Synthesis of Spiro-lactams and Polysubstituted Pyrroles via Ceric Ammonium Nitrate-Mediated Oxidative Cyclization of N-Furan-2-ylmethyl-β-Enaminones

Abstract

Spiro-lactams and polysubstituted pyrroles were synthesized by reactions of furfurylamines with ynones followed by oxidation. Specifically, the protocol involved in situ generation of N-furan-2-ylmethyl-β-enaminones and their subsequent oxidation by ceric ammonium nitrate (6 equiv for spiro-lactam formation, 3 equiv for pyrrole formation). This useful dearomatizing oxidation, which likely proceeds via a free-radical pathway, can be expected to extend the synthetic applications of furan and pyrrole derivatives.

Conjugated Ynones in Organic Synthesis

“…The reactions with ammonia and primary and secondary amines have been carried out under a variety of conditions. Some reactions have been performed at room temperature, ,,, but higher temperatures are more common, ,,− even as high as 120 °C , and 140 °C, and typically with 1.0–1.1 molar eq of the amine and no additional reagent(s), although the amine has also been used as solvent. ,,,, A variety of solvents have been applied, including alcohols ,, and nonprotic solvents like PhMe, , MeCN, DCM, THF, , DMSO, , 1,4-dioxane, , and DMF . The reaction time is usually short, but when anilines with one or several electron-withdrawing groups attached to the ring are used, even days have been required to obtain some product …”

“…A crucial factor in these cases is the presence of at least one additional reactive moiety in the enaminones, in a position that makes it possible to interact with the enaminone motif. This is illustrated by the examples in Scheme which show the reactivity of functionalized enaminones 354 under basic conditions with K 3 PO 4 (to pyrroles 356 ) and t -BuOK (to pyridines 359 ), acid catalysis (to benzoquinolinenaphtoquinones 361 ), and metal-induced oxidations with cerium­(IV) (to pyrroles 357 and 358 ), copper­(II) (to pyrroles 355 ), and palladium(0) (to quinolones 360 ) …”

Tandem Reactions of Ynones: via Conjugate Addition of Nitrogen‐, Carbon‐, Oxygen‐, Boron‐, Silicon‐, Phosphorus‐, and Sulfur‐Containing Nucleophiles

“…Moreover, the innovative application of N ‐furfuryl‐β ‐ enaminones has shown its success in the diversity of products. In 2016, Yin and co‐workers described the in situ generation of N ‐furfuryl‐β ‐ enaminones 20.1 and their subsequent oxidation by ceric ammonium nitrate (6 equivalents for spirolactam 20.2 formation, 3 equivalents for pyrrole 20.3 formation) [Eq. (20‐1)] (Scheme ).…”

Synthesis and Antimicrobial Activity of Some New 3,4‐Disubstituted Pyrroles and Pyrazoles

“…Moreover, pyrrole and their derivatives possess antimicrobial , antitumor , anti‐inflammatory , antibacterial , antioxidant , and antifungal activities. Among the various protocols including the Hantzsch, Paal–Knorr multicomponent reactions , ring opening‐based annulations , alkyne‐based cycloaddition , enamine‐based cascade annulations , disubstituted pyrroles have also been synthesized from activated olefins with tosylmethyl isocyanide . On the other hand, substituted pyrazoles display pronounced biological activities viz., antimicrobial, anticancer, antibacterial, anti‐inflammatory, and antioxidant .…”