Modular Chiral Bisoxalamide–Copper-Catalyzed Asymmetric Oxo-Diels–Alder Reaction: Carbonyl Coordination for High Enantio- and Diastereocontrols

Abstract

The chiral bis-oxalamides (CBOA), readily derived from optically pure 1,2-diphenylethylenediamine (DPEN), were proven to be a class of efficient C 2 -symmetric chiral ligands for copper(II)-catalyzed asymmetric inverse-electron demand oxo-Diels− Alder reactions between β,γ-unsaturated α-ketoesters and 2,3-dihydrofuran or 3,4-dihydro-2H-pyran. The reactions proceeded smoothly under mild conditions to afford the corresponding [4 + 2] cycloadducts in high yields with good enantioselectivities (up to 94% ee) and diastereoselectivities (up to 99:1 dr). DFT calculations demonstrated that carbonyl coordination of the chiral ligand to Cu(II) was crucial for the high stereoinduction. These CBOA ligands exhibited high catalytic efficiency in this reaction, which combined with some other salient features of structural fine tunability, chemical stability, and ready accessibility might endow more practical applications in asymmetric catalytic reactions.

Chiral‐at‐Iron Catalyst for Highly Enantioselective and Diastereoselective Hetero‐Diels‐Alder Reaction

“…Feng and coworkers introduced chiral N,N’‐dioxide/erbium(III) catalyst erbium(III)‐N,N'dioxide catalysts for the asymmetric reaction of β,γ‐unsaturated α‐ketoester with enol ether, [16] while X.‐W. Wang, Xia, and Z. Wang recently reported a copper(II)‐bis(oxalamide) catalyst for this transformation [17] . However, to the best of our knowledge, our work marks the first example of iron‐catalyzed asymmetric hetero‐Diels‐Alder cycloadditions between β,γ‐unsaturated α‐ketoester and enol ether, including one example with vinylazide as the dienophile.…”

Nickel-Catalyzed Regiodivergent Asymmetric Cycloadditions of α,β-Unsaturated Carbonyl Compounds

“…Asymmetric hetero-Diels-Alder reactions have attracted considerable attention due to their ability to produce optically active heterocyclic molecules. [65][66][67][68][69][70][71] We conjectured that this nickel-catalyzed system was applicable to the inverse-electron-demand oxa-Diels-Alder ([4+2] annulation) of the α,β-unsaturated 2-acyl imidazoles once employing electron-rich alkenes as dienophiles. Indeed, under the identical conditions and in the presence of the same chiral nickel catalyst, the reaction of 2,3-dihydrofuran (2r) with the imidazole or benzimidazole substrates (1a, 1i-1s) gave the chiral bicyclic products (5a-5l) in 75-91% yields, with 11:1->20:1 dr and 87-Page 14 of 25 CCS Chemistry 97% ee (Scheme 5).…”

Further developments of β,γ-unsaturated α-ketoesters as versatile synthons in asymmetric catalysis

“…It is noteworthy that the yield of the fused bicyclic product could be further increased by addition of AgNTf 2 , indicating the electron-deficient gold(I) catalysis was favored for the transformation. Besides, [4 + 2] annulation reactions of β,γ -unsaturated α -ketoesters with preformed enol ether had been established by Wang, Xia and Wang et al., utilizing their newly developed C 2 -symmetric chiral bis-oxalamides/Cu(II) complex as catalyst ( scheme 19 E) ( Chen et al., 2020 ). The authors highlighted the carbonyl coordination of the chiral ligand to Cu(II) contributing to superior asymmetric induction.…”