Green Chemistry in the Synthesis of Pharmaceuticals

Chemical Reviews, Год журнала: 2021, Номер 122(3), С. 3637 - 3710

Опубликована: Дек. 15, 2021

The principles of green chemistry (GC) can be comprehensively implemented in synthesis pharmaceuticals by choosing no solvents or (preferably water), alternative reaction media, and consideration one-pot synthesis, multicomponent reactions (MCRs), continuous processing, process intensification approaches for atom economy final waste reduction. GC's execution performed using a holistic design the active pharmaceutical ingredient's (API) life cycle, minimizing hazards pollution, capitalizing resource efficiency technique. Thus, presented review accounts comprehensive exploration metrics, an appropriate implication those ideas each step schemes, from raw material to intermediate product's into scalable industry-based production. For real-life examples, we have discussed series established generic pharmaceuticals, starting with materials, intermediates corresponding pharmaceuticals. Researchers industries thoughtfully instigated control reduction protect environment. We extensively significant relevant cascade MCRs, intensification, which may contribute future sustainable APIs.

Язык: Английский

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Transition-Metal-Catalyzed C–H Bond Activation for the Formation of C–C Bonds in Complex Molecules

Chemical Reviews, Год журнала: 2023, Номер 123(12), С. 7692 - 7760

Опубликована: Май 10, 2023

Site-predictable and chemoselective C–H bond functionalization reactions offer synthetically powerful strategies for the step-economic diversification of both feedstock fine chemicals. Many transition-metal-catalyzed methods have emerged selective activation bonds. However, challenges regio- chemoselectivity with application to highly complex molecules bearing significant functional group density diversity. As molecular complexity increases within structures risks catalyst intolerance limited applicability grow number groups potentially Lewis basic heteroatoms. Given abundance bonds already diversified such as pharmaceuticals, natural products, materials, design selection reaction conditions tolerant catalysts has proved critical successful direct functionalization. such, innovations formation carbon–carbon been discovered developed overcome these limitations. This review highlights progress made metal-catalyzed C–C forming including alkylation, methylation, arylation, olefination targets.

Язык: Английский

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C–H deuteration of organic compounds and potential drug candidates

Chemical Society Reviews, Год журнала: 2022, Номер 51(8), С. 3123 - 3163

Опубликована: Янв. 1, 2022

This review summarises deuteration methods of various organic motifs containing C(sp 2 )−H and 3 bonds utilizing C−H bond functionalisation as a key step along with variety catalysts, exemplifies their biological relevance.

Язык: Английский

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Nickel and Palladium Catalysis: Stronger Demand than Ever

ACS Catalysis, Год журнала: 2022, Номер 12(2), С. 1180 - 1200

Опубликована: Янв. 5, 2022

Key similarities and differences of Pd Ni in catalytic systems are discussed. Overall, catalyze a vast number similar C–C C–heteroatom bond-forming reactions. However, the smaller atomic radius lower electronegativity Ni, as well more negative redox potentials low-valent species, often provide higher reactivity oxidative addition or insertion reactions persistence alkyl-Ni intermediates against β-hydrogen elimination, thus enabling activation reluctant electrophiles, including alkyl electrophiles. Another key point relates to stability open-shell electronic configurations Ni(I) Ni(III) compared with Pd(I) Pd(III). Nickel very involve interconvertible Ni(n+) active species variable oxidation states (Ni(0), Ni(I), Ni(II), Ni(III)). In contrast, involving Pd(III) still relatively less developed may require facilitation by special ligands merging photo- electrocatalysis. high Pd(n+) ensure their facile reduction Pd(0) under assistance numerous reagents solvents, providing concentrations molecular Pd1(0) complexes that can reversibly aggregate into Pdn clusters nanoparticles form cocktail Pdn(0) various nuclearities (i.e., values "n"). Ni(0) strong reductants; they sensitive deactivation air other oxidizers and, consequence, operate at catalyst loadings than palladium same The ease robustness versatility for catalysis, whereas variety enables diverse uncommon reactivity, albeit requiring efforts stabilization nickel systems. As discussion, we note easily "cocktail particles" different but (Pd1, Pdn, NPs), behave species" is stable nuclearities. Undoubtedly, there stronger demand ever not only develop improved efficient catalysts also understand mechanisms

Язык: Английский

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Iron-Catalyzed C(Sp³)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(13), С. 7600 - 7611

Опубликована: Март 23, 2023

Catalytic C(sp3)-H functionalization has provided enormous opportunities to construct organic molecules, facilitating the derivatization of complex pharmaceutical compounds. Within this framework, direct hydrogen atom transfer (HAT) photocatalysis becomes an appealing approach goal. However, viable substrates utilized in these protocols are limited, and site selectivity shows preference activated thermodynamically favored bonds. Herein, we describe development undirected iron-catalyzed borylation, thiolation, sulfinylation reactions enabled by photoinduced ligand-to-metal charge (LMCT) process. These exhibit remarkably broad substrate scope (>150 examples total), most importantly, all three show unconventional regioselectivity, with occurrence preferentially at distal methyl position. The procedures operationally simple readily scalable provide access high-value products from hydrocarbons one step. Mechanistic studies control experiments indicate that afforded is not only relevant HAT species but also largely affected use boron- sulfone-based radical acceptors.

