Accelerated photochemical reactions at oil-water interface exploiting melting point depression.

Water can accelerate a variety of organic reactions far beyond the rates observed in classical organic solvents. However, using pure water as a solvent introduces solubility constraints that have limited the applicability of efficient photochemistry in particular. We report here the formation of aggregates between pairs of arenes, heteroarenes, enamines, or esters with different electron affinities in an aqueous medium, leading to an oil-water phase boundary through substrate melting point depression. The active hydrogen atoms in the reactants engage in hydrogen bonds with water, thereby accelerating photochemical reactions. This methodology realizes appealingly simple conditions for aqueous coupling reactions of complex solid molecules, including complex drug molecules that are poorly soluble in water.

Side-Selective Solid-Phase Metallaphotoredox N(in)-Arylation of Peptides.

Postsynthetic diversification of peptides through selective modification of endogenous amino acid side chains has enabled significant advances in peptide drug discovery while expanding the biological and medical chemistry space. However, current tools have been focused on the modification of reactive polar and ionizable side chains, whereas the decoration of aromatic systems (e.g., the N(in) of the tryptophan) has been a long-standing challenge. Here, we introduce metallaphotocatalysis in solid-phase peptide synthesis for the on-resin orthogonal N-arylation of relevant tryptophan-containing peptides. The protocol allows the chemoselective introduction of a new C(sp2)-N bond at the N(in) of tryptophan in biologically active protected peptide sequences in the presence of native redox-sensitive side chains. The fusion of metallaphotocatalysis with solid-phase peptide synthesis opens new perspectives in diversifying native amino acid side chains.

Enforced Electronic-Donor-Acceptor Complex Formation in Water for Photochemical Cross-Coupling.

The amino alcohol meglumine solubilizes organic compounds in water and enforces the formation of electron donor acceptor (EDA) complexes of haloarenes with indoles, anilines, anisoles or thiols, which are not observed in organic solvents. UV-A photoinduced electron transfer within the EDA complexes induces the mesolytic cleavage of the halide ion and radical recombination of the arenes leading, after rearomatization and proton loss to C-C or C-S coupling products. Depending on the substitution pattern selective and unique cross-couplings are observed. UV and NMR measurements reveal the importance of the assembly for the photoinduced reaction. Enforced EDA aggregate formation in water allows new activation modes for organic photochemical synthesis.

Energy- and atom-efficient chemical synthesis with endergonic photocatalysis.

Endergonic photocatalysis is the use of light to perform catalytic reactions that are thermodynamically unfavourable. While photocatalysis has become a powerful tool in facilitating chemical transformations, the light-energy efficiency of these processes has not gathered much attention. Exergonic photocatalysis does not take full advantage of the light energy input, producing low-energy products and heat, whereas endergonic photocatalysis incorporates a portion of the photon energy into the reaction, yielding products that are higher in free energy than the reactants. Such processes can enable catalytic, atom-economic syntheses of reactive compounds from bench-stable materials. With respect to environmental friendliness and carbon neutrality, endergonic photocatalysis is also of interest to large-scale industrial manufacturing, where better energy efficiency, less waste and value addition are highly sought. We therefore assess here the thermochemistry of several classes of reported photocatalytic transformations to showcase current advances in endergonic photocatalysis and point to their industrial potential.

Transition Metal Catalyst-Free, Base-Promoted 1,2-Additions of Polyfluorophenylboronates to Aldehydes and Ketones.

A novel protocol for the transition metal-free 1,2-addition of polyfluoroaryl boronate esters to aldehydes and ketones is reported, which provides secondary alcohols, tertiary alcohols, and ketones. Control experiments and DFT calculations indicate that both the ortho-F substituents on the polyfluorophenyl boronates and the counterion K+ in the carbonate base are critical. The distinguishing features of this procedure include the employment of commercially available starting materials and the broad scope of the reaction with a wide variety of carbonyl compounds giving moderate to excellent yields. Intriguing structural features involving O-H⋅⋅⋅O and O-H⋅⋅⋅N hydrogen bonding, as well as arene-perfluoroarene interactions, in this series of racemic polyfluoroaryl carbinols have also been addressed.

Photoinduced Borylation for the Synthesis of Organoboron Compounds.

Organoboron compounds have important synthetic value and can be applied in numerous transformations. The development of practical and convenient ways to synthesize boronate esters has thus attracted significant interest. Photoinduced borylations originated from stoichiometric reactions of alkanes and arenes with well-defined metal-boryl complexes. Now, photoredox-initiated borylations, catalyzed by either transition metal or organic photocatalysts, and photochemical borylations with high efficiency have become a burgeoning area of research. In this Focus Review, we summarize research on photoinduced borylations, especially emphasizing recent developments and trends. This includes the photoinduced borylation of arenes, alkanes, aryl/alkyl halides, activated carboxylic acids, amines, alcohols, and so on based on transition metal catalysis, metal-free organocatalysis, and direct photochemical activation. We focus on reaction mechanisms involving single-electron transfer, triplet-energy transfer, and other radical processes.

Photocatalytic synthesis of tetra-substituted furans promoted by carbon dioxide.

