Groebke-Blackbum reaction

In 2010, Al-Tel s group described the synthesis of polyfunctional structures using a one-pot five- and six-component sequential process [61]. In this process, firstly the imine 66 was formed in the presence of SclOTOj and then the solution could be directly used in the next [4-i-l]-cycloaddition (Groebke-Blackbum reaction). The cycloaddition product 67 contained an acid moiety, which allowed a subsequent Ugi-4CR. Thus, the final Ugi products 68 were obtained from isocyanides, aldehydes, and amines in good yields (Schane 7.28). 

The imidazo[l,2-a]quinoxaline scaffold 233 was developed by Krasavin et al. via two isocyanide-based multicomponent reactions sequentially introducing four diversity elements to the final products [70]. The first step involves the synthesis of quinoxaUnes 237 from o-phenylenediamines 234 and followed by the Groebke-Blackbum-Bienayme multicomponent reaction (Scheme 43). The described methodology provides a tool to constmct the medicinally relevant heterocycles. 

Rostamnia, S., Lamei, K., Mohammadquli, M., Sheykhan, M. and Heydari, A. 2012. An efficient, fast, and reusable green catalyst for the Ugi-like Groebke-Blackbum-Bienayme three-component reaction under solvent-free conditions. Tetrahedron Lett. 53(39) 5257-5260. 

The same group also showed the use of other starting imines, which were formed in the same manner, and subsequently subjected to the Groebke-Blackbum/Ugi reaction (see starting imines in Fig. 7.2). In all cases, good yields were reported for the sequential process (55-73% yield). 

FIGURE 7.2 Different starting imines used in the Groebke-Blackbum/Ugi reaction. 

The multicomponent reaction of 2-amino-3-arylquinoxalines 132 with aldehydes and isocyanides under the conditions of the Groebke-Blackbum-Bienayme reaction (Blackburn et al. 1998 Groebke et al. 1998 Ivachtchenko et al. 2010) leading to l-aminoimidazo[l,2-fl]quinoxalines 142a-l is an example of synthesis of such compounds according to variant EIq (Table 4.3) (Krasavin and Parchinsky 2008 Krasavin et al. 2009). 

Table 4.3 The Groebke-Blackbum-Bienayme reaction in the l-aminoimidazo[l,2-a]quinoxali-...

Isocyanide derivatives are undoubtedly the most important reactants in MCRs because they show both nucleophilic and electrophilic characters within a single functionality. For example, IMCRs include the Ugi four-component reaction (Ugi-4CR) [11, 12], the Passerini three-component reaction (Passerini-3CR) [10], the Groebke-Blackbum-Bienayme reaction [44—46], the van Leusen three-... 

The Bienayme-Blackbum-Groebke reaction [14—16] provides access to a variety of fused heterocyclic ring systems in one, atom-economical, synthetic step. 

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). 

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