Chiral Squaramides as Highly Enantioselective Catalysts for Michael Addition Reactions of 4‐Hydroxycoumarins and 4‐Hydroxypyrone to β,γ‐Unsaturated α‐Keto Esters

Squaramides: Bridging from Molecular Recognition to Bifunctional Organocatalysis

“…Furthermore, the squaramide motif has recently made their entrance in organocatalysis as very efficient bifunctional catalysts for a number of important enantioselective organic transformations. [11][12][13][14][15][16][17][18] In an attempt to account for their efficiency, theoretical rationale concerning molecular-recognition properties of squaramides is provided below. Moreover, based on the above-mentioned five main aspects, explanations of their performances as organocatalysts and the difference in reactivity compared with urea/thiourea analogues are also addressed in this minireview.…”

Highly enantioselective Michael addition of α‐nitroacetate to α,β‐unsaturated pyrazolamide catalyzed by a bifunctional squaramide

“…The stereochemical outcome of the present Michael addition can be rationalized based on a dual hydrogen bond working model, as depicted in Scheme . The squaramide moiety interacted with α,β‐unsaturated pyrazolamide via double hydrogen bonding.…”

“…10 The stereochemical outcome of the present Michael addition can be rationalized based on a dual hydrogen bond working model, as depicted in Scheme 3. 66 The squaramide moiety interacted with α,β-unsaturated pyrazolamide via double hydrogen bonding. In addition to carbonyl group, the pyrazole motif provided another H-bond acceptor site for better organization, therefore leading to high levels of enantioselectivity for the titled conjugate addition.…”

Discovery of a Highly Selective PLD2 Inhibitor (ML395): A New Probe with Improved Physiochemical Properties and Broad‐Spectrum Antiviral Activity against Influenza Strains

“…Since these initial discoveries, a number of cinchona‐alkaloid‐derived bifunctional squaramide catalysts have demonstrated efficacy in asymmetric conjugate additions with a variety of pronucleophiles. Among these are conjugate additions of mercaptans to chalcones 70 (Figure 10, a),37 coumarin additions to β,γ‐unsaturated α‐keto esters 71 ,38 and nucleophilic additions to α,β‐unsaturated acylphosphonates ( 72 ) 39. Aligning well with experimental results, HF/6‐31+G (d,p) binding models provided computational evidence that squaramide activation of β,γ‐unsaturated α‐keto esters is superior to thiourea activation (Figure 10, b), causing a more electrophilic γ‐carbon to be formed through complexation (natural bond orbital analysis) 38…”