Feng Ligand: Privileged Chiral Ligand in Asymmetric Catalysis

Remote C6-Enantioselective C–H Functionalization of 2,3-Disubstituted Indoles through the Dual H-Bonds and π–π Interaction Strategy Enabled by CPAs

Chiral (dihydro)furo-fused heterocycles are significant structural motifs in numerous natural products, functional materials and pharmaceuticals. Therefore, developing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein, we develop an effective, modular method by a dipeptide-phosphonium salt-catalyzed regio- and stereoselective cascade reaction of readily available linear β,γ-unsaturated ketones with aromatic alkenes, affording a wide variety of structurally fused heterocyclic molecules in high yields with excellent stereoselectivities. Of note, this method provides a platform for building three types of valuable dihydrofuro-fused rigid tricyclic architectures that have great synthetic challenges. Moreover, mechanistic investigations revealed that the bifunctional phosphonium salt catalyst controlled the regio- and stereoselectivities of this cascade transformation, particularly proceeding through the initial ketone α-addition followed by O -participated substitution; and the multiple hydrogen-bonding interactions between Bronsted acid moieties of catalyst and nitro group of aromatic alkene were crucial in asymmetric induction. Given the generality, versatility, and high efficiency of this method, we anticipate that it will have broad synthetic utilities.

Highly Regio- and Stereoselective Cascade of β,γ-Unsaturated Ketones by Dipeptided Phosphonium Salt Catalysis: Stereospecific Construction of Dihydrofuro-Fused [2,3-b] Skeletons.

N-Aminopyridinium salts generate nitrogen-centered radicals by means of photoredox catalysis. Herein, we report that they can be trapped by enol equivalents to give α-amino carbonyl compounds in ex...

Visible-Light-Mediated Amination of π-Nucleophiles with N-Aminopyridinium Salts

Benzosultams represent one category of multi-heteroatom heterocyclic scaffolds, which have been frequently found in pharmaceuticals, agricultural agents, and chiral catalysts. Given the diversely significant functions of these compounds in organic and medicinal chemistry, great efforts have been made to develop novel catalytic systems for the efficient construction of benzosultam motifs over the past decades. Herein, in this review, we mainly summarize the recent advances in the field of catalytic synthesis of benzosultams from 2017 to August of 2020, with an emphasis on the scopes and mechanisms of representative reactions.

https://www.mdpi.com/1420-3049/25/19/4367/pdf

Recent Advances in Catalytic Synthesis of Benzosultams.

A new catalytic asymmetric tandem α-alkenyl addition/proton shift reaction of silyl enol ethers with ketimines was serendipitously discovered in the presence of chiral N,N'-dioxide/ZnII complexes. The proton shift preferentially proceeded instead of a silyl shift after α-alkenyl addition of silyl enol ether to the ketimine. A wide range of β-amino silyl enol ethers were synthesized in high yields with good to excellent ee values. Control experiments suggest that the Mukaiyama-Mannich reaction and tandem α-alkenyl addition/proton shift reaction are competitive reactions in the current catalytic system. The obtained β-amino silyl enol ethers were easily transformed into β-fluoroamines containing two vicinal tetrasubstituted carbon centers.

Chiral Zinc(II)-Catalyzed Enantioselective Tandem α-Alkenyl Addition/Proton Shift Reaction of Silyl Enol Ethers with Ketimines.

The investigation of diverse reactivity of β,γ-unsaturated carbonyl compounds is of great value in asymmetric catalytic synthesis. Numerous enantioselective transformations have been well developed with β,γ-unsaturated carbonyl compounds as nucleophiles, however, few example were realized by utilizing them as not only nucleophiles but also electrophiles under a same catalytic system. Here we report a regioselective catalytic asymmetric tandem isomerization/α-Michael addition of β,γ-unsaturated 2-acyl imidazoles in the presence of chiral N,N′-dioxide metal complexes, delivering a broad range of optically pure 1,5-dicarbonyl compounds with two vicinal tertiary carbon stereocenters in up to >99% ee under mild conditions. Meanwhile, stereodivergent synthesis is disclosed to yield all four stereoisomers of products. Control experiments suggest an isomerization process involved in the reaction and give an insight into the role of NEt3. In addition, Mannich reaction and sulfur-Michael addition of β,γ-unsaturated 2-acyl imidazoles proceed smoothly as well under the same catalytic system. The investigation of reactivity of β,γ-unsaturated carbonyl compounds is of great synthetic value, especially in asymmetric transformations. Here, the authors report a catalytic asymmetric tandem isomerization/α-Michael addition of β,γ-unsaturated 2-acyl imidazoles in presence of chiral N,N′-dioxide metal catalysts.

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Lewis acid-catalyzed asymmetric reactions of β,γ-unsaturated 2-acyl imidazoles

Photocatalysis opens up a new window for carbonyl chemistry. Despite a multitude of photochemical reactions of carbonyl compounds, visible light-induced catalytic asymmetric transformations remain elusive and pose a formidable challenge. Accordingly, the development of simple, efficient, and economic catalytic systems is the ideal pursuit for chemists. Herein, we report an enantioselective radical photoaddition to ketones through a Lewis acid-enabled photoredox catalysis wherein the in situ formed chiral N,N'-dioxide/Sc(III)-ketone complex serves as a temporary photocatalyst to trigger single-electron transfer oxidation of silanes for the generation of nucleophilic radical species, including primary, secondary, and tertiary alkyl radicals, giving various enantioenriched aza-heterocycle-based tertiary alcohols in good to excellent yields and enantioselectivities. The results of electron paramagnetic resonance (EPR) and high-resolution mass spectrum (HRMS) measurements provided favorable evidence for the stereocontrolled radical addition process involved in this reaction.

Enantioselective Radical Addition to Ketones through Lewis Acid-Enabled Photoredox Catalysis.

Enantioselective Imino-Ene Reaction of N-Sulfonyl Ketimines with Silyl Enol Ethers: Access to Chiral Benzosultams.

A diastereo- and enantioselective photoenolization/Mannich (PEM) reaction of ortho-alkyl aromatic ketones with benzosulfonimides was established by utilizing a chiral N,N′-dioxide/Ni(OTf)2 complex as the Lewis acid catalyst. It afforded a series of benzosulfonamides and the corresponding ring-closure products, and a reversal of diastereoselectivity was observed through epimerization of the benzosulfonamide products under continuous irradiation. On the basis of the control experiments, the role of the additive LiNTf2 in achieving high stereoselectivity was elucidated. This PEM reaction was proposed to undergo a direct nucleophilic addition mechanism rather than a hetero-Diels–Alder/ring-opening sequence. A possible transition state model with a photoenolization process was proposed to explain the origin of the high level of stereoinduction.

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Liuzhen Hou

Papers

Chiral Zinc(II)-Catalyzed Enantioselective Tandem α-Alkenyl Addition/Proton Shift Reaction of Silyl Enol Ethers with Ketimines.

Lewis acid-catalyzed asymmetric reactions of β,γ-unsaturated 2-acyl imidazoles

Enantioselective Radical Addition to Ketones through Lewis Acid-Enabled Photoredox Catalysis.

Enantioselective Imino-Ene Reaction of N-Sulfonyl Ketimines with Silyl Enol Ethers: Access to Chiral Benzosultams.

NickelII-catalyzed asymmetric photoenolization/Mannich reaction of (2-alkylphenyl) ketones