Alkene reactions with superoxide radical anions in flow electrochemistry.

Alkenes were cleaved to ketones by using dioxygen in an electrochemical flow set-up. The pressurised system allowed efficient gas-liquid mixing with a stabilised flow. This mild and straightforward approach avoids the use of transition metals and harsh oxidants.

Oxidative Cleavage of Alkenes by Photosensitized Nitroarenes

This article highlights the recent seminal findings on the possibility to use photoexcited nitroarenes as modular and easily dosable reagents which can mimic the reactivity of ozonolysis for the oxidative conversion of alkenyl bonds into carbonyl groups in a highly selective fashion.

Photosensitized Intermolecular Carboimination of Alkenes through the Persistent Radical Effect.

An intermolecular, two-component vicinal carboimination of alkenes has been accomplished by energy transfer catalysis. Oxime esters of alkyl carboxylic acids were used as bifunctional reagents to generate both alkyl and iminyl radicals. Subsequently, addition of the alkyl radical to an alkene generates a transient radical for selective radical-radical cross-coupling with the persistent iminyl radical. Furthermore, this process provides direct access to aliphatic primary amines and α-amino acids by simple hydrolysis.

Visible-Light-Photosensitized Aryl and Alkyl Decarboxylative Functionalization Reactions.

Despite significant progress in aliphatic decarboxylation, an efficient and general protocol for radical aromatic decarboxylation has lagged far behind. Herein, we describe a general strategy for rapid access to both aryl and alkyl radicals by photosensitized decarboxylation of the corresponding carboxylic acids esters followed by their successive use in divergent carbon-heteroatom and carbon-carbon bond-forming reactions. Identification of a suitable activator for carboxylic acids is the key to bypass a competing single-electron-transfer mechanism and "switch on" an energy-transfer-mediated homolysis of unsymmetrical σ-bonds for a concerted fragmentation/decarboxylation process.

Highly Enantioselective [5 + 2] Annulations through Cooperative N-Heterocyclic Carbene (NHC) Organocatalysis and Palladium Catalysis.

The highly enantioselective [5 + 2] annulation of enals with vinylethylene carbonates through a cooperative N-heterocyclic carbene (NHC)/Pd catalytic system is reported. The use of a bidentate phosphine ligand was crucial to prevent coordination of the NHC organocatalyst to the active Pd catalyst. The complementary and matched combination of the chiral NHC catalyst and chiral phosphine ligand promotes high levels of both reactivity and enantioselectivity (mostly ≥99% ee).

DMSO as a Switchable Alkylating Agent in Heteroarene C-H Functionalization.

Herein, we report a novel strategy for the activation of DMSO to act as a versatile alkylating agent in heteroarene C-H functionalization. This direct, simple, and mild switch between methylation/trideuteromethylation and methylthiomethylation of heteroarenes was achieved under reagent-controlled photoredox catalysis conditions. The proposed mechanism is supported by both experimental and computational studies.

Decarboxylation as the Key Step in C-C Bond-Forming Reactions.

C-C bond forming reactions incarnate the core of organic synthesis because of their fundamental applications to molecular diversity and complexity. In recent years, use of carboxylic acid as one of the coupling partners in place of conventional organometallic reagents has seen an upsurge due to its potency to generate similar organometallic intermediates after decarboxylation. This Review provides an overview on the most recent progress in the field of C-C bond formation involving decarboxylation as a key step. Different important developments, which are not included in earlier Reviews in this area, have been summarized with representative examples and discussions on their reaction mechanisms.

Palladium-Catalyzed Directed para C-H Functionalization of Phenols.

Various practical methods for the selective C-H functionalization of the ortho and recently also of the meta position of an arene have already been developed. Following our recent development of the directing-group-assisted para C-H functionalization of toluene derivatives, we herein report the first remote para C-H functionalization of phenol derivatives by using a recyclable silicon-containing biphenyl-based template. The effectiveness of this strategy was illustrated with different synthetic elaborations and by the synthesis of various phenol-based natural products.

