Multicomponent Enantioselective Synthesis of Tetrahydropyridazinones Employing Chiral α,β-Unsaturated Acylammonium Salts

An enantioselective three-component reaction was developed for the synthesis of tetrahydropyridazinones employing chiral alpha,beta-unsaturated acylammonium salts, malonates, and azodicarboxylates. An initial alpha-amination of a malonate with an azodicarboxylate and a subsequent chiral Lewis-base-catalyzed Michael/proton transfer/lactamization process delivered optically active tetrahydropyridazinones (up to 99:1 er). Subsequent transformations of these adducts were explored, revealing some unexpected rearrangements, and the use of an allyl methyl malonate enabled a subsequent deallylative decarboxylation and the introduction of a second stereocenter.

Automated summary

An enantioselective three-component reaction was developed for the synthesis of tetrahydropyridazinones, delivering optically active products with unexpected rearrangements explored. The use of allyl methyl malonate introduced a second stereocenter during subsequent transformations.