A PdII‐catalyzed asymmetric aminohydroxylation of 1,3‐dienes with N‐tosyl‐2‐aminophenols was developed by making use of a chiral pyridinebis(oxazoline) ligand. The highly regioselective reaction ...provides direct and efficient access to chiral 3,4‐dihydro‐2H‐1,4‐benzoxazines in high yield and enantioselectivity (up to 96:4 e.r.). The reaction employs readily available N‐tosyl‐2‐aminophenols as a unique aminohydroxylation reagent and is complementary to known asymmetric aminohydroxylation methods.
Give me a ring: A palladium‐catalyzed asymmetric aminohydroxylation reaction of 1,3‐dienes with N‐tosyl‐2‐aminophenols was developed by employing a chiral pyridinebis(oxazoline) ligand. This reaction furnishes optically active 3,4‐dihydro‐2H‐1,4‐benzoxazines in high yields and with high levels of regio‐ and stereoselectivity.
Allylamines are important building blocks in the synthesis of bioactive compounds. The direct coupling of allylic C−H bonds and commonly available amines is a major synthetic challenge. An allylic ...C−H amination of 1,4‐dienes has been accomplished by palladium catalysis. With aromatic amines, branch‐selective allylic aminations are favored to generate thermodynamically unstable Z‐allylamines. In addition, more basic aliphatic cyclic amines can also engage in the reaction, but linear dienyl allylic amines are the major products.
A Pd‐catalyzed branch‐ and Z‐selective allylic C−H amination from 1,4‐dienes and aromatic amines has been established for the efficient synthesis of thermodynamically unstable Z‐allylamines. In addition, more basic aliphatic cyclic amines also smoothly engage in the allylic C−H amination reaction without any Lewis acid additive, preferentially giving linear‐selective allylamines as the major regioisomers.
Branched selectivity in asymmetric allylic C−H alkylation is enabled by using 2‐acylimidazoles as nucleophiles in the presence of a chiral phosphoramidite‐palladium catalyst. A wide range of terminal ...alkenes, including 1,4‐dienes and allylarenes, are nicely tolerated and provide chiral 2‐acylimidazoles in moderate to high yields and with high levels of regio‐, and enantio‐, and E/Z‐selectivities. Mechanistic studies using density‐functional theory calculations suggest a nucleophile‐coordination‐enabled inner‐sphere attack mode for the enantioselective carbon–carbon bond‐forming event.
Branching out: Palladium‐chiral phosphoramidite catalysis is used for an unprecedented branched‐selective asymmetric allylic C−H alkylation by using 2‐acylimidazoles as model coordinating nucleophiles. Density‐functional theory calculations suggest an unusual inner‐sphere mechanism for the carbon–carbon bond‐forming process.
The first catalytic enantioselective decarboxylative propargylation/hydroamination reaction of ethynyl benzoxazinanones with malononitriles enabled by organo/copper cooperative catalysis was ...established. Various 3-indolin-malononitrile derivatives, displaying a high tolerance for functional groups, could be obtained in good yields with high levels of enantioselectivity (up to 85% yield, 96:4 er). More importantly, this organo/metal cooperative catalytic system will provide a powerful synthetic strategy for new reaction development.
Monodentate phosphorus ligands have been found to enable the palladium-catalyzed allylic C–H alkylation reaction of terminal alkenes with a wide variety of carbon nucleophiles. Moreover, an ...asymmetric allylic C–H alkylation of terminal alkenes with pyrazol-5-ones has been established in the presence of chiral phosphoramidite ligand and chiral phosphoric acid as co-catalyst. Mechanistic studies suggest that a ternary Pd(0) complex, coordinated with a monodentate phosphorus ligand, benzoquinone, and alkene, is most likely to be an active species.
An enantio- and diastereodivergent 2+2+1 annulation reaction of allyl ketones, acidic methylene compounds, and nitroalkenes to assemble highly functionalized cyclopentanes from readily available ...substances enabled by asymmetric relay catalysis of chiral bifunctional squaramide and palladium complex has been established. This method showcases that allyl ketones can serve as latent 1,2-dication synthons via a linear-selective allylic C–H functionalization and sequential 1,4-conjugated addition, enabling the rapid assembly of cyclopentane skeleton with a broad scope of methylene nucleophiles and nitroalkenes. Notably, chiral bifunctional squaramide catalyst engages in both the intermolecular and intramolecular Michael addition reactions accompanying with a kinetic resolution behavior to amplify the enantioselection. In addition, the stereodivergent synthesis of diastereomers from the resultant chiral cyclopentane derivatives is also accessible by a simple manipulation with base.
Herein, we developed an enantio- and diastereodivergent 2 + 2+1 annulation reaction for the synthesis of tetrasubstituted cyclopentanes enabled by chiral bifunctional squaramide/palladium relay catalysis. This protocol stands out by employing simple α-alkenes to serve as 1,2-dication synthons, enabling rapid assembly of densely functionalized chiral cyclopentanes from readily available starting materials. The enantioselection is controlled by chiral bifunctional squaramide via asymmetric catalysis and kinetic resolution in the bond-forming process. In particular, thermodynamically stable diastereomers are also accessible by a simple manipulation with base. Display omitted
An asymmetric allylic C–H alkylation of allyl ethers has been established by chiral phosphoramidite-palladium catalysis, affording a wide variety of functionalized chiral 2-acylimidazoles in moderate ...to high yields and with high levels of enantioselectivity. Moreover, this protocol could be applied to a concise asymmetric synthesis of a tachykinin receptor antagonist.
The diverse functionalization of 1,3-butadiene provides wide applicability toward the synthesis of abundant and useful allylic compounds. Here, we describe a three-component and redox-neutral ...assembly of readily available CX compounds, 1,3-butadiene, and various nucleophiles by merging photoredox and nickel catalysis, enabling the rapid synthesis of structurally diverse homoallyl amines and homoallylic alcohols.
The selective functionalization of C(sp3)–H bonds has emerged as a transformative approach for streamlining synthetic routes, offering remarkable efficiency in the preparation and modification of ...complex organic molecules. However, the direct enantioselective transformation of hydrocarbons to medicinally valuable chiral molecules remains a significant challenge that has yet to be addressed. In this study, we adopt an atom transfer radical coupling (ATRC) strategy to achieve the asymmetric functionalization of C(sp3)–H bonds in hydrocarbons. This approach involves intermolecular H atom transfer (HAT) between a hydrocarbon and an alkoxy radical, leading to the formation of a carbon-centered radical. The resulting radical adds to alkenes, generating a new radical species that is intercepted by a chiral copper-mediated C–O bond coupling. By employing this method, we can directly access valuable chiral lactones bearing a quaternary stereocenter with high efficiency and excellent enantioselectivity. Importantly, ATRC exhibits great potential as a versatile platform for achieving stereoselective transformations of hydrocarbons.
In the presence of chiral phosphoramidite ligand, a palladium-catalyzed asymmetric allylic C–H alkylation of 1,4-dienes with cyclic β-keto esters has been established to afford chiral ...α,α-disubstituted β-keto esters in good to excellent yields, with high levels of regioselectivity, E/Z selectivity, and enantioselectivity. 1,4-Dienes bearing a wide scope of functional groups, such as ketone, chloride, ester, and amide as well, have been nicely tolerated. In addition, preliminary application of this method enables a concise formal synthesis of (−)-tanikolide.
