Tunable Gold(I)-Catalyzed [4 + 3] Cycloaddition for Divergent Synthesis of Furan-Fused N,O-Heterocycles

Abstract

By choosing suitable ligand-directed gold catalysts, two types of gold-containing all-carbon 1,4-dipoles could be generated selectively from the gold(I)-catalyzed cycloisomerizations of allenyl ketones bearing a cyclopropyl moiety, which undergo [4 + 3] cycloadditions with nitrones to produce two regiomers of furan-condensed N,O-seven-membered rings in moderate to excellent yields highly selectively.I ntermolecular cycloaddition represents a powerful tool to create a myriad of functionalized carbocyclic and heterocyclic frameworks in a highly regio-and stereocontrolled fashion. 1 While traditional protocols by applying stable conjugated 1,3-dipoles to react with unsaturated bonds to produce cyclic motifs are well documented, 2 studies on utilizing nonclassical all-carbon 1,4-dipoles, a class of highly reactive variants without a fully conjugated system, 3 for cycloaddition reactions remain a critical challenge and are of high value in organic chemistry.Benefiting from the development of the transition-metal catalysis in organic synthesis, 4 a few approaches have been established to enter the polarized four-carbon units, binding a relatively strong carbon−metal bond via elaborate design of substrates. 5 For example, in 2007, an elegant work involving the generation of 1,4-zwitterionic dipoles with a π-allylpalladium moiety from a palladium(0)-catalyzed oxidative addition into the γ-methylidene-δ-valerolactones and decarboxylation process was first disclosed by Hayashi 6 and co-workers (Scheme 1, eq 1). Later, vinyl benzoxazinanone derivatives have also been successfully used as valuable precursors of an aromatic ring containing 1,4-dipoles undergoing a similar decarboxylation process. 7 The homogeneous gold catalysis has emerged as a continuously growing field of investigation. 8 Owing to the exceptional π-acidity of cationic gold(I) complexes to activate unsaturated carbon−carbon bonds, Zhang's group 9 developed the first gold(I)-catalyzed cycloisomerization of 1-(1-alkynyl)cyclopropyl ketones toward

Gold-Catalyzed Reactions of Specially Activated Alkynes, Allenes, and Alkenes

“…On the other hand, using [(Ph 3 P)­Au]­OTf as the catalyst led to a completely nonselective process and furans produced by trapping of both intermediates 1068 and 1069 could be observed. This reactivity was further exploited by the same authors who reported that trapping of reactive intermediates with nitrones 1070 led to formal [4 + 3] cycloaddition products 1071 and 1072 (Scheme , part B) …”

“…This reactivity was further exploited by the same authors who reported that trapping of reactive intermediates with nitrones 1070 led to formal [4 + 3] cycloaddition products 1071 and 1072 (Scheme 250, part B). 438 Interestingly, the regiochemistry of the process could be controlled by the choice of the catalytic system and the temperature employed for the reaction. By using [(Ph 3 P)Au]-OTf and running the reaction at −5 °C, a trapping of 1,4-dipole 1073 derived from carbene 1068 took place, which finally led to the formation of oxazepine derivative 1071.…”

Construction of Medium-Sized Rings by Gold Catalysis

“…Recently, Ren, Miao, and co-workers also disclosed a divergent synthesis of furan-fused N,O-heterocycles through Au-catalyzed cycloisomerizations. 148 3.2.3. Acyloxy Rearrangement.…”

Ascending of Cycloaddition Strategy for N–O Heterocycles

“…48 Recently, Miao and Ren group engineered a [4+3] cycloaddition strategy with a non-classical all carbon based unconjugated 1,4 dipole with nitrones via Au(I) catalysis. 52 The 1,4-dipoles are in situ generated from cyclopropylidine group containing allenyl ketones. Intriguingly, the regioselectivity of this process can be reversed by changing the ligands on Au(I) catalyst (Scheme 27).…”