A new strategy for designing non-C2-symmetric monometallic bifunctional catalysts and their application in enantioselective cyanation of aldehydes.
A monometallic bifunctional catalyst, in which only one imidazolyl moiety is directly attached at the 3-position of a binaphthol moiety, has been developed. The ligand (R)-1, which lacks C2-symmetry and flexible linkers, in combination with Ti(OiPr)4, has been demonstrated to promote the enantioselective cyanation of aldehydes with trimethylsilylcyanide (TMSCN), giving excellent enantioselectivities of up to 98 % ee and high yields of up to 99 %. The use of this bifunctional catalytic system obviates the need for additives and is extremely simple as the reagents are added in one portion at the beginning of the reaction. The protocol has been found to tolerate a relatively wide range of aldehydes when 10 mol % of the (R)-1/Ti(OiPr)4 complex is deployed in CH2Cl2 at -40 degrees C, the conditions which proved most practical and effective. The asymmetric cyanations also proceeded with lower catalyst loadings (5 mol %, or even 2 mol %), still giving satisfactory enantiomeric excesses and yields. Interestingly, the use of freshly distilled TMSCN dried over CaH2 gave a low enantioselectivity and only a moderate yield of the adduct as compared with direct use of the commercial reagent. The results of 13C NMR spectroscopic studies implicate HCN as the actual reactive nucleophile.
Yang
Fei
F
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry and State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China.
Wei
Siping
S
Chen
Chien-An
CA
Xi
Peihua
P
Yang
Li
L
Lan
Jingbo
J
Gau
Han-Mou
HM
You
Jingsong
J
D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D003486:Cyanides / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry; D008024:Ligands; D008968:Molecular Conformation; D009284:Naphthols / Q000737:chemistry; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D014025:Titanium / Q000737:chemistry; D014297:Trimethylsilyl Compounds / Q000737:chemistry*
D000447:Aldehydes; C406944:BINOL, naphthol; D003486:Cyanides; D007093:Imidazoles; D008024:Ligands; D009284:Naphthols; D009570:Nitriles; D009942:Organometallic Compounds; D014297:Trimethylsilyl Compounds; C058010:trimethylsilyl cyanide; D014025:Titanium