A highly selective decarboxylative deuteration of carboxylic acids

In this paper, we report a mild and practical method for precise deuteration of aliphatic carboxylic acids by synergistic photoredox and HAT catalysis. The reaction delivers excellent D-incorporation (up to 99%) at predicted sites even in substrates bearing reactive C–H bonds or versatile functional groups. The use of a recirculation reactor with a peristaltic pump supports a scalable preparative ability (up to 50 mmol) under very mild reaction conditions. The practical and precise deuteration of readily available complex carboxylic acids makes this protocol promising for the preparation of deuterium-labelled compounds.

A scalable, practical and general method for precise deuteration of aliphatic carboxylic acids via synergistic photoredox and HAT catalysis has been developed. The use of recirculation reactor achieved the preparative scale deuteration.     

Suzuki-type cross-coupling of alkyl trifluoroborates with acid fluoride enabled by NHC/photoredox dual catalysis

The Suzuki–Miyaura cross-coupling of C(sp³)-hybridised boronic compounds still remains a challenging task, thereby hindering the broad application of alkyl boron substrates in carbon–carbon bond-forming reactions. Herein, we developed an NHC/photoredox dual catalytic cross-coupling of alkyl trifluoroborates with acid fluorides, providing an alternative solution to the classical acylative Suzuki coupling chemistry. With this protocol, various ketones could be rapidly synthesised from readily available materials under mild conditions. Preliminary mechanistic studies shed light on the unique radical reaction mechanism.

An acylative Suzuki-type cross-coupling of alkyl trifluoroborates and acid fluorides was developed by merging NHC organocatalysis with photoredox catalysis. A broad spectrum of ketones could be facilely synthesised under mild reaction conditions.     

Direct,stereoselective thioglycosylation enabled by an organophotoredox radical strategy

While strategies involving a 2e⁻ transfer pathway have dictated glycosylation development, the direct glycosylation of readily accessible glycosyl donors as radical precursors is particularly appealing because of high radical anomeric selectivity and atom- and step-economy. However, the development of the radical process has been challenging owing to notorious competing reduction, elimination and/or S_N side reactions of commonly used, labile glycosyl donors. Here we introduce an organophotocatalytic strategy through which glycosyl bromides can be efficiently converted into corresponding anomeric radicals by photoredox mediated HAT catalysis without a transition metal or a directing group and achieve highly anomeric selectivity. The power of this platform has been demonstrated by the mild reaction conditions enabling the synthesis of challenging α-1,2-cis-thioglycosides, the tolerance of various functional groups and the broad substrate scope for both common pentoses and hexoses. Furthermore, this general approach is compatible with both sp² and sp³ sulfur electrophiles and late-stage glycodiversification for a total of 50 substrates probed.

Organophotoredox mediated HAT catalysis is developed for achieving high anomerically selective thioglycosylation of glycosyl bromides.     

Allylic C(sp3)–H alkylation via synergistic organo- and photoredox catalyzed radical addition to imines

A new catalytic method for the direct alkylation of allylic C(sp³)–H bonds from unactivated alkenes via synergistic organo- and photoredox catalysis is described. The transformation achieves an efficient, redox-neutral synthesis of homoallylamines with broad functional group tolerance, under very mild reaction conditions. Mechanistic investigations indicate that the reaction proceeds through the N-centered radical intermediate which is generated by the allylic radical addition to the imine.

A new catalytic method for the direct alkylation of allylic C(sp³)–H bonds from unactivated alkenes via synergistic organo- and photoredox catalysis is described.     

Cyanine-based near infra-red organic photoredox catalysis

Direct metal-free near infra-red photoredox catalysis is applied to organic oxidation, photosensitization and reduction, involving cyanines as photocatalysts. This photocatalyst is competitive with conventional reactions catalyzed under visible light. Kinetic and quenching experiments are also reported. Interestingly, these systems are compatible with water media, opening perspective for various applications.

