Highly Enantioselective Construction of Strained Spiro[2,3]hexanes through a Michael Addition/Ring Expansion/Cyclization Cascade.

We herein report a general organocatalytic enantioselective strategy for the construction of highly strained spiro[2,3]hexane skeletons from methylenecyclopropanes and a broad selection of α,ß-unsaturated aldehydes. The reaction proceeds through a Michael addition followed by ring expansion of methylenecyclopropanes and nucleophilic attack of an enamine to realize the construction of spiro[2,3]hexanes. Key to the success of this approach are the utilization of an electron-deficient difluoro-substituted secondary amine catalyst and the intrinsic reactivity of methylenecyclopropanes.

Dual Catalytic Switchable Divergent Synthesis: An Asymmetric Visible-Light Photocatalytic Approach to Fluorine-Containing γ-Keto Acid Frameworks.

Herein, we describe a novel and efficient method for constructing a series of fluorine-containing γ-keto acid derivatives through combining visible-light photoredox catalysis and chiral Lewis acid catalysis. With this dual catalytic strategy, a variety of chiral γ-keto amides containing a gem-difluoroalkyl group and a series of fluorine-containing α,ß-unsaturated-γ-keto esters were successfully constructed with high stereoselectivities, respectively. A series of experiments showed that the chemoselectivity of this process was highly dependent on the fluorine reagents besides the Lewis acid catalysts. This approach facilitates rapid access to γ-keto acid derivatives, an important class of precursors for pharmaceuticals, plasticizers, and various other additives.

Visible Light Photoredox-Catalyzed α-Alkylation of Cyclic Tertiary Arylamines.

An efficient method was successfully developed to obtain cyclic ß-amino ketones via visible-light photoredox catalysis. With this catalytic system, vinyl azides and N-Ph pyrrolidines react to form cyclic ß-amino ketones by α-amino radical addition. This method provides a simple, mild, straightforward, and novel paradigm to prepare important ß-amino ketones.

Dehydrogenative Silylation of Alkenes for the Synthesis of Substituted Allylsilanes by Photoredox, Hydrogen-Atom Transfer, and Cobalt Catalysis.

A synergistic catalytic method combining photoredox catalysis, hydrogen-atom transfer, and proton-reduction catalysis for the dehydrogenative silylation of alkenes was developed. With this approach, a highly concise route to substituted allylsilanes has been achieved under very mild reaction conditions without using oxidants. This transformation features good to excellent yields, operational simplicity, and high atom economy. Based on control experiments, a possible reaction mechanism is proposed.

Transition-Metal-Free Selective C-H Benzylation of Tertiary Arylamines by a Dearomatization-Aromatization Sequence.

Due to the significance of hybrid systems in drug discovery, there is an urgent need to assemble multiple biologically active ingredients into a single molecule. Here, we report a general transition-metal-free selective C-H benzylation of tertiary arylamines in good to excellent yields with a broad substrate scope and high functional-group tolerance under mild conditions. Besides arylamines, some other benzene derivatives also readily furnished the corresponding diaryl methane derivatives with this protocol. A series of control experiments and theoretical calculations indicated that this transition-metal-free reaction is a dearomatization-aromatization process.

Direct Decarboxylative-Decarbonylative Alkylation of α-Oxo Acids with Electrophilic Olefins via Visible-Light Photoredox Catalysis.

The decarbonylation of primary, secondary, and tertiary alkyl-substituted acyl radicals has been investigated through photoredox catalysis. A series of quaternary carbons and γ-ketoesters have been directly constructed by the photoredox 1,4-conjugate addition of the corresponding alkyl ketoacids with electrophilic alkenes. And, the tertiary alkyl ketoacids have proved to be good precursors of tertiary alkyl radicals.

Dual C(sp3 )-H Bond Functionalization of N-Heterocycles through Sequential Visible-Light Photocatalyzed Dehydrogenation/[2+2] Cycloaddition Reactions.