Remote para-C-H Functionalization of Arenes by a D-Shaped Biphenyl Template-Based Assembly.

Site-selective C-H functionalization has emerged as an efficient tool in simplifying the synthesis of complex molecules. Most often, directing group (DG)-assisted metallacycle formation serves as an efficient strategy to ensure promising regioselectivity. A wide variety of ortho- and meta-C-H functionalizations stand as examples in this regard. Yet despite this significant progress, DG-assisted selective para-C-H functionalization in arenes has remained unexplored, mainly because it involves the formation of a geometrically constrained metallacyclic transition state. Here we report an easily recyclable, novel Si-containing biphenyl-based template that directs efficient functionalization of the distal p-C-H bond of toluene by forming a D-shaped assembly. This DG allows the required flexibility to support the formation of an oversized pre-transition state. By overcoming electronic and steric bias, para-olefination and acetoxylation were successfully performed while undermining o- and m-C-H activation. The applicability of this D-shaped biphenyl template-based strategy is demonstrated by synthesizing various complex molecules.

Electrocatalytic continuous flow chlorinations with iodine(I/III) mediators.

Electrochemistry offers tunable, cost effective and environmentally friendly alternatives to carry out redox reactions with electrons as traceless reagents. The use of organoiodine compounds as electrocatalysts is largely underdeveloped, despite their widespread application as powerful and versatile reagents. Mechanistic data reveal that the hexafluoroisopropanol assisted iodoarene oxidation is followed by a stepwise chloride ligand exchange for the catalytic generation of the dichloroiodoarene mediator. Here, we report an environmentally benign iodine(I/III) electrocatalytic platform for the in situ generation of dichloroiodoarenes for different reactions such as mono- and dichlorinations as well as chlorocyclisations within a continuous flow setup.

Four-center oxidation state combinations and near-infrared absorption in [Ru(pap)(Q)2]n (Q = 3,5-di-tert-butyl-N-aryl-1,2-benzoquinonemonoimine, pap = 2-phenylazopyridine).

The complex series [Ru(pap)(Q)2](n) ([1](n)-[4](n); n = +2, +1, 0, -1, -2) contains four redox non-innocent entities: one ruthenium ion, 2-phenylazopyridine (pap), and two o-iminoquinone moieties, Q = 3,5-di-tert-butyl-N-aryl-1,2-benzoquinonemonoimine (aryl = C6H5 (1(+)); m-(Cl)2C6H3 (2(+)); m-(OCH3)2C6H3 (3(+)); m-(tBu)2C6H3 (4(+))). A crystal structure determination of the representative compound, [1]ClO4, established the crystallization of the ctt-isomeric form, that is, cis and trans with respect to the mutual orientations of O and N donors of two Q ligands, and the coordinating azo N atom trans to the O donor of Q. The sensitive C-O (average: 1.299(3) Å), C-N (average: 1.346(4) Å) and intra-ring C-C (meta; average: 1.373(4) Å) bond lengths of the coordinated iminoquinone moieties in corroboration with the N-N length (1.292(3) Å) of pap in 1(+) establish [Ru(III)(pap(0))(Q(·-))2 ](+) as the most appropriate electronic structural form. The coupling of three spins from one low-spin ruthenium(III) (t2g(5)) and two Q(·-) radicals in 1(+)-4(+) gives a ground state with one unpaired electron on Q(·-), as evident from g = 1.995 radical-type EPR signals for 1(+)-4(+). Accordingly, the DFT-calculated Mulliken spin densities of 1(+) (1.152 for two Q, Ru: -0.179, pap: 0.031) confirm Q-based spin. Complex ions 1(+)-4(+) exhibit two near-IR absorption bands at about λ = 2000 and 920 nm in addition to intense multiple transitions covering the visible to UV regions; compounds [1]ClO4-[4]ClO4 undergo one oxidation and three separate reduction processes within ±2.0 V versus SCE. The crystal structure of the neutral (one-electron reduced) state (2) was determined to show metal-based reduction and an EPR signal at g = 1.996. The electronic transitions of the complexes 1(n)-4(n) (n = +2, +1, 0, -1, -2) in the UV, visible, and NIR regions, as determined by using spectroelectrochemistry, have been analyzed by TD-DFT calculations and reveal significant low-energy absorbance (λmax >1000 nm) for cations, anions, and neutral forms. The experimental studies in combination with DFT calculations suggest the dominant valence configurations of 1(n)-4(n) in the accessible redox states to be [Ru(III)(pap(0))(Q(·-))(Q(0))](2+) (1(2+)-4(2+))→[Ru(III)(pap(0))(Q(·-))2](+) (1(+)-4(+))→[Ru(II)(pap(0))(Q(·-))2] (1-4)→[Ru(II)(pap(·-))(Q(·-))2](-) (1(-)-4(-))→[Ru(III)(pap(·-))(Q(2-))2](2-) (1(2-)-4(2-)).

