Enantioselective Organocatalyzed Synthesis of 2-Amino-3-cyano-4H-chromene Derivatives

Abstract

Abstract:The structural motif that results from the fusion of a benzene ring to a heterocyclic pyran ring, known as chromene, is broadly found in nature and it has been reported to be associated with a wide range of biological activity. Moreover, asymmetric organocatalysis is a discipline in expansion that is already recognized as a well-established tool for obtaining enantiomerically enriched compounds. This review covers the particular case of the asymmetric synthesis of 2-amino-3-cyano-4H-chromenes using organocatalysis. Herein, we show the most illustrative examples of the methods developed by diverse research groups, following a classification based on these five different approaches: (1) addition of naphthol compounds to substituted α,α-dicyanoolefins; (2) addition of malononitrile to substituted o-vinylphenols; (3) addition of malononitrile to N-protected o-iminophenols; (4) Michael addition of nucleophiles to 2-iminochromene derivatives; and (5) organocatalyzed formal [4+2] cycloaddition reaction. In most cases, chiral thioureas have been found to be effective catalysts to promote the synthetic processes, and generally a bifunctional mode of action has been envisioned for them. In addition, squaramides and cinchona derivatives have been occasionally used as suitable catalysts for the substrates activation.

Ultrasound-assisted multicomponent synthesis of 4H-pyrans in water and DNA binding studies

“…Among them, the synthesis of 2-amino-3-cyanopyran derivatives has aroused special attention in the last few years, as part of 2-amino-3-cyano-4 H -chromenes 3 , also because of their biological properties (Fig. 1 ).…”

“…Highly functionalized 4H-pyrans are an important family of oxygen-containing heterocycles with a wide spectrum of biological properties. The 4H-pyran core can be found in many natural products or pharmaceutical compounds, commonly as part of 4H-chromene skeletons (4H-1-benzopyrans) [1][2][3] . Their interesting pharmacological profile varies from antitumor, antiallergic, antimicrobial to antibacterial agent, among other properties [4][5][6][7][8][9][10] .…”

Chiral Bifunctional Thioureas and Squaramides Grafted into Old Polymers of Intrinsic Microporosity for Novel Applications

“…The 2-amino-4H-chromenes as biological active compounds [47] lets us consider the synthesis of enantioenriched 2,3,4-trisubstituted 4H-chromenes by using I – VI as organocatalysts following a cascade process related to others previously described [48]. The reaction of 2-hydroxynitrostyrene ( 8 ) with malononitrile ( 9 ) proceeded smoothly in CH 2 Cl 2 , leading to a very good 2-amino-3-cyano-4-nitromethyl-4H-chromene ( 10 ) yield (Scheme 3) but to an unfortunately moderate enantioselectivity (Table 2).…”

Cysteic acid grafted to magnetic graphene oxide as a promising recoverable solid acid catalyst for the synthesis of diverse 4H-chromene

“…4 H -chromenes represent an important class of oxygen-containing heterocycles and a key building block of many natural products. They are also widely found in nature, in some edible fruits and vegetables, to name but a few, and these compounds also are broadly used as cosmetics and pigments 1 – 3 . 4 H -chromene scaffolds exhibit pharmacological properties and biological activities such as antioxidant 4 , antimicrobial 5 , 6 , antiviral, antibacterial, pro-apoptotic 7 – 11 , anticancer 12 , antifungal, anticoagulant, antinociceptive 13 , antiproliferative 14 , antitubercular, antiallergic, antibiotic, hypolipidemic, and immunomodulating activities.…”