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.

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.