Synthesis最新文献

The demand for green and efficient methods for preparing silanols is significant. In this study, we employed inexpensive cesium carbonate as a catalyst to facilitate the hydrolysis of hydrosilanes for silanol production. This approach offers numerous advantages, including mild reaction conditions, broad substrate compatibility, straightforward post-treatment procedures, high yields, and scalability to gram-level synthesis. Our method demonstrated compatibility with diverse organosilanes bearing alkyl, aryl, alkynyl, and heterocyclic substituents, including sterically hindered variants. The significance of these findings extends beyond scientific inquiry, offering practical utility in the synthesis of silanols.

Discovery Process Chemistry (DPC) is an emerging intersectoral space that is characterized by the development of new chemical reactions or syntheses that enable the efficient elucidation of structure-activity relationships (SARs) and structure-property relationships (SPRs) as well as a rapid transition to process development. Drug discovery and development are accelerated by such efforts and this has led chemists in academia and industry alike to place an increasing importance on these aims. In this Short Review, we explore recent advances in DPC and the impact that it can have on SAR/SPR interrogation and downstream drug development efforts.

1 Introduction

2 Enabling SAR/SPR Interrogation with Bioisosteres

3 Couplings of Diversifiable Reaction Partners

4 Late-Stage Functionalization

5 Conclusion and Outlook

Target-first drug discovery relies heavily on protein structure information, which severely limits its application. In recent years, fragment-based drug Design (FBDD) has been identified as an alternative solution, where screening of smaller molecules for lower affinity allowed the use of focused libraries with a higher hit rate. It is shown that coupling an sp²-rich heteroaromatic group with a monofunctional sp³-rich core gives fragments (186 examples) with advantageous physical-chemical properties, covering a chemical space often neglected in traditional libraries.

Diazophosphonates function as indispensable synthetic intermediates within the domain of organic chemistry, serving as precursors for a diverse range of molecules, with potential applications as bioactive compounds. α-Diazomethylphosphonates showcase expansive reactivity and elevated levels of enantioselectivity in asymmetric transformations, especially in conjunction with suitable catalyst systems. This review compiles the latest advancements in diazophosphonate chemistry from 2016 to 2024, highlighting their reactivity and transformative potential in organic synthesis. Diazophosphonates, regarded as revolutionary compounds, exhibit unique attributes as carbene precursors, driving diverse chemical reactions such as [3+2] cycloaddition, asymmetric [3+2] cycloaddition, asymmetric [3+3] cycloaddition, and asymmetric substitution reactions. Their adaptability in functional group conversions underscores their pivotal role in various synthetic methodologies. The review highlights the growing interest in diazophosphonate reactions among synthetic chemists, fostering novel synthetic strategies and expanding their application horizons. The multifaceted utility of diazophosphonates as reagents, synthetic intermediates, precursors, and catalysts underscores their significance in modern organic chemistry and pharmaceutical applications, prompting further exploration into this dynamic field.

1 Introduction

2 [3+2] Cycloaddition Reactions

3 Asymmetric [3+2] Cycloaddition Reactions

4 Asymmetric [3+3] Cycloaddition Reactions

5 Asymmetric Substitution Reactions

6 Diazophosphonates as Carbene Precursors

7 Diazophosphonates in the Chemistry of Fluorinated Compounds

8 Other Reactions

9 Future Directions

10 Conclusion

Fluoroalkylation serves as a pivotal strategy for chemists to precisely alter the properties of small molecules. Among the established fluoroalkylation protocols, sulfone and sulfinate reagents stand out as versatile tools for these reactions, particularly in mono-, di-, and trifluoromethylations. Their versatility lies in offering multiple pathways, encompassing electrophilic, nucleophilic, as well as radical mechanisms, thus providing diverse routes for controlled molecular modifications through a variety of very exciting mechanistic paths.

1 Introduction

2 Monofluoromethylation Strategies

2.1 Fluorobis(phenylsulfonyl)methane (FBSM)

2.2 2-Fluoro-1,3-benzodithiole-1,1,3,3-tetraoxide (FBDT)

2.3 Benzothiazole-SO₂CH₂F, NaSO₂CH₂F, and ClSO₂CH₂F

2.4 PhSO₂CH₂F

3 Difluoromethylation Strategies

3.1 PhSO₂CF₂H

3.2 Benzothiazole-SO₂CF₂H

3.3 2-PyrSO₂CF₂H

3.4 NaSO₂CF₂H

4 Trifluoromethylation Strategies

4.1 PhSO₂CF₃

4.2 2-PyrSO₂CF₃

4.3 Benzothiazole-SO₂CF₃

4.4 NaSO₂CF₃

4.4.1 Electrochemical Approaches

4.4.2 Photochemical Approaches

4.4.3 Other Noteworthy Approaches

5 Conclusion

An operationally simple catalyst-free protocol for the direct regiospecific synthesis of C3-arylated/alkenylated pyrroles has been developed. The enamine-intermediate, in situ generated from succinaldehyde and a primary amine, was trapped with activated carbonyls before the Paal–Knorr reaction in a direct multicomponent ‘just-mix’ protocol to furnish pyrroles in good yields. Several C3-substituted N-alkylpyrroles have been prepared under open-flask conditions, avoiding protection-deprotection chemistry.

We report the photocatalytic alkylation of o-hydroxyarylenaminones with acceptor–acceptor diazo compounds to access 3-alkyl chromones. The reaction involves triplet sensitization of the diazo substrate via energy transfer from the photosensitizer. The notable features of the protocol are operational simplicity, wide substrate scope, and generally high yields of the products.

Trioxygenation is a highly effective method for rapidly increasing molecular complexity by incorporating three C–O bonds from simple, readily available raw materials. In this study, we present an electrochemical trioxygenation protocol for allylarenes, which enables the synthesis of a diverse array of triacetoxylation products without external chemical oxidants. These products, which are difficult to obtain through conventional methods, highlight the potential of electrochemistry in promoting sustainable synthesis.

Photocatalytic technology is considered to be a sustainable strategy to convert H₂O and O₂ into H₂O₂. However, constructing photocatalytically active and stable organic photocatalyst remain a challenge. In this study, a new class of porous aromatic framework photocatalysts (BF-PAFs) were designed and synthesized, in which 9,9′-bifluorenylidene (99′-BF) and different alkynes are alternately connected. The BF-PAFs were constructed and served as photocatalysts for H₂O₂ synthesis. Experimental results show that the introduction of different alkynes can effectively regulate the optical band gap and energy band structure, which may further determine their photocatalytic performance. Upon visible light irradiation, PAF-370 exhibits high efficiency for photosynthesis of H₂O₂ with a production rate of 730 μmol g^–1 h^–1 in the presence of sacrificial reagent from water and oxygen via oxygen reduction reaction (ORR) pathway. Furthermore, up to 61 μmol H₂O₂ could be generated from this photocatalytic system after 14 hours.

A visible-light mediated one-pot synthesis of N-aryl γ-lactams is developed following a cascade radical addition/cyclization sequence. This transition metal-free approach proceeds efficiently at room temperature, employing an organic dye as the photocatalyst. Inexpensive N-arylglycines and acrylic acid derivatives were used as the starting materials and a vast array of diversely substituted N-aryl γ-lactams were synthesized in moderate to excellent yields. Detailed mechanistic experiments and comprehensive photophysical studies elucidated a plausible reaction mechanism.