Stereodivergent Construction of 1,3‐Chiral Centers via Tandem Asymmetric Conjugate Addition and Allylic Substitution Reaction

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(10)

Published: Jan. 4, 2023

Herein, we report a synthesis of cyclohexanones bearing multi-continuous stereocenters by combining copper-catalyzed asymmetric conjugate addition dialkylzinc reagents to cyclic enones with iridium-catalyzed allylic substitution reaction. Good excellent yields, diastereoselectivity and enantioselectivity can be obtained. Unlike the stereodivergent construction adjacent (1,2-position) reported in literature, current reaction achieve nonadjacent (1,3-position) proper combination two chiral catalysts different enantiomers.

Language: Английский

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Diastereo‐ and Enantioselective Synthesis of Bisbenzannulated Spiroketals and Spiroaminals by Ir/Ag/Acid Ternary Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(42)

Published: Aug. 4, 2022

Abstract We reported herein an iridium/silver/acid ternary catalytic system to access bisbenzannulated [6,6]‐spiroketals in high efficiency with generally diastereo‐ and enantioselectivities (up >20 : 1 dr, >99 % ee). In this procedure, readily available o ‐alkynylacetophenones undergo cycloisomerization generate isochromenes situ that participate stereoselective allylation/spiroketalization sequence 2‐(1‐hydroxyallyl)phenols. Meanwhile, 2‐(1‐hydroxyallyl)anilines were also compatible cascade reaction, furnishing structurally novel [6,6]‐spiroaminals good diastereoselectivities (8 1–12 dr) excellent (98 %–>99 Moreover, experimental studies theoretical calculations performed illustrate the reaction mechanism stereochemistry.

Language: Английский

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Silver/chiral pyrrolidinopyridine relay catalytic cycloisomerization/(2 + 3) cycloadditions of enynamides to asymmetrically synthesize bispirocyclopentenes as PDE1B inhibitors

Communications Chemistry, Journal Year: 2023, Volume and Issue: 6(1)

Published: June 19, 2023

Significant progress has been made in asymmetric synthesis through the use of transition metal catalysts combined with Lewis bases. However, a dual catalytic system involving 4-aminopyridine and received little attention. Here we show metal/Lewis base relay featuring silver acetate modified chiral pyrrolidinopyridine (PPY). It was successfully applied cycloisomerization/(2 + 3) cycloaddition reaction enynamides. Bispirocyclopentene pyrazolone products could be efficiently synthesized stereoselective economical manner (up to >19:1 dr, 99.5:0.5 er). Transformations product access stereodivergent diastereoisomers densely functionalized polycyclic derivatives. Mechanistic studies illustrated model origin uncommon chemoselectivity. In subsequent bioassays, containing privileged drug-like scaffold exhibited isoform-selective phosphodiesterase 1 (PDE1) inhibitory activity vitro. The optimal lead compound displayed good therapeutic effect for ameliorating pulmonary fibrosis via inhibiting PDE1 vivo.

Language: Английский

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Stereodivergent Construction of 1,3‐Chiral Centers via Tandem Asymmetric Conjugate Addition and Allylic Substitution Reaction

Angewandte Chemie, Journal Year: 2023, Volume and Issue: 135(10)

Published: Jan. 4, 2023

Abstract Herein, we report a synthesis of cyclohexanones bearing multi‐continuous stereocenters by combining copper‐catalyzed asymmetric conjugate addition dialkylzinc reagents to cyclic enones with iridium‐catalyzed allylic substitution reaction. Good excellent yields, diastereoselectivity and enantioselectivity can be obtained. Unlike the stereodivergent construction adjacent (1,2‐position) reported in literature, current reaction achieve nonadjacent (1,3‐position) proper combination two chiral catalysts different enantiomers.

Language: Английский

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Copper Catalyzed [3+2] Annulation Reaction of Exocyclic Sulfonyl Enamides for the Synthesis of N,O‐Spiroketal and Spiroketal

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(44)

Published: June 1, 2024

A copper-catalyzed [3+2] annulation reaction of exocyclic enamines/enol ethers with 1,4-benzoquinone esters has been developed, providing facile access to N,O-spiroketals and spiroketals under mild conditions broad substrate scope (26 examples, 71-94 % yields). Gram scale synthesis chemical transformations demonstrated that this method is potentially useful in the natural products drugs containing a N,O- spiroketal moiety. The chiral N,O-spiroketal could be obtained 98 ee after recrystallization, when SaBOX ligand was employed.

Language: Английский

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Diastereo‐ and Enantioselective Synthesis of Bisbenzannulated Spiroketals and Spiroaminals by Ir/Ag/Acid Ternary Catalysis

Angewandte Chemie, Journal Year: 2022, Volume and Issue: 134(42)

Published: Aug. 4, 2022

Abstract We reported herein an iridium/silver/acid ternary catalytic system to access bisbenzannulated [6,6]‐spiroketals in high efficiency with generally diastereo‐ and enantioselectivities (up >20 : 1 dr, >99 % ee). In this procedure, readily available o ‐alkynylacetophenones undergo cycloisomerization generate isochromenes situ that participate stereoselective allylation/spiroketalization sequence 2‐(1‐hydroxyallyl)phenols. Meanwhile, 2‐(1‐hydroxyallyl)anilines were also compatible cascade reaction, furnishing structurally novel [6,6]‐spiroaminals good diastereoselectivities (8 1–12 dr) excellent (98 %–>99 Moreover, experimental studies theoretical calculations performed illustrate the reaction mechanism stereochemistry.

Language: Английский

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