The Mg‐Oppenauer Oxidation as a Mild Method for the Synthesis of Aryl and Metallocenyl Ketones

Abstract

Magnesium alkoxides undergo a hydride‐transfer oxidation with benzaldehyde as the oxidant. This magnesium variant of the Oppenauer oxidation was used for the synthesis of polyfunctional biaryl ketones. LiCl was found to promote this reaction by enhancing the solubility of magnesium alkoxides. This mild oxidation method was especially useful for preparing ketones bearing a metallocenyl unit as well as various new ferrocenyl ketones and tricarbonylchromium complexes. This last class of ketones was reduced with the CBS catalyst (CBS=Corey–Bakshi–Shibata, diphenyl oxazaborolidine) to chiral benzhydrol complexes with high enantioselectivity enabling an asymmetric synthesis of electron‐rich or ‐poor benzhydryl alcohols (up to 94 % ee).

An interesting sidetrack in the tofisopam synthesis: lithium variant of a stereospecific Oppenauer oxidation

“…19 Interestingly, the presence of LiCl in the reaction mixture considerably accelerated the oxidation reaction. It was suggested that the role of LiCl was both to solubilise the primarily formed magnesium chloride alkoxide and to activate the carbonyl function of benzaldehyde as a Lewis acid.…”

Catalytic Enantioselective Synthesis of Diarylmethanols from Aryl Bromides and Aldehydes by Using Organolithium Reagents

“…The combined organic layers were washed successively with aqueous 5 % NaHCO 3 and brine, dried (MgSO 4 ), and concentrated in vacuo. Flash chromatography (silica gel; 1 % ethyl acetate in toluene) of the residue gave 0.186 g (94 % yield) of 5a 12 (92 % ee ): HPLC analysis: Chiralcel OD column, 0.5 mL/min, 5 % i PrOH in hexane; retention times: 30.9 min [major ( S ) enantiomer], 34.6 min [minor ( R ) enantiomer]. This data is in agreement with published values 12…”

Zr-SBA-15 Lewis Acid Catalyst: Activity in Meerwein Ponndorf Verley Reduction

“…Typical MPV-active catalysts are based on transition metal complexes, including aluminum [4,5], boron [6], magnesium [7] and zirconium [8] complexes. Despite the several advantages of these homogeneous catalysts, their heterogeneous counterparts are preferred because of practicality, due to their easier separation from the reaction media or their higher resistance against moisture.…”