A new copper(I)-tetrahydrosalen-catalyzed asymmetric Henry reaction and its extension to the synthesis of (S)-norphenylephrine.
A new chiral hydrogenated salen catalyst has been developed for the asymmetric Henry reaction which produces the expected products in moderate to high yields (up to 98 %) with excellent enantioselectivities (up to 96 % ee). A variety of aromatic, heteroaromatic, enal, and aliphatic aldehydes were found to be suitable substrates in the presence of hydrogenated salen 1 f (10 mol %), (CuOTf)(2)C(7)H(8) (5 mol %), and 4 A molecular sieves. This process is air-tolerant and easily manipulated with readily available reagents, and has been successfully extended to the synthesis of (S)-norphenylephrine in 67 % overall yield, starting from commercially available m-hydroxybenzaldehyde. Based on experimental investigations and MM+ calculations, a possible catalytic cycle including a transition state (8 or A) has been proposed to explain the origin of reactivity and asymmetric inductivity.
Xiong
Yan
Y
Key Laboratory of Green Chemistry and Technology (Sichuan University), Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China.
Wang
Fei
F
Huang
Xiao
X
Wen
Yuehong
Y
Feng
Xiaoming
X
D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D005029:Ethylenediamines / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D015394:Molecular Structure; D009655:Octopamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D005029:Ethylenediamines; D009942:Organometallic Compounds; D009655:Octopamine; D003300:Copper; C011452:disalicylaldehyde ethylenediamine; C005310:norfenefrine