Phosphine-Initiated General Base Catalysis: Facile Access to Benzannulated 1,3-Diheteroatom Five-Membered Rings via Double-Michael Reactions of Allenes

Abstract

General base-catalyzed double-Michael reactions of allenes with various dinucleophiles are described. The reactions are facilitated most efficiently by a catalytic amount of trimethylphosphine, affording six types of C2-functionalized benzannulated five-membered heterocycles: benzimidazolines, benzoxazolines, benzothiazolines, 1,3-benzodioxoles, 1,3-benzoxathioles, and 1,3-benzodithioles. This atom-economical reaction is operationally simple and provides the product heterocycles in good to excellent yields. Careful mechanistic studies unveiled the phosphine-triggered general base catalysis pathway. Furthermore, the double-Michael reaction can serve as an alternative method for the selective mono-ketalization of β-diketones.

Advances in nucleophilic phosphine catalysis of alkenes, allenes, alkynes, and MBHADs

“…17 The mechanism of this powerful reaction is proposed to be a general base catalysis triggered by the phosphine (Scheme 18). Facile formation of the phosphonium dienolate 26 prompts the activation of the tethered di-pronucleophile 27 .…”

Bimolecular coupling reactions through oxidatively generated aromatic cations: scope and stereocontrol

“…Nucleophilic addition into these intermediates would provide heteroatom-rich products that are difficult to access through conventional protocols. For example direct condensation reactions between o -disubstituted benzene derivatives and aldehydes often fails because of the kinetically disfavored cyclization step, 18 and Kwon’s elegant phosphine-mediated protocol 19 requires the use of electron-deficient allenes.…”

Synthesis of Organofluoro Compounds Using Methyl Perfluoroalk-2-ynoates as Building Blocks

“…[18] The traditional methods for the synthesis of benzoxazolines and benzothiazolines have involved harsh conditions such as the use of strong acids or toxic catalysts and high thermal conditions with long reaction time. [19] We then endeavored to explore the application of methyl perfluoroalk-2-ynoates 1 for the catalyst-free synthesis of 2-perfluoroalkylated benzoxazolines 25a and benzothiazolines 25b. Treatment of 2-aminophenols 24a or 2-aminothiophenols 24b with methyl perfluoroalk-2-ynoates 1 in refluxing MeOH (Scheme 8) successfully gave cyclic 25a or 25b successfully.…”