Overriding ortho selectivity by template assisted meta-C-H activation of benzophenones.

An orthogonal selectivity for distal meta-C-H activation of benzophenone is acheived by overriding the inherent proximal ortho-selectivity through a template assisted metalation approach. This strategy has been successfully utilized in Pd-catalyzed regioselective C-C and C-Si bond formation.

Copper mediated decarboxylative direct C-H arylation of heteroarenes with benzoic acids.

Decarboxylative coupling reactions to date require a stoichiometric oxidant (such as copper and silver salts) for decarboxylation purposes along with a metal catalyst (e.g. palladium) for cross-coupling. In this communication, an economic and sustainable approach by using a simple copper salt was developed in the presence of molecular oxygen as the sole oxidant. A wide range of 5-membered heteroarenes undergo aryl-heteroaryl cross-coupling with electron deficient aryl carboxylic acids.

Sequential meta-C-H olefination of synthetically versatile benzyl silanes: effective synthesis of meta-olefinated toluene, benzaldehyde and benzyl alcohols.

Tremendous progress has been made towards ortho-selective C-H functionalization in the last three decades. However, the activation of distal C-H bonds and their functionalization has remained fairly underdeveloped. Herein, we report sequential meta-C-H functionalization by performing selective mono-olefination and bis-olefination with late stage modification of the C-Si as well as Si-O bonds. Temporary silyl connection was found to be advantageous due to its easy installation, easy removal and wide synthetic diversification.

Meta-selective arene C-H bond olefination of arylacetic acid using a nitrile-based directing group.

A nitrile-based template attached with a phenylacetic acid framework promoted meta-selective C-H bond olefination. This palladium-catalyzed protocol is applicable to a wide range of substituted phenylacetic acids and tolerates a variety of functional groups. The versatility of this operationally simple method has been demonstrated through drug diversification.

Nickel-catalyzed decyanation of inert carbon-cyano bonds.

Nickel catalyzed decyanation of aryl and aliphatic cyanides with hydrosilane as the hydride source has been developed. This method is easy to handle, scalable and can be carried out without a glove box. The method has been applied in the cyanide directed functionalization reaction and α-substitution of benzyl cyanide.

Nickel-catalyzed hydrogenolysis of unactivated carbon-cyano bonds.

Selective hydrogenolysis of C-CN bonds can allow chemists to take advantage of ortho-directing ability, α-C-H acidity and electron withdrawing ability of the cyano group for synthetic manipulations. We have discovered hydrogenolysis of aryl and aliphatic cyanides under just 1 bar of hydrogen by using a nickel catalyst. This protocol was applied in the aryl cyanide directed functionalization reaction and α-substitution of benzyl cyanides.

A general and efficient aldehyde decarbonylation reaction by using a palladium catalyst.

A facile decarbonylation reaction of aldehydes has been developed by employing Pd(OAc)(2). A wide variety of substrates are decarbonylated, without using any exogenous ligand for palladium as well as CO-scavenger.