Synthesis of Purines and Related Molecules by Cyclization ­Reactions of Heterocyclic Enamines

Abstract

A great variety of pharmacologically relevant fluorinated purine analogues are available by cyclization reactions of heterocyclic enamines with 1,3-dielectrophiles. The reactions usually proceed with excellent regioselectivities. As electrophiles, 1,3-diketones, enaminones or 3-chloro-2-en-1-ones were used. Other synthetic strategies are based on inverse-electron-demand Diels–Alder reactions of heterocyclic enamines with triazines. Purine analogues were further functionalized by transition-metal-catalyzed CH-coupling reactions or oxidative cyclizations, giving rise to more complex polycyclic products. Amidino-C-glycosides in their reactions with 1,3-dielectrophiles afforded pyrimidine-C-glycosides. Multicomponent reactions of heterocyclic enamines afforded complex products, including spirocyclic derivatives.1 Introduction2 1,3-Diketones3 Enaminones4 3-Chloro-2-en-1-ones5 Triazines6 Transition-Metal-Catalyzed Functionalizations7 Pyrimidine-C-Nucleosides8 Multicomponent Reactions9 Conclusions

Adventures in CH-Arylation Chemistry

“…As mentioned in the introduction, we have been studying in my group the synthesis of new purine analogues by cyclization of heterocyclic enamines with 1,3-dielectrophiles. 12 Based on the work of Guo 17 related to CH-activation reactions of pyridines, we had the idea to study CH-activation reactions of nitro-substituted purine analogues. The nitrosubstituted purine analogues were usually prepared by employing the sodium salt of 2-nitromalonic aldehyde (3) as a 1,3-dielectrophile in cyclization reactions with heterocyclic enamines.…”

“…11 In addition, we started to investigate the synthesis of fluorinated, nitro-and amino-substituted purine analogues by cyclization of heterocyclic enamines with various 1,3-dielectrophiles. 12 In this context and based on our experience in the field of Pd-catalyzed cross-coupling reactions, we became more and more interested in CH activation reactions of heterocyclic substrates and their applications. The present article aims to give a personalized account of this topic.…”

Adventures in Coumarin Chemistry

“…In analogy to his reactions of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 4-chloro-3-formylcoumarin (7), Olumide also studied reactions with 4-chloro-3-nitrocoumarin (10). The TiCl 4 -mediated reaction of 10 with 1,3bis(trimethylsilyloxy)-1,3-butadienes 6a-k afforded adducts 43a-k, which were transformed by hydrogenation into chromeno[3,4-b]pyrrol-4(3H)-ones (pyrrolocoumarins) 44a-k (Scheme 18).…”

“…Muhammad Zeeshan, a doctoral student from Pakistan in my group, studied the reaction of 4-chloro-3-nitrocoumarin (10) with 1,3-dicarbonyl compounds. It was a great tragedy and loss that he died while swimming in the Baltic Sea.…”

“…In 2009, we started to investigate heterocyclic enamines (heterocycles containing an enamine moiety) as 1,3-dinucleophiles in cyclization reactions with chromones 9 and other 1,3dielctrophiles. 10 At that time, we also became interested in the application of coumarins as electrophilic building blocks in cyclization reactions.…”