A catalytic asymmetric strecker-type reaction promoted by Lewis acid-Lewis base bifunctional catalyst.
A general asymmetric Strecker-type reaction is reported, catalyzed by the Lewis acid-Lewis base bifunctional catalyst 1. The reaction of trimethylsilyl cyanide (TMSCN) with various fluorenyl imines, including n-aldimines and alpha,beta-unsaturated imines, proceeds with good to excellent enantioselectivities in the presence of a catalytic amount of phenol as additive (20 mol%) (catalytic system 1). The products were successfully converted to the corresponding amino acid derivatives in high yields without loss of enantiomeric purity. Furthermore, hydrogenation or dihydroxylation of the products from alpha,beta-unsaturated imines afforded saturated or functionalized aminonitriles also without loss of enantiomeric purity. The absolute configuration of the products and a control experiment using catalyst 2 supported the proposed dual activation of the imine and TMSCN by the Lewis acid (Al) and the Lewis base moiety (phosphine oxide) of 1. From the mechanistic studies including kinetic and NMR experiments of the catalytic species, the role of PhOH seems to be a proton source to protonate the anionic nitrogen of the intermediate. Specifically, we have found that TMSCN is more reactive than HCN in this catalytic system, probably due to the activation ability of the phosphine oxide moiety of 1 toward TMSCN. This fact prompted us to develop the novel catalytic system 2, consisting of 1 (9 mol%), TMSCN (20 mol%) and HCN (1.2 mol eq). This new system afforded comparable results with obtained by system 1 (1 (9 mol%)-TMSCN (2 mol eq)-PhOH (20 mol%)).
Takamura
M
M
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Hamashima
Y
Y
Usuda
H
H
Kanai
M
M
Shibasaki
M
M
D000143:Acids / Q000737:chemistry*; D000468:Alkalies / Q000737:chemistry*; D002384:Catalysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure
D000143:Acids; D000468:Alkalies