Formal Transformation of Benzylic Carboxylic Acids to Phenols.

Phenols play a crucial role as core structural motifs in natural products and also serve as fundamental building blocks in synthetic chemistry. Apart from the known protocols for the conversion of aryl precursors to phenols (i. e.

Photoinduced fluoroalkylation-peroxidation of alkenes enabled by ligand-to-iron charge transfer mediated decarboxylation.

We report here a photoinduced iron-catalyzed fluoroalkylation-peroxidation of activated and/or unactivated alkenes with fluoroalkyl carboxylic acids and hydroperoxide. The ligand-to-iron charge transfer strategy effectively overcomes the high redox potential of the fluoroalkyl carboxylic acids, facilitating the difunctionalization reaction to occur smoothly under mild reaction conditions. The late-stage functionalization of drug and natural product derivatives was also demonstrated.

Photocatalytic Sulfonyl Peroxidation of Alkenes via Deamination of -Sulfonyl Ketimines.

A photocatalytic three-component sulfonyl peroxidation of alkenes with -sulfonyl ketimines and -butyl hydroperoxide is reported. The reaction takes place via the photoinduced EnT process, which allows the efficient synthesis of a variety of β-peroxyl sulfones under mild reaction conditions in the absence of a transition metal catalyst. The downstream derivatizations of the peroxides were also performed.

Pd/IPr-Catalyzed Hydrodefluorination of -Difluorocyclopropanes: Regioselective Synthesis of Terminal Fluoroalkenes.

Developing new strategies to enable chemo- and regioselective reductions is an important topic in chemical research. Herein, an efficient and regioselective Pd/IPr-catalyzed ring-opening hydrodefluorination of -difluorocyclopropanes to access terminal fluoroalkenes is developed. The success of this transformation was attributed to the use of 3,3-dimethylallyl Bpin as a novel hydride donor.

Pd-IHept-Catalyzed Ring-Opening of -Difluorocyclopropanes with Malonates Via Selective C-C Bond Cleavage: Synthesis of Monofluoroalkenes.

Monofluoroalkene scaffolds are frequently found in various functional molecules. Herein, we report a Pd-IHept-catalyzed (NHC = N-heterocyclic carbene) defluorinative functionalization approach for the synthesis of monofluoroalkenes from -difluorocyclopropanes and malonates. The flexible yet sterically hindered ,'-bis(2,6-di(4-heptyl)phenyl)imidazol-2-ylidene ligand plays a key role in ensuring the high reaction efficiency.

Amine-Induced Selective C-C Bond Cleavage of 2,2,2-Trifluoroethyl Carbonyls for the Synthesis of Ureas and Amides.

An efficient and selective transformation of 2,2,2-trifluoroethyl carbonyls into ureas/amides with amines is reported. This protocol allows the selective cleavage of the C-C bond of 2,2,2-trifluoroethyl carbonyls under transition metal-free and oxidant-free conditions, which is in contrast to the analogous C-F or C-CF bond functionalization. This reaction reveals the unexplored reactivity of 2,2,2-trifluoroethyl carbonyls and exhibits a broad substrate range and good functional group tolerance.

Chemo-, Stereo- and Regioselective Fluoroallylation/Annulation of Hydrazones with gem-Difluorocyclopropanes via Tunable Palladium/NHC Catalysis.

Defluorinative manipulation of polyfluorinated molecules has shown great promise due to its granting of synthetic versatility to inert C-F bonds. The development of chemo-, stereo- and regioselective strategies to realize highly efficient formation of either the linear/branched or E/Z products from gem-difluorocyclopropanes (gem-F CPs) is a challenging task. Herein, we have realized palladium/NHC-catalyzed fluoroallylation/annulation of hydrazones with gem-F CPs that incorporate the hydrazone N moiety into the products.

Copper-Catalyzed Germyl-Azidation of Alkenes with Germanium Hydrides and Trimethylsilyl Azide.

The incorporation of a germyl group and another functional fragment across the C═C bond is a challenging task due to the prevailing hydrogermylation reaction. Herein, an efficient copper-catalyzed three-component reaction of alkenes, germanium hydrides, and trimethylsilyl azide has been disclosed. This transformation allows the concomitant introduction of germyl and azide groups across the double bonds in a highly regioselective manner with -butyl hydroperoxides as the bystanding oxidant.

Copper-Catalyzed Three-Component Germyl Peroxidation of Alkenes.

The concurrent incorporation of a germyl fragment and another functional group (beyond the hydrogen atom) across the C═C double bond is a highly appealing yet challenging task. Herein we demonstrate the efficient germyl peroxidation of alkenes with germanium hydrides and -butyl hydroperoxide via a copper-catalyzed three-component radical relay strategy. This protocol exhibits excellent functional group tolerance and exquisite chemo- and regioselectivity under mild conditions and represents a rare example of constructing synthetically challenging metal-embedded organic peroxides.

