title: Synthesis of 9-amino(9-deoxy)epi cinchona alkaloids, general chiral organocatalysts for the stereoselective functionalization of carbonyl compounds.
abstract: We describe two procedures for the synthesis of primary amines derived from 9-amino(9-deoxy)epi cinchona alkaloids, valuable catalysts used in the asymmetric functionalization of carbonyl compounds. The first approach allows the one-pot 5-g-scale syntheses of four cinchona-based analogs (1, 3, 5 and 7) from the alkaloids quinine (QN), quinidine (QD), dihydroquinine (DHQN) and dihydroquinidine (DHQD), respectively, performed by means of a Mitsunobu reaction to introduce an azide group, followed by reduction and hydrolysis. Demethylation of 1, 3, 5 and 7 with BBr(3) provided direct access to the bifunctional aminocatalysts 2, 4, 6 and 8. A second approach, more convenient for scale-up (tested to a 20-g scale), is also provided. In this second procedure, the azides, formed from the O-mesylated derivatives of QN and QD, are selectively reduced with LiAlH(4) to afford catalysts 1 and 3, whereas hydrogenation (Pd/C) provides 5 and 7. Demethylation of 1, 3, 5 and 7 using an alkylthiolate affords 2, 4, 6 and 8 in a process in which the less-expensive QN and QD are the only starting materials used.
authors: Institute of Chemical Research of Catalonia (ICIQ), Tarragona, Spain.
authors: Carlo
authors: C
authors: Cassani
authors: Rafael
authors: R
authors: Martín-Rapún
authors: Elena
authors: E
authors: Arceo
authors: Fernando
authors: F
authors: Bravo
authors: Paolo
authors: P
authors: Melchiorre
mesh_terms: D017607:Aluminum Compounds; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D002930:Cinchona Alkaloids / Q000138:chemical synthesis*; D006865:Hydrogenation; D006868:Hydrolysis; D018020:Lithium Compounds; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011802:Quinidine / Q000031:analogs & derivatives / Q000737:chemistry; D011803:Quinine / Q000737:chemistry
chemical_list: D017607:Aluminum Compounds; D002930:Cinchona Alkaloids; D018020:Lithium Compounds; C042073:lithium aluminum hydride; C014486:hydroquinidine; D011803:Quinine; D011802:Quinidine