Heteroatom Bond Research Articles

Recent Advances in Transition Metal-Catalyzed B—H Bond Activation for Synthesis of o-Carborane Derivatives with B—Heteroatom Bond

Recent Advances in Transition Metal-Catalyzed B—H Bond Activation for Synthesis of <i>o</i>-Carborane Derivatives with B—Heteroatom Bond

FUNCIONALIZAÇÃO DE LIGAÇÕES C—H EM ESTÁGIO TARDIO EM SÍNTESE ORGÂNICA

LATE-STAGE FUNCTIONALIZATION OF C—H BONDS IN ORGANIC SYNTHESIS. The development of new strategies for the functionalization of the historically inert C—H bond arises as an excellent way to create new carbon—carbon and carbon— heteroatom bonds. With increasingly chemo- and site-selective methods that enables the late-stage functionalization of C—H bonds, the modification of specific sites in natural products and pharmaceuticals without altering their scaffold emerges as a powerful means for the diversification of complex molecules. In this review, we will introduce concepts of late-stage modifications, the use of C—H bond functionalization to forge new carbon—carbon and carbon—heteroatom bonds using metal catalysis and photochemistry in simple examples and their applications in natural products and pharmaceuticals. The aim of the review is to update and display to the reader the contributions and implications of this methodology to organic synthesis.

Electrochemical synthesis and transformation of organoboron compounds

This review highlights the recent advances in both electrochemical borylation and hydroboration to synthesize organoboron compounds and electrochemical transformation of organoboron compounds to construct carbon–carbon and carbon–heteroatom bonds.

Catalyst-controlled stereoselective carbon–heteroatom bond formations by N-heterocyclic carbene (NHC) organocatalysis

This review highlights recent advances in stereoselective carbon–heteroatom bond forming reactions, including C–N, C–O, C–S, C–F, C–P, etc., that were enabled by NHC organocatalysis with a focus on new activation modes and reactive intermediates.

Sustainable and practical formation of carbon-carbon and carbon-heteroatom bonds employing organo-alkali metal reagents.

Metal-catalysed cross-coupling reactions are amongst the most widely used methods to directly construct new bonds. In this connection, sustainable and practical protocols, especially transition metal-catalysed cross-coupling reactions, have become the focus in many aspects of synthetic chemistry due to their high efficiency and atom economy. This review summarises recent advances from 2012 to 2022 in the formation of carbon-carbon bonds and carbon-heteroatom bonds by employing organo-alkali metal reagents.

HFIP-assisted reductive C–S, C–N, and C–X coupling of carbonyl compounds: a combined computational and experimental mechanistic study

Owing to the importance of carbon–heteroatom bonds in synthetic organic chemistry and pharmaceuticals, developing reliable and catalyst-free methods for their construction sets a significant goal of high practical value for modern chemistry.

Lewis Base-Boryl Radicals Enabled Borylation Reactions and Selective Activation of Carbon-Heteroatom Bonds.