Язык: Английский

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Replacement of Less-Preferred Dipolar Aprotic and Ethereal Solvents in Synthetic Organic Chemistry with More Sustainable Alternatives

Chemical Reviews, Год журнала: 2022, Номер 122(6), С. 6749 - 6794

Опубликована: Фев. 24, 2022

Dipolar aprotic and ethereal solvents comprise just over 40% of all organic utilized in synthetic organic, medicinal, process chemistry. Unfortunately, many the common "go-to" are considered to be "less-preferable" for a number environmental, health, safety (EHS) reasons such as toxicity, mutagenicity, carcinogenicity, or practical handling flammability volatility. Recent legislative changes have initiated implementation restrictions on use commonly employed dipolar dimethylformamide (DMF) N-methyl-2-pyrrolidinone (NMP), ethers 1,4-dioxane. Thus, with growing legislative, EHS, societal pressures, need identify implement alternative that greener, safer, more sustainable has never been greater. Within this review, ubiquitous nature is discussed respect physicochemical properties made them so appealing chemists. An overview current being imposed discussed. A variety alternative, garnered attention past decade then examined, case studies examples where less-preferable successfully replaced safer highlighted. Finally, general guidance solvent selection replacement included Supporting Information review.

Язык: Английский

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Skeletal Editing: Interconversion of Arenes and Heteroarenes

Helvetica Chimica Acta, Год журнала: 2023, Номер 106(3)

Опубликована: Янв. 13, 2023

Abstract Skeletal editing involves making specific point‐changes to the core of a molecule through selective insertion, deletion or exchange atoms. It thus represents potentially powerful strategy for step‐economic modification complex substrates and is perfect complement methods such as C−H functionalization that target molecular periphery. Given their ubiquity in biologically active compounds, ability perform skeletal on – therefore interconvert between aromatic heterocycles especially valuable. This review summarizes both recent key historical examples applied interconversion rings; we anticipate it will serve highlight not only innovative enabling nature current methods, but also tremendous opportunities still exist field.

Язык: Английский

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Cobalt-Catalyzed Enantioselective C–H Arylation of Indoles

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(2), С. 798 - 806

Опубликована: Янв. 10, 2022

Atropoisomeric (hetero)biaryls are scaffolds with increasing importance in the pharmaceutical and agrochemical industries. Although it is most obvious disconnection to construct such compounds, direct enantioselective C–H arylation through concomitant induction of chiral information remains extremely challenging uncommon. Herein, unprecedented earth-abundant 3d-metal-catalyzed atroposelective reported, furnishing rare atropoisomeric C2-arylated indoles. Kinetic studies DFT computation revealed an uncommon mechanism for this asymmetric transformation, oxidative addition being rate- enantio-determining step. Excellent stereoselectivities were reached (up 96% ee), while using unusual N-heterocyclic carbene ligand bearing essential remote substituent. Attractive dispersion interactions along positive C–H---π exerted by identified as key factors guarantee excellent enantioselection.

Язык: Английский

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Skeletal Editing of (Hetero)Arenes Using Carbenes

Chemistry - A European Journal, Год журнала: 2023, Номер 29(42)

Опубликована: Май 26, 2023

Abstract (Hetero)arenes continue to prove their indispensability in pharmaceuticals, materials science, and synthetic chemistry. As such, the controllable modification of biologically significant (hetero)arenes towards diverse more‐potent complex molecular scaffolds through peripheral skeletal editing has been considered a challenging goal organic Despite many excellent reviews on ( i. e ., C−H functionalization) (hetero)arenes, editings via single atom insertion, deletion, or transmutations have received less attention review literature. In this review, we systematically summarize state‐of‐the‐art reactions using carbenes, with focus general mechanistic considerations applications natural product syntheses. The potential opportunities inherent challenges encountered while developing these strategies are also highlighted.

Язык: Английский

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Transition metal–catalyzed remote C─H borylation: An emerging synthetic tool

Science Advances, Год журнала: 2023, Номер 9(16)

Опубликована: Апрель 21, 2023

Transition metal–catalyzed C─H bond activation and borylation is a powerful synthetic method that offers versatile transformation from organoboron compounds to virtually all other functional groups. Compared the ortho-borylation, remote remains more challenging owing inaccessibility of these bonds. Enforcing metal catalyst toward bonds needs well-judged design through proper ligand development. This review article aims summarize recent discoveries for by employment new catalyst/ligand with help steric ligand, noncovalent interactions. It has been found now takes part in total synthesis natural products shorter route. Whereas, Ir-catalyzed predominant, cobalt also started affect this field sustainable cost-effective

Язык: Английский

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