Asymmetric Conjugate Addition of α-Cyanoketones to Enones Using Diaminomethylenemalononitrile Organocatalyst

Abstract

A diaminomethylenemalononitrile organocatalyst efficiently catalyzed the asymmetric conjugate addition of α-cyanoketones to vinyl ketones to give the corresponding 1,5-dicarbonyl compounds, which bear an all-carbon quaternary stereogenic center with high enantioselectivities. This report is the first example of the asymmetric conjugate addition of α-cyanoketones to vinyl ketones using an organocatalyst.

Cinchona–Diaminomethylenemalononitrile Organocatalyst for the Highly Enantioselective Hydrophosphonylation of Ketones and Enones

“…Asymmetric reactions using organocatalysts bearing thiourea and squaramide motifs as double hydrogen bond donors have attracted considerable attention over the past decade because of their excellent stereoselectivity and environmentally benign properties. Recently, we have demonstrated that the diaminomethylenemalononitrile (DMM) motif also acts as a double hydrogen-bond donor and that the organocatalysts bearing it efficiently promote many valuable asymmetric reactions . In particular, DMM organocatalysts efficiently catalyze the hydrophosphonylation of aldehydes using diaryl phosphonate, achieving high stereoselectivity compared with thiourea and squaramide organocatalysts .…”

Diaminomethylenemalononitriles and Diaminomethyleneindanediones as Dual Hydrogen Bond Donors for Anion Recognition

“…The parallel (but for the most part, separate) searches for more potent anion receptors and more effective organocatalysts have led to the recent investigation of a number of alternative dual hydrogen bond donors (e.g., thiosquaramides, croconamides, − deltamides, , cyanoguanidines, diamino­methylene­malonitriles, − and diamino­methylene­indane­diones , ). In general, where both properties have been investigated, there is a correlation between potent anion receptors and effective organocatalysts, and this has been attributed to the relative hydrogen bonding ability of the different motifs. ,, This hydrogen bonding ability is governed by a combination of factors including the Brønsted acidity , and the conformational preferences of the dual hydrogen bond donor motifs. ,,, Both of these factors are important when designing anion receptors and organocatalysts; energetic penalties apply if a conformational change is required for the formation of both H-bonds to a guest or substrate, while it is generally accepted that increased Brønsted acidity correlates with an increase in hydrogen bond strength that is required for effective substrate binding.…”

“…In recent work, Miura and co-workers have evaluated both diamino­methylene­malonitriles − DMMs) and diamino­methylene­indane­diones , (DMIs) as organocatalysts for a range of asymmetric conjugate addition reactions and found them to be superior to the analogous thiourea and squaramide catalysts. However, the anion binding properties of these dual hydrogen bond donor motifs have not been reported.…”

Asymmetric Conjugate Addition of Phosphonates to Enones Using Cinchona–Diaminomethylenemalononitrile Organocatalysts

“…Chiral organocatalysts with double hydrogen bond donor motifs such as thiourea or squaramide exhibit good catalytic activity over a wide range of asymmetric reactions and provide a simple route to enantiomerically enriched products. Recently, we reported that the diaminomethylenemalononitrile (DMM) group can act as a hydrogen bond donor and was a useful scaffold to generate organocatalysts that were applied in several important asymmetric reactions . DMM catalysts effectively promoted the asymmetric conjugate additions of aldehyde to vinyl sulfone, ketone to nitroalkene, malonate to enone, 1,3-diketone to nitroalkene, 5-benzylfurfural to nitoroalkene, and α-cyanoketone to enone .…”