Recent Advances in Photoinduced Oxidative Cleavage of Alkenes.

Oxidative cleavage of alkenes leading to valuable carbonyl derivatives is a fundamental transformation in synthetic chemistry. In particular, ozonolysis is the mainstream method for the oxidative cleavage of alkenes that has been widely implemented in the synthesis of natural products and pharmaceutically relevant compounds. However, due to the toxicity and explosive nature of ozone, alternative approaches employing transition metals and enzymes in the presence of oxygen and/or strong oxidants have been developed.

Aziridination via Nitrogen-Atom Transfer to Olefins from Photoexcited Azoxy-Triazenes.

Herein, we report that readily accessible azoxy-triazenes can serve as nitrogen atom sources under visible light excitation for the phthalimido-protected aziridination of alkenes. This approach eliminates the need for external oxidants, precious transition metals, and photocatalysts, marking a departure from conventional methods. The versatility of this transformation extends to the selective aziridination of both activated and unactivated multisubstituted alkenes of varying electronic profiles.

Identifying general reaction conditions by bandit optimization.

Reaction conditions that are generally applicable to a wide variety of substrates are highly desired, especially in the pharmaceutical and chemical industries. Although many approaches are available to evaluate the general applicability of developed conditions, a universal approach to efficiently discover these conditions during optimizations is rare. Here we report the design, implementation and application of reinforcement learning bandit optimization models to identify generally applicable conditions by efficient condition sampling and evaluation of experimental feedback.

Photoinduced Nitroarenes as Versatile Anaerobic Oxidants for Accessing Carbonyl and Imine Derivatives.

Herein, we report a protocol for the anaerobic oxidation of alcohols, amines, aldehydes, and imines promoted by photoexcited nitroarenes. Mechanistic studies support the idea that photoexcited nitroarenes undergo double hydrogen atom transfer (HAT) steps with alcohols and amines to provide the respective ketone and imine products. In the presence of aldehydes and imines, successive HAT and oxygen atom transfer (OAT) events occur to yield carboxylic acids and amides, respectively.

Anaerobic Hydroxylation of C(sp)-H Bonds Enabled by the Synergistic Nature of Photoexcited Nitroarenes.

A photoexcited-nitroarene-mediated anaerobic C-H hydroxylation of aliphatic systems is reported. The success of this reaction is due to the bifunctional nature of the photoexcited nitroarene, which serves as the C-H bond activator and the oxygen atom source. Compared to previous methods, this approach is cost- and atom-economical due to the commercial availability of the nitroarene, the sole mediator of the reaction.

Photoinduced Oxygen Transfer Using Nitroarenes for the Anaerobic Cleavage of Alkenes.

Herein we report the anaerobic cleavage of alkenes into carbonyl compounds using nitroarenes as oxygen transfer reagents under visible light. This approach serves as a safe and practical alternative to mainstream oxidative cleavage protocols, such as ozonolysis and the Lemieux-Johnson reaction. A wide range of alkenes possessing oxidatively sensitive functionalities underwent anaerobic cleavage to generate carbonyl derivatives with high efficiency and regioselectivity.

Ni/Photoredox-Catalyzed Enantioselective Cross-Electrophile Coupling of Styrene Oxides with Aryl Iodides.

A Ni/photoredox-catalyzed enantioselective reductive coupling of styrene oxides and aryl iodides is reported. This reaction affords access to enantioenriched 2,2-diarylalcohols from racemic epoxides via a stereoconvergent mechanism. Multivariate linear regression (MVLR) analysis with 29 bioxazoline (BiOx) and biimidazoline (BiIm) ligands revealed that enantioselectivity correlates with electronic properties of the ligands, with more electron-donating ligands affording higher ee's.

Bayesian reaction optimization as a tool for chemical synthesis.

Reaction optimization is fundamental to synthetic chemistry, from optimizing the yield of industrial processes to selecting conditions for the preparation of medicinal candidates. Likewise, parameter optimization is omnipresent in artificial intelligence, from tuning virtual personal assistants to training social media and product recommendation systems. Owing to the high cost associated with carrying out experiments, scientists in both areas set numerous (hyper)parameter values by evaluating only a small subset of the possible configurations.

Regioselective Cross-Electrophile Coupling of Epoxides and (Hetero)aryl Iodides via Ni/Ti/Photoredox Catalysis.

A cross-electrophile coupling reaction of epoxides and (hetero)aryl iodides that operates via the merger of three catalytic cycles involving a Ni-, Ti-, and organic photoredox catalyst has been developed. Three distinct classes of epoxides, styrene oxides, cyclic epoxides, and terminal aliphatic epoxides, all undergo coupling in moderate to good yield and high regioselectivity with the use of three different nitrogen-based ligands for Ni under otherwise identical reaction conditions. The mild reaction conditions accommodate a broad scope of abundant and complex coupling partners.

Aliphatic Radical Relay Heck Reaction at Unactivated C(sp )-H Sites of Alcohols.

