Palladium-Catalyzed Asymmetric Cross-Coupling Reactions of Cyclobutanols and Unactivated Olefins

Abstract

Transition-metal-catalyzed activations of carbon–carbons bonds of small strained rings have widespread applications in synthetic and medicinal chemistry. However, coupling reactions of cyclobutanols involving β-carbon elimination to construct C­(sp3)–C­(sp3) bonds have scarcely been developed. Here, we demonstrate a highly enantioselective Pd-catalyzed intermolecular C­(sp3)–C­(sp3) coupling reaction of a broad range of cyclobutanol derivatives and unactivated alkenes, allowing convenient access to a series of chiral benzene-fused cyclic compounds in a highly regio-, chemo-, and enantioselective manner.

Pd-Catalyzed alkynyl aryl iodide cyclization/alkylation with cyclobutanols

“…Cyclobutanols have been recognized as powerful and versatile alkylation reagents to construct γ-substituted ketones via palladium-catalyzed ring-opening of the strained cyclic C–C bond. 10 The initial work of the palladium-catalyzed ring-opening of cyclobutanols was reported by the Uemura group. 10 a This strategy was further expanded to the palladium-catalyzed alkylation of aryl halides, vinyl halides, benzyl chlorides and alkynyl bromides by Uemura, Cha, Martin and Xu groups.…”

Palladium-catalyzed Heck cyclization/allylation with homoallyl alcoholsviaretro-allylation

“…N -Me-Xu3, which was developed by the Zhang group, has demonstrated efficient performances in palladium-catalyzed asymmetric cascade Heck reactions. 5 j , l ,8,9 e ,13 g ,16 Gratifyingly, using N -Me-Xu3 as a chiral ligand could afford product 3-1′ in 49% yield with 87% ee. Further studies on this enantioselective process are underway (Table 5).…”

“…4 The domino sequence involves intramolecular carbopalladation of olefins affording active σ-alkylpalladium species, which can be further functionalized. Since Grigg's seminal contributions, this strategy has been extensively studied by Zhu, Lautens, Zhang, Li, Gu, Jia, Chen and other groups, and (hetero)arylation, 5 alkenylation, 5 e , j ,6 alkynylation, 7 alkylation, 5 j ,8 iodination, 9 cyanation, 10 carboxylation, 7 e ,11 phosphorylation, 12 hydrogenation 13 and borylation 14 of σ-alkylpalladium have been achieved. Although significant achievements have been made in palladium-catalyzed aryl halide-tethered alkene cyclization/functionalization, to the best of our knowledge, allylation of σ-alkylpalladium has rarely been explored.…”

Synthesis of Benzofused O- and N-Heterocycles through Cascade Carbopalladation/Cross-Alkylation of Alkynes Involving the C–C Cleavage of Cyclobutanols

“…49 Very recently, Murakami, Chen, and co-workers reported the synthesis of 2,3dihydrobenzofurans through the use of alkenyl-tethered aryliodides and benzocyclobutanols (d, Scheme 1). 50,51 With these precedents in mind, and given our interest in the topics of Pd chemistry and the processes related to C−C cleavage, 52−57 we aimed to extend the applicability of these types of cascades to the synthesis of heterocycles bearing an alkylated olefine moiety (Scheme 1).…”