摘要：Laboratory of Synthesis and NaturalProducts, Institute of Chemical Sciences and Engineering, EPFL-SB-ISIC-LSPN,CH-1015 Lausanne, S

转自：康龙化成

Chemoselectivity in Pd-Based Dyotropic Rearrangement Development and Application in TotalSynthesis of Pheromones

JingGong, Qian Wang, Jieping Zhu*

Laboratory of Synthesis and NaturalProducts, Institute of Chemical Sciences and Engineering, EPFL-SB-ISIC-LSPN,CH-1015 Lausanne, Switzerland

—J.Am. Chem. Soc., 2025, https://doi.org/10.1021/jacs.4c15764.

Recommended by Shi Li_MOC

KEYWORDS:Pdcatalysis (反应类型), domino process (反应类型),Dyotropic rearrangement (反应类型), fluorination (反应类型), C(sp3)–O (成键类型),C(sp3)–F (成键类型),γ-hydroxyalkenes (原料),γ,δ-dihydroxyalkenes (原料), 6,8-dioxabicyclo[3.2.1]-octanes (产物), pheromones (产物)

ABSTRACT: Jieping Zhu’s group report that it is possible tomodulate the shifting groups by adjusting the metal’s coordination sphere inPd-based dyotropic rearrangement. In the presence of a catalytic amount ofPd(II) salt, the reaction of γ-hydroxyalkenes or γ,δ-dihydroxyalkenes with Selectfluor affords fluorinated tetrahydropyranols or6,8-dioxabicyclo[3.2.1]octanes, respectively. In this domino process, two C(sp2) and one allylic C(sp3) are sequentially activated andfunctionalized through a pivotal conformation-controlled chemoselective C(sp3)–C(sp3) and C(sp3)–Pd(IV) bond metathesisreaction. Mechanistic studies suggest a reaction sequence including 5-exo-trigoxypalladation, Pd oxidation, and chemoselective ring expansion 1,2-Csp3/Pd(IV) dyotropic rearrangement,followed by hydroxypalladation of in situ generateddihydropyrans. These findings provide a unique retrosynthetic disconnection forthe synthesis of 6,8-DOBCO. They showcase its potential by developing a concisesynthesis of three important pheromones.

DyotropicRearrangement: Conformational Effect

(a) Dyotropic rearrangement of β-lactone. (b) Generic presentation ofPd-based dyotropic rearrangement. (c) Chemoselectivity inPd-based dyotropic rearrangement. (d) Reversing the intrinsic migratoryaptitude: development and application in natural product synthesis (this work)

Mechanistic Investigation

Substrate scope: Conversion of Substituted Pent-4-en-1-olsto Fluorinated Tetrahydropyran Derivatives

Substrate scope: Migrative Biscyclization of γ,δ-Dihydroxyalkenes to6,8-Dioxabicyclo[3.2.1]octanes

Application in Total Synthesisof Natural Products

Prof. Jieping Zhu et al developed a Pd(II)-catalyzed domino process that hinges on a key chemoselective ring expansion, 1,2-C(sp3)/Pd(IV) dyotropic rearrangement of a Pd intermediate,generated from the 5-exo-trig oxypalladation and Pd oxidation sequence. Thestraightforward procedure efficiently transforms γ-hydroxyalkenesand γ,δ-dihydroxyalkenes into fluorinated tetrahydropyranols and 6,8-dioxabicyclo[3.2.1]- octanes (6,8-DOBCO), respectively,in good yields. Despite the fact that the oxygen atom has a higher migratory aptitude than the sp3 carbon indyotropic rearrangement, they have demonstrated that it is possible to overturnthis tendency by judiciously controlling the conformation of the Pdintermediate undergoing the rearrangement. The result provides a uniqueretrosynthetic disconnection for accessing 6,8- DOBCO. This is illustrated byaccomplishing total synthesis of three important pheromones leveraging thisunprecedented biscyclization methodology.

来源：新浪财经