Photoinduced Pd-Catalyzed Direct Sulfonylation of Allylic C-H Bonds.

Allylic sulfones are valuable motifs due to their medicinal and biological significance and their versatile chemical reactivities. While direct allylic C-H sulfonylation represents a straightforward and desirable approach, these methods are primarily restricted to terminal alkenes, leaving the engagement of the internal counterparts a formidable challenge. Herein we report a photocatalytic approach that accommodates both cyclic and acyclic internal alkenes with diverse substitution patterns and electronic properties.

General Regio- and Diastereoselective Allylic C-H Oxygenation of Internal Alkenes.

Branched allylic esters and carboxylates are fundamental motifs prevalent in natural products and drug molecules. The direct allylic C-H oxygenation of internal alkenes represents one of the most straightforward approaches, bypassing the requirement for an allylic leaving group as in the classical Tsuji-Trost reaction. However, current methods suffer from limited scope─often accompanied by selectivity issues─thus hampering further development.

Visible Light-Induced Reactions of Diazo Compounds and Their Precursors.

In recent years, visible light-induced reactions of diazo compounds have attracted increasing attention in organic synthesis, leading to improvement of existing reactions, as well as to the discovery of unprecedented transformations. Thus, photochemical or photocatalytic generation of both carbenes and radicals provide milder tools toward these key intermediates for many valuable transformations. However, the vast majority of the transformations represent new reactivity modes of diazo compounds, which are achieved by the photochemical decomposition of diazo compounds and photoredox catalysis.

Recent Advances in Visible Light Induced Palladium Catalysis.

Visible light-induced Pd catalysis has emerged as a promising subfield of photocatalysis. The hybrid nature of Pd radical species has enabled a wide array of radical-based transformations otherwise challenging or unknown via conventional Pd chemistry. In parallel to the ongoing pursuit of alternative, readily available radical precursors, notable discoveries have demonstrated that photoexcitation can alter not only oxidative addition but also other elementary steps.

Advances in Selected Heterocyclization Methods.

This Account summarizes efforts in our group toward synthesis of heterocycles in the past decade. Selected examples of transannulative heterocyclizations, intermediate construction of reactive compounds to these important motifs, and newer developments of a radical approach are outlined.

Escape from Hydrofunctionalization: Palladium Hydride-Enabled Difunctionalization of Conjugated Dienes and Enynes.

Palladium hydrides are traditionally employed in hydrofunctionalization (i.e. monofunctionalization) of conjugated dienes and enynes, owning to its facile protic hydropalladation of electron-rich (or neutral) unsaturated bonds.

One-Pot Formal Carboradiofluorination of Alkenes: A Toolkit for Positron Emission Tomography Imaging Probe Development.

We report the first one-pot formal alkene carboradiofluorination reaction employing easily accessible alkenes as both prosthetic group precursors and coupling partners. The methodology features rapid sequential Markovnikov-selective iodofluorination and photoinduced Pd(0/I/II)-catalyzed alkyl Heck reaction as a mild and robust fluorine-18 (F) radiochemical approach for positron emission tomography (PET) imaging probe development. A new class of prosthetic groups for PET imaging probe synthesis was isolated as iodofluorinated intermediates in moderate to excellent yields.

Merging of Light/Dark Palladium Catalytic Cycles Enables Multicomponent Tandem Alkyl Heck/Tsuji-Trost Homologative Amination Reaction toward Allylic Amines.

A visible light-induced palladium-catalyzed homologative three-component synthesis of allylic amines has been developed. This protocol proceeds a unique mechanism involving two distinct cycles enabled by the same Pd(0) catalyst: a visible light-induced hybrid radical alkyl Heck reaction between 1,1-dielectrophile and styrene, followed by the "in dark" classical Tsuji-Trost-type allylic substitution reaction. This method works well with a broad range of primary and secondary amines, aryl alkenes, dielectrophiles, and in complex settings.

Enhanced Excited-State Hydricity of Pd-H Allows for Unusual Head-to-Tail Hydroalkenylation of Alkenes.

