Copper(I)-Catalyzed Kinetic Resolution of<i>exo</i>-3-Oxodicyclopentadienes and<i>endo</i>-3-Oxodicyclopentadiene

Chang, Xin; Sun, Xi-Shang; Che, Chao; Hu, Yuanzheng; Tao, Hai‐Yan; Wang, Chun‐Jiang

doi:10.1021/acs.orglett.9b00136

Cited by 17 publications

(7 citation statements)

References 94 publications

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“…In addition, the unique ligand-controlled regioselectivity was observed and systematically studied via control experiments and DFT calculations. In the same year, we also established the kinetic resolution of exo -3-oxodicyclopentadienes 27 and endo -3-oxodicyclopentadiene 29 catalyzed by Cu(I)/( S , R p )- L3a , providing a more practical alternative for synthesizing important chiral exo - and endo -oxodicyclopentadienes (Scheme c) …”

Section: Catalytic Asymmetric 13-dipolar Cycloaddition Of N-metallate...mentioning

confidence: 95%

Catalytic Asymmetric Reactions with N-Metallated Azomethine Ylides

2020

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Conspectus Optically active nitrogen-containing compounds have attracted substantial attention due to their ubiquity in the cores of natural products and bioactive molecules. Among the various synthetic approaches to nitrogenous frameworks, catalytic asymmetric 1,3-dipolar cycloadditions are one of the most attractive methods because of their powerful ability to rapidly construct various chiral N-heterocycles. In particular, N-metallated azomethine ylides, common and readily available 1,3-dipoles, have been extensively applied in dipolar cycloaddition reactions. Despite the fact that asymmetric transformations of azomethine ylides have been investigated for decades, most of the efforts have been directed toward the preparation of pyrrolidines using glycinate-derived α-unsubstituted aldimine esters as the precursors of the azomethine ylides. While α-substituted azomethine ylides derived from amino esters other than glycinate have seldom been harnessed, the construction of non-five-membered chiral N-heterocycles via 1,3-dipolar cycloadditions remains underexplored. In addition, the asymmetric α-functionalization of aldimine esters to prepare acyclic nitrogenous compounds such as α-amino acids, in which an in situ-generated N-metallated azomethine ylide serves as the nucleophile, has not been sufficiently described. In this Account, we mainly discuss the achievements we have made in the past decade toward broadening the applications of N-metallated azomethine ylides for the preparation of nitrogen-containing compounds. We began our investigation with the design and synthesis of a new type of chiral ligand, TF-BiphamPhos, which not only coordinates with Lewis acids to activate dipolar species but also serves as an H-bond donor to increase the reactivity of dipolarophiles with significantly enhanced stereochemical control. Using the Cu(I) or Ag(I)/TF-BiphamPhos complex as the catalyst, we achieved highly stereoselective (3+2) cycloadditions of glycinate and non-glycinate-derived azomethine ylides with diverse dipolarophiles, producing a variety of enantioenriched pyrrolidines with multiple stereocenters in a single step. To further expand the synthetic utility of N-metallated azomethine ylides, we successfully developed higher order cycloadditions with fulvenes, tropone, 2-acyl cycloheptatrienes, and pyrazolidinium ylides serving as the reaction partner, and this reaction provides straightforward access to enantioenriched fused piperidines, bridged azabicyclic frameworks, and triazines via (3+6)- and (3+3)-type cycloadditions. Using N-metallated azomethine ylides as the nucleophile, we realized Cu(I)-catalyzed asymmetric 1,4-Michael additions with α,β-unsaturated bisphosphates/Morita–Baylis–Hillman products, furnishing an array of structurally diverse unnatural α-amino acids. Based on the strategy of synergistic activation, we achieved highly efficient dual Cu/Pd and Cu/Ir catalysis for the α-functionalization of aldimine esters via the asymmetric allylic/allenylic alkylation of N-metallated azomethine ylides. No...

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Section: Catalytic Asymmetric 13-dipolar Cycloaddition Of N-metallate...mentioning

confidence: 95%

Catalytic Asymmetric Reactions with N-Metallated Azomethine Ylides

2020

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“…The same group resolved a series of racemic exo-3oxodicyclopentadienes in a copper catalysed 1,3-cycloaddition reaction with a glycine aldimino ester (Scheme 42). 106 They obtained excellent enantioselectivities for both the recovered exo-3-oxodicyclopentadienes and polycyclic pyrrolidine products. One racemic endo-3-oxodicyclopentadiene was resolved under the same conditions and achieved excellent enantioselectivities of 95% ee for both recovered starting material and pyrrolidine product.…”

Section: Multisubstituted Pyrrolidinesmentioning

confidence: 96%

Current applications of kinetic resolution in the asymmetric synthesis of substituted pyrrolidines

Berry

Jones

2021

Org. Biomol. Chem.

