Copper-Catalyzed Radical Allene C(sp2 )-H Cyanation.

While the hydrogen atom abstraction (HAA) from C(sp3 )-H bond has been well explored, the radical-mediated chemo- and regio-selective functionalization of allenic C(sp2 )-H bond via direct HAA from C(sp2 )-H bond of allene remains an unsolved challenge in synthetic chemistry. This is primarily due to inherent challenges with addition of radical intermediates to allenes, regioselectivity of HAA process, instability of allenyl radical toward propargyl radical et al. Herein, we report a copper catalyzed allenic C(sp2 )-H cyanation of an array of tri- and di-substituted allenes with exceptional site-selectivity, while mono-substituted allene was successfully cyanated, albeit with a low yield. In the developed strategy, steric N-fluoro-N-alkylsulfonamide, serving as precursor of hydrogen atom abstractor, plays a crucial role in achieving the desired regioselectivity and avoiding addition of N-centered radical to allene.

Visible-Light-Promoted Cyanoalkylation/Cyclization Cascade Reaction to Assemble Polyheterocycles in Continuous Flow.

This study describes a visible-light-induced cascade reaction for preparing cyanoalkyl-containing polyheterocycles initiated by the photoinduced radical cascade addition of N-arylacrylamide derivatives using cyclic oxime esters as radical sources followed by cyanoalkyl-mediated cyclization. This protocol features outstanding functional group compatibility, providing a variety of desired phenanthridine derivatives in moderate to good yields. Moreover, the application of a microflow technique enhanced these reactions compared with the equivalent batch reaction, significantly reducing reaction times to 10 min.

Electrochemical Tri- and Difluoromethylation-Triggered Cyclization Accompanied by the Oxidative Cleavage of Indole Derivatives.

Considering their unique roles in organic synthesis, and pharmaceutical and agrochemical applications, the development of fluoroalkylation, cyclization, and indole oxidative cleavage are important topics. Herein, an unprecedented electrochemical tri- and difluoromethylation/cyclization/indole oxidative cleavage process occurring in an undivided cell is presented. The protocol employs a readily prepared Langlois reagent as the fluoroalkyl source, affording a series of tri- or difluoromethylated 2-(2-acetylphenyl)isoquinoline-1,3-diones in good yields with excellent stereoselectivity. It is worth noting that this new methodology merges the fluoroalkylation/cyclization of N-substituted acrylamide alkenes with the oxidative cleavage of an indole C(2)=C(3) bond under external oxidant-free conditions.

I2-Catalyzed Multicomponent Reactions for Accessing Densely Functionalized Pyrazolo[1,5-a]pyrimidines and Their Disulphenylated Derivatives.

New I2-catalyzed multicomponent bicyclization reactions of ß-ketonitriles with sulfonyl hydrazides have been established, providing a direct and metal-free access toward unreported pyrazolo[1,5-a]pyrimidin-4-ium sulfonates. The latter could be quantitatively converted into densely functionalized pyrazolo[1,5-a]pyrimidines in the presence of bases. Using sulfonyl hydrazides as a sulfenylating agent, the resulting pyrazolo[1,5-a]pyrimidines enabled I2-catalyzed unprecedented disulphenylations to access fully substituted pyrazolo[1,5-a]pyrimidines through direct C(sp(2))-H bond bifunctionalization.

Catalytic Dual 1,1-H-Abstraction/Insertion for Domino Spirocyclizations.

A catalytic domino spirocyclization of 1,7-enynes with simple cycloalkanes and cyclo-1,3-dicarbonyls has been established via multiple C-C bond formations from alkynyl/alkenyl functions and dual α,α-C(sp(3))-H abstraction/insertion. The reaction involves addition, 6-exo-dig cyclization and radical coupling sequences under convenient catalytic conditions and provides a concise access to spiro cyclopenta[c]quinolines in good to excellent yields.

Metal-Free Iodine-Catalyzed Synthesis of Fully Substituted Pyrazoles and Its Sulphenylation.

A direct and metal-free access toward fully substituted pyrazoles and its sulphenylation has been established through an iodine-mediated three-component [3 + 2] annulation of ß-ketonitrile (or pentane-2,4-dione), arylhydrazines, and aryl sulfonyl hydrazides. The reaction allows the formation of one C-S and two C-N bonds by the multiple bond cleavage including sulfur-oxygen, sulfur-nitrogen, and carbon-oxygen bonds. The method features low-cost and readily accessible substrates, bond-forming efficiency, and broad substrate scopes as well as simple one-pot operation, which makes this strategy highly attractive.

2-(Hy-droxy-meth-yl)pyridin-3-ol.

In the crystal structure of the title compound, C(6)H(7)NO(2), the mol-ecules are are linked by inter-molecular O-H⋯N and O-H⋯O hydrogen bonds; π-π stacking is observed between parallel pyridine rings of adjacent mol-ecules [centroid-to-centroid distance = 3.7649 (12) Å].

rac-Methyl 2-(2-formyl-4-nitro-phen-oxy)hexa-noate.

In the racemic title compound, C(14)H(17)NO(6), the plane of the ester group of the methyl hexa-noate side chain makes a dihedral angle of 80.0 (2)° with the benzene ring, while the nitro group is approximately coplanar with the benzene ring [dihedral angle = 10.3 (2)°]. In the crystal, mol-ecules form weak aromatic C-H⋯O(nitro) hydrogen-bonding inter-actions, giving inversion dimers [graph set R(2) (2)(8)].

