Organocatalytically Generated Donor − Acceptor Cyclopropanes in Domino Reactions. One-Step Enantioselective Synthesis of Pyrrolo[1,2 ‑ a ]quinolines

Abstract

An easy and straightforward procedure has been developed for the synthesis of highly enantioenriched pyrrolo-[1,2-a]quinolines through a one-pot process that comprises a domino cyclopropane ring opening/aza-Michael/aldol reaction followed by acid-promoted lactamization. The key feature of the synthetic approach relies on the ability of conveniently functionalized cyclopropaneacetaldehydes to undergo organocatalytic activation by a chiral secondary amine that enables the catalytic generation of a donor acceptor cyclopropane. This intermediate has the potential to undergo a ring opening that generates an electrophilic alpha,beta-unsaturated iminium ion that subsequently reacts through the already mentioned domino sequence and in which stereochemical information is very efficiently transferred from the amine catalyst to the final products. Moreover, one of the alkoxycarbonyl moieties can be easily removed by standard hydrolysis/decarboxylation, providing access to the target adducts as single stereoisomers.