Direct metal-free near infra-red photoredox catalysis is applied to oxidation, reduction and photosensitization, involving cyanines as photocatalysts. Mechanistic insights through kinetic and quenching experiments are also reported.     

Photocatalytic redox-neutral hydroxyalkylation of N-heteroaromatics with aldehydes

Hydroxyalkylation of N-heteroaromatics with aldehydes was achieved using a binary hybrid catalyst system comprising an acridinium photoredox catalyst and a thiophosphoric acid organocatalyst. The reaction proceeded through the following sequence: (1) photoredox-catalyzed single-electron oxidation of a thiophosphoric acid catalyst to generate a thiyl radical, (2) cleavage of the formyl C–H bond of the aldehyde substrates by a thiyl radical acting as a hydrogen atom transfer catalyst to generate acyl radicals, (3) Minisci-type addition of the resulting acyl radicals to N-heteroaromatics, and (4) a spin-center shift, photoredox-catalyzed single-electron reduction, and protonation to produce secondary alcohol products. This metal-free hybrid catalysis proceeded under mild conditions for a wide range of substrates, including isoquinolines, quinolines, and pyridines as N-heteroaromatics, as well as both aromatic and aliphatic aldehydes, and tolerated various functional groups. The reaction was applicable to late-stage derivatization of drugs and their leads.

Hydroxyalkylation of N-heteroaromatics with aldehydes was achieved using a binary hybrid catalyst system comprising an acridinium photoredox catalyst and a thiophosphoric acid organocatalyst.     

Light opens a new window for N-heterocyclic carbene catalysis

N-Heterocyclic carbenes (NHCs) are efficient Lewis basic catalysts for the umpolung of various polarized unsaturated compounds usually including aldehydes, imines, acyl chlorides and activated esters. NHC catalysis involving electron pair transfer steps has been extensively studied; however, NHC catalysis through single-electron transfer (SET) processes, despite having the potential to achieve chemical transformations of inert chemical bonds and using green reagents, has long been a challenging task in organic synthesis. In parallel, visible-light-induced photocatalysis and photoexcitation have been established as powerful tools to facilitate sustainable organic synthesis, as they enable the generation of various reactive radical intermediates under extremely mild conditions. Recently, a number of elegant visible-light-induced, NHC-catalyzed transformations were developed for accessing valuable organic compounds. As a result, this minireview will highlight the recent advances in this field.

This minireview summarized the recent advances on the photoinduced, NHC-catalyzed organic reactions according to the function of visible light.     

Ceramic boron carbonitrides for unlocking organic halides with visible light

Photochemistry provides a sustainable pathway for organic transformations by inducing radical intermediates from substrates through electron transfer process. However, progress is limited by heterogeneous photocatalysts that are required to be efficient, stable, and inexpensive for long-term operation with easy recyclability and product separation. Here, we report that boron carbonitride (BCN) ceramics are such a system and can reduce organic halides, including (het)aryl and alkyl halides, with visible light irradiation. Cross-coupling of halides to afford new C–H, C–C, and C–S bonds can proceed at ambient reaction conditions. Hydrogen, (het)aryl, and sulfonyl groups were introduced into the arenes and heteroarenes at the designed positions by means of mesolytic C–X (carbon–halogen) bond cleavage in the absence of any metal-based catalysts or ligands. BCN can be used not only for half reactions, like reduction reactions with a sacrificial agent, but also redox reactions through oxidative and reductive interfacial electron transfer. The BCN photocatalyst shows tolerance to different substituents and conserved activity after five recycles. The apparent metal-free system opens new opportunities for a wide range of organic catalysts using light energy and sustainable materials, which are metal-free, inexpensive and stable.

A metal-free photoredox system was introduced for the transformation of organic halides to afford C–H, C–C, and C–S bonds without the addition of any metals, ligands, extra reductants or additives.     