ConspectusThe past decades have witnessed tremendous progress on radical reactions. However, in comparison with carbon, nitrogen, oxygen, and other main group element centered radicals, the synthetic chemistry of boron centered radicals was less studied, mainly due to the high electron-deficiency and instability of such 3-center-5-electron species. In the 1980s, Roberts and co-workers found that the coordination of a Lewis base (amines or phosphines) with the boron center could form 4-center-7-electron boryl radicals (Lewis base-boryl radicals, LBRs) that are found to be more stable. However, only limited synthetic applications were developed. In 2008, Curran and co-workers achieved a breakthrough with the discovery of N-heterocyclic carbene (NHC) boryl radicals, which could enable a range of radical reduction and polymerization reactions. Despite these exciting findings, more powerful and valuable synthetic applications of LBRs would be expected, given that the structures and reactivities of LBRs could be easily modulated, which would provide ample opportunities to discover new reactions. In this Account, a summary of our key contributions in LBR-enabled radical borylation reactions and selective activation of inert carbon-heteroatom bonds will be presented.Organoboron compounds have shown versatile applications in chemical society, and their syntheses rely principally on ionic borylation reactions. The development of mechanistically different radical borylation reactions allows synthesizing products that are inaccessible by traditional methods. For this purpose, we progressively developed a series of NHC-boryl radical mediated chemo-, regio-, and stereoselective radical borylation reactions of alkenes and alkynes, by which a wide variety of structurally diverse organoboron molecules were successfully prepared. The synthetic utility of these borylated products was also demonstrated. Furthermore, we disclosed a photoredox protocol for oxidative generation of NHC-boryl radicals, which enabled useful defluoroborylation and arylboration reactions.Selective bond activation is an ideal way to convert simple starting materials to value-added products, while the cleavage of inert chemical bonds, in particular the chemoselectivity control when multiple identical bonds are present in similar chemical environments, remains a long-standing challenge. We envisaged that finely tuning the properties of LBRs might provide a new solution to address this challenge. Recently, we disclosed a 4-dimethylaminopyridine (DMAP)-boryl radical promoted sequential C-F bond functionalization of trifluoroacetic acid derivatives, in which the α-C-F bonds were selectively snipped via a spin-center shift mechanism. This strategy enables facile conversion of abundantly available trifluoroacetic acid to highly valuable mono- and difluorinated molecules. Encouraged by this finding, we further developed a boryl radical enabled three-step sequence to construct all-carbon quaternary centers from a range of trichloromethyl groups, where the three C-Cl bonds were selectively cleaved by the rational choice of suitable boryl radical precursors in each step. Furthermore, a boryl radical promoted dehydroxylative alkylation of α-hydroxy carboxylic acid derivatives was achieved, allowing for the efficient conversion of some biomass platform molecules to high value products.

Samarium-Mediated Asymmetric Synthesis

Samarium is an efficient reducing agent, a radical generator in cyclization and a cascade addition reaction. Interestingly, samarium metal has crucial impact on numerous C-C and C-X (X = hetero atom) bond forming transformations. It has been established as an exceptional chemo-selective and stereoselective reagent. The reactivity of the samarium catalyst/reagent is remarkably enhanced in the presence of various additives, ligands and solvents through effective coordination and an increase in reduction potential. It has inherent character to act as electron donor for a wide range of transformations including the asymmetric version of various reactions. This review accentuates the developments in samarium-mediated/catalyzed asymmetric organic synthesis over the past 12 years, where the chirality has been induced from ligand, a nearby asymmetric center within the substrate or through coordination directed stereospecific reactions.

Synthesis of N-acyl sulfenamides via copper catalysis and their use as S-sulfenylating reagents of thiols

Sulfur–heteroatom bonds such as S–S and S–N are found in a variety of natural products and often play important roles in biological processes. Despite their widespread applications, the synthesis of sulfenamides, which feature S–N bonds that may be cleaved under mild conditions, remains underdeveloped. Here, we report a method for synthesis of N-acyl sulfenamides via copper-catalyzed nitrene-mediated S-amidation reaction of thiols with dioxazolones. This method is efficient, convenient, and broadly applicable. Moreover, the resulting N-acetyl sulfenamides are highly effective S-sulfenylation reagents for the synthesis of unsymmetrical disulfides under mild conditions. The S-sulfenylation protocol enables facile access to sterically demanding disulfides that are difficult to synthesize by other means.

Modulating the Surface and Photophysical Properties of Carbon Dots to Access Colloidal Photocatalysts for Cross-Couplings

Photoredox-mediated Ni-catalyzed cross-couplings are powerful transformations to form carbon–heteroatom bonds and are generally photocatalyzed by noble metal complexes. Low-cost and easy-to-prepare carbon dots (CDs) are attractive quasi-homogeneous photocatalyst alternatives, but their applicability is limited by their short photoluminescence (PL) lifetimes. By tuning the surface and PL properties of CDs, we designed colloidal CD nano-photocatalysts for a broad range of Ni-mediated cross-couplings between aryl halides and nucleophiles. In particular, a CD decorated with amino groups permitted coupling to a wide range of aryl halides and thiols under mild, base-free conditions. Mechanistic studies suggested dynamic quenching of the CD excited state by the Ni co-catalyst and identified that pyridinium iodide (pyHI), a previously used additive in metallaphotocatalyzed cross-couplings, can also act as a photocatalyst in such transformations.

