LongLarf

Synthesis
DOI: 10.1055/s-0040-1719930

N-Tosylhydrazones are highly versatile precursors for in situ carbene formation and are frequently used in metal-catalyzed cross-coupling reactions. Due to their many applications in organic synthesis, including C–C, C–O, C–N, and C–S bond formation, N-tosylhydrazones have recently received much interest. They can be simply synthesized by reacting an aldehyde or ketone with N-tosylhydrazine to produce a solid N-tosylhydrazone, which is a ‘green’ precursor of diazo compounds. Using a suitable metal catalyst, N-tosylhydrazones show versatile substrate scope for the synthesis of substituted diaminopyrroles, chromenopyrazoles, alkenylpyrazoles, benzofuran thioethers, tetrahydropyridazines, sulfur-containing heterocycles, and benzofurans with potent biological activities and even regioselective N-functionalization reactions. Metal-catalyzed reactions of N-tosylhydrazones for the construction of bioactive heterocycles are still highly in demand. Hence, this review focuses on the recent synthetic application of N-tosylhydrazones influenced by different transition metals with notable features like simple workup procedures, gram-scale synthesis, broad substrate scope, multicomponent processes, cyclization, and carbon–heteroatom bond formation.1 Introduction2 Applications of N-Tosylhydrazones3 Conclusion
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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Synthesis
DOI: 10.1055/a-1845-3810

Numerous studies on the activation of carbon–fluorine bonds have been reported in recent years. For example, acyl fluorides have been utilized as versatile reagents for acylation, arylation, and even fluorination. In this review, we focus on acyl fluorides as compounds with carbon–fluorine bonds, and highlight recent advances in strategies for the activation of their C–F bonds via transition-metal catalysis, N-heterocyclic carbene (NHCs) catalysis, organophosphine catalysis, and classical nucleophilic substitution reactions.1 Introduction2 Transition-Metal-Mediated C–F Bond Activation2.1 Acylation (Carbonyl-Retentive) Coupling Reactions2.2 Decarbonylative Reactions2.3 C–F Bond Activation by Other Transition Metals3 C–F Bond Activation by N-Heterocyclic Carbenes (NHCs)3.1 NHC-Catalyzed Cycloaddition of Acyl Fluorides3.2 NHC-Catalyzed Radical Functionalization of Acyl Fluorides3.3 NHC-Catalyzed Nucleophilic Fluorination of (Hetero)aromatics4 C–F Bond Activation by Phosphines4.1 Phosphine-Catalyzed Direct Activation of the C–F Bond of Acyl Fluorides4.2 Phosphine-Catalyzed Indirect Activation of the C–F Bond of Acyl Fluorides5 C–F Bond Activation by Classical Nucleophilic Substitution6 Miscellaneous Examples7 Summary and Perspective
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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C4-regioselective prenylation of 5-substituted tryptophans as well as truncated tryptophan derivatives was achieved using a set of prenlyltransferases. Conversions were increased by designing improved variants and the feasibility of preparative transformations was successfully demonstrated reaching isolated yields up to 90 %.

Abstract

Regioselective carbon−carbon bond formation belongs to the challenging tasks in organic synthesis. In this context, C−C bond formation catalyzed by 4-dimethylallyltryptophan synthases (4-DMATSs) represents a possible tool to regioselectively synthesize C4-prenylated indole derivatives without site-specific preactivation and circumventing the need of protection groups as used in chemical synthetic approaches. In this study, a toolbox of 4-DMATSs to produce a set of 4-dimethylallyl tryptophan and indole derivatives was identified. Using three wild-type enzymes as well as variants, various C5-substituted tryptophan derivatives as well as N-methyl tryptophan were successfully prenylated with conversions up to 90 %. Even truncated tryptophan derivatives like tryptamine and 3-indole propanoic acid were regioselectively prenylated in position C4. The acceptance of C5-substituted tryptophan derivatives was improved up to 5-fold by generating variants (e. g. T108S). The feasibility of semi-preparative prenylation of selected tryptophan derivatives was successfully demonstrated on 100 mg scale at 15 mM substrate concentration, allowing to reduce the previously published multistep chemical synthetic sequence to just a single step.

Under (low) pressure: Glycerol carbonate can be produced from glycidol and CO₂ using cheap and abundant biobased catalysts that can be operated under mild pressure conditions, comparatively low temperatures, and no halide additives. The biocatalysts are investigated by kinetics and various controls, showing the importance of a multi-interaction-type substrate activation. The process is extended to a heterogeneous protocol demonstrating high stability and reuse of the biobased catalyst.

