Pyrazinones scaffold decoration

Transition-Metal-Catalyzed Decoration of the 2(lH)-Pyrazinone Scaffold. 274... 

Abstract An overview on the microwave-enhanced synthesis and decoration of the 2(lH)-pyrazinone system is presented. Scaffold decoration using microwave-enhanced transition-metal-catalyzed reactions for generating structural diversity, as well as the conversion of the 2(lH)-pyrazinone skeleton applying Diels-Alder reactions to generate novel heterocyclic moieties are discussed. The transfer of the solution phase to polymer-supported chemistry (SPOS) is also described in detail. 

There has been a plethora of recent hterature regarding the synthetic manipulations of the 2(lH)-pyrazinone skeleton. Even though the addition-elimination reactions at the C-3 position to decorate the pyrazinone scaffold are well documented [24], the versatihty of such approaches can be found somewhat limited. Selective attack of nucleophiles on the chloroimine group of the pyrazinone system can generate 3-alkoxy- and 3-amino-pyrazinones (Scheme 9) [27,28]. The 3-CN group was introduced via a Rosemund-von Braun reaction with copper(I)cyanide under harsh conditions (heating in NMP at 150 °C) [27] (Scheme 9). 

It has recently been shown that the transition metal-mediated decoration of the pyrazinone scaffold can greatly benefit from microwave irradi-... 

Transition-metal-catalyzed cyanation [38] at the C-3 position for the decoration of the pyrazinone scaffold was also reported by the same authors. 

For the further decoration of the pyrazinone scaffold via transition metal-catalyzed chemistry, the Sonogashira reaction [45-50] has also been investigated on the C-3 position of the pyrazinone, applying microwave irradiation conditions (Scheme 17) [29]. It was found that microwave irradiation at 120 °C for 15 min of a mixture of the starting material, Pd(OAc)2, Cul and PPha in TEA/DMF were the appropriate reaction conditions. 

Decoration of the 2(1//)-Pyrazinone Scaffold Applying "Click Chemistry"... 

As the Diels-Alder reactions of 2( lff)-pyrazinones with richly substituted acetylenes can be used to generate diversely substituted pyridines and pyridi-nones, these cyclo additions were investigated under microwave irradiation conditions on the 1,2,3-triazole decorated pyrazinone scaffold. As a proof of concept, the pyrazinones bearing a 1,4-disubstituted-1,2,3-triazole unit, linked via a C-0 bond, were reacted with the symmetrical dienophile dimethyl acetylenedicarboxylate (DMAD), in view of minimizing regioselect-ivity problems (Scheme 28). 

Recently it has been shown that the microwave-assisted decoration of the 2(lff)-pyrazinone scaffold can allow an easy introduction of different substituents at the C-3 and even to the less reactive C-5 position [29]. Taking full advantage of combinatorial principles, some of these pathways were transferred to microwave-enhanced solid-phase chemistry, opening the way for the generation of many biologically interesting structures [108]. 

In a recent study, the group of Van der Eycken described the decoration of polymer-bound 2(lH)-pyrazinone scaffolds by performing various transition metal-catalyzed transformations [42]. The readily prepared pyrazinone was specifically decorated at the C3 position by employing microwave-mediated Suzuki, Stille, Sonogashira, and Ullmann protocols (Scheme 7.24), thereby introducing additional diver-... 

Scheme 7.24 Scaffold decoration of polymer-bound pyrazinone scaffolds.

---