Cycloalkylation of C(sp³)‑H Bond with Neighboring Carboxylic Acid as Traceless Activating Group

Selective functionalization of inert C­(sp³)-H bond is one of cutting-edge challenges in chemical synthesis. A novel strategy for selective C­(sp³)-H bond cycloalkylation is developed with neighboring carboxylic acid as a traceless activating group. Primary and secondary alkyl carboxylic acids undergo decarboxylation/α-C­(sp³)-H cleavage/cycloalkylation to give the five-membered cyclization products, while tertiary acids undergo decarboxylation/β-C­(sp³)-H cleavage/cycloalkylation to generate the six-membered cyclization products

Iron-Catalyzed Radical [2 + 2 + 2] Annulation of Benzene-Linked 1,7-Enynes with Aldehydes: Fused Pyran Compounds

An iron-catalyzed radical [2 + 2 + 2] annulation of benzene-linked 1,7-enynes with aldehydes has been developed. With this method, a variety of fused [6.6.6] pyran molecules are built in an efficient and selective manner. The aldehydic radical-mediated strategy exhibits a particularly attractive dual role, which triggers and terminates the domino cyclization

Pd-IHept-Catalyzed Ring-Opening of <i>gem</i>-Difluorocyclopropanes with Malonates Via Selective C–C Bond Cleavage: Synthesis of Monofluoroalkenes

Monofluoroalkene scaffolds are frequently found in various functional molecules. Herein, we report a Pd-IHept-catalyzed (NHC = N-heterocyclic carbene) defluorinative functionalization approach for the synthesis of monofluoroalkenes from gem-difluorocyclopropanes and malonates. The flexible yet sterically hindered N,N′-bis(2,6-di(4-heptyl)phenyl)imidazol-2-ylidene ligand plays a key role in ensuring the high reaction efficiency. In addition, sterically hindered 1,1- and 1,2-disubstituted gem-difluorocyclopropanes could also be used in this transformation

Iron-Catalyzed Convergent Radical Cyclization of Aldehydes with Two Alkenes to 3,4-Dihydropyrans

A novel convergent radical cyclization of an aldehyde with two alkenes has been developed. With this method, polyfunctionalized 3,4-dihydropyrans are built in an efficient and selective manner. The iron-catalyzed redox radical recombinations are proposed for the formation of a 3,4-dihydropyran skeleton

Iron-Catalyzed Acylation-Oxygenation of Terminal Alkenes for the Synthesis of Dihydrofurans Bearing a Quaternary Carbon

Iron-catalyzed acylation-oxygenation of terminal alkenes is reported. Acyl radicals generated by the oxidation of aldehydes add to terminal alkenes and followed by intramolecular oxygenation give functionalized 2,3-dihydrofuran derivatives bearing a quaternary carbon

Benzannulation of Indoles to Carbazoles and Its Applications for Syntheses of Carbazole Alkaloids

A novel and efficient method for the benzannulation of indoles to carbazoles is reported. γ-Carbonyl <i>tert</i>-butylperoxide is applied as a new diene building block for the π-extension of simple indoles. The synthetic utility of this method is demonstrated by concise and selective total syntheses of naturally occurring carbazole alkaloids, olivacine, and asteropusazole A

Iron-Catalyzed Divergent Tandem Radical Annulation of Aldehydes with Olefins toward Indolines and Dihydropyrans

Iron-catalyzed divergent tandem radical annulations of aldehydes with olefins are reported. The new strategy allows the rapid and efficient construction of various multifunctionlized indolines (R = Ar) and dihydropyrans (R = Me), which are significant skeletons in bioactive natural products and pharmaceuticals. The substituents of tertiary amines play vital roles to facilitate the desired transformation. Mechanistic studies on indoline formation disclose that the homolytic cleavage of the carbonyl C–H bond might be involved in the rate-determining step, while dissociation of the aromatic C–H bond was most likely included in the product-determining step

Cross-Coupling of Phenol Derivatives with Umpolung Aldehydes Catalyzed by Nickel

A nickel-catalyzed cross-coupling to construct the C­(sp²)–C­(sp³) bond was developed from two sustainable biomass-based feedstocks: phenol derivatives with umpolung aldehydes. This strategy features the in situ generation of moisture/air-stable hydrazones from naturally abundant aldehydes, which act as alkyl nucleophiles under catalysis to couple with readily available phenol derivatives. The avoidance of using both halides as the electrophiles and organometallic or organoboron reagents (also derived from halides) as the nucleophiles makes this method more sustainable. Water tolerance, great functional group (ketone, ester, free amine, amide, etc.) compatibility, and late-stage elaboration of complex biological molecules exemplified its practicability and unique chemoselectivity over organometallic reagents