Catalytic Asymmetric Dearomative [2 + 2] Photocycloaddition/Ring-Expansion Sequence of Indoles with Diversified Alkenes.

Developing novel strategies for catalytic asymmetric dearomatization (CADA) reactions is highly valuable. Visible light-mediated photocatalysis is demonstrated to be a powerful tool to activate aromatic compounds for further synthetic transformations. Herein, a catalytic asymmetric dearomative [2 + 2] photocycloaddition/ring-expansion sequence of indoles with simple alkenes was reported, providing a facile access to enantioenriched cyclopenta[b]indoles with good to high yields and enantioselectivities by means of chiral lanthanide photocatalysis. This protocol exhibited a broad substrate scope and good functional group tolerance, as well as potential applications in the synthesis of bioactive molecules. Mechanistic studies, including control experiments, UV-vis absorption spectroscopy, emission spectroscopy, and DFT calculations, were carried out, shedding insights into the reaction mechanism and the origin of enantioselectivity.

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

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.

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

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 ß-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 ß-amino silyl enol ethers were easily transformed into ß-fluoroamines containing two vicinal tetrasubstituted carbon centers.

Catalytic asymmetric transformation of nitrones and allenes to dihydropyridoindoles via chiral N,N'-dioxide/cobalt(II) catalysis.

A chiral N,N'-dioxide/cobalt(II) complex catalytic system is developed to promote the multistep cascade reaction of α,ß-unsaturated-N-aryl nitrones with allenes, giving a variety of chiral dihydropyridoindoles in moderate to good yields with excellent dr and ee values. Mechanistic studies support a [3+2] cycloaddition/[3,3]-rearrangement/retro-Mannich process.

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

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.

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

A highly efficient asymmetric imino-ene reaction of cyclic ketimines with silyl enol ethers was developed. Various chiral benzosultam derivatives were obtained in excellent yields (up to 99%), enantioselectivities (up to 99% ee), and diastereoselectivities (up to >19:1 dr) by utilizing a Ni(BF4)2·6H2O/N,N'-dioxide complex as the catalyst. A possible transition state model was proposed to explain the stereoinduction. Furthermore, the synthetic utility of the protocol provided quick access to optically pure HIV-1 inhibitor.

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

The investigation of diverse reactivity of ß,γ-unsaturated carbonyl compounds is of great value in asymmetric catalytic synthesis. Numerous enantioselective transformations have been well developed with ß,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 ß,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 ß,γ-unsaturated 2-acyl imidazoles proceed smoothly as well under the same catalytic system.