Asymmetric Hydrocyanation of α,β‐Unsaturated Ketones into β‐Cyano Ketones with the [Ru(phgly)₂(binap)]/C₆H₅OLi Catalyst System

Abstract

Catalytic asymmetric hydrocyanation of a,b-unsaturated ketones into the corresponding chiral b-cyano ketones is a challenging scientific endeavor. Four major hurdles must be cleared before this reaction can be realized: 1) use of HCN as a cyanide source, [1] 2) high 1,4-addition selectivity over 1,2-addition, 3) sufficient enantioface selectivity and, 4) high catalytic activity (low catalyst loading). Recently, Shibasaki and co-workers reported pioneering studies on asymmetric 1,4-addition of cyanide to the conjugate enones catalyzed by chiral Gd and Sr compounds. [2][3][4][5] A wide range of 1,4-adducts were obtained in high enantiomeric excess (ee), but two equivalents of a tert-C 4 H 9 (CH 3 ) 2 SiCN/2,6-dimethylphenol system were required as a cyanide source to achieve the best catalyst performance.[6] Furthermore, the substrate-tocatalyst molar ratio (S/C) of 10-200 in these reactions was relatively low. [2] Our research group recently reported the asymmetric cyanation of aldehydes and a-keto esters catalyzed by our original [Ru(phgly) 2 (binap)]/Li salt systems. [7,8] The corresponding cyanated products were obtained in high ee. The spectroscopic analysis suggested that the bimetallic species [Li·Ru(phgly) 2 (binap)]+ acted as a chiral Lewis acidic catalyst. Herein, we describe the efficient asymmetric conjugate addition of HCN to a,b-unsaturated ketones catalyzed by the combined system of [Ru(phgly) 2 (binap)] and C 6 H 5 OLi. The reaction was carried out with an S/C of 200-1000 at À20-0 8C to afford the b-cyano ketones in up to 98 % ee.

Structural Study‐Guided Development of Versatile Phase‐Transfer Catalysts for Asymmetric Conjugate Additions of Cyanide

“…Feng [7] and coworkers have reported a modular titanium catalyst for the cyanation of alkylidine malonates. Very recently, Ohkuma [8] and coworkers disclosed a chiral Ru-complex for the conjugate addition of TMSCN to enones. These existing reactions, while representing remarkable success in establishing general substrate scope and high catalyst efficiency, require the use of various trialkylmetal cyanides in super-stoichiometric amounts.…”

Total synthesis of natural products using hypervalent iodine reagents

“…A further asymmetric hydrocyanation using Ohkuma's ruthenium-based catalyst (Kurono et al, 2011 ) 30 followed by a Peterson reaction under acidic conditions led to the corresponding diene 32 (Scheme 9 ). At this stage, the bromine atoms were introduced through classic electrophilic aromatic substitution and the cyclohexene moiety was generated during a ring closure metathesis reaction in the presence of a catalytic amount of Grubbs Hoveyda II.…”

Enantioselective Hydrocyanation of N-Protected Aldimines

“…4,5 A series of aromatic and aliphatic β-cyano ketones was obtained in high ee. The bimetallic species [Li{Ru(phgly) 2 -(binap)}] þ prepared in situ is expected to act as a chiral Lewis acidic catalyst.…”