Secondary Amine Catalysed Diastereoselective Cross Domino Reaction: Simple and Efficient Synthesis of Heteroaryl-Substituted Cyclohexanols

• Published in: Russian journal of general chemistry Vol. 92; no. 4; pp. 694 - 701
• Main Authors: Patel, P. N., Talati, K. S., Deshmukh, A. G., Desai, D. H., Patel, N. C.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.04.2022; Springer Nature; Springer; Springer Nature B.V
• Subjects: Cascade chemical reactions; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemistry, Multidisciplinary; Chemistry/Food Science; Enantiomers; High performance liquid chromatography; Infrared spectroscopy; NMR; Nuclear magnetic resonance; Nuclear magnetic resonance spectroscopy; Physical Sciences; Science & Technology; Stereoisomers; Stereoselectivity; Steric hindrance; Substitutes; cyclohexanol; сross domino reaction; diastereoselectivity; pyrrolidine; SPECTROSCOPY; cross domino reaction; CRYSTAL-STRUCTURE; STEREOCHEMISTRY; CHEMISTRY; ALDEHYDES; TRIKETONE; METAL-FREE
• ISSN: 1070-3632; 1608-3350
• DOI: 10.1134/S1070363222040107

An effective secondary amine catalysed approach to the diastereoselective synthesis substituted cyclohexanols was proposed. A steric hindrance driven diastereoselective cross domino reaction gave manifold heteroaryl substituted cyclohexanols with five asymmetric centres in 92–98% yields. The sequence of inter- and intramolecular domino reactions includes Claisen–Schmidt condensation followed by 1,4-Michael addition of heteroaryl carbaldehydes and heteroaryl acetyl derivatives. HPLC study of the reactions shows outstanding self diastereoselectivity ( dr > 99%) in the formation of one set of enantiomers out of sixteen possible enantiomeric pairs. The structures of all the synthesized molecules were confirmed by HRMS, NMR and IR spectroscopy methods.