Convenient Access to 2,3‐Disubstituted‐cyclobut‐2‐en‐1‐ones under Suzuki Conditions and Their Synthetic Utility

Abstract

A regioselective synthesis of general applicability has been designed for the one‐pot preparation of 2,3‐disubstituted‐cyclobutenones from iodoalkynes through cyclobutenylation, Suzuki CC coupling, and ketone formation. This one‐pot methodology has been applied to the selective synthesis of an orally active cyclooxygenase II inhibitor. Furthermore, the obtained cyclobut‐2‐en‐1‐ones were used as synthons in several transformations, such as, the preparation of β‐lactams, phthalazines, cyclohexa‐2,5‐dien‐1‐ones, and cyclopent‐3‐en‐1‐ones.

Substrate-Controlled Regioselective Bromination of 1,2-Disubstituted Cyclobutenes: An Application in the Synthesis of 2,3-Disubstituted Cyclobutenones

“…1 H NMR (500 MHz, CDCl 3 ) δ 7.71–7.68 (m, 4H), 7.31 (d, J = 7.0 Hz, 2H), 6.97 (d, J = 8.9 Hz, 2H), 3.89 (s, 3H), 3.63 (s, 2H), 2.47 (s, 3H). 13 C­{ 1 H} NMR (126 MHz, CDCl 3 ) δ 188.4, 160.0, 159.8, 142.0, 140.4, 130.0, 129.5, 129.0, 128.8, 122.6, 114.0, 55.3, 49.4, 21.7, in accordance with the literature …”

“…Our review of the literature revealed that the vast majority of disubstituted cyclobutenones can be prepared via the [2+2] cycloaddition process, which affords functionalized cyclobutenones that can be further modified by means of the Suzuki reaction or halogen reduction . The oxidation of cyclobutenyl alcohols en route to the substituted cyclobutenones can be ruled out, as such alcohols are usually prepared via the reduction of cyclobutenones . A direct approach to the preparation of substituted cyclobutenones based on the modification of the cyclobutene skeleton has not yet been published.…”

Copper-Catalyzed Borylation and Silylation of Dichlorocyclobutenones

“…To further illustrate the synthetic potential of this method, additional diversifications of silicon-containing products were conducted. Cyclobutenones could be engaged in nucleophilic processes ( 11 and 12 ) and reduced to an alcohol ( 13 ) as well as undergo thermal ring opening ( 14 ) and Wittig reaction ( 15 ) …”

A Fluorinated Carbanionic Substituent for Improving Water Solubility and Lipophilicity of Fluorescent Dyes

“…Water solubilizations of BODIPYs through the introduction of sulfonato group(s) [11] or conjugation with water-soluble peptides, saccharides, and poly(oxyalkylene)s [12] were examined. To investigate the effects of the fluorinated carbanionic substituent to the macroscopic properties of fluorescence dyes, we examined the reaction of BODIPY 2 a using 2fluoropyridinium ethanide 1, [13,14] an effective reagent for in situ generation of Tf 2 C=CH 2 (Scheme 1). [15] Fortunately, the reaction of 2 a with 2.1 equiv of 1 was quickly completed (< 15 min) in acetonitrile at room temperature to give 2,6dialkylated product 3 a-H.…”