Asymmetric synthesis of new chiral long chain alcohols

• Published in: Tetrahedron: asymmetry 2010-12, Vol.21 (24), p.2981-2987
• Main Authors: Yıldız, Tülay, Yusufoğlu, Ayşe
• Format: Article
• Language: English
• ISSN: 0957-4166; 1362-511X
• DOI: 10.1016/j.tetasy.2010.12.010

Sixteen new chiral alcohols with alkyl (C11–C19) and aryl, substituted aryl, hetero aryl and biaryl groups 2a–2t were synthesized by three different asymmetric reduction methods from their corresponding ketones 1a–1t. Chiral NaBH4 (method A), chiral BH3 (method B) and chiral AIP (method C) were used as asymmetric reduction catalysts. Chiral NaBH4 was modified by four different ligands 3a–3d, chiral BH3 and chiral AIP by four different ligands 4a–4d. Ligand 4c was synthesized for the first time in this work. Chiral NaBH4 generated chiral alcohols of (R)-configuration and chiral BH3 and chiral AIP of (S)-configuration with high enantiomeric excesses, were analysed by chiral HPLC. In order to determine the ee values by chiral HPLC, sixteen corresponding racemic alcohols, synthesized by reducing their corresponding ketones via NaBH4, were used for chiral resolution on a Daicel OD HPLC column. The sixteen starting ketones were synthesized in this study by Friedel–Craft acylation. The new chiral alcohols were characterized by IR, NMR, (1H and 13C), MS, elemental analyses and specific rotation. The reduction methods A, B and C were applied to these ketones for the first time in this study and were compared with each other. The relationship between the structure of the ketone and the yield and the enantiomeric excess was discussed.