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“…We conducted a comparative ligand evaluation in kinetic resolution of the racemic convex (±)-endo-3-oxodicyclopentadiene and (±)-endo-3-oxodicyclopentadiene via Cu(I)catalyzed 1,3-dipolar cycloaddition, and (S,R p )-PPFA was originally revealed as the superior chiral ligand in effecting such asymmetric transformations. 19 The newly developed (S,R p )-17b was also found equally potent in this Cu(I)catalyzed kinetic resolution protocol with racemic (±)-endo-3oxodicyclopentadiene 18 as the dipolarophile, affording the recovered (−)-endo-18 in 46% yield with 97% enantiomeric excess (ee), accompanied by the cycloadduct endoendo-20 in 49% yield with exclusive diastereoselectivity and 97% ee (S = 278) (Scheme 6a). Although (S,R p )-PPFA was also identified as the best ligand for the kinetic resolution of racemic (±)-exo-3-oxodicyclo-pentadienes, racemic (±)-2-phenyl-substituted exo-3-oxo-dicyclopentadiene 21 was revealed as a challenging molecule and was only resolved with S factor of 28 (45% yield and 82% ee for endoexo-22; 42% yield and 86% ee for exo-(−)-21) through this protocol in previous work.…”

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confidence: 99%

“…Pleasingly, employing (S,R p )-17b as the chiral ligand under otherwise identical reaction conditions, (±)-exo-21 could be efficiently resolved with the significantly enhanced S factor (52), delivering a 47% yield of recovered exo-(−)-21 with 99% ee, accompanied by a 48% yield of cycloadduct endoexo-22 with 82% ee (Scheme 6b), which is obviously better than that obtained with the corresponding (S,R p )-PPFA. 19 Cu-catalyzed asymmetric Michael addition of organometallic reagents to α,β-unsaturated compounds has been extensively investigated over the past decades. 20 (R,S p )-Josiphos and (R)-Tol-BINAP have been demonstrated to be the highly enantioselective ligands for Cu(I)-catalyzed asymmetric Michael addition of Grignard reagents to α,β-unsaturated esters for the synthesis of enantioenriched β-substituted esters.…”

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confidence: 99%

Chiral Ugi-Type Amines: Practical Synthesis, Ligand Development, and Asymmetric Catalysis

Dong

Chang

et al. 2020

ACS Catal.

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Ugi's amine has become one type of privileged chiral skeleton for chiral ligand design bearing central/planar chirality, and such ligands have exhibited tremendous success in various asymmetric catalysis. However, the current access to enantiopure Ugi's amine is quite tedious and relies heavily on optical resolution, which impedes its practical applications, to some extent. Herein, we present a facile asymmetric synthesis of enantioenriched Ugi-type amines bearing a long-carbon chain through Ir-catalyzed cascade allylation/2-aza-Cope rearrangement, followed by amino exchange and Pd/C-catalyzed one-pot hydrogenation/reductive amination. The protocol could be readily scaled up, and it has been conducted in 20-g-scale asymmetric synthesis of (S)-Ugi-type amine from commercially available reagents, in >99% ee and >70% overall yield in four steps with one short silica gel-plug purification. (S,R p )-PPFA-type and (S,R p )-Josiphos-type ligands, readily prepared from the achieved Ugi-type amine, exhibited higher or comparable asymmetric induction and catalytic efficacy in several Cu(I)-catalyzed asymmetric reactions, which indicated great potential of the applications of the readily accessible Ugi-type amines in ligand/catalyst design.

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Copper(I)-Catalyzed Kinetic Resolution ofexo-3-Oxodicyclopentadienes andendo-3-Oxodicyclopentadiene

Cited by 17 publications

References 94 publications

Catalytic Asymmetric Reactions with N-Metallated Azomethine Ylides

Catalytic Asymmetric Reactions with N-Metallated Azomethine Ylides

Current applications of kinetic resolution in the asymmetric synthesis of substituted pyrrolidines

Chiral Ugi-Type Amines: Practical Synthesis, Ligand Development, and Asymmetric Catalysis

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