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

Abstract

An enantioselective three-component reaction was developed for the synthesis of tetrahydropyridazinones employing chiral α,β-unsaturated acylammonium salts, malonates, and azodicarboxylates. An initial α-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.

Synthesis of Chiral Diazabicycloalkanes via Organocatalytic aza‐Michael/Aldol Reaction

“…[2][3][4][5][6][7] multiple reaction steps. [15] Other methods utilized for this purpose include hetero-Diels-Alder reactions, [10] [3 + 3] cycloadditions, [16][17][18][19] Michael-induced multicomponent, [8] as well as organo-cascade [11,14,20] and transition-metal cascade reactions. [21] To synthesize the annulated product P1, a multi-step synthesis starting from IM1 is often required, involving protecting-group cleavage and subsequent modifications to enable cyclization.…”

“…[1][2][3][4][5][6][7] Symmetric diazabicycloalkanes boast a distinctive structure characterized by a condensed bicyclic ring system bridged by two nitrogen atoms. While there are several well-established methods for synthesizing chiral pyridazines, [8][9][10][11][12][13][14] the one-step synthesis of the more complex chiral diazabicycloalkane moiety remains an ongoing challenge. The typical indirect strategy for synthesizing the bicyclic moiety involves the preparation of the chiral precursor IM1, followed by annulation to form the final product, P1 (Scheme 1, top).…”