With Ketones Aldehydes and Isocyanide

Multicomponent reactions (MCRs) have become important tools in modem preparative synthetic chemistry because they increase efficiency by combining several operational steps without the isolation of intermediates or changing the reaction conditions (Litvinov 2003 Zhu and Bienayme 2005). MCRs have emerged as valuable tools for the preparation of stracturally diverse chemical libraries of dmg-like heterocyclic compounds (Ugi et al. 1994, 2000 Tietze and Modi 2000). Isocyanide-based MCRs are especially important in this area (Domling and Ugi 2000 DomUng 2006). 

Shaabani and coworkers simply used 1,2-DAB or 1,2-DACH instead of heterocyclic systems containing a H2N-C = N fragment in the known Groehke-Blackbum-Bienayme MCR reaction (Groebke et al. 1998 Blackburn et al. 1998 Bienayme and Bouzid 1998) (Ugi-type MCR reaction). 

To explore the scope and limitations of this reaction, the procedure was extended to various alkyl, benzyl, and alicyclic isocyaitides and aliphatic, alicychc, and aromatic ketones, aliphatic and aromatic aldehydes with electron-withdrawing and electron-releasing groups at their para positions in aromatic diamines. The reaction 

The reaction proceeds under mild conditions and is compatible with a wide range of functional groups. It is noteworthy that five substituents in the products (R -R ) can be varied independently of each other. 

It might be well to point out that after the initial paper (Shaabani et al. 2008), very simple, efficient, clean, and practical methods for the synthesis of highly substituted quinoxalin-2-amine derivatives in good yields have been reported. They proceed in the presence of HCl (33-54 %) (Krasavin and Parchinsky 2008 Krasavin et al. 2009), ferric perchlorate (91-93 %) (Heravi et al. 2009), cerium(IV) ammonium nitrate (CAN) (71-96 %) (Li et al. 2009a), and ethylenediaminete-traacetic acid (72-95 %) (KoUa and Lee 2010) as efficient catalysts correspondingly in MeOH, MeCN, EtOH, or H2O. 

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