Abstract

Glycerol carbonate (GC) has emerged as an attractive synthetic target due to various promising technological applications. Among several viable strategies to produce GC from CO₂ and glycerol and its derivatives, the cycloaddition of CO₂ to glycidol represents an atom-economic an efficient strategy that can proceed via a halide-free manifold through a proton-shuttling mechanism. Here, it was shown that the synthesis of GC can be promoted by bio-based and readily available organic salts leading to quantitative GC formation under atmospheric CO₂ pressure and moderate temperatures. Comparative and mechanistic experiments using sodium citrate as the most efficient catalyst highlighted the role of both hydrogen bond donor and weakly basic sites in the organic salt towards GC formation. The citrate salt was also used as a catalyst for the conversion of other epoxy alcohols. Importantly, the discovery that homogeneous organic salts catalyze the target reaction inspired us to use metal alginates as heterogeneous and recoverable bio-based catalysts for the same process.

The catalytic pyrolysis of various CO₂-based polycarbonates in bulk recovers epoxide monomers quantitatively using a simple Cr^III-Salen catalyst. It even proceeds very efficiently for chemical recycling of poly(cyclohexene carbonate) from a plastic waste mixture and thus provides a closed-loop approach towards a circular plastic economy in applications of CO₂-based polycarbonates.

Abstract

Chemical recycling of polymers to their constituent monomers is the foremost challenge in building a sustainable circular plastics economy. Here, we report a strategy for highly efficient depolymerization of various CO₂-based alicyclic polycarbonates to epoxide monomers in solvent-free conditions by a simple Cr^III-Salen complex mediated catalytic pyrolysis process. The chemical recycling of the widely studied poly(cyclohexene carbonate) exhibits excellent reactivity (TOF up to 3000 h⁻¹, 0.1 mol % catalyst loading) and high epoxide monomer selectivity (>99 %). Mechanistic investigation reveals that the process proceeds in a sequential fashion via a trans-carbonate intermediate.

Nature Chemistry, Published online: 27 June 2022; doi:10.1038/s41557-022-00964-7

A strategy for protecting redox-active ortho-quinones, which show promise as anticancer agents but suffer from redox-cycling behaviour and systemic toxicity, has been developed. The ortho-quinones are derivatized to redox-inactive para-aminobenzyl ketols. Upon amine deprotection, an acid-promoted, self-immolative C–C bond-cleaving 1,6-elimination releases the redox-active hydroquinone. The strategy also enables conjugation to a carrier for targeted delivery of ortho-quinone species.

A route involving both enzymatic and spontaneous chemical reactions was designed for the synthesis of L-homophenylalanine from inexpensive building blocks. One enzyme in the cascade, EcQOR, was identified as the first ene reductase to catalyze the reduction of an unsaturated aromatic keto acid. This study shows the potential of introducing spontaneous chemical reactions into enzymatic cascades for the synthesis of valuable chemicals.

Abstract

L-Homophenylalanine (L-HPA) is a vital building block for the synthesis of numerous chiral drugs. However, the high cost of starting materials limits the industrial production of L-HPA. In this study, an enzymatic-spontaneous chemical cascade route for L-HPA production was designed based on retrosynthetic analysis. This route, using simple benzaldehyde and pyruvate as starting materials, is extremely cost-effective. The enzymes were screened and further assembled in E. coli, and TipheDH was identified as the rate-limiting enzyme. Therefore, TipheDH was engineered to improve its specific activity (by 82 %) and expression level (by 254 %), thus generating the best strain (W14). W14 exhibited the optimum enzyme activity ratio (1.7 : 1.1 : 1 : 1.8) and demonstrated production of 100.9 g L⁻¹ of L-HPA (with 94 % conversion, >99 % ee) in a 5-L reactor. This route effectively exploits the power of cascades and offers insight into avenues for synthesizing other valuable chemicals from inexpensive building blocks.

Publication date: Available online 27 June 2022

Source: Chem

Author(s): Qilei Zhu, Daniel G. Nocera

Publication date: 14 July 2022

Source: Chem, Volume 8, Issue 7

Author(s): Ferran Esteve, Belén Altava, Eduardo García-Verdugo, Santiago V. Luis, Jean-Marie Lehn

Nature Communications, Published online: 23 June 2022; doi:10.1038/s41467-022-31260-0

Our peer review programme was launched in 2020 to support Early Career Researchers in building confidence to participate in peer review. The initiative has proved very successful and popular with both ECRs and editors and we are pleased to invite applicants to apply to our 2022 programme.

Buchwald-Hartwig amination of 1,3,5-tribromobenzene with commercially available or easily prepared amino-pyridine derivatives and consecutive N−H/C−H coupling using a hypervalent iodine reagent realized a two-step protocol for various polyazatruxenes. The quantum yield of the hexaazatruxene reached ca. 0.80.

