The merging of click chemistry with discrete photochemical processes has led to the creation of a new class of click reactions, collectively known as photoclick chemistry. These light-triggered click reactions allow the synthesis of diverse organic structures in a rapid and precise manner under mild conditions. Because light offers unparalleled spatiotemporal control over the generation of the reactive intermediates, photoclick chemistry has become an indispensable tool for a wide range of spatially addressable applications including surface functionalization, polymer conjugation and cross-linking, and biomolecular labeling in the native cellular environment. Over the past decade, a growing number of photoclick reactions have been developed, especially those based on the 1,3-dipolar cycloadditions and Diels-Alder reactions owing to their excellent reaction kinetics, selectivity, and biocompatibility. This review summarizes the recent advances in the development of photoclick reactions and their applications in chemical biology and materials science. A particular emphasis is placed on the historical contexts and mechanistic insights into each of the selected reactions. The in-depth discussion presented here should stimulate further development of the field, including the design of new photoactivation modalities, the continuous expansion of λ-orthogonal tandem photoclick chemistry, and the innovative use of these unique tools in bioconjugation and nanomaterial synthesis.

Light-Triggered Click Chemistry.

In this paper, a novel and efficient synthesis of 2-alkenylindoles and 2-alkenylindole-3-carboxylates via the cascade reactions of N-nitrosoanilines with propargyl alcohols is presented. Mechanistically, the formation of the title compounds is triggered by a Rh(III)-catalyzed C(sp2)–H alkenylation of N-nitrosoaniline with propargyl alcohol followed by the simultaneous intramolecular amination/cyclization, NO extrusion, and dehydration. With this method, a variety of diversely substituted 2-alkenylindole derivatives were prepared in good efficiency and exclusive site-selectivity. To the best of our knowledge, this is the first example in which the indoyl and the alkenyl units are formed sequentially in one pot from halide-free substrates through a redox neutral C–H bond activation. In addition, the utility of the 2-alkenylindole products thus obtained was remarkably showcased by their facile transformations into synthetically and biologically significant compounds such as 2-acylindole, benzocarbazole, indo...

Regioselective Synthesis of 2-Alkenylindoles and 2-Alkenylindole-3-carboxylates through the Cascade Reactions of N-Nitrosoanilines with Propargyl Alcohols.

Enantioenriched indole derivatives are widely found in natural products, pharmaceuticals and bioactive compounds. Therefore, developing efficient methods for the synthesis of enantioenriched indole derivatives has become an important goal in the community of organic chemistry. To this end, chemists have designed and developed a variety of indole-containing platform molecules and their related catalytic asymmetric reactions. Among these approaches, vinylindoles have proved to be versatile platform molecules for accessing enantioenriched indole derivatives via catalytic asymmetric reactions, especially organocatalytic asymmetric reactions. Based on this approach, a plethora of chiral indole derivatives have been synthesized with optical purity and structural complexity. This review summarizes advances in vinylindole-based organocatalytic asymmetric reactions since 2008 and includes the applications of some methodologies in the total synthesis of natural products. In addition, this review points out the remaining challenges in this research area to be confronted by organic chemists, which will shed light on the future development of this area.

Advances in organocatalytic asymmetric reactions of vinylindoles: powerful access to enantioenriched indole derivatives

Light-mediated coupling of acylsilanes with indoles is reported. This photo click reaction occurs under mild conditions (415 nm) mostly in quantitative yield and provides stable silylated N,O-acetals via light mediated siloxycarbene generation with subsequent indole-N-H insertion. We show that this very efficient and fully atom economic coupling process can be applied to conjugate complex systems, as documented by the clicking of carbohydrates with indole alkaloids. The method is also applicable to the conjugation of polymer chains. The linking acetal moiety can be readily cleaved and it is also shown that wavelength-selective coupling and cleavage with acyl silanes bearing a second photoactive moiety is possible. This is documented by a successful polymerization/depolymerization sequence and by a polymer folding/unfolding process.

Photo Click Reaction of Acylsilanes with Indoles.

Hydrogen-bonding organocatalysts L-pyroglutamic sulphonamides were readily synthesized for the first time by fully exploiting the potentials of L-pyroglutamic acid. The newly designed catalyst was successfully applied in catalyzing asymmetric Diels–Alder cyclization of methyleneindolinones with 2-vinyl-1H-indoles to efficiently assemble carbazolespirooxindoles in excellent stereoselectivity (up to 99% ee, >20:1 dr) and yields (up to 99%). Mechanistic studies disclosed that the well-designed hydrogen-bonding modes between L-pyroglutamic sulphonamide and substrates were crucial for stereocontrol in the cyclization.

L-Pyroglutamic Sulphonamide as Hydrogen-Bonding Organocatalyst: Enantioselective Diels–Alder Cyclization to Construct Carbazolespirooxindoles

Synthesis of Indole Substituted Twistenediones from a 2-Quinonyl Boronic Acid

Quinones were firstly used as dipolarophiles in a photoclick 1,3-cycloaddition with 2,5-diaryltetrazoles, as photoactivatable predipoles, providing a novel and efficient access to three types of pyrazole-fused quinones (indazoledione derivatives). Distinctive features of this protocol include the use of light as the unique reagent and readily available, stable, and easy to handle starting materials and good to excellent yields. Photophysical and electrochemical properties of the quinones and their potential application as photoredox catalysts are also detailed.

Light‐Induced Tetrazole‐Quinone 1,3‐Dipolar Cycloadditions

A general synthetic route to γ-oxo alkyl or α-hydroxy benzyl 2-substituted benzoquinones has been developed through a one-pot Rh-catalyzed C–C bond formation/oxidative demethylation sequence from 2,5-dimethoxy aryl boronic acids and several electron deficient alkenes or aldehydes. The process allows rapid access to functionalized benzoquinones under very mild conditions and good yields. We disclose the first example of a Rh-catalyzed 1,4-addition reaction of benzoquinonyl boronic acid to methyl vinyl ketone and other conjugate acceptors, which allows the direct synthesis of 2-(γ-functionalized alkyl) substituted benzoquinones.

Jaime Rojas-Martín

Papers

Synthesis of Indole Substituted Twistenediones from a 2-Quinonyl Boronic Acid

Light‐Induced Tetrazole‐Quinone 1,3‐Dipolar Cycloadditions

Synthesis of functionalized alkyl substituted benzoquinones by Rh-catalyzed additions of boronic acids