Lithium Binaphtholate-Catalyzed Michael Reaction of Malonates with Maleates and Its Application to the Enantioselective Synthesis of Tricarboxylic Acid Derivatives

Abstract

The Michael reaction of malonates with maleates afforded the corresponding adducts in high yields with high enantioselectivities (up to 98% enantiomeric excess (ee)) by using dilithium 3,3′-dichlorobinaphtholate as a catalyst. The obtained Michael adducts could be converted to optically active tricarboxylic acid (TCA) derivatives via the Krapcho reaction.

Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters

“… 7 However, the addition of less reactive, stabilized carbon nucleophiles, such as malonates, remains an unsolved challenge. The current state of the art was demonstrated by Nakamura and co-workers in 2016, who employed a chiral lithium binaphtholate complex 1 to promote the highly enantioselective addition of malonates to symmetric maleic esters, 8 but this was limited by the lack of variability at the β position of the Michael acceptor ( Scheme 1 A). As a result of the importance of this bond disconnection, alternative enantioselective methods with a broad scope would be a welcome addition to the synthetic toolbox.…”