Reactivity of Dipyrromethanes towards Azoalkenes: Synthesis of Functionalized Dipyrromethanes, Calix[4]pyrroles, and Bilanes

Abstract

The introduction of side chains at the 1‐ and 9‐positions of dipyrromethanes was explored by using the hetero‐Diels–Alder reaction of azoalkenes. New 5,5′‐diethyldipyrromethanes and 5‐phenyldipyrromethanes that were functionalized with open‐chain hydrazone moieties, including derivatives with tetrazolyl groups, were prepared. Furthermore, the synthesis of new calix[4]pyrroles and bilanes was achieved by employing the bis(hetero‐Diels–Alder) reaction of azoalkenes with 5,5′‐diethyldipyrromethane.

Biological Evaluation of Dipyrromethanes in Cancer Cell Lines: Antiproliferative and Pro‐apoptotic Properties

“…Scheme2.Functionalization of dipyrromethanesv ia hetero-Diels-Alder reactions of nitrosoalkenes and azoalkenes. [18,19] Scheme3.On-water synthesis of 5-substituted dipyrromethanesfrom the reaction of azo-and nitrosoalkenes withp yrrole. [20] 5-Phenyldipyrromethane (5b)a lso reactedw ith 3-(1-benzyl-1Htetrazol-5-yl)nitrosoethylene, generatedf rom oxime 9e,g iving dipyrromethanes 14 d and 15 d (entry 4).…”

“… Functionalization of dipyrromethanes via hetero‐Diels–Alder reactions of nitrosoalkenes and azoalkenes …”

“…[17] We explored this chemistry as an ew strategy for the functionalization of dipyrromethanes. [17][18][19] It was demonstrated that 5,5'-diethyl-(5a)a nd 5-phenyldipyrromethanes (5b)p articipate in hetero-Diels-Alder reactions with nitrosoalkenesa nd azoalkenes to give dipyrromethanes 6 and 7 with side chains containing oxime and hydrazone groups, respectively,a tp ositions 1a nd 9. By controlling the reactions toichiometry,i ti s possible to obtain mono-o r1 ,9-disubstituted derivatives (Scheme 2).…”

“…The study of the reactivity of nitrosoalkenes and azoalkenes provided access to a range of dipyrromethane and pyrrole derivatives incorporating oximes or hydrazones. Herein, the biological evaluation as anticancer agents of heterocyclic compounds 4 a , 4 b , 6 a – 6 i , 7 a – 7 c , and 8 a – 8 e , the synthesis of which was previously described, as well as of other new derivatives ( 12 a , b , 13 a , b , 14 a – d , 15 a – d ) is described (Scheme ).…”

Sequential MCR via Staudinger/Aza-Wittig versus Cycloaddition Reaction to Access Diversely Functionalized 1-Amino-1H-Imidazole-2(3H)-Thiones

“…To validate our hypothesis we began to explore the process step by step. Thus, α-chlorohydrazone derivative 1a [26,27,28,29,30] (2.0 mmol) dissolved in THF (9.0 mL) subjected to α-azidation using an ice-cooled aqueous solution of NaN 3 [31] (2.0 mmol/1.0 mL) under magnetic stirring at room temperature. After the evaporation of the solvent and an appropriate extraction, the α-azidohydrazone derivative 2a was obtained in 70% yield.…”