Asymmetric Henry reaction of trifluoromethyl ketone and aldehyde using Cu(II)-complex: computational study offers the origin of enantioselectivity with varied size of catalysts

• Published in: Tetrahedron 2015-08, Vol.71 (33), p.5229-5237
• Main Authors: Das, Anjan, Choudhary, Manoj K., Kureshy, Rukhsana I., Jana, Kalyanashis, Verma, Shailesh, Khan, Noor-ul H., Abdi, Sayed H.R., Bajaj, Hari C., Ganguly, Bishwajit
• Format: Article
• Language: English
• Subjects: Chirality; Computational study; Nitroaldol reaction; Trifluoroketone
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2015.06.033

Chiral ligand 3 was synthesised from inexpensive and readily available (1R,2R)-(+)-1,2-diphenyl-1,2-diaminoethane and tert-butylbromoacetate. In situ generated complex obtained by the reaction of ligand 3 with copper triflate was used as catalyst for asymmetric Henry reaction of trifluoromethyl ketone having different substituents in the aromatic ring with nitromethane at 0 °C in presence of N,N-DIPEA as additive to give nitroaldol products in excellent enantioselectivity (ee upto 99%) with good yield (upto 80%). Ligand 3 with in situ generated complex with copper acetate was also found to be good catalyst for asymmetric nitroaldol reaction of aldehydes (ee up to 80–92%, yield up to 85%) with nitromethane at −5 °C. The DFT calculations performed with B3LYP and M06-2X functionals revealed the role of non-covalent interactions (such as π–π interaction and hydrogen bonding) and the steric factors in the catalyst play important role towards the enhancement of enantioselectivity. [Display omitted]