ABSTRACT
An efficient enantioselective total synthesis of (R)-rolipram and an efficient enantioselective formal synthesis of (3S,4R)-paroxetine has been achieved using the highly enantioselective Michael addition of malonate nucleophiles as key steps in both cases.
Subject(s)
Paroxetine/chemical synthesis , Rolipram/chemical synthesis , Catalysis , Malonates/chemistry , Molecular Structure , Paroxetine/chemistry , Rolipram/chemistry , StereoisomerismABSTRACT
5-Aryl-1,3-dioxolan-4-one heterocycles derived from mandelic acid derivatives and hexafluoroacetone have been identified as new and effective pro-nucleophiles in highly diastereo- and enantioselective Michael addition reactions to nitro olefins catalyzed by bifunctional epi-9-amino-9-deoxy cinchona alkaloid derivatives. Diastereoselectivities up to 98% and enantioselectivities up to 89% for a range of nitro olefins and 5-aryl-1,3-dioxolan-4-ones under mild reaction conditions are reported.
ABSTRACT
A family of 9-amino(9-deoxy) epicinchonine derivatives, possessing a range of mono- and bidentate hydrogen bond donor groups at the 9-position, were synthesised and evaluated for asymmetric organocatalytic activity in the dimethyl malonate Michael addition to beta-nitrostyrene; thiourea derivative was identified as the most effective bifunctional organic catalyst and found to induce high enantioselectivity in the malonate ester Michael addition reaction to a range of nitro olefins.