Regiodivergent sulfonylarylation of 1,3-enynes via nickel/photoredox dual catalysis

Catalytic difunctionalization of 1,3-enynes represents an efficient and versatile approach to rapidly assemble multifunctional propargylic compounds, allenes and 1,3-dienes. Controlling selectivity in such addition reactions has been a long-standing challenging task due to multiple reactive centers resulting from the conjugated structure of 1,3-enynes. Herein, we present a straightforward method for regiodivergent sulfonylarylation of 1,3-enynes via dual nickel and photoredox catalysis. Hinging on the nature of 1,3-enynes, diverse reaction pathways are feasible: synthesis of α-allenyl sulfones via 1,4-sulfonylarylation, or preparation of (E)-1,3-dienyl sulfones with high chemo-, regio- and stereoselectivity through 3,4-sulfonylarylation. Notably, this is the first example that nickel and photoredox catalysis are merged to achieve efficient and versatile difunctionalization of 1,3-enynes.

A mild reaction protocol for regiodivergent sulfonylarylation of 1,3-enynes via dual nickel and photoredox catalysis has been developed, which led to efficient synthesis of α-allenyl sulfones or 1,3-dienyl sulfones.     

Selective α,δ-hydrocarboxylation of conjugated dienes utilizing CO2 and electrosynthesis

To date the majority of diene carboxylation processes afford the α,δ-dicarboxylated product, the selective mono-carboxylation of dienes is a significant challenge and the major product reported under transition metal catalysis arises from carboxylation at the α-carbon. Herein we report a new electrosynthetic approach, that does not rely on a sacrificial electrode, the reported method allows unprecedented direct access to carboxylic acids derived from dienes at the δ-position. In addition, the α,δ-dicarboxylic acid or the α,δ-reduced alkene can be easily accessed by simple modification of the reaction conditions.

Selective electrosynthetic α,δ-hydrocarboxylation of 1,3-dienes is reported, utilising non-sacrificial electrodes that provide access to the previously challenging δ-carboxylated regioisomer.     

GaN nanowires as a reusable photoredox catalyst for radical coupling of carbonyl under blacklight irradiation

Employing photo-energy to drive the desired chemical transformation has been a long pursued subject. The development of homogeneous photoredox catalysts in radical coupling reactions has been truly phenomenal, however, with apparent disadvantages such as the difficulty in separating the catalyst and the frequent requirement of scarce noble metals. We therefore envisioned the use of a hyper-stable III–V photosensitizing semiconductor with a tunable Fermi level and energy band as a readily isolable and recyclable heterogeneous photoredox catalyst for radical coupling reactions. Using the carbonyl coupling reaction as a proof-of-concept, herein, we report a photo-pinacol coupling reaction catalyzed by GaN nanowires under ambient light at room temperature with methanol as a solvent and sacrificial reagent. By simply tuning the dopant, the GaN nanowire shows significantly enhanced electronic properties. The catalyst showed excellent stability, reusability and functional tolerance. All reactions could be accomplished with a single piece of nanowire on Si-wafer.

A highly efficient re-usable semiconductor as a radical coupling catalyst in MeOH.     

The Morita–Baylis–Hillman reaction for non-electron-deficient olefins enabled by photoredox catalysis

A strategy for overcoming the limitation of the Morita–Baylis–Hillman (MBH) reaction, which is only applicable to electron-deficient olefins, has been achieved via visible-light induced photoredox catalysis in this report. A series of non-electron-deficient olefins underwent the MBH reaction smoothly via a novel photoredox-quinuclidine dual catalysis. The in situ formed key β-quinuclidinium radical intermediates, derived from the addition of olefins with quinuclidinium radical cations, are used to enable the MBH reaction of non-electron-deficient olefins. On the basis of previous reports, a plausible mechanism is suggested. Mechanistic studies, such as radical probe experiments and density functional theory (DFT) calculations, were also conducted to support our proposed reaction pathways.

A strategy for overcoming the limitation of the Morita–Baylis–Hillman (MBH) reaction, which is only applicable to electron-deficient olefins, has been achieved via visible-light induced photoredox catalysis in this report.     

