Synergistic Catalysis: Highly Enantioselective Cascade Reaction for the Synthesis of Dihydroacridines

Abstract

The first stereoselective synthesis of dihydroacridines through synergistic catalysis, achievingt he final target compounds with good to excellent yields and good to excellent enantioselectivities and diastereoselectivities, is reported. The synergistic approachc onsists in the activation of substituted quinolines with aL ewisa cid catalyst that react in ac ascade fashion with activated enals in the iminiumf orm. Mechanistic calculations support ac onsecutive Michael-aldol reaction, followed by dehydration.

Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross‐Cycloadditions: DFT‐Supported Homo‐Synergistic Organocatalytic Approach

“…(1) and (2)]. Thus,when 7a was reacted with E-nitrostyrene (14)inthe presence of C1 (20 mol %), the corresponding bicyclicc ompound 15 was Table 2: Substrate scope for the chemo-, regio-, and enantioselective synthesis of bicyclic uracils 9. [a] [a] All reactions were run under an inert atmosphere in 0.1 m solutions of dry CH 2 Cl 2 .Yields refer to isolated products 9.E nantiomeric excesses (ee)w ere determined by HPLC analysis on achiral stationary phase.…”

Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross‐Cycloadditions: DFT‐Supported Homo‐Synergistic Organocatalytic Approach

“…(1) and (2)]. Thus,when 7a was reacted with E-nitrostyrene (14)inthe presence of C1 (20 mol %), the corresponding bicyclicc ompound 15 was Tabelle 2: Substrate scope for the chemo-, regio-, and enantioselective synthesis of bicyclic uracils 9. [a] [a] All reactions were run under an inert atmosphere in 0.1 m solutions of dry CH 2 Cl 2 .Yields refer to isolated products 9.E nantiomeric excesses (ee)w ere determined by HPLC analysis on achiral stationary phase.…”

“…Organocatalyzed cross-or self-condensations of aldehydes are known in the literature, but in-depth studies supported by calculations and/or experimental evidence about their mechanism are quite rare and could hardly help us in this endeavor. [14] To test the hypothesis that ad ouble activation of reactants by C1 was operative, acouple of control experiments was carried out, where either of the two reactants was replaced by an on-aldehyde nonactivatable congener [Scheme 4, Eqs. (1) and (2)].…”

Enamine/Transition Metal Combined Catalysis: Catalytic Transformations Involving Organometallic Electrophilic Intermediates

“…Furthermore, the group of Rios also successfully disclosed various strategies for the preparation of carbocycles type molecules. For instance, through the enantioselective ring expansion of vinyl cyclopropanes, providing highly substituted [86], formal ring contraction for the generation of spiropyrazolones 106 [87], the asymmetric synthesis of cyclopentanes with four stereogenic centers 108 [88], the enantioselective acetyl aza-arene addition to α,β-unsaturated aldehydes affording chiral 2-acyl pyridines and pyrazines 110 [89], or, very recently disclosed, the highly enantioselective cascade reaction for the synthesis of dihydroacridines 112 (Scheme 23) [90]. Topics in Current Chemistry (2019) 377:38…”