Substrate‐Controlled Divergent Synthesis of Enaminones and Pyrroles from Indolizines and Nitroso Compounds

Abstract

It is imperative to learn new synthetic transformations to succeed in drug discovery and development. We report the substrate-driven synthesis of β-enaminones and N-aryl pyrroles from indolizines and nitrosoarenes; aryl-substituted indolizines lead to β-enaminones in a regio-and diastereoselective manner, whereas alkyl-substituted indolizines produce tetrasubstituted pyrroles. All products contain a pyridine unit, the second most abundant ring (after phenyl) in the FDA Orange Book. In both cases, the reactions proceed at room temperature without any catalyst. Moreover, both types of products can be obtained in one pot from commercial materials as well as at a gram scale. It is worthy of note that the regioselectivity of the βenaminones is inaccessible by the standard literature methods and their utility has been exemplified in the synthesis of diverse heterocycles. We have made every endeavor to put forward the corresponding reaction mechanisms based on thorough experimental work.

Copper Nanoparticles on Montmorillonite K-10: A Versatile Catalyst for the One-Pot Synthesis of 3,5-Disubstituted Isoxazoles Using Various Methodologies

“…MS (GC): m/z (%) = 239 (10) [M + ], 238 (27), 210 (23), 183 (10), 182 (20), 172 (13), 159 (27), 156 (10), 145 (13), 144 (100), 136 (40), 130 (12), 118 (16), 117 (83), 116 (29), 108 (10), 107 (14), 104 (14), 103 (10), 94 (13), 93 (11), 89 (20), 79 (18), 78 (12), 77 (84), 63 (10), 55 (22), 53 (12), 51 (27) 7b,13 Method B (106 mg, 83%).…”

Sustainable Synthesis of Indole-Substituted Densely Functionalized Pyrrole

“…However, one-pot chromatography and catalyst-free Paal–Knorr cyclization is a challenging and rather underrepresented area. Although various synthetic techniques for the densely substituted pyrrole derivatives such as base-mediated, iron-mediated oxidation domino reaction, gold-catalyzed cascade hydroamination/cyclization reaction, copper-catalyzed annulation reaction, and substrate-controlled divergent synthesis have been attempted, all of these methods report the synthesis of a partly substituted pyrrole scaffold . Thus, the development of a straightforward synthetic strategy for the construction of highly substituted pyrrole derivatives from simple and cheap starting materials under environmentally friendly conditions is still highly desirable.…”

Efficient Solvent-Free Synthesis of Indolizines Using CuBr Catalyst from Pyridine, Acetophenone, and Electron-Deficient Alkenes

“…Additionally, functionalization of the indolizine core enables the introduction of diverse substituents, further expanding the scope of potential applications. Despite the numerous synthetic methods developed for indolizine derivatives, there remain certain hurdles to overcome [16][17][18][19]. For instance, the synthesis method reported by the Kan research group allows the reaction to occur under relatively mild temperature conditions but requires stepwise procedures (Scheme 1) [20].…”