Highly Enantioselective Synthesis of α‐Stereogenic Esters through Catalytic Asymmetric Michael Addition of 4‐Oxo‐4‐arylbutenoates

Abstract

Highly enantioselective Michael addition of 1,3-dicarbonyl compounds and nitromethane to 4-oxo-4-arylbutenoates catalyzed by N,N'-dioxide-Sc(OTf)(3) complexes has been developed. Using 0.5-2 mol % catalyst loading, various alpha-stereogenic esters were obtained regioselectively with excellent yields (up to 97 %) and enantioselectivities (up to >99 % ee). Moreover, the reaction performed well under nearly solvent-free conditions. The products with functional groups are ready for further transformation, which showed the potential value of the catalytic approach. According to the experimental results and previous reports, a plausible working model has been proposed to explain the origin of the activation and the asymmetric induction.

Efficient Synthesis of Chiral Trisubstituted 1,2‐Allenyl Ketones by Catalytic Asymmetric Conjugate Addition of Malonic Esters to Enynes

“…Based on the determination of the absolute configuration of product 3 cd , control experiments, and our previous study, a possible catalytic cycle with a transition‐state model was proposed (Figure ). First, the N ‐oxides and amide oxygen atoms of l ‐PiEt 2 Me coordinate to Sc 3+ in a tetradentate manner to form two six‐membered chelate rings.…”

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

“…Recently, unsaturated 1,4-dicarbonyl compounds, such as 1,4-ketoesters [6–8], 1,4-diketones [9], 1,4-ketoamides [9–10] and dialkylfumarates [11], have been the substrates for this reaction. The reaction products can undergo further chemical transformations, allowing the possibility of cascade reactions, making the method attractive for the synthesis of several valuable compounds, such as drugs and natural products.…”

“…Miura et al achieved an asymmetric addition of α,α-disubstituted aldehydes to maleimides catalyzed by primary amine thiourea organocatalyst [13]. Wang et al reported the addition of dialkylmalonates and nitromethane to 4-oxo-4-arylbutenoates catalyzed by N,N´ -dioxide-Sc(OTf) 3 complexes [8]. Despite these and other successful experimental results, the asymmetric addition of malonates to symmetric aromatic unsaturated 1,4-diketones has not been systematically studied.…”

Efficient Synthesis of Chiral Trisubstituted 1,2‐Allenyl Ketones by Catalytic Asymmetric Conjugate Addition of Malonic Esters to Enynes

“…Based on the determination of the absolute configuration of product 3cd, [16] control experiments,a nd our previous study, [26] ap ossible catalytic cycle with at ransition-state model was proposed (Figure 1). First, the N-oxides and amide oxygen atoms of l-PiEt 2 Me coordinate to Sc 3+ in atetradentate manner to form two six-membered chelate rings.T hen, enynes 1 attach to Sc 3+ at the favorable equatorial position to give intermediate T1.A dditionally,t he enolates are generated from malonates 2 assisted by nBu 3 N. The Re face of enynes 1 are strongly shielded by the nearby benzyl ring.…”