Chemoselectivity in Pd-Based Dyotropic Rearrangement: Development and Application in Total Synthesis of Pheromones DOI
Jing Gong,

Qian Wang,

Jieping Zhu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 147(2), P. 2077 - 2085

Published: Dec. 30, 2024

In the dyotropic rearrangement of molecules with semiflexible structures, characterized by a freely rotating static C-C bond, formation mixture products is common due to coexistence several energetically comparable conformers. Herein, we report that it possible modulate shifting groups adjusting metal's coordination sphere in Pd-based rearrangement. presence catalytic amount Pd(II) salt, reaction γ-hydroxyalkenes or γ,δ-dihydroxyalkenes Selectfluor affords fluorinated tetrahydropyranols 6,8-dioxabicyclo[3.2.1]octanes (DOBCO), respectively. this domino process, two C(sp2) and one allylic C(sp3) are sequentially activated functionalized through pivotal conformation-controlled chemoselective C(sp3)-C(sp3) C(sp3)-Pd(IV) bond metathesis reaction. Mechanistic studies suggest sequence including 5-exo-trig oxypalladation, Pd oxidation, ring expansion 1,2-Csp3/Pd(IV) rearrangement, followed hydroxypalladation situ generated dihydropyrans. These findings provide unique retrosynthetic disconnection for synthesis 6,8-DOBCO. We showcase its potential developing concise three important pheromones. Notably, (+)-frontalin synthesized from commercially available 1,5-diene only steps, utilizing Sharpless asymmetric dihydroxylation Pd-catalyzed cyclization developed study.

Language: Английский

Pd-Catalyzed Strain-Releasing Dyotropic Rearrangement: Ring-Expanding Amidofluorination of Methylenecyclobutanes DOI Creative Commons

Baochao Yang,

Guoqiang Yang, Qian Wang

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 2, 2025

Under the Pd(II)/Pd(IV) catalytic cycle, cyclization of pent-4-en-1-amine derivatives typically yields either pyrrolidines or piperidines depending on N-protecting group. We report herein an unprecedented Pd(II)-catalyzed oxidative domino process that converts readily accessible N-protected 2-(2-amidoethyl)-1-methylenecyclobutane to 1-fluoro-2-azabicyclo[3.2.1]octanes. This transformation constructs three chemical bonds under mild conditions [Pd(hfacac)2 (5.0 mol %), Selectfluor (2.0 equiv), MeCN, 60 °C, 10 min] through a sequence involving 5-exo-trig amidopalladation/Pd(II)–oxidation/chemoselective dyotropic rearrangement/C–F bond-forming reductive elimination. Notably, mode remains independent group these conditions. Furthermore, diverse functional groups can be introduced at bridgehead position bicyclic compound via apparent anti-Bredt iminium intermediate.

Language: Английский

Citations

2
Mechanistic Insights into a Palladium-Catalyzed Quaternary Carbon-Editing Strategy: A DFT Study DOI
Feiyun Jia, Chenghua Zhang,

Yongsheng Yang

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 12, 2025

Direct editing of quaternary carbon remains highly challenging. In this study, we computationally investigated a palladium-catalyzed carbon-editing strategy using density functional theory (DFT) to elucidate its principal characteristics and address key mechanistic issues. A mechanism driven by sequential Pd migration was established. The results indicate that the total free energy barrier for transformation is 29.5 kcal mol-1, which reasonable under studied reaction conditions, with 1,3-PdIV identified as rate-determining step. Distortion-interaction (D/I) analysis revealed smaller distortion responsible selective palladation. These calculations confirm kinetically more favorable than 1,3-PdII migration. Selectfluor can effectively lower migration, thereby facilitating conversion. Furthermore, amide bond in starting reactant (1) plays critical role strategy, particularly palladation 1,3-Pd Notably, discovered novel involving 1,2-methyl/PdIV dyotropic rearrangement β-hydride elimination. This process exhibits significantly barrier, methyl HF elimination occurring simultaneously form C═C double bond. Thus, these findings enhance understanding strategies potentially provide theoretical support future research.

Language: Английский

Citations

0
Chemoselective Pd-Based Dyotropic Rearrangement: Fluorocyclization and Regioselective Wacker Reaction of Homoallylic Amides DOI
Chen‐Xu Liu, Qian Wang, Jieping Zhu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(44), P. 30014 - 30019

Published: Oct. 25, 2024

Fluorocyclization of alkenes tethered with a pronucleophile is an efficient transformation that converts easily accessible starting materials to fluorinated heterocycles in single step. We report herein unprecedented Pd(II)-catalyzed oxidative domino process transforms homoallylic amides 5,6-dihydro-4H-1,3-oxazines through oxypalladation/PdII–oxidation/dyotropic rearrangement/reductive elimination sequence. Three chemical bonds are created under these operationally simple conditions. Taking advantage the facile hydrolysis α-fluoro tertiary alkyl ether acidic conditions, one-pot conversion homologated ketones subsequently developed, which represents rare example regioselective Wacker oxidation reaction 1,1-disubstituted alkenes.

Language: Английский

Citations

1
Chemoselectivity in Pd-Based Dyotropic Rearrangement: Development and Application in Total Synthesis of Pheromones DOI
Jing Gong,

Qian Wang,

Jieping Zhu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 147(2), P. 2077 - 2085

Published: Dec. 30, 2024

In the dyotropic rearrangement of molecules with semiflexible structures, characterized by a freely rotating static C-C bond, formation mixture products is common due to coexistence several energetically comparable conformers. Herein, we report that it possible modulate shifting groups adjusting metal's coordination sphere in Pd-based rearrangement. presence catalytic amount Pd(II) salt, reaction γ-hydroxyalkenes or γ,δ-dihydroxyalkenes Selectfluor affords fluorinated tetrahydropyranols 6,8-dioxabicyclo[3.2.1]octanes (DOBCO), respectively. this domino process, two C(sp2) and one allylic C(sp3) are sequentially activated functionalized through pivotal conformation-controlled chemoselective C(sp3)-C(sp3) C(sp3)-Pd(IV) bond metathesis reaction. Mechanistic studies suggest sequence including 5-exo-trig oxypalladation, Pd oxidation, ring expansion 1,2-Csp3/Pd(IV) rearrangement, followed hydroxypalladation situ generated dihydropyrans. These findings provide unique retrosynthetic disconnection for synthesis 6,8-DOBCO. We showcase its potential developing concise three important pheromones. Notably, (+)-frontalin synthesized from commercially available 1,5-diene only steps, utilizing Sharpless asymmetric dihydroxylation Pd-catalyzed cyclization developed study.

Language: Английский

Citations

1