Frontispiece: Controlled Modification of Axial Coordination for Transition‐Metal Single‐Atom Electrocatalyst

M−N−C single-atom catalysts have emerged as a novel frontier in electrocatalysis. Their catalytic behavior is optimized by the lack of metal–metal bonds and ability to adjust the coordination configuration and electronic structure of their metal–heteroatom bonds. In particular, this concept discusses the importance of the axial coordination strategy toward single atom catalyst. For more details, see the Concept by B. Wang and co-workers. (DOI: 10.1002/chem.202201471).

Steric, Electronic and Conformational Synergistic Effects in the Gold(I)‐catalyzed α‐C−H Bond Functionalization of Tertiary Amines**

AbstractDirect C−H bond functionalization is a useful strategy for the straightforward formation of C−C and C−Heteroatom bonds. In the present work, a unique approach for the challenging electrophilic Au‐catalyzed α‐C−H bond functionalization of tertiary amines is presented. Electronic, steric and conformational synergistic effects exerted by the use of a malonate unit in the substrate were key to the success of this transformation. This new reactivity was applied to the synthesis of tetrahydro‐γ‐carboline products which, under oxidative conditions, could be converted into valuable structural motifs found in bioactive alkaloid natural products.

Selective C-S Bond Constructions Using Inorganic Sulfurs via Photoinduced Electron Donor-Acceptor Activation.

By complementing traditional transition metal catalysis, photoinduced catalysis has emerged as a versatile and sustainable way to achieve carbon-heteroatom bond formation. This work discloses a visible-light-induced reaction for the formation of a C-S bond from aryl halides and inorganic sulfuration agents via electron donor-acceptor (EDA) complex photocatalysis. Divergent formations of organic sulfide and disulfide have been demonstrated under mild conditions. Preliminary mechanistic studies suggest that visible-light-induced intracomplex charge transfer within the monosulfide-anion-containing EDA complex permits the C-S bond construction reactivity.

Photoredox-catalyzed C–C bond cleavage of cyclopropanes for the formation of C(sp3)–heteroatom bonds

Sterically congested C–O and C–N bonds are ubiquitous in natural products, pharmaceuticals, and bioactive compounds. However, the development of a general method for the efficient construction of those sterically demanding covalent bonds still remains a formidable challenge. Herein, a photoredox-driven ring-opening C(sp3)–heteroatom bond formation of arylcyclopropanes is presented, which enables the construction of structurally diversified while sterically congested dialkyl ether, alkyl ester, alcohol, amine, chloride/fluoride, azide and also thiocyanate derivatives. The selective single electron oxidation of aryl motif associated with the thermodynamic driving force from ring strain-release is the key for this transformation. By this synergistic activation mode, C–C bond cleavage of otherwise inert cyclopropane framework is successfully unlocked. Further mechanistic and computational studies disclose a complete stereoinversion upon nucleophilic attack, thus proving a concerted SN2-type ring-opening functionalization manifold, while the regioselectivity is subjected to an orbital control scenario.

Group-VI-Chalcogenide-Based Nanomaterials in Photo/Thermal Organic Transformations

