Palladium-catalyzed direct γ-C(sp³)–H arylation of β-alkoxy cyclohexenones: reaction scope and mechanistic insights

Abstract

Direct γ-C(sp3)-arylation of unactivated electron-rich enones is a long-standing challenge. Herein, we report a mild Pd-catalyzed method for direct γ-C(sp3)-arylation of various unactivated β-alkoxy cyclohexenones. The method is not only...

A Practical Approach to 6H-Indol-6-ones Enables the Formal Synthesis of γ-Lycorane

“…1-Substituted 6H-indol-6-one (1) 1 (Figure 1) belongs to Nheterobicyclic enone, which is the core skeleton of biologically active benzylphenethylamine-type alkaloids, 2 and widely found in Amaryllidaceae alkaloids, for example, lycorane (1a), lycorine (1b), lycoris (1c), kirkine (1d), fortucine (1e), and others. 3 Due to the important biological activities and the attractive chemical structures of these alkaloids, extensive advances in their total synthesis have been achieved.…”

Insights into the Mechanism and Regioselectivity of Palladium-Catalyzed Arylation of α,β-Unsaturated Ketones

“…In 2021, Li-Dong Shao et al 25 reported Pd-catalyzed direct γ-C(sp 3 )-H arylation of β-alkoxy cyclohexenones, and they found the phenomenon that the H on C(γ) was transferred to the C(α') position during the deuterium labeling experiments. Therefore, they launched a DFT mechanism study on the H migration step, only to find that the energy barrier for direct [1,5]-H shift is so high that it is almost impossible to occur under the experimental conditions (Scheme 1c).…”

“…23 Recently, On Ying Yuen reported the first ligand control of Pd-catalyzed site-selective αand γ-arylation of α,βunsaturated ketones with aryl halides (Scheme 1b), and Li-Dong Shao reported the Pd-catalyzed γ-arylation of β-alkoxy cyclohexenones (Scheme 1c). 24,25 Through experimental mechanism investigations, they all observed that there was an H shift phenomenon during their reaction, and Shao proposed that it was mainly determined by the tunneling effect. Since α,β-unsaturated ketone (enone) fragments have multiple reaction sites and exist in many biologically active substances, 26,27 the reactions discovered by Yuen and Shao have important theoretical and practical significance.…”

A silicon-containing aryl/penta-1,4-dien-3-one/amine hybrid exhibits antiproliferative effects on breast cancer cells by targeting the HSP90 C-terminus without inducing heat-shock response

“…In addition, the preliminary toxicity of 1z was also tested using human embryonic kidney cells (293T). 51 As a result, 1z [IC 50 = 32.65 μM, selectivity index (SI) towards MCF-7: ∼4.2] was less toxic than both DDP (IC 50 = 10.81 μM) and GA (IC 50 = 0.53 μM), but more toxic than NB (IC 50 > 100 μM, data not shown) (Fig. S1 †), thereby establishing a foundation for subsequent optimization of this category of HSP90 inhibitors.…”