Ni-Catalyzed Intramolecular Reductive 1,2-Dicarbofunctionalization of Alkene: Facile Access to Podophyllum Lignans Core

Jian Xiao; Ya-Wen Wang; Zhong-Ping Qiu; Yu Peng

doi:10.1055/s-0040-1707188

Synlett, Table of Contents

Synlett 2021; 32(16): 1662-1664
DOI: 10.1055/s-0040-1707188

cluster

Modern Nickel-Catalyzed Reactions

Ni-Catalyzed Intramolecular Reductive 1,2-Dicarbofunctionalization of Alkene: Facile Access to Podophyllum Lignans Core

Authors

Jian Xiao

^aSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. of China
Ya-Wen Wang

^aSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. of China
Zhong-Ping Qiu∗

^aSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. of China
Yu Peng ∗

^aSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, P. R. of China

^bState Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China

Abstract

All articles of this category

In memory of Prof. Xuan Tian

Abstract

The facile access to the tetracyclic skeleton of podophyllotoxin, a medicinally important lignan natural product, was efficiently achieved via a unique intramolecular alkylarylation of the tethered alkene in a dihalide under mild conditions using reductive nickel catalysis.

Key words

nickel - reductive coupling - intramolecular - cyclization - synthesis

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References

References and Notes

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10 In a 100 mL round-bottom flask, enol ether 7 (1.50 g, 3.1 mmol) was dissolved in anhydrous CH₂Cl₂ (35 mL) and cooled to 0 °C. To this solution was added TBCD (97%, 1.57 g, 3.7 mmol, 1.2 equiv) portionwise, and the mixture was stirred for 30 min at 0 °C. A solution of allyl alcohol (3.6 mL, 62 mmol, 20.0 equiv) in CH₂Cl₂ (5 mL) was then added dropwise, and the resulting mixture was gradually warmed to room temperature and stirred further for 9 h. The reaction was quenched with saturated aqueous NaHCO₃ (3 mL), Na₂SO₃ (3 mL), and stirred further for 30 min. The resulting mixture was extracted with CH₂Cl₂ (2 × 50 mL), and the combined organic layers were washed with water (2 × 15 mL) and brine (15 mL), respectively, dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (petroleum ether/EtOAc = 10:1 → petroleum ether/EtOAc = 4:1) on silica gel to afford 8 (1.519 g, 79% yield) as a yellow oil. R_f = 0.36 (petroleum ether/EtOAc = 2:1). IR (film): ν_max = 2930, 2838, 1590, 1504, 1479, 1461, 1422, 1383, 1326, 1265, 1229, 1128, 1037, 929, 845, 792, 736, 701, 685, 582 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ (major isomer) = 7.19 (s, 1 H), 6.99 (s, 1 H), 6.52 (s, 2 H), 5.93 (s, 1 H), 5.89 (s, 1 H), 5.86–5.80 (m, 1 H), 5.35 (dd, J = 17.2, 1.6 Hz, 1 H), 5.13 (dd, J = 10.8, 1.6 Hz, 1 H), 4.76 (d, J = 10.8 Hz, 1 H), 4.55 (dd, J = 11.2, 2.8 Hz, 1 H), 4.26 (dd, J = 13.2, 4.8 Hz, 1 H), 4.00 (d, J = 2.4 Hz, 1 H), 3.88 (dd, J = 12.8, 5.2 Hz, 1 H), 3.76 (s, 6 H), 3.74 (s, 3 H), 3.31 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 153.3 (2 C), 148.7, 147.3, 137.23, 137.17, 135.6, 133.8, 119.0, 116.7, 107.0, 105.3 (2 C), 102.0, 101.8, 90.5, 69.7, 60.8, 57.7, 57.3, 56.21 (2 C), 56.17 ppm. HRMS (ESI): m/z calcd for C₂₃H₂₆O₇ ⁷⁹BrINa⁺ [M + Na]⁺: 642.9799; found: 642.9791.
11 Xiao J, Nan G, Wang Y.-W, Peng Y. Molecules 2018; 23: 3037

Supplementary Material

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