ConspectusWith the growing awareness of the need to have greener, economical, and sustainable alternatives in synthetic chemistry, the scientific community has come up with strategies that are based on materials in general and nanomaterials in particular. Nanomaterials can be tuned to obtain the desired properties. These methods include modification of the surface by functionalization, controlling the defects at the edge and the basal plane, and doping with metals, other nanomaterials, or heteroatoms. At the lower dimensions, they bear an enhanced surface-to-volume ratio. These act as potential sites for catalysis, and hence, nanomaterials have an immense ability to mediate organic transformations. Although these have not yet taken over the reported metal/ligand-based catalysts completely, one can agree to the fact that nanoscience and nanotechnology have a charisma of their own. Over the years, they have acquired importance in industries as well, chiefly because of their heterogeneous nature that allows one to reuse them in subsequent runs. In this Account, we have made an effort to introduce the readers to the various forms of transition metal chalcogenides (TMCs) that have been used in photo or thermal catalysis as well as our contributions in this regard. To date, various accounts or reviews centered around these materials have focused chiefly on energy related applications or electrocatalytic transformations like the water-splitting process, the hydrogen evolution reaction (HER), and the oxygen evolution/reduction reaction (OER/ORR) and electronics such as transistors, solar cells, photodetectors, etc. Also, these materials have gained popularity in drug delivery systems and sensing applications. Very few reports have brought about the role of TMCs in catalysis. Herein, we have laid emphasis on the use of these materials in organic transformations, chiefly categorized as oxidation–reduction reactions and C–C or C–heteroatom bond forming reactions, mediated thermally or photochemically. It is also possible to merge the multifaceted applications of TMCs, as demonstrated in our recent report on the cross dehydrogenative coupling (CDC) reaction synchronized with HER. Apart from this, we have discussed some of the other reactions such as hydrodesulfurization (HDS) and hydrodeoxygenation (HDO) as well. Some of the key challenges persisting in this field include the design of chiral materials for various enantioselective or diastereoselective reactions, correlation of the experimental output with theoretical studies, controlling the extent of doping, and detailed analysis of TMCs mediated organic transformations. In a nutshell, TMC mediated catalysis is a relatively unexplored, yet a highly promising field, and overcoming these challenges would enhance the potential of this field manifold in various sectors.

Photoredox-Mediated Desulfonylative Radical Reactions: An Excellent Approach Towards C–C and C–Heteroatom Bond Formation

AbstractIn recent times, desulfonylative radical-cross-coupling (RCC) has come to the forefront in synthetic organic, bio, and material chemistry as a powerful strategy to form C–C and C–heteroatom bonds. Diverse functionalization through metal- and photoredox-catalyzed desulfonylation reactions has attracted the scientific community due to the mild reaction conditions, wide functional group tolerance, and excellent synthetic efficacy. In this review, we have highlighted photoredox-mediated desulfonylation reactions developed since 2000. This review will summarize the newly reported methodologies, with particular emphasis on their mechanistic aspects and selectivity issues which have paved a new way towards sustainable C–C and C–X (X = H or heteroatom) bond formation.1 Introduction2 Photoredox-Catalyzed C–C Bond Formation2.1 Aryl Sulfones as Radical Precursor2.2 Reactions of Allyl Sulfones3 Photoredox-Catalyzed C–Heteroatom Bond Formation4 Conclusion

A “one size fits all” ligand for photoredox and metallaphotoredox catalysis

In this issue of <i>Chem</i>, Li and co-workers provide a solution for a long-standing challenge of photoredox catalysts by designing a photoactive ligand that can engage a slew of inexpensive first-row transition metals to replace precious-metal catalysts in forging various C–C and C–heteroatom bonds.

Benign-Metal-Catalyzed Carbon–Carbon and Carbon–Hetero­atom Bond Formation

AbstractCarbon–carbon and carbon–heteroatom bond-formation reactions catalyzed by benign and inexpensive metals are of much interest in organic synthesis, as these reactions provide green and cost-effective routes. This account summarizes our recent contributions to the construction of carbon–carbon and carbon–heteroatom bonds by using benign-metal catalysts. A number of carbon–heteroatom bond formations, including C–N, C–O, C–S, C–Se, C–Te, and C–P bond formations, are discussed. Mechanistic insights into several reactions are also reported1 Introduction2 C–C Bond Formation3 C–N and C–O Bond Formation4 Carbon–Chalcogen (C–S, C–Se, C–Te) and C–P Bond Formation5 Conclusions

Unraveling the Chemistry of High Valent Arylcopper Compounds and Their Roles in Copper-Catalyzed Arene C-H Bond Transformations Using Synthetic Macrocycles.