Sequential C–O decarboxylative vinylation/C–H arylation of cyclic oxalates via a nickel-catalyzed multicomponent radical cascade

A selective, sequential C–O decarboxylative vinylation/C–H arylation of cyclic alcohol derivatives enabled by visible-light photoredox/nickel dual catalysis is described. This protocol utilizes a multicomponent radical cascade process, i.e. decarboxylative vinylation/1,5-HAT/aryl cross-coupling, to achieve efficient, site-selective dual-functionalization of saturated cyclic hydrocarbons in one single operation. This synergistic protocol provides straightforward access to sp³-enriched scaffolds and an alternative retrosynthetic disconnection to diversely functionalized saturated ring systems from the simple starting materials.

A selective, sequential C–O decarboxylative vinylation/C–H arylation of cyclic alcohol derivatives enabled by visible-light photoredox/nickel dual catalysis has been described.     

Stereoselective synthesis of unnatural α-amino acid derivatives through photoredox catalysis

A protocol for stereoselective C-radical addition to a chiral glyoxylate-derived N-sulfinyl imine was developed through visible light-promoted photoredox catalysis, providing a convenient method for the synthesis of unnatural α-amino acids. The developed protocol allows the use of ubiquitous carboxylic acids as radical precursors without prior derivatization. The protocol utilizes near-stoichiometric amounts of the imine and the acid radical precursor in combination with a catalytic amount of an organic acridinium-based photocatalyst. Alternative mechanisms for the developed transformation are discussed and corroborated by experimental and computational studies.

A protocol for stereoselective C-radical addition to a chiral glyoxylate-derived N-sulfinyl imine was developed through visible light-promoted photoredox catalysis, providing a convenient method for the synthesis of unnatural α-amino acids.     

A visible-light mediated ring opening reaction of alkylidenecyclopropanes for the generation of homopropargyl radicals

Classical cyclopropylcarbinyl radical clock reactions have been widely applied to conduct mechanistic studies for probing radical processes for a long time; however, alkylidenecyclopropanes, which have a similar molecular structure to methylcyclopropanes, surprisingly have not yet attracted researcher''s attention for similar ring opening radical clock processes. In recent years, photocatalytic NHPI ester activation chemistry has witnessed significant blooming developments and provided new synthetic routes for cross-coupling reactions. Herein, we wish to report a non-classical ring opening radical clock reaction using innovative NHPI esters bearing alkylidenecyclopropanes upon photoredox catalysis, providing a brand-new synthetic approach for the direct preparation of a variety of alkynyl derivatives. The potential synthetic utility of this protocol is demonstrated in the diverse transformations and facile synthesis of bioactive molecules or their derivatives and medicinal substances.

A non-classical ring opening radical clock reaction using the innovative NHPI esters bearing alkylidenecyclopropanes upon photoredox catalysis has been demonstrated, providing a brand-new synthetic approach to access a variety of alkynyl derivatives.     

Directed Markovnikov hydroarylation and hydroalkenylation of alkenes under nickel catalysis

We report a full account of our research on nickel-catalyzed Markovnikov-selective hydroarylation and hydroalkenylation of non-conjugated alkenes, which has yielded a toolkit of methods that proceed under mild conditions with alkenyl sulfonamide, ketone, and amide substrates. Regioselectivity is controlled through catalyst coordination to the native Lewis basic functional groups contained within these substrates. To maximize product yield, reaction conditions were fine-tuned for each substrate class, reflecting the different coordination properties of the directing functionality. Detailed kinetic and computational studies shed light on the mechanism of this family of transformations, pointing to transmetalation as the turnover-limiting step.

Native Lewis basic functional groups enable the nickel-catalyzed Markovnikov-selective hydroarylation and hydroalkenylation of unactivated alkenes with organoboron reagents.     