5-Methyl-N-[2-(trifluoro-meth-yl)phen-yl]isoxazole-4-carboxamide.

In the title compound, C(12)H(9)F(3)N(2)O(2), the benzene ring is nearly perpendicular to the isoxazole ring, making a dihedral angle of 82.97 (2)°. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds into a supra-molecular chain running along the c axis.

N-(2,4-Difluoro-phen-yl)-5-methyl-1,2-oxazole-4-carboxamide hemihydrate.

In the title compound, C(11)H(8)F(2)N(2)O(2)·0.5H(2)O, the dihedral angle between the benzene and isoxazole rings is 8.08 (3)°. In the crystal, the components are linked by O-H⋯N and N-H⋯O hydrogen bonds, in which the water mol-ecule acts as both a donor and an acceptor, into a tape with an R(4) (4)(16) graph-set motif along the a axis. The water mol-ecule is located on a twofold rotation axis. The methyl H atoms were treated as disordered groups over two sites with a refined site-occupancy ratio of 0.48 (6):0.52 (6).

Visible-Light Photocatalytic Tri- and Difluoroalkylation Cyclizations: Access to a Series of Indole[2,1-a]isoquinoline Derivatives in Continuous Flow.

A process for achieving photocatalyzed tri- and difluoromethylation/cyclizations for constructing a series of tri- or difluoromethylated indole[2,1-a]isoquinoline derivatives is described. This protocol utilized an inexpensive organic photoredox catalyst and provided good yields. Moreover, the combination of continuous flow and photochemistry, designed to provide researchers with a unique green process, was also shown to be key to allowing the reaction to proceed (product yield of 83% in flow vs 0% in batch).

Photocatalytic radical defluoroalkylation of unactivated alkenes via distal heteroaryl ipso-migration.

Currently, the selective activation of C(sp3)-F bonds and C-C bonds constitute one of the most widely used procedures for the synthesis of high-value products that range from pharmaceuticals to agrochemical applications. While numerous examples of these two methods have been reported in their respective fields, the processes which merge the activation of both single C(sp3)-F bonds and C-C bonds in one step still remain elusive. Here, we demonstrate the controllable defluoroalkylation-distal functionalization of trifluoromethylarenes with unactivated alkenes via distal heteroaryl migration. This is proposed to proceed via tandem C(sp3)-F and C-C bond cleavage using visible-light photoredox catalysis combined with Lewis acid activation. This strategy provides facile and flexible access to multiply functionalized α,α-difluorobenzylic ketones in useful yields (up to 88%) under mild conditions. The products can be further transformed into other valuable compounds, demonstrating the method's utility.

Electrochemical Sulfonylation/Heteroarylation of Alkenes via Distal Heteroaryl ipso-Migration.

A direct electrooxidative sulfonylation/heteroarylation reaction of alkenes with sulfinic acids, which proceeds through distal heteroaryl ipso-migration and C-S and C-C bond formations, is reported. This electro-synthetic method offers an efficient and environmentally friendly entry to prepare various sulfonated functionalized heteroarenes under an undivided cell at room temperature, avoiding the use of any metal catalysts, additives, and oxidants. Preliminary mechanistic studies indicated a radical pathway.

Silver-Mediated Radical C(sp3)-H Biphosphinylation and Nitration of ß-Alkynyl Ketones for Accessing Functional Isochromenes.

Silver-mediated C(sp3)-H functionalization and 6-endo-dig oxo-cyclization of conjugated ß-alkynyl ketones have been established under oxidative conditions. The reaction leads to the concise formation of a wide range of isochromenes via C(sp3)-H bond-breaking and radical addition steps. Dual and monofunctional isochromene products were selectively controlled by using either electron-rich or electron-deficient radical sources.

A new cascade halosulfonylation of 1,7-enynes toward 3,4-dihydroquinolin-2(1H)-ones via sulfonyl radical-triggered addition/6-exo-dig cyclization.

A new cascade three-component halosulfonylation of 1,7-enynes for efficient synthesis of densely functionalized 3,4-dihydroquinolin-2(1H)-ones has been established from readily accessible arylsulfonyl hydrazides and NIS (or NBS). The reaction pathway involves in situ-generated sulfonyl radical-triggered α,ß-conjugated addition/6-exo-dig cyclization/radical coupling sequence, resulting in continuous multiple bond-forming events including C-S, C-C and C-I (or C-Br) bonds to rapidly build up molecular complexity.

Catalytic Arylsulfonyl Radical Triggered 1,7-Enyne Bicyclizations.

A new metal-free bicyclization reaction of 1,7-enynes anchored by α,ß-conjugates with arylsulfonyl radicals generated in situ from sulfonyl hydrazides has been established using tert-butyl hydroperoxide and tetrabutylammonium iodide. The reactions occurred through sulfonylation/6-exo-dig/6-exo-trig bicyclization/in situ desulfonylation/5-exo-trig cyclization/alkyl or alkenyl migration cascade mechanism to give benzo[j]phenanthridines regioselectively.

Selective sulfonylation and diazotization of indoles.

A metal-free synthesis of bifunctionalized indole derivatives was developed through a novel TBHP/TBAI-mediated oxidative coupling of C2,C3-unsubstituted indoles with arylsulfonyl hydrazide. Under the same conditions C3-methyl substituted indoles underwent a diazotization process, affording 2-sulfonyldiazenyl-1H-indoles. The former reaction simultaneously established C-S and C-N bonds through selective sulfonylation and diazotization of the indole framework, enabling a mild and practical access to polyfunctionalized indoles with good to excellent yields.