Recent decades have witnessed a resurgence of the study of copper-catalyzed organic reactions. As the surrogate of noble metal catalysts, copper salts have been shown to exhibit remarkable versatility in activating various C-H bonds enabling the construction of diverse carbon-carbon and carbon-heteroatom bonds. Advantageously, copper salts are also naturally abundant, inexpensive, and less toxic in comparison to precious metals. Despite significant developments in synthesis, the mechanism of copper catalysis remains elusive. Hypothetical pathways such as the two-electron Cu(III)/Cu(I) and Cu(II)/Cu(0) catalytic cycles and the one-electron Cu(II)/Cu(I) catalytic cycle have been invoked to diagram C-H bond transformations because of the formidable challenges to isolate and characterize transient high valent organocopper intermediates. In fact, organocopper chemistry has been dominated for a long time by the acknowledged nucleophilic organocopper(I) compounds. Since the beginning of the new millennium, we have been systematically studying the supramolecular chemistry of heteracalix[n]aromatics. Owing to the ease of their synthesis and selective functionalizations, self-tunable conformation and cavity structures resulting from the interplay of heteroatoms with aromatic subunits, and outstanding properties in molecular recognition and self-assembly, heteracalix[n]aromatics have become a class of privileged synthetic macrocyclic hosts. Our journey to the chemistry of high valent organocopper compounds started with a serendipitous discovery of the facile formation of a stable organocopper compound, which contains astonishingly a Ph-Cu(III) σ-bond under very mild aerobic conditions. When we examined routinely the effect of the macrocyclic structures on noncovalent complexation properties, titration of tetraazacalix[1]arene[3]pyridine with Cu(ClO4)2·6H2O resulted in the precipitation of dark-purple crystals of phenylcopper(III) diperchlorate. Our curiosity about the transformation of an arene C-H bond into an Ar-Cu(III) bond prompted us to conduct an in-depth investigation of the reaction of macrocyclic arenes with copper(II) salts, leading to the isolation of arylcopper(II) compounds which are unprecedented and the missing link in organocopper chemistry. With structurally well-defined organometallics in hand, we have explored extensively the reactivities of both arylcopper(II) and arylcopper(III) compounds, demonstrating their versatility and uniqueness in chemical synthesis. Novel and fascinating arene C-H transformations under copper catalysis have been developed. Using acquired high valent arylcopper compounds as molecular probes, and employing the functionalizations of tetraazacalix[1]arene[3]pyridines as model reactions, we have revealed the diverse mechanisms of copper-promoted arene C-H bond reactions. Elusive reaction pathways of some copper-catalyzed C-X bond activations have also been unraveled. In the meantime, we have also witnessed pleasingly the rapid development of field with the advent of new high valent organocopper compounds. Without any doubt, studies of the synthesis, reactivity, and catalysis of high valent organocopper compounds have been reshaping the field of organocopper chemistry. This Account summarizes our endeavors to explore the chemistry of structurally well-defined arylcopper(II) and arylcopper(III) compounds and the mechanisms of copper-catalyzed arene C-H and C-X bond transformations. We hope this Account will inspire chemists to study thoroughly the fundamentals and the cutting-edge catalysis of high valent organocopper compounds advancing and redefining the discipline of organocopper chemistry.

Functionalization of Alkyl Groups Adjacent to Azoles: Application to the Synthesis of α-Functionalized Carboxylic Acids

AbstractA plethora of bioactive compounds and natural products bears an azole subunit within their complex structural frameworks. A footstep to realize those complex structures in atom economic fashion rely on the direct functionalization of C–H bonds adjacent to an azole group. In addition, the resulting functionalized azole compounds can be simply modified into practically significant genre of α-functionalized carboxylic acids that are otherwise inaccessible through a formal α-functionalization strategy. In this Account, we describe an up-to-date progress on the functionalization of a methyl and/or methylene group(s) adjacent to an azole ring enabled by late and earth-abundant transition metals. Contributions made by our group and that by others in the field are elaborated in this Account article.1 Introduction2 Mode of Reactivity of C–H Bonds Next to Azoles under Transition-Metal Catalysis3 Pd-Catalyzed Functionalization of Alkyl Groups Adjacent to an Azole Ring3.1 Functionalization through C–C Bond Formation3.2 Functionalization through C–Heteroatom Bond Formation4 3d-Metal-Catalyzed Functionalization of Alkyl Groups Adjacent to an Azole Ring5 Other Metal-Catalyzed Functionalization of Alkyl Groups Adjacent to an Azole Ring6 Conclusion and Future Prospects