Zinc Acetate‐Catalyzed Enantioselective Hydrosilylation of Ketones

Abstract

Zinc acetate complexes with ac hiral diphenylethylenediamine (DPEDA)-derived ligand have been proved to be efficient catalysts for the enantioselective hydrosilylation of aryl ketones.R eplacing pyrophoric dialkylzinc with the readily available zinc salt simplifies the procedures and provides excellent conversions (up to > 99%) and enantioselectivities(eesupt o9 7%).Keywords: asymmetric synthesis;c hiral alcohols; hydrosilylation;reduction;zinc Asymmetric hydrosilylation of prochiral ketones followed by hydrolysis of the resulting silylether is avaluable tool for the synthesis of enantiopure secondary alcohols,w hich are important building blocks in pharmaceutical, agrochemical, fragrance and flavoring chemistry.[1] Reductiono fk etones,i ncluding asymmetrich ydrosilylation, was commonly carriedo ut using platinum-group metals such as Ru, Rh or Ir. [2] Recently,e nvironmentally benign and less expensive catalysts have also been exhaustively exploredl eading to broad acceptance of earth-abundant metals such as zinc [3] and iron [4] in asymmetric synthesis. Particularly stimulating progress has been observed recently in the asymmetric hydrosilylation of ketones promoted by ironc omplexes.S ince Nishiyama [5] and Beller [6] reported the first examples of Fe(OAc) 2 -catalyzed asymmetric hydrosilylation with (EtO) 2 MeSiH and (EtO) 3 SiH, manyi ron-based catalysts have been studied for the asymmetric hydrosilylation of ketones.[7] However, ironc omplexes are often sensitive to the reactionc onditions due to the easy oxidation of iron(II)a nd also require relatively elevatedt emperatures. Only recently, an example of am ore reactive and enantioselective iron complex with the boxmi ligand has been presented by Gade. [8] In contrast to iron, zinc has only one oxidation state anda sarelatively more stable elements hould deserve certain attention. Surprisingly,s uccessfula pplications of Zn catalysts for asymmetric hydrosilylation are mostly limited to diethylzinc. Theprotocolinvolving application of Et 2 Zn with chiral ligands for the enantioselective reductiono fc arbonyl compounds with PMHS was developed by Mimouni nt he late 1990s.[9] Theb est results for the asymmetric hydrosilylation of acetophenonew ere achieved when diamine ligands were used (eesu pt o8 8%).[10] Zinc complexes with various chiral diamine scaffolds were furtheri nvestigated by Walsh, [11] Carpentier [12] andM ikami [13] providing chiral alcohols with good enantioselectivities (up to 85% ee). Va riationso fc hiral diaminocyclohexane (DACH)-based ligands have been also demonstrated [14] including an interesting applicationo f am acrocyclic oligoamine for asymmetric reduction with eesu pt o8 9%. [15] In contrast to well-developed applicationo fdiethylzinc with various ligands,h ydrosililation promoted by inorganic Zn salts is stilli ni ts infancy.I n2 009, Nishiyama developed more sustainable catalysts for asymmetrich ydrosilylation by replacing the highly reactive and hazardous dialkylzinc with zinca cetate.[16] Ligandsb earing thiophene ri...

Desymmetrization Approach to the Synthesis of Optically Active P-Stereogenic Phosphin-2-en-4-ones

“…The reaction mixtures were purified by column chromatography over silica gel (60–240 mesh). The chiral amines 7 – 12 , 21 15 – 16 , 22 17 , 23 18 , 24 25 , 25 26 , 26 27 , 27 and 28 – 30 28 were prepared according to the literature procedures. Analytical data for those amines are in accordance with those previously reported.…”

Zinc‐Catalyzed Enantioselective Hydrosilylation of Ketones and Imines under Solvent‐Free Conditions

“…Recently, we elaborated a convenient protocol for the enantioselective hydrosilylation of prochiral ketones, and imines by using readily available chiral Zn(OAc) 2 complexes. However, the relatively high catalyst loading (5 mol %) was considered to be a potential limitation for industrial application of our method.…”

Recent developments in enantioselective zinc-catalyzed transformations

“…In contrast, hydrosilylation catalyzed by inorganic Zn salts, such as cheap Zn(OAc) 2 , is still undeveloped. To fill this gap, Mlynarski et al disclosed in 2015 the first example of highly enantioselective hydrosilylation of aromatic ketones 226 promoted by a chiral complex in situ generated from 5 mol% of Zn (OAc) 2 and 10 mol% of chiral 1,2-diamine ligand 227 (Scheme 78) [110]. The reaction carried out in THF at 25 °C led to the formation, after subsequent hydrolysis of the formed intermediate silyl ethers, to chiral alcohols 228 in good to high yields (40-93%) and high enantioselectivities (76-95% ee).…”