Umpolung carbonyls enable direct allylation and olefination of carbohydrates.

Mother Nature has its own arts to build a vast number of carbohydrates; however, there is still a lack of tools for selective functionalization of native carbohydrates through C─C bond formation. Such a long-standing challenge for the synthetic community lies into the intrinsic problems related to the innate properties of carbohydrates, e.g.

Ligand-controlled regioselective and chemodivergent defluorinative functionalization of -difluorocyclopropanes with simple ketones.

Modulating the reaction selectivity is highly attractive and pivotal to the rational design of synthetic regimes. The defluorinative functionalization of -difluorocyclopropanes constitutes a promising route to construct β-vinyl fluorine scaffolds, whereas chemo- and regioselective access to α-substitution patterns remains a formidable challenge. Presented herein is a robust Pd/NHC ligand synergistic strategy that could enable the C-F bond functionalization with exclusive α-regioselectivity with simple ketones.

β-Perfluoroalkyl Peroxides as Fluorinated C3-Building Blocks for the Construction of Benzo[4,5]imidazo[1,2-]pyridines.

An efficient and selective protocol for the synthesis of perfluoroalkyl-group-substituted benzo[4,5]imidazo[1,2-]pyridines has been developed in which β-perfluoroalkyl peroxides act as novel fluorinated C3-building blocks to implement regioselective [3 + 3] annulation with 2-cyanomethyl benzimidazole under metal-free conditions. The application of the synthesized perfluoroalkylated BIPs as potent anticancer reagents versus the nonfluorinated ones demonstrated the biological utility of this method.

Three-Component Reactions of α-CF Carbonyls, NaN, and Amines for the Synthesis of -1,2,3-Triazoles.

The development of methods for the assembly of 1,2,3-triazoles is an important topic due to the broad applications of this motif in various scientific fields. In this work, we demonstrate that the three-component assembly of α-CF carbonyls, NaN, and amines was achieved for the selective construction of a variety of 5-amino -1,2,3-triazoles under transition-metal-free and open-air conditions. The method provides a general and operationally simple route to functionalized biologically important molecules including carbohydrates, nucleosides, and peptides and exhibits broad substrate scopes.

Iron-Catalyzed Ring-Opening Reactions of Cyclopropanols with Alkenes and TBHP: Synthesis of 5-Oxo Peroxides.

The ring opening of cyclopropanols is rarely used in multicomponent reactions. Herein we report the three-component reaction of cyclopropanols with alkenes and -butyl hydroperoxide (TBHP) catalyzed by an iron catalyst. This protocol enables the incorporation of both the β-carbonyl fragment and a peroxy unit across the C═C double bond regioselectively, thus allowing an efficient, facile access to 5-oxo peroxides.

Iron-catalysed radical cyclization to synthesize germanium-substituted indolo[2,1-]isoquinolin-6(5)-ones and indolin-2-ones.

A simple and efficient strategy for iron-catalysed cascade radical cyclization was developed, by which an array of germanium-substituted indolo[2,1-]isoquinolin-6(5)-ones and indolin-2-ones were obtained in one pot with germanium hydrides as radical precursors. A rapid intramolecular radical trapping mode enabled the selective arylgermylation of alkenes over the prevalent hydrogermylation reaction.

A Mn-catalyzed remote C(sp)-H bond peroxidation triggered by radical trifluoromethylation of unactivated alkenes.

A manganese-catalyzed radical relay strategy for the remote trifluoromethylation-peroxidation of unactivated alkenes is disclosed. The electrophilic CF3 group was added to the C[double bond, length as m-dash]C double bonds to afford remote C-centered radicals upon 1,5-HAT, which could be efficiently trapped by Mnn+1OOBu-t species to deliver 1,6-difunctionalized products selectively under mild conditions. t-BuOOH serves as both the oxidant and the peroxy precursor in this transformation.

Annulative π-Extension (APEX) of Indoles to Pyrido[1,2-]indoles Using 4-Oxo Peroxides as C4 Units.

Annulative π-extension (APEX) of 3-substituted indoles to pyrido[1,2-]indoles is developed by using 4-oxo peroxides as π-extending reagents, which are employed as versatile C4 building blocks. This transformation is initiated by Brønsted acid-mediated Hock rearrangement of the peroxyl group. Notably, the pyrido[1,2-]indole products are obtained by elimination of the indole moiety from the corresponding dihydropyrido[1,2-]indoles, which could be selectively formed at room temperature.

Ruthenium catalyzed β-selective alkylation of vinylpyridines with aldehydes/ketones NH mediated deoxygenative couplings.