We report a simple protocol for the transition metal-free, visible-light-driven conversion of 1,3-diketones to tetra-substituted furan skeleton compounds in carbon dioxide (CO2) atmosphere under mild conditions. It was found that CO2 could be incorporated at the diketone enolic OH position, which was key to enabling the cleavage of a C-O bond during the rearrangement of a cyclopropane intermediate. This method allows for the same-pot construction of two isomers of the high-value tetra-substituted furan scaffold. The synthetic scope and preliminary mechanistic investigations are presented.

Visible-Light-Induced Ni-Catalyzed Radical Borylation of Chloroarenes.

A highly selective and general photoinduced C-Cl borylation protocol that employs [Ni(IMes)2] (IMes = 1,3-dimesitylimidazoline-2-ylidene) for the radical borylation of chloroarenes is reported. This photoinduced system operates with visible light (400 nm) and achieves borylation of a wide range of chloroarenes with B2pin2 at room temperature in excellent yields and with high selectivity, thereby demonstrating its broad utility and functional group tolerance. Mechanistic investigations suggest that the borylation reactions proceed via a radical process. EPR studies demonstrate that [Ni(IMes)2] undergoes very fast chlorine atom abstraction from aryl chlorides to give [NiI(IMes)2Cl] and aryl radicals. Control experiments indicate that light promotes the reaction of [NiI(IMes)2Cl] with aryl chlorides generating additional aryl radicals and [NiII(IMes)2Cl2]. The aryl radicals react with an anionic sp2-sp3 diborane [B2pin2(OMe)]- formed from B2pin2 and KOMe to yield the corresponding borylation product and the [Bpin(OMe)]•- radical anion, which reduces [NiII(IMes)2Cl2] under irradiation to regenerate [NiI(IMes)2Cl] and [Ni(IMes)2] for the next catalytic cycle.

Copper-Catalyzed Oxidative Cross-Coupling of Electron-Deficient Polyfluorophenylboronate Esters with Terminal Alkynes.

We report herein a mild procedure for the copper-catalyzed oxidative cross-coupling of electron-deficient polyfluorophenylboronate esters with terminal alkynes. This method displays good functional group tolerance and broad substrate scope, generating cross-coupled alkynyl(fluoro)arene products in moderate to excellent yields. Thus, it represents a simple alternative to the conventional Sonogashira reaction.

Ni-Catalyzed Traceless, Directed C3-Selective C-H Borylation of Indoles.

A highly efficient and general protocol for traceless, directed C3-selective C-H borylation of indoles with [Ni(IMes)2] as the catalyst is reported. Activation and borylation of N-H bonds by [Ni(IMes)2] is essential to install a Bpin moiety at the N-position as a traceless directing group, which enables the C3-selective borylation of C-H bonds. The N-Bpin group which is formed is easily converted in situ back to an N-H group by the oxidative addition product of [Ni(IMes)2] and in situ-generated HBpin. The catalytic reactions are operationally simple, allowing borylation of a variety of substituted indoles with B2pin2 in excellent yields and with high selectivity. The C-H borylation can be followed by Suzuki-Miyaura cross-coupling of the C-borylated indoles in an overall two-step, one-pot process providing an efficient method for synthesizing C3-functionalized heteroarenes.

Selective Photocatalytic C-F Borylation of Polyfluoroarenes by Rh/Ni Dual Catalysis Providing Valuable Fluorinated Arylboronate Esters.

A highly selective and general photocatalytic C-F borylation protocol that employs a rhodium biphenyl complex as a triplet sensitizer and the nickel catalyst [Ni(IMes)2] (IMes = 1,3-dimesitylimidazoline-2-ylidene) for the C-F bond activation and defluoroborylation process is reported. This tandem catalyst system operates with visible (blue, 400 nm) light and achieves borylation of a wide range of fluoroarenes with B2pin2 at room temperature in excellent yields and with high selectivity. Direct irradiation of the intermediary C-F bond oxidative addition product trans-[NiF(ArF)(IMes)2] leads to very fast decomposition when B2pin2 is present. This destructive pathway can be bypassed by indirect excitation of the triplet states of the nickel(II) complex via the photoexcited rhodium biphenyl complex. Mechanistic studies suggest that the exceptionally long-lived triplet excited state of the Rh biphenyl complex used as the photosensitizer allows for efficient triplet energy transfer to trans-[NiF(ArF)(IMes)2], which leads to dissociation of one of the NHC ligands. This contrasts with the majority of current photocatalytic transformations, which employ transition metals as excited state single electron transfer agents. We have previously reported that C(arene)-F bond activation with [Ni(IMes)2] is facile at room temperature, but that the transmetalation step with B2pin2 is associated with a high energy barrier. Thus, this triplet energy transfer ultimately leads to a greatly enhanced rate constant for the transmetalation step and thus for the whole borylation process. While addition of a fluoride source such as CsF enhances the yield, it is not absolutely required. We attribute this yield-enhancing effect to (i) formation of an anionic adduct of B2pin2, i.e., FB2pin2-, as an efficient, much more nucleophilic {Bpin-} transfer reagent for the borylation/transmetalation process, and/or (ii) trapping of the Lewis acidic side product FBpin by formation of [F2Bpin]- to avoid the formation of a significant amount of NHC-FBpin and consequently decomposition of {Ni(NHC)2} species in the reaction mixture.