Facile Methods for the Synthesis of 8‐Ylidene‐1,2,3,8‐tetrahydrobenzazecines

Abstract

We have elaborated a general and simple microwave-assisted method for the synthesis of original 8-ylidene decorated benzazecines. We have shown that under the action of electron-deficient alkynes in acetic acid the starting benzoannulated azacyclic allenes or 1-alkyl(benzyl)-1-phenylethynylsubstituted isoquinolines underwent transformations leading to benzazecines in high yields. In acetic acid all reactions pro-[a] Dr. A. A. Titov, M. S. Results and DiscussionWe initiated our study with estimating the influence of protonic solvents on the transformations of phenylethynyl decorated isoquinolines 1a-g under the action electron-deficient alkynes. The starting 1-alkyl(benzyl)-1-phenylethynyl-6,7-dimethoxyisoquinolines 1a-g were synthesized according to the previously described procedure [23] from 1-alkyl(benzyl)-3,4-dihydroisoquinolinium methiodide derived via the Bischler-Napieralski reaction followed by alkylation [20] (Scheme 1). Scheme 1. Synthesis of starting 1-alkyl(benzyl)-1-phenylethynyl-6,7-dimethoxyisoquinolines 1a-g.Scheme 3. Reactions of isoquinolines 1b-g with methyl propiolate in HFIP.

Zinc Iodide Catalyzed Synthesis of Trisubstituted Allenes from Terminal Alkynes and Ketones

“…Notably, the other carbon in 12 , previously α to the cyclohexanone carbonyl carbon (in the product, allylic on the cyclohexane ring), was found to have a 0.76( H )/1.24( D ) ratio. Based on these findings and related literature precedence, 41 we hypothesize that the allene product is a precursor to the diene byproduct, which is most probably obtained via the activation of the allene moiety by ZnI 2 .…”

Away from Flatness: Unprecedented Nitrogen-Bridged Cyclopenta[a]indene Derivatives as Novel Anti-Alzheimer Multitarget Agents

“…Compounds 1 – 10 have been prepared following a described method. − Compounds 5 and 9 were novel. Phenylacetylene (100 mmol) was added with stirring under nitrogen to a solution of appropriate 3,4-dihydro-isoquinolinium iodide (10 mmol) in dry CH 2 Cl 2 (80 mL).…”

“…Compounds 11 – 25 have been prepared following a described method. − Compounds 16 , 22 , and 23 were novel. A solution of appropriate tetrahydroisoquinoline 1 – 10 (1.0 mmol) and methyl propiolate (1.2 mmol) or acetylacetylene (1.2 mmol) in trifluoroethanol (10 mL) was kept at 7 °C for 1 or 3 days, monitoring the reaction progress by TLC (eluent EtOAc–hexane, 1:2 v/v).…”

“…As shown in Scheme , the starting racemic cyclic allenes 11 –25 were synthesized, according to the previously described procedure, from 1-R 2 -1-phenylethynyl-1,2,3,4-tetrahydroisoquinolines 1 – 10 and terminal electron-deficient alkynes in trifluoroethanol. − …”

“…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 …”