Synthesis of Difluoromethylated and Phosphorated Spiro[5.5]trienones via Dearomative Spirocyclization of Biaryl Ynones

Abstract

Copper- or silver-catalyzed cascade radical addition/dearomative spirocyclization of biaryl ynones with fluoroalkyl bromides or diethylphosphite has been realized for the first time. This method provides a novel and step-economical protocol for the divergent synthesis of a wide range of difluoromethylated or monofluoromethylated and phosphorated spiro[5.5]trienones in moderate to high yields.

Ynones in Reflex‐Michael Addition, CuAAC, and Cycloaddition, as Well as their Use as Nucleophilic Enols, Electrophilic Ketones, and Allenic Precursors

“…As a brief summary, similar annulations of ynones with alkanes,[3c] BrCF 2 CO 2 Et,[3b], [3c] R 3 SiH,[8a] HPO(OMe) 2 ,[10b] ArSH,[12h] RSO 2 H,[12c] and AgSCF 3 [12e] were presented in Scheme . The addition afforded radical intermediate 3.1 , then subsequent cyclization and dehydrogenation gave indenone derivatives 3.2 .…”

“…The addition afforded radical intermediate 3.1 , then subsequent cyclization and dehydrogenation gave indenone derivatives 3.2 . Both metal‐catalyzed[3b], [3c], [8a], [10b] and metal‐free methodologies[3a], [12c], [12e], [12h] have been developed in this decade. An oxidation or photoreaction condition was usually required (Scheme ).…”

“…As shown in Scheme , radical annulations of functional ynones with · CF 3 ,[3c] · CF 2 CO 2 Et,[3d] · PO(OEt) 2 ,[10a] RSO 2 · ,[12i] and ArSO 2 · [12d] could be applied in similar processes (Eq. 5‐1).…”

“…Firstly, the reflex‐Michael addition (compared to Michael addition, the addition took place on the other position of alkenes) afforded radical intermediate 5.1 . Then, the subsequent cyclization with aldehydes,[3c], [3d] methoxylarenes[10a], [12i] or azides[12d] yielded naphthoquinones 5.2 , 5.3 ,[3c], [3d] spiro[5.5]trienones 5.5 , 5.6 [10a], [12i] and quinolones 5.4 [12d] respectively (Scheme ). We believe alkenes, alkynes, nitriles, esters and thioethers can also be used as acceptors for the addition of radicals.…”

“…Radical phosphorylation has become a highly efficient approach to synthesize phosphonates. Recently, Zhu[10a] and Zhang[10b] independently depicted these annulations, affording naphthoquinones 17.4 (Eq. 17‐1) and indenones 17.8 (Eq.…”