Herein we describe a mild method for the dual C(sp3 )-H bond functionalization of saturated nitrogen-containing heterocycles through a sequential visible-light photocatalyzed dehydrogenation/[2+2] cycloaddition procedure. As a complementary approach to the well-established use of iminium ion and α-amino radical intermediates, the elusive cyclic enamine intermediates were effectively generated by photoredox catalysis under mild conditions and efficiently captured by acetylene esters to form a wide array of bicyclic amino acid derivatives, thus enabling the simultaneous functionalization of two vicinal C(sp3 )-H bonds.

PPh3 Mediated Reductive Annulation Reaction between Isatins and Electron Deficient Dienes to Construct Spirooxindole Compounds.

A PPh3 mediated reductive annulation reaction between isatins and 4,4-dicyano-2-methylenebut-3-enoates was developed. The reaction provided an alternative method for constructing five- and three-membered all-carbon spirooxindole compounds. Lithium chloride as a Lewis acid played a key role in the synthesis of spirocyclopentenyl oxindole compounds.

PPh3O as an Activating Reagent for One-Pot Stereoselective Syntheses of Di- and Polybrominated Esters from Simple Aldehydes.

An efficient one-pot method for the syntheses of di- and polybrominated esters from readily available aldehydes is reported. The direct use of the in situ generated byproduct PPh3O in the following reactions greatly improves the efficiency of the cascade. Also, the substrate scope of the reaction is proved to be broad.

Enantioselective Amine-Catalyzed [4 + 2] Annulations of Allene Ketones and 2,3-Dioxopyrrolidine Derivatives: Synthesis of 4H-Pyran Derivatives.

An efficient cinchona alkaloid-derived amine catalyzed asymmetric [4 + 2] cycloaddition is successfully developed. 4H-Pyran fused pyrrolin-2-one products are readily obtained in moderate to high yields with good enantioselectivites by employing allene ketones and 2,3-dioxopyrrolidine derivatives as substrates.

A lutidine-promoted photoredox catalytic atom-transfer radical cyclization reaction for the synthesis of 4-bromo-3,3-dialkyl-octahydro-indol-2-ones.

Reported herein is a visible-light-catalyzed photoredox atom-transfer radical cyclization (ATRC) halo-alkylation of 1,6-dienes with α-halo-ketones as the ATRC reagent. This process exhibits high atom economy, high step economy, and high redox economy, which can directly construct a 4-bromo-3,3-dialkyl-octahydro-indol-2-one core under mild conditions in one pot, and lutidine is found to be the key promoter for this ATRC process.

Aroylchlorination of 1,6-Dienes via a Photoredox Catalytic Atom-Transfer Radical Cyclization Process.

A method using aroyl chlorides as atom-transfer radical cyclization agents in a novel visible-light photocatalytic aroylchlorination reaction is developed. The overall transformation involves the formation of two new C-C bonds and one new C-Cl bond in a one-pot process. The advantages of this reaction include high atom/step/redox economy, mild conditions, operational simplicity, and broad substrate scopes.

A new approach to access difluoroalkylated diarylmethanes via visible-light photocatalytic cross-coupling reactions.

Difluoroalkylated diarylmethanes with biological and pharmacological potentials were synthesized from para-quinone methides (p-QMs) and difluoroalkylating reagents via a visible light photocatalysis strategy. Mechanism studies showed that the excited photocatalyst, *fac-Ir(ppy)3, was primarily quenched by p-QMs and the generated diarylmethane radical intermediates then underwent a radical-radical cross-coupling reaction with difluoroalkyl radicals. This reaction features mild conditions, high efficiency and wide functional group compatibility.

Alkene functionalization for the stereospecific synthesis of substituted aziridines by visible-light photoredox catalysis.

A novel strategy involving visible-light-induced functionalization of alkenes for the synthesis of substituted aziridines was developed. The readily prepared N-protected 1-aminopyridinium salts were used for the generation of N-centered radicals. This approach allowed the synthesis of aziridines bearing various functional groups with excellent diastereoselectivity under mild conditions. Moreover, this protocol was successfully applied to prepare structurally diverse nitrogen-containing frameworks.