Cyclic Ether Synthesis via Palladium-Catalyzed Directed Dehydrogenative Annulation at Unactivated Terminal Positions

Abstract

Here, a palladium-catalyzed functionalization of unactivated sp(3) C-H bonds with internal alcohol nucleophiles is described. Directed by an oxime-masked alcohol, annulation chemoselectively occurs at the β position, leading to a range of aliphatic cyclic ethers with four- to seven-membered rings. Tethered primary, secondary, and tertiary free hydroxyl groups can all react to give the corresponding cyclized products. In addition, benzyl and silyl protected alcohols can also be directly coupled. An sp(3) C-H activation/intramolecular SN2 pathway was proposed.

Palladium(II)‐Catalyzed ortho‐Arylation of Aromatic Alcohols with a Readily Attachable and Cleavable Molecular Scaffold

“…Transformations reported by Hartwig, [7] Yu, [8] Tan, [9] Dong, [10] Zhao, [11] and us [12] demonstrated the feasibility of this concept in C–H functionalization. Specifically, a recent report from Zhao and coworkers [11b] demonstrated the Pd-catalyzed ortho -selective arylation to construct biaryls, using oximes as the surrogate species.…”

C–O Bonds from Pd‐Catalyzed C(sp3)–H Reactions Mediated by Heteroatomic Groups

“…Intramolecular reaction between hydroxy and methyl groups in the substrates shown in Equations (23) and (24) was also mediated by the Pd(OAc) 2 /PhI(OAc) 2 system, giving cyclic ethers with four-to seven-membered rings. [51] The hydroxy group can be formed through in situ cleavage of a silyl ether under the reaction conditions, a process slightly improved by addition of a fluoride source [Equation (25)]. …”

“…The alcohol could be produced from the reaction between Pd intermediates and either H 2 O 2 formed in situ [65] or O 2 , through the heterolytic cleavage of the C-Pd bond [66] as already proposed for oxidation of the Pd II -Me bond. [69] With regard to their catalytic aerobic reactions [Equations (51) and (52)], the authors discussed the Pd II /Pd 0 and Pd II / Pd IV catalytic cycles but without decisive support for either one of them. [65] We suspect that the redox catalytic cycle of the acetoxylation of 8-methylquinolines depends on the procedure.…”

Recent advances in the synthesis of tetrahydrofurans and applications in total synthesis

“…Recently, the group of Dong developed a THF synthesis, by oxime-directed C-H activation of a methyl group, and further cyclization involving a primary, secondary or tertiary alcohol (Scheme 38). 127 The process is catalyzed by Pd(OAc) 2 , and used PhI(OAc) 2 as an oxidant. The oxime directing group can then be removed to get the interesting 3-hydroxy-THF motif in good yield.…”