The Mizoroki-Heck reaction is one of the most efficient methods for alkenylation of aryl, vinyl, and alkyl halides. Given its innate nature, this protocol requires the employment of compounds possessing a halogen atom at the site of functionalization. However, the accessibility of organic molecules possessing a halogen atom at a particular site in aliphatic systems is extremely limited.

General, Mild, and Selective Method for Desaturation of Aliphatic Amines.

A novel method for desaturation of aliphatic amines into enamines as well as allylic and homoallylic amines has been developed. This general protocol operates via putative aryl hybrid Pd-radical intermediates, which combine the signature features of radical chemistry, a hydrogen atom transfer (HAT) process, and transition metal chemistry, a selective β-hydride elimination step, to achieve efficient and selective desaturation of amines. These hybrid Pd-radical intermediates are efficiently generated under mild photoinduced conditions and are capable of a 1,n-HAT (n = 5-7) event at C(sp)-H sites.

Palladium-Catalyzed Atom-Transfer Radical Cyclization at Remote Unactivated C(sp )-H Sites: Hydrogen-Atom Transfer of Hybrid Vinyl Palladium Radical Intermediates.

A novel mild, visible-light-induced palladium-catalyzed hydrogen atom translocation/atom-transfer radical cyclization (HAT/ATRC) cascade has been developed. This protocol involves a 1,5-HAT process of previously unknown hybrid vinyl palladium radical intermediates, thus leading to iodomethyl carbo- and heterocyclic structures.

General, Auxiliary-Enabled Photoinduced Pd-Catalyzed Remote Desaturation of Aliphatic Alcohols.

A general, efficient, and site-selective visible light-induced Pd-catalyzed remote desaturation of aliphatic alcohols into valuable allylic, homoallylic, and bis-homoallylic alcohols has been developed. This transformation operates via a hybrid Pd-radical mechanism, which synergistically combines the favorable features of radical approaches, such as a facile remote C-H HAT step, with that of transition-metal-catalyzed chemistry (selective β-hydrogen elimination step). This allows achieving superior degrees of regioselectivity and yields in the desaturation of alcohols compared to those obtained by the state-of-the-art desaturation methods.

Visible Light-Induced Room-Temperature Heck Reaction of Functionalized Alkyl Halides with Vinyl Arenes/Heteroarenes.

The first visible light-induced Pd-catalyzed Heck reaction of α-heteroatom substituted alkyl iodides and -bromides with vinyl arenes/heteroarenes has been developed. This transformation efficiently proceeds at room temperature and enables synthesis of valuable functionalized allylic systems, such as allylic silanes, boronates, germanes, stannanes, pivalates, phosphonates, phthalimides, and tosylates from the corresponding α-substituted methyl iodides. Notably, synthesis of the latter substrates failed under existing thermally induced Pd-catalyzed conditions, which highlights the importance of visible light for this transformation.

Visible light-induced transition metal-catalyzed transformations: beyond conventional photosensitizers.

Employment of simple transition metal (TM = Co, Fe, Cu, Pd, Pt, Au)-based photocatalyst (PC) has led to the dramatic acceleration of known TM-catalyzed reactions, as well as to the discovery of unprecedented chemical transformations. Compared to the conventional cooperative/dual photocatalysis (type B), this new class of unconventional PCs operates via a single photoexcitation/catalytic cycle, where the TM complex plays a "double duty" role by harvesting light and catalyzing the chemical transformation. Also, these TM photocatalysts participate in the bond-forming/breaking event in the transformation via a substrate-TM interaction, an aspect that is uncommon for conventional photocatalysis (type A).

Silicon-Tethered Strategies for C-H Functionalization Reactions.

Selective and efficient functionalization of ubiquitous C-H bonds is the Holy Grail of organic synthesis. Most advances in this area rely on employment of strongly or weakly coordinating directing groups (DGs) which have proven effective for transition-metal-catalyzed functionalization of C(sp)-H and C(sp)-H bonds. Although most directing groups are important functionalities in their own right, in certain cases, the DGs become static entities that possess very little synthetic leverage.

Photoinduced Formation of Hybrid Aryl Pd-Radical Species Capable of 1,5-HAT: Selective Catalytic Oxidation of Silyl Ethers into Silyl Enol Ethers.

A direct visible light-induced generation of a hybrid aryl Pd-radical species from aryl iodide and Pd(0) is reported to enable an unprecedented (for hybrid Pd-radical species) hydrogen atom-transfer event. This approach allowed for efficient desaturation of readily available silyl ethers into synthetically valuable silyl enols. Moreover, this oxidation reaction proceeds at room temperature without the aid of exogenous photosensitizers or oxidants.

Endo-selective Pd-catalyzed silyl methyl Heck reaction.

A palladium (Pd)-catalyzed endo-selective Heck reaction of iodomethylsilyl ethers of phenols and aliphatic alkenols has been developed. Mechanistic studies reveal that this silyl methyl Heck reaction operates via a hybrid Pd-radical process and that the silicon atom is crucial for the observed endo selectivity. The obtained allylic silyloxycycles were further oxidized into (Z)-alkenyldiols.