Photoinduced enhancement of hydricity of palladium hydride species enables unprecedented hydride addition-like ("hydridic") hydropalladation of electron-deficient alkenes, which allows for chemoselective head-to-tail cross-hydroalkenylation of electron-deficient and electron-rich alkenes. This mild and general protocol works with a wide range of densely functionalized and complex alkenes. Notably, this approach also allows for highly challenging cross-dimerization of electronically diverse vinyl arenes and heteroarenes.

Recent advances in visible light-induced C( )-N bond formation.

Synthetic chemists have long focused on selective C( )-N bond-forming approaches in response to the high value of this motif in natural products, pharmaceutical agents and functional materials. In recent years, visible light-induced protocols have become an important synthetic platform to promote this transformation under mild reaction conditions. These photo-driven methods rely on converting visible light into chemical energy to generate reactive but controllable radical species.

General and Selective Metal-Free Radical -C-H Borylation of Aliphatic Amines.

Despite recent developments, selective C(sp)-H borylation of feedstock amines remains a formidable challenge. Herein, we have developed a general, mild, and photoinduced transition metal- and strong base-free method for -C(sp)-H borylation of amines. This protocol features a regioselective 1,5-hydrogen atom transfer process to access key -aminoalkyl radical intermediate using commercially available easy-to-install/remove iodobenzoyl radical translocating group.

Asymmetric intermolecular allylic C-H amination of alkenes with aliphatic amines.

Aliphatic allylic amines are found in a great variety of complex and biorelevant molecules. The direct allylic C-H amination of alkenes serves as the most straightforward method toward these motifs. However, use of widely available internal alkenes with aliphatic amines in this transformation remains a synthetic challenge.

Palladium Hydride-Enabled Hydroalkenylation of Strained Molecules.

We report the first palladium hydride enabled hydroalkenylation of strained molecules. This new mild protocol proceeds via a regio- and chemoselective hydropalladation step, followed by a photoinduced radical alkyl Heck reaction. This methodology represents a new reactivity mode for strained molecules and opens new avenues for photoinduced palladium catalysis.

Targeting lipid-protein interaction to treat Syk-mediated acute myeloid leukemia.

Membrane lipids control the cellular activity of kinases containing the Src homology 2 (SH2) domain through direct lipid-SH2 domain interactions. Here we report development of new nonlipidic small molecule inhibitors of the lipid-SH2 domain interaction that block the cellular activity of their host proteins. As a pilot study, we evaluated the efficacy of lipid-SH2 domain interaction inhibitors for spleen tyrosine kinase (Syk), which is implicated in hematopoietic malignancies, including acute myeloid leukemia (AML).

Accessing Illusive Isomers of α-Ester Hydrazones via Visible-Light-Induced Pd-Catalyzed Heck-Type Alkylation.

A visible-light-induced Pd-catalyzed stereoselective synthesis of alkylated ester hydrazones has been developed. This method operates via generation of a nucleophilic carbon-centered radical from alkyl bromide, iodide, or redox-active ester, followed by its addition to hydrazone, and a subsequent desaturation by palladium. The majority of products have configuration, which are inaccessible by conventional condensation methods.

Three-Component Visible-Light-Induced Palladium-Catalyzed 1,2-Alkyl Carbamoylation/Cyanation of Alkenes.

A mild visible-light-induced Pd-catalyzed one-pot three-component alkyl-carbamoylation and cyanation of alkenes was developed. This general transformation, which proceeds via the in situ formation of a reactive ketenimine intermediate, allows for a rapid construction of a broad range of valuable amides and nitriles from readily available alkenes, alkyl iodides, and isocyanides. An efficient synthesis of tetrazole and amidine via this approach was also demonstrated.

Visible Light Induced Brønsted Acid Assisted Pd-Catalyzed Alkyl Heck Reaction of Diazo Compounds and N-Tosylhydrazones.

