Thiourea‐Promoted Cascade Dihalogenation‐Cyclization of Cyclohexadienone‐Containing 1,6‐Enynes

Abstract

Organohalogens play an important role in the drug discovery and functional materials. However, the convenient preparation of organohalogens still remains a challenging task. Herein, we report a metal‐free cascade dihalogenation‐cyclization of cyclohexadienone‐containing 1,6‐enynes in a biodegradable solvent to generate the dibrominated cis‐tetrahydrobenzofuran‐5(4H)‐ones and cis‐dihydrobenzopyran‐6(5H)‐ones respectively bearing 1,4‐dibromobut‐1‐enyl subunit in trans‐trans and trans‐cis form. A subgram‐scale experiment and several downstream transformations are presented for elaborating the synthetic utility. Moreover, the potent anticancer activity is observed against MDA‐MB‐468 cells for the corresponding products.

DBDMH-Promoted Methylthiolation in DMSO: A Metal-Free Protocol to Methyl Sulfur Compounds with Multifunctional Groups

“…Compared with other brominating agents, such as NBS, or N-bromoacetamide, DB-DMH as a special brominating agent has many advantages, e.g., high active bromine content, good storage stability and economic use [53][54][55]. In addition, acting as an oxidant in chemical synthesis, it also can be widely used in various transformations [56,57].…”

Ruthenium and Iodine Anion Cocatalyzed Cascade Dihalogenation and Cyclization of Internal Alkyne-Tethered Cyclohexadienones with 1,2-Dihaloethanes

“…However, most of these transformations afforded the fused heterocyclic products with monofunctionalization of the cyclohexadienone moiety, leaving the α position of the cyclohexanone moiety unfunctionalized . To date, only a few reports have demonstrated the difunctionalization and cascade cyclizations, and the Sasai group first reported a palladium-catalyzed diacetoxylation by using molecular oxygen as an oxidant . On the other hand, halogenated compounds are central functional compounds, which are widely used as the synthetic precursors and building blocks in organic synthetic chemistry, especially in cross-coupling reactions .…”

“…Based on the above preliminary experimental results and literature reports, , a possible mechanism was proposed for the ruthenium­(II) and iodine anion cocatalyzed dihalogenation and cascade cyclizations (Scheme ), which contains two catalytic cycles, the iodine cycle and the ruthenium cycle. To begin with, the iodine anion promoted dehalogenation of 1,2-dihaloroethanes delivering IX 2 – (in equilibrium with IX and X – ) with the release of ethylene gas, which was used as both the oxidant and the halogen source.…”