Strain-release 2-azaallyl anion addition/borylation of [1.1.1]propellane: synthesis and functionalization of benzylamine bicyclo[1.1.1]pentyl boronates

We report a 3-component reaction between N-benzyl ketimines, [1.1.1]propellane, and pinacol boronates to generate benzylamine bicyclo[1.1.1]pentane (BCP) pinacol boronates. These structures are analogous to highly sought diarylmethanamine cores, which are common motifs in bioactive molecules. We demonstrate the versatility of the boronate ester handle via downstream functionalization through a variety of reactions, including a challenging Pd-catalyzed (hetero)arylation that exhibits a broad substrate scope. Together, these methods enable the synthesis of high-value BCP benzylamines which are inaccessible by existing methods. Furthermore, we demonstrate the successful application of these newly developed (hetero)arylation conditions to a variety of challenging tertiary pinacol boronates, including nitrogen-containing heterocycles, 1,1-disubstituted cyclopropanes, and other BCP cores.

We report a 3-component reaction between N-benzyl ketimines, [1.1.1]propellane, and pinacol boronates to generate benzylamine bicyclo[1.1.1]pentane (BCP) pinacol boronates.     

Asymmetric β-arylation of cyclopropanols enabled by photoredox and nickel dual catalysis

The enantioselective functionalization and transformation of readily available cyclopropyl compounds are synthetically appealing yet challenging topics in organic synthesis. Here we report an asymmetric β-arylation of cyclopropanols with aryl bromides enabled by photoredox and nickel dual catalysis. This dual catalytic transformation features a broad substrate scope and good functional group tolerance at room temperature, providing facile access to a wide array of enantioenriched β-aryl ketones bearing a primary alcohol moiety in good yields with satisfactory enantioselectivities (39 examples, up to 83% yield and 90% ee). The synthetic value of this protocol was illustrated by the concise asymmetric construction of natural product calyxolane B analogues.

An asymmetric β-arylation of cyclopropanols with aryl bromides was enabled by enantioselective photoredox and nickel dual catalysis.     

Mapping the multi-step mechanism of a photoredox catalyzed atom-transfer radical polymerization reaction by direct observation of the reactive intermediates

The rapid development of new applications of photoredox catalysis has so far outpaced the mechanistic studies important for rational design of new classes of catalysts. Here, we report the use of ultrafast transient absorption spectroscopic methods to reveal both mechanistic and kinetic details of multiple sequential steps involved in an organocatalyzed atom transfer radical polymerization reaction. The polymerization system studied involves a N,N-diaryl dihydrophenazine photocatalyst, a radical initiator (methyl 2-bromopropionate) and a monomer (isoprene). Time-resolved spectroscopic measurements spanning sub-picosecond to microseconds (i.e., almost 8 orders of magnitude of time) track the formation and loss of key reactive intermediates. These measurements identify both the excited state of the photocatalyst responsible for electron transfer and the radical intermediates participating in propagation reactions, as well as quantifying their lifetimes. The outcomes connect the properties of N,N-diaryl dihydrophenazine organic photocatalysts with the rates of sequential steps in the catalytic cycle.

Short-lived intermediates are tracked in real-time by transient absorption spectroscopy during a multi-step photoredox catalysed polymerization reaction.     

Design,scope and mechanism of highly active and selective chiral NHC–iridium catalysts for the intramolecular hydroamination of a variety of unactivated aminoalkenes

Chiral, cationic NHC–iridium complexes are introduced as catalysts for the intramolecular hydroamination reaction of unactivated aminoalkenes. The catalysts show high activity in the construction of a range of 5- and 6-membered N-heterocycles, which are accessed in excellent optical purity, with various functional groups being tolerated with this system. A major deactivation pathway is presented and eliminated by using alternative reaction conditions. A detailed experimental and computational study on the reaction mechanism is performed providing valuable insights into the mode of action of the catalytic system and pointing to future modifications to be made for this catalytic platform.

Chiral, cationic NHC–iridium complexes are introduced as catalysts for the intramolecular hydroamination reaction of unactivated aminoalkenes.