Umpolung (polarity reversal) tactics of aldehydes/ketones have greatly broadened carbonyl chemistry by enabling transformations with electrophilic reagents and deoxygenative functionalizations. Herein, we report the first ruthenium-catalyzed β-selective alkylation of vinylpyridines with both naturally abundant aromatic and aliphatic aldehyde/ketones NH mediated deoxygenative couplings. Compared with one-electron umpolung of carbonyls to alcohols, this two-electron umpolung strategy realized reductive deoxygenation targets, which were not only applicable to the regioselective alkylation of a broad range of 2/4-alkene substituted pyridines, but also amenable to challenging 3-vinyl and steric-embedded internal pyridines as well as their analogous heterocyclic structures.

Palladium-catalyzed hydroalkylation of methylenecyclopropanes with simple hydrazones.

A palladium-catalyzed hydroalkylation reaction of methylenecyclopropanes highly selective C-C σ-bond scission was achieved under mild conditions, in which simple hydrazones served as carbanion equivalents. This method featured good functional group compatibility, affording high yields of C-alkylated terminal alkenes.

Palladium-Catalyzed Defluorinative Alkylation of gem-Difluorocyclopropanes: Switching Regioselectivity via Simple Hydrazones.

Conventional approaches for Pd-catalyzed ring-opening cross-couplings of gem-difluorocyclopropanes with nucleophiles predominantly deliver the β-fluoroalkene scaffolds (linear selectivity). Herein, we report a cooperative strategy that can completely switch the reaction selectivity to give the alkylated α-fluoroalkene skeletons (branched selectivity). The unique reactivity of hydrazones that enables analogous inner-sphere 3,3'-reductive elimination driven by denitrogenation, as well as the assistance of steric-embedded N-heterocyclic carbene ligand, are the key to switch the regioselectivity.

Iron-catalyzed acylation-functionalization of unactivated alkenes with aldehydes.

Herein, an iron-catalyzed acylation-functionalization of unactivated alkenes with aldehydes via distal group ipso-migration is reported. This strategy overcame the energy barrier and reversibility in the difunctionalization of unactivated alkenes with nucleophilic acyl radicals, and a variety of β-heteroarylated, -cyanated and -oximated unsymmetrical 1,6- and 1,7-diketones were obtained regioselectively, chemoselectively and efficiently.

Light-Driven Metal-Free Direct Deoxygenation of Alcohols under Mild Conditions.

Hydroxyl is widely found in organic molecules as functional group and its deprivation plays an inevitable role in organic synthesis. However, the direct cleavage of Csp-O bond in alcohols with high selectivity and efficiency, especially without the assistance of metal catalyst, has been a formidable challenge because of its strong bond dissociation energy and unfavorable thermodynamics. Herein, an efficient metal-free strategy that enables direct deoxygenation of alcohols has been developed for the first time, with hydrazine as the reductant induced by light.

Palladium-Catalyzed Formal Hydroalkylation of Aryl-Substituted Alkynes with Hydrazones.

We have developed an unprecedented Pd-catalyzed formal hydroalkylation of alkynes with hydrazones, which are generated in situ from naturally abundant aldehydes, as both alkylation reagents and hydrogen donors. The hydroalkylation proceeds with high regio- and stereoselectivity to form (Z)-alkenes, which are more difficult to generate compared to (E)-alkenes. The reaction is compatible with a wide range of functional groups, including hydroxy, ester, ketone, nitrile, boronic ester, amine, and halide groups.

Switch in Selectivity for Formal Hydroalkylation of 1,3-Dienes and Enynes with Simple Hydrazones.

Controlling reaction selectivity is a permanent pursuit for chemists. Regioselective catalysis, which exploits and/or overcomes innate steric and electronic bias to deliver diverse regio-enriched products from the same starting materials, represents a powerful tool for divergent synthesis. Recently, the 1,2-Markovnikov hydroalkylation of 1,3-dienes with simple hydrazones was reported to generate branched allylic compounds when a nickel catalyst was used.

Synergistic Relay Reactions To Achieve Redox-Neutral α-Alkylations of Olefinic Alcohols with Ruthenium(II) Catalysis.

Herein, we report a ruthenium-catalyzed redox-neutral α-alkylation of unsaturated alcohols based on a synergistic relay process involving olefin isomerization (chain walking) and umpolung hydrazone addition, which takes advantage of the interaction between the two rather inefficient individual reaction steps to enable an efficient overall process. This transformation shows the compatibility of hydrazone-type "carbanions" and active protons in a one-pot reaction, and at the same time achieves the first Grignard-type nucleophilic addition using olefinic alcohols as latent carbonyl groups, providing a higher yield of the corresponding secondary alcohol than the classical hydrazone addition to aldehydes does. A broad scope of unsaturated alcohols and hydrazones, including some complex structures, can be successfully employed in this reaction, which shows the versatility of this approach and its suitability as an alternative, efficient means for the generation of secondary and tertiary alcohols.