Direct synthesis of branched amines enabled by dual-catalyzed allylic C─H amination of alkenes with amines.

Direct conversion of hydrocarbons into amines represents an important and atom-economic goal in chemistry for decades. However, intermolecular cross-coupling of terminal alkenes with amines to form branched amines remains extremely challenging. Here, a visible-light and Co-dual catalyzed direct allylic C─H amination of alkenes with free amines to afford branched amines has been developed. Notably, challenging aliphatic amines with strong coordinating effect can be directly used as C─N coupling partner to couple with allylic C─H bond to form advanced amines with molecular complexity. Moreover, the reaction proceeds with exclusive regio- and chemoselectivity at more steric hinder position to deliver primary, secondary, and tertiary aliphatic amines with diverse substitution patterns that are difficult to access otherwise.

Unified metal-free intermolecular Heck-type sulfonylation, cyanation, amination, amidation of alkenes by thianthrenation.

Direct and site-selective C-H functionalization of alkenes under environmentally benign conditions represents a useful and attractive yet challenging transformation to access value-added molecules. Herein, a unified protocol for a variety of intermolecular Heck-type functionalizations of Csp2-H bond of alkenes has been developed by thianthrenation. The reaction features metal-free and operationally simple conditions for exclusive cine-selective C-H functionalization of aliphatic and aryl alkenes to forge C-C, C-N, C-P, and C-S bonds at room temperature, providing a general protocol for intermolecular Heck-type reaction of alkenes with nucleophiles (Nu = sulfinates, cyanides, amines, amides). Alkenes undergo cine-sulfonylation, cyanation, amination to afford alkenyl sulfones, alkenyl nitriles and enamines.

Organophotocatalysed synthesis of 2-piperidinones in one step via [1 + 2 + 3] strategy.

Six-membered N-containing heterocycles, such as 2-piperidinone derivatives, with diverse substitution patterns are widespread in natural products, drug molecules and serve as key precursors for piperidines. Thus, the development of stereoselective synthesis of multi-substituted 2-piperidinones are attractive. However, existing methods heavily rely on modification of pre-synthesized backbones which require tedious multi-step procedure and suffer from limited substitution patterns. Herein, an organophotocatalysed [1 + 2 + 3] strategy was developed to enable the one-step access to diverse substituted 2-piperidinones from easily available inorganic ammonium salts, alkenes, and unsaturated carbonyl compounds. This mild protocol exhibits exclusive chemoselectivity over two alkenes, tolerating both terminal and internal alkenes with a wide range of functional groups.

Access to Trifluoromethylketones from Alkyl Bromides and Trifluoroacetic Anhydride by Photocatalysis.

Aliphatic trifluoromethyl ketones are a type of unique fluorine-containing subunit which play a significant role in altering the physical and biological properties of molecules. Catalytic methods to provide direct access to aliphatic trifluoromethyl ketones are highly desirable yet remain underdeveloped, partially owing to the high reactivity and instability of trifluoroacetyl radical. Herein, we report a photocatalytic synthesis of trifluoromethyl ketones from alkyl bromides with trifluoroacetic anhydride. The reaction features dual visible-light and halogen-atom-transfer catalysis, followed by an enabling radical-radical cross-coupling of an alkyl radical with a stabilized trifluoromethyl radical. The reaction provides straightforward access to aliphatic trifluoromethyl ketones from readily available and cost-effective alkyl halides and trifluoroacetic anhydride (TFAA).

Intermolecular Metal-Free Cyclopropanation and Aziridination of Alkenes with XH2 (X=N, C) by Thianthrenation.

Three-membered cyclic structures are widely existing in natural products and serve as enabling intermediates in organic synthesis. However, the efficient and straightforward access to such structures with diversity remains a formidable challenge. Herein, a general and practical protocol to aziridines and cyclopropanes synthesis using free XH2 (X=C or N) with alkenes by thianthrenation is presented. This metal-free protocol features the direct aziridination and cyclopropanation with unprotected XH2 . Free sulfonamides, amides, carbamates, amines, and methylene with acidic protons, are good precursors, providing an attractive alternative for straightforward synthesis of aziridines and cyclopropanes from easily available starting materials.

Synthesis of ß-Thiolated-α-arylated Ketones Enabled by Photoredox and N-Heterocyclic Carbene-Catalyzed Radical Relay of Alkenes with Disulfides and Aldehydes.

ß-Thiolated-α-arylated ketones are perversive in bioactive molecules and serve as potential bidentate ligands for catalysis. Herein, a straightforward protocol to access ß-thiolated ketones from aldehydes, alkenes, and disulfides enabled by the combination of photocatalysis and N-heterocyclic carbene catalysis is reported. The sequential radical addition to alkenes and subsequent radical-radical coupling cascade process simultaneously forge C-S and C-C bonds. The mild conditions allow for radical relay coupling with a broad functional group tolerance.

Metal-free allylic C-H nitrogenation, oxygenation, and carbonation of alkenes by thianthrenation.

Selective functionalization of allylic C-H bonds into other chemical bonds is among the most straightforward and attractive, yet challenging transformations. Herein, a transition-metal-free protocol for direct allylic C-H nitrogenation, oxygenation, and carbonation of alkenes by thianthrenation was developed. This operationally simple protocol allows for the unified allylic C-H amination, esterification, etherification, and arylation of vinyl thianthrenium salts. Notably, the reaction furnishes multialkyl substituted allylic amines, ammonium salts, sulfonyl amides, esters, and ethers in good yields. The reaction proceeds under mild conditions with excellent functional group tolerance and could be applied to late-stage allylation of natural products, drug molecules and peptides with excellent chemoselectivity.

Synthesis of gem-Difluoroalkenes via Zn-Mediated Decarboxylative/Defluorinative Cross-Coupling.

An efficient and mild Zn-mediated decarboxylative/defluorinative alkylation of α-trifluoromethyl alkenes using N-hydroxyphthalimide esters as radical precursors was developed. Several α-trifluoromethyl alkenes were readily coupled to a wide range of primary, secondary, and tertiary radicals, affording the desired gem-difluoroethylenes in moderate to excellent yields. This reaction protocol was also successfully applied to the construction of complex molecules such as the bioactive natural dehydroabietic acid and glycosyl groups bearing the gem-difluoroethylene moiety.

Synthesis of Monofluoroalkenes through Visible-Light-Promoted Defluorinative Alkylation of gem-Difluoroalkenes with 4-Alkyl-1,4-dihydropyridines.

In this study, a facile and efficient method to synthesize monofluoroalkenes by photoredox catalytic defluorinative alkylation of gem-difluoroalkenes with 4-alkyl-1,4-dihydropyridines under mild conditions (room temperature) is described. This novel strategy is applicable for a broad range of gem-difluoroalkene substrates with good functional group tolerance and a variety of 4-alkyl-1,4-dihydropyridines (including primary, secondary, and even tertiary alkyl radicals). Moreover, it also allows the challenging radical coupling with glycosyl-based 4-alkyl-1,4-dihydropyridines (DHPs) to synthesize monofluoroalkenylated saccharides.