Umpolung Asymmetric 1,5‐Conjugate Addition via Palladium Hydride Catalysis

Wang, Yuchao; Xiao, Zhao-Xin; Wang, Miao; Yang, Shao-Qian; Liu, Jinbiao; He, Zhi‐Tao

doi:10.1002/ange.202215568

“…The N-protected product 5c was also efficiently converted into useful diol 11 through reduction using LiAlH 4 as the reducing agent with a retention of ee . Further derivatizations of this diol produced enantioenriched 1,3-dioxan-2-one 12 and 1,3,2-dioxaborinane 13 smoothly and in high yields . Notably, in all cases, the enantiomeric excesses of substrates were conserved.…”

Section: Resultsmentioning

confidence: 90%

Enantioselective Construction of Quaternary Stereocenters via A Chiral Spiro Phosphoric Acid-Assisted Formal Gold Carbene gem-Dialkylation Reaction

Chen,

Zhou,

Li

et al. 2024

J. Am. Chem. Soc.

2

0

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Enantioselective construction of all-carbon quaternary stereocenters has attracted much attention over the past few decades. A variety of catalytic asymmetric methods have been disclosed based on the use of presynthesized complex reagents that impart congested steric hindrance to the reaction center, which generally produce the chiral molecules through forming one C−C bond. The use of readily available reagents that could build two C− C bonds on the same carbonic center with the concomitant assembly of quaternary stereocenters remains challenging. Herein, we disclose a catalytic asymmetric alkyne multifunctionalization reaction using a gold complex and a chiral spiro phosphoric acid (SPA) for synergistic catalysis. In this method, the readily accessible internal alkynes served as the key gold carbene precursors, followed by carbene gem-dialkylation through Mannich-type addition of enolate species or stepwise formal cycloaddition with methylenimines that are derived from 1,3,5-triazinanes in the presence of SPA. The reaction provides practical access to polyfunctionalized chiral linear and cyclic ketones that bear two adjacent quaternary stereocenters in generally good yields and excellent enantioselectivities, leading to an essential complement to the asymmetric construction of quaternary stereocenters using readily available materials with high bond formation efficiency.

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Palladium(0) and Brønsted Acid Co‐Catalyzed Enantioselective Hydro‐Cyclization of 2,4‐Dienyl Hydrazones and Oximes

Li,

Gui,

Pi

et al. 2024

Angewandte Chemie

0

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The transition metal‐catalyzed asymmetric hydro‐functionalization of 1,3‐dienes has been well explored, but most reactions focus on electron‐neutral substrates in an intermolecular manner. Here we first demonstrate that readily available 2,4‐dienyl hydrazones and oximes can be efficiently utilized in the hydro‐cyclization reaction under co‐catalysis of a Brønsted acid and a chiral palladium complex, furnishing multifunctional dihydropyrazones and dihydroisoxazoles, respectively. Diverse substitution patterns for both types of electron‐deficient diene compounds are tolerated, and corresponding heterocycles were generally constructed with moderate to excellent enantioselectivity, which can be elaborated to access products with higher molecular complexity and diversity. Control experiments and density functional theory calculations support that α‐regioselective protonation of dienyl substrates by acid and concurrent π‐Lewis base activation of Pd0 complex is energetically favoured in the formation of active π‐allylpalladium intermediates, and an outer‐sphere allylic amination or etherification mode is adopted to deliver the observed cyclized products enantioselectively.

show abstract

Palladium(0) and Brønsted Acid Co‐Catalyzed Enantioselective Hydro‐Cyclization of 2,4‐Dienyl Hydrazones and Oximes

Li,

Gui,

Pi

et al. 2024

Angew Chem Int Ed

0

View full text Add to dashboard Cite

The transition metal‐catalyzed asymmetric hydro‐functionalization of 1,3‐dienes has been well explored, but most reactions focus on electron‐neutral substrates in an intermolecular manner. Here we first demonstrate that readily available 2,4‐dienyl hydrazones and oximes can be efficiently utilized in the hydro‐cyclization reaction under co‐catalysis of a Brønsted acid and a chiral palladium complex, furnishing multifunctional dihydropyrazones and dihydroisoxazoles, respectively. Diverse substitution patterns for both types of electron‐deficient diene compounds are tolerated, and corresponding heterocycles were generally constructed with moderate to excellent enantioselectivity, which can be elaborated to access products with higher molecular complexity and diversity. Control experiments and density functional theory calculations support that α‐regioselective protonation of dienyl substrates by acid and concurrent π‐Lewis base activation of Pd0 complex is energetically favoured in the formation of active π‐allylpalladium intermediates, and an outer‐sphere allylic amination or etherification mode is adopted to deliver the observed cyclized products enantioselectively.

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Umpolung Asymmetric 1,5‐Conjugate Addition via Palladium Hydride Catalysis

Cited by 3 publications

References 105 publications

Enantioselective Construction of Quaternary Stereocenters via A Chiral Spiro Phosphoric Acid-Assisted Formal Gold Carbene gem-Dialkylation Reaction

Enantioselective Construction of Quaternary Stereocenters via A Chiral Spiro Phosphoric Acid-Assisted Formal Gold Carbene gem-Dialkylation Reaction

Palladium(0) and Brønsted Acid Co‐Catalyzed Enantioselective Hydro‐Cyclization of 2,4‐Dienyl Hydrazones and Oximes

Palladium(0) and Brønsted Acid Co‐Catalyzed Enantioselective Hydro‐Cyclization of 2,4‐Dienyl Hydrazones and Oximes

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