 °C, the above cyclic allenes underwent unusual transformation into isomeric complex benzo-fused N -bridged tricyclic derivatives (general structure I in Figure ), namely, (epiminomethano)­cyclopenta­[ a ]­indenes 28 – 40 (Scheme ), as major products of thermal rearrangement …”

“…22 Interestingly, under microwave irradiation conditions in toluene at 150 °C, the above cyclic allenes underwent unusual transformation into isomeric complex benzo-fused N-bridged tricyclic derivatives (general structure I in Figure 1), namely, (epiminomethano)cyclopenta-[a]indenes 28−40 (Scheme 1), as major products of thermal rearrangement. 23 In addition to their chemical novelty, these "bristly" molecules, bearing a bridging basic nitrogen and a nonplanar rigid hydrophobic core, caught our attention because of a certain degree of 3D shape similarity with the alkaloids huperzine A (II) and huprines (III), both investigated and developed as anti-AD agents (Figure 1). 15 The natural huperzine A, a potent reversible inhibitor of AChE and NMDAR antagonist, is available as cognition enhancer in dietary supplements for age-related memory impairments.…”