Recent advances in organocatalytic asymmetric oxa-Michael addition triggered cascade reactions

Abstract

Oxa‐Michael cascade reaction, as an important part of Michael reaction, has also been significantly developed in recent decade. This is because the problem of reactivity and selectivity of the addition...

Recent Advances in Organocatalytic Asymmetric Michael Addition Reactions to α, β‐Unsaturated Nitroolefins

“…[88] Also, calixarene based organocatalysts with chiral units have diverse applications in various field. [89] A group of calix [4] arene-based chiral squaramide catalysts were formed in 2016 by Mustafa Durmaz's group and among them, catalyst 160 was successfully catalyzed the enantioselective Michael addition of acetylacetone 157 to substituted nitroolefins 158. Different aromatic substituted nitroolefins 158 were well-explored leading to the good to excellent yield and moderate ee of the Michael adducts 159, in the absence of any additives.…”

“…[102] A similar approach for the enantioselective Michael addition reaction of acetylacetone 157 to nitroolefins 210 was developed by Tangxin Xiao et al in 2018. In this approach, calix [4]thiourea catalyst 212 was employed as a suitable catalyst for stimulating the reaction and provided chiral γ-nitro carbonyl adducts 211 in high yield with satisfactory enantioselectivity in a 1 : 2 water-toluene medium. Mechanistically, TS A reveals that the nitro group was activated through hydrogen bonding with the thiourea group and enolates forming a bond with the amine part of 212 to provide the enantioselective product 211 (Scheme 55).…”

“…Decades-long, asymmetric organocatalytic transformations have witnessed historic advancements to attain enantiomerenriched products without purification of the intermediates and protection or deprotection manipulation. [1][2][3][4][5][6][7][8][9][10][11] Along with, the organocatalysis [12][13][14] has prodigiously modified the outline of many asymmetric reactions such as Diels-Alder reaction, [15] aldol reaction, [16][17] Mannich reaction, [18] Michael addition reactions, [19] hetero-Michael addition reactions, [20] Shi Epoxidation [21] and organocatalytic transfer hydrogenation. [22] Among all these above organocatalytic reactions, Michael addition reactions are quite significant in the field of modern organic synthesis since these reactions produce the key precursors of natural products by constructing carbon-carbon and carbon-heteroatom bonds.…”

“…Scheme 42. Reaction of acetylacetone to nitroolefins promoted by chiral calix[4]arene-based squaramide catalyst.…”

Squaramide-Catalyzed Asymmetric Intramolecular Oxa-Michael Reaction of α,β-Unsaturated Carbonyls Containing Benzyl Alcohol: Construction of Chiral 1-Substituted Phthalans

“…The oxa-Michael reaction, conjugate addition of oxygen-centered nucleophiles to α,β-unsaturated compounds, is one of the simplest and most direct strategies to develop carbon–oxygen bonds . In the last decade, the asymmetric catalytic oxa-Micheal reaction has been used as a powerful tool in the synthesis of chiral oxygen-containing heterocycles through the combination of cascade reactions and utilization of organocatalysts . The catalytic asymmetric intramolecular oxa-Michael reaction (AIOM) strategy has been used to directly and effectively access chiral tetrahydrofuran (THF), tetrahydropyran (THP), 2,3-dihydrobenzofuran, and chromane rings. , In 2012, Matsubara and co-worker succeeded in the enantioselective intramolecular oxa-Micheal reaction of ε-hydroxy-α,β-unsaturated ketone substrates catalyzed by a cinchona thiourea-based bifunctional organocatalyst for the construction of chiral THF and THP .…”