A mild visible light-induced palladium-catalyzed alkyl Heck reaction of diazo compounds and N-tosylhydrazones is reported. A broad range of vinyl arenes and heteroarenes with high functional group tolerance, as well as a range of different diazo compounds, can efficiently undergo this transformation. This method features Brønsted acid-assisted generation of hybrid palladium C(sp )-centered radical intermediate, which allowed for new selective C-H functionalization protocol.

Visible Light-Induced Transition Metal Catalysis.

In recent years, visible light-induced transition metal catalysis has emerged as a new paradigm in organic photocatalysis, which has led to the discovery of unprecedented transformations as well as the improvement of known reactions. In this subfield of photocatalysis, a transition metal complex serves a double duty by harvesting photon energy and then enabling bond forming/breaking events mostly via a single catalytic cycle, thus contrasting the established dual photocatalysis in which an exogenous photosensitizer is employed. In addition, this approach often synergistically combines catalyst-substrate interaction with photoinduced process, a feature that is uncommon in conventional photoredox chemistry.

Visible Light-Induced Pd-Catalyzed Alkyl-Heck Reaction of Oximes.

A visible light-induced palladium-catalyzed oxidative C-H alkylation of oximes has been developed. This mild protocol allows for an efficient atom economical C-C bond construction of alkyl-substituted oximes. A broad range of primary, secondary, and tertiary alkyl bromides and iodides, as well as a range of different formaldoximes, can efficiently undergo this transformation.

On the possibility of recording and studying human movement activity with seismic sensors of a new type: Advantages and prospects of the single-layer flat-coil-oscillator technology based sensors.

This paper presents main classes and varieties of sensors developed on the basis of the single-layer flat-coil-oscillator (SFCO) technology. The results of registration of human activity (steps and jumps) by seismic sensors based on this technology are presented and discussed in this paper. We applied some algorithms for digital processing of "RAW" data coming from vibrational seismic SFCO sensors, which made it possible to detect and mark out human steps and jumps from the background of natural ground vibrations.

C-H functionalization reactions enabled by hydrogen atom transfer to carbon-centered radicals.

Selective functionalization of ubiquitous unactivated C-H bonds is a continuous quest for synthetic organic chemists. In addition to transition metal catalysis, which typically operates under a two-electron manifold, a recent renaissance in the radical approach relying on the hydrogen atom transfer (HAT) process has led to tremendous growth in the area. Despite several challenges, protocols proceeding HAT are highly sought after as they allow for relatively easy activation of inert C-H bonds under mild conditions leading to a broader scope and higher functional group tolerance and sometimes complementary reactivity over methods relying on traditional transition metal catalysis.

Contemporary methods for generation of aryl radicals.

The synthetic utility of aryl radicals has been established in the last century, however, their broad applications were hampered by ineffective generation methods. It was in the last decade, that a rapid development of various redox systems took place, thus triggering a renaissance of aryl radical chemistry. This tutorial review focuses on the start-of-the-art methods for generation of aryl radicals.

Co-Catalyzed Transannulation of Pyridotriazoles with Isothiocyanates and Xanthate Esters.

An efficient radical transannulation reaction of pyridotriazoles with isothiocyanates and xanthate esters was developed. This method features conversion of pyridotriazoles into two -fused heterocyclic aromatic systems-imino-thiazolopyridines and oxo-thiazolopyridine derivatives-via one-step Co(II)-catalyzed transannulation reaction proceeding via a radical mechanism. The synthetic usefulness of the developed method was illustrated in the synthesis of amino acid derivatives and further transformations of obtained reaction products.

Denitrogenative Transformations of Pyridotriazoles and Related Compounds: Synthesis of -Containing Heterocyclic Compounds and Beyond.

The high demand for new and efficient routes toward synthesis of nitrogen-containing heterocyclic scaffolds has inspired organic chemists to discover several methodologies over recent years. This Perspective highlights one standout approach, which involves the use of pyridotriazoles and related compounds in denitrogenative transformations. Readily available pyridotriazoles undergo ring-chain isomerization to produce uniquely reactive α-diazoimines.