Abstract

Truxene is a C ₃-symmetric compound with characteristic photophysical properties, and it has great potential as a light-emitting material and building block. In this study, we demonstrate the synthesis of hexaazatruxenes using a two-step protocol. First, the hexaazatruxene precursors were prepared through the Buchwald-Hartwig amination of 1,3,5-tribromobenzene with commercially available or easily prepared amino-pyridine derivatives. Then, hexaazatruxenes were synthesized through consecutive N−H/C−H coupling using a hypervalent iodine reagent. To the best of our knowledge, this is the first report on the synthesis of truxenes containing more than three heteroatoms in the main skeleton.

Publication date: 13 August 2022

Source: Tetrahedron, Volume 120

Author(s): Shutao Wang, Yongliang Gao, Shaoli Song, Xinze Li, Zhuoqi Zhang, Jinbao Xiang, Lianyou Zheng

Mild, rapid, and efficient demethylation of aryl alkyl ethers is accomplished using tris(pentafluorophenyl)borane via the Piers-Rubinsztajn reaction. This two-step deprotection allows alkyl ethers to be used as effective phenol protecting groups without the need for harsh deprotection conditions.

Abstract

We report that the Piers-Rubinsztajn reaction enables rapid deprotection of aryl alkyl ethers under ambient conditions. This chemistry leverages tris(pentafluorophenyl)borane and silyl hydrides to convert aryl methyl ethers to siloxanes, which can then be cleaved using 1 % HCl in EtOH. We examined 26 derivatives and routinely obtained yields >85 %, even in the presence of sterically demanding groups and complex substrate structures. Other alkyl ethers including ethyl, propyl, isopropyl, tert-butyl, and benzyl groups were also easily removed.

Synlett
DOI: 10.1055/a-1865-2556

A synthesis of 3-alkyl-2-arylindoles was performed by sequential oxidation and reduction of 2-(2-nitrophenyl)ethanols that were prepared by base-catalyzed three-component reactions of vinylarenes, aldehydes, and various pronucleophiles, including nitroalkanes, thiols, and malonates. In addition to indoles, a selective synthesis of an N-hydroxyindole was accomplished. The highly nucleophilic character of transient benzylic anions in DMSO was also clarified for the three-component reactions.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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The fruitful merger of organoboron chemistry and photocatalysis has led to the development of new technologies to access complex (non)borylated frameworks. Central to the success is control of boron hybridisation. This Minireview highlights the current state of the art in photocatalytic processes utilising organoboron compounds, paying particular attention to the role of boron hybridisation for the target transformation.

Abstract

Recently the fruitful merger of organoboron chemistry and photocatalysis has come to the forefront of organic synthesis, resulting in the development of new technologies to access complex (non)borylated frameworks. Central to the success of this combination is control of boron hybridisation. Contingent on the photoactivation mode, boron as its neutral planar form or tetrahedral boronate can be used to regulate reactivity. This Minireview highlights the current state of the art in photocatalytic processes utilising organoboron compounds, paying particular attention to the role of boron hybridisation for the target transformation.

Science, <a href="https://www.science.org/toc/science/376/6600">Volume 376, Issue 6600</a>, Page 1433-1441, June 2022.

A crown-ether-protein adhesive was synthesized by host–guest molecular engineering. The internal dynamic molecular interactions endow the adhesives with extraordinary adhesion performance over a wide temperature range from −196 to 200 °C. Extremely strong adhesion, long-lasting adhesion, and biomedical sealing have been achieved. This work offers a promising molecular engineering strategy to fabricate robust supramolecular adhesives for applications under extreme conditions.

Abstract

The inherently tenuous adhesion strength and limited environmental tolerance of supramolecular adhesives severely restrict their application scenarios. It is challenging for the development of robust adhesives with extreme temperature tolerance. Herein, we report a new type of temperature-resistant crown-ether-protein (CEP) adhesive by harnessing synergistic host–guest molecular interactions between engineered crown ether and protein building blocks. The outputs of CEP adhesive demonstrate ultrahigh shearing adhesion strength of ≈22 MPa over a wide temperature range from −196 to 200 °C, superior to other established supramolecular or polymeric adhesives. The temperature-induced phase transition and internal bound water stabilized the system and led to superb adhesion under extreme conditions. Thus, this work pioneers a molecular engineering approach for the generation of adhesives with tailored applications in extreme settings.

Publication date: 8 September 2022

Source: Chem, Volume 8, Issue 9

Author(s): Yuman Qin, Tong Zhang, H.Y. Vincent Ching, Gandhi Siva Raman, Shoubhik Das