Asymmetric functionalization of the C(sp3)–H bond is an attractive yet challenging strategy to achieve versatile bond-forming events, enabling the precise assembly of molecular complexity with ...minimal manipulation of functional groups. Here, we report an asymmetric C(sp3)–H/C(sp3)–H umpolung coupling of N-allylimine and coordinating α-aryl carbonyls by using chiral phosphoramidite-palladium catalysis. A wide variety of α-heteroaryl ketones and 2-acylimidazoles are nicely tolerated to open a convenient and tunable avenue for efficient synthesis of enantioenriched β-amino-γ,δ-unsaturated carbonyl derivatives with high levels of regio- and stereoselectivities, capable of providing a key intermediate for asymmetric synthesis of Focalin. This protocol showcases an umpolung reactivity of the N-allylimines through a concerted proton and two-electron transfer process to cleave the allylic C–H bond, effectively complementing established methodology for allylic C–H functionalization. An inner-sphere allylation pathway for both α-heteroaryl carbonyls and 2-acylimidazoles to attack the π-allylpalladium species is suggested by computational studies and experimental facts, wherein the nitrogen coordination to the palladium center enables the preference of branched regioselectivity.
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.
In the presence of visible-light photoredox and chiral phosphate catalysts, a novel asymmetric Friedel–Crafts reaction of indoles and readily accessible α-amino acid derived redox-active esters is ...established to afford enantioenriched 1-indolyl-1-alkylamine derivatives in moderate to high yields and with high levels of enantioselectivities. This method not only shows a mild and efficient alternative for the in situ generation of N-acyl imines but also indicates the feasibility of a multicatalyst system for asymmetric photoredox catalysis.
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
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 hybrid Au(I)/Brønsted acid binary catalyst system enables enynes to serve as latent 1,3-silyloxydienes capable of participating in the first cascade hydrosiloxylation of an enynyl ...silanol/asymmetric Diels–Alder reaction. A variety of polycyclic compounds bearing multistereogenic centers were obtained in high yields and excellent enantioselectivities from the relay catalytic cascade reaction between (2-(but-3-en-1-ynyl)phenyl) silanols and quinones catalyzed by the combined achiral gold complex and chiral N-triflyl phosphoramide.
A regioselective Pd-catalyzed allylic amination reaction of dienyl allylic carbonates and aromatic amines has been developed by means of phosphoramidite-palladium catalysis. The regioselectivity ...could be altered by the counterion of the π-allylpalladium intermediate. As a result, either branched Z-dienyl allylic amines or linear conjugated allylic amines were generated in high levels of regioselectivity from the same substrates by tuning the reaction conditions.
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Asymmetric metal/organo relay catalysis, utilizing a metal complex and a chiral organocatalyst in a one-pot cascade reaction, is aimed to sequentially impart activation on multiple steps by distinct ...catalysts. Such a catalysis merges the advantages of both metal catalysis and organocatalysis, providing step-economy, and, more importantly, the potential to achieve inaccessible reactivity by a single catalyst. Chiral phosphoric acids are among the most robust organocatalysts, rendering a broad range of enantioselective bond-forming reactions. The combination of metal complexes and chiral phosphoric acids in a single vessel has been well documented. In particular, the asymmetric relay catalysis of metal complex with chiral phosphoric acid has grown rapidly since 2008. Several excellent reviews have been published to cover almost all examples in this area from 2008 to early 2014; therefore, in this chapter, we will mainly highlight progress from 2014 to mid-2019.
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.
