Asymmetric cyanohydrin synthesis from aldehydes and ketones using chiral metal (salen) complex as catalyst

摘要

Asymmetric addition of (CH3)(3)SiCN to carbonyl compounds and subsequent hydrolysis produces chiral cyanohydrins [1-3]. Such chiral compounds are useful intermediates for synthesis of pharmaceutics. The two functional groups (-OH and -CN) can be easily transformed into various homochiral ones including alpha-hydroxy acids [4,5], alpha-hydroxy aldehydes [6], alpha-hydroxy ketones [6], beta-hydroxy amines [5,6] and alpha-amino acid derivatives [7]. N-Methylmorphorin-N-oxide, cesium fluoride, potassium fluoride, and zirconium complex were, respectively, used as a catalyst for achiral silylcyanation [8-12] of aldehydes and ketones. Shibasaki has reported enantioselective catalytic additions of trimethylsilyl cyanide (TMSCN) to various ketones utilizing bifunctional ligand and Ti(OiPr)(4) or the lanthanide complexes [13]. The concept of dual activation was pioneered by Shibasaki's group. Deng first described the method of cyanosilylation of ketones employing chiral Lewis bases which are free of metal ions [14]. Snapper and Hoveyda described the addition of TMSCN to ketones catalyzed by peptidic chiral ligand and Al(OiPr)(3) [15]. Feng and Jiang employed chiral N-oxide/titanium(IV) complex for the cyanosilylation of ketones [16]. Feng utilized a catalytic double-activation method using chiral salen-Ti(IV) complex and various achiral N-oxides for the cyanosilylation of ketones [17]. Recently, Corey has shown that chiral oxazaborolidium salt is an excellent catalyst for the cyanosilylation of methyl ketones[18]. This method used TMSCN and diphenylmethyl phosphine oxide as co-reactants to generate Ph2MePOTMS(N=C:) as a reactive intermediate.