亲核酰化反应的研究进展

本文综述了近年来亲核酰化反应的研究进展,分别讨论了亲核酰化试剂的类型、结构、特点以及在有机合成中的应用。     

Carbocations as Lewis Acid Catalysts in Diels–Alder and Michael Addition Reactions

In general, Lewis acid catalysts are metal‐based compounds that owe their reactivity to a low‐lying empty orbital. However, one potential Lewis acid that has received negligible attention as a catalyst is the carbocation. We have demonstrated the potential of the carbocation as a highly powerful Lewis acid catalyst for organic reactions. The stable and easily available triphenylmethyl (trityl) cation was found to be a highly efficient catalyst for the Diels–Alder reaction for a range of substrates. Catalyst loadings as low as 500 ppm, excellent yields, and good endo/exo selectivities were achieved. Furthermore, by changing the electronic properties of the substituents on the tritylium ion, the Lewis acidity of the catalyst could be tuned to control the outcome of the reaction. The ability of this carbocation as a Lewis acid catalyst was also further extended to the Michael reaction.     

Template‐Induced Diverse Metal–Organic Materials as Catalysts for the Tandem Acylation–Nazarov Cyclization

In our continuing quest to develop a metal–organic framework (MOF)‐catalyzed tandem pyrrole acylation–Nazarov cyclization reaction with α,β‐unsaturated carboxylic acids for the synthesis of cyclopentenone[b]pyrroles, which are key intermediates in the synthesis of natural product (±)‐roseophilin, a series of template‐induced Zn‐based ( 1–3 ) metal‐organic frameworks (MOFs) have been solvothermally synthesized and characterized. Structural conversions from non‐porous MOF 1 to porous MOF 2 , and back to non‐porous MOF 3 arising from the different concentrations of template guest have been observed. The anion–π interactions between the template guests and ligands could affect the configuration of ligands and further tailor the frameworks of 1–3 . Futhermore, MOFs 1–3 have shown to be effective heterogeneous catalysts for the tandem acylation–Nazarov cyclization reaction. In particular, the unique structural features of 2 , including accessible catalytic sites and suitable channel size and shape, endow 2 with all of the desired features for the MOF‐catalyzed tandem acylation–Nazarov cyclization reaction, including heterogeneous catalyst, high catalytic activity, robustness, and excellent selectivity. A plausible mechanism for the catalytic reaction has been proposed and the structure–reactivity relationship has been further clarified. Making use of 2 as a heterogeneous catalyst for the reaction could greatly increase the yield of total synthesis of (±)‐roseophilin.     

The First Magnetic Nanoparticle‐Supported Chiral DMAP Analogue: Highly Enantioselective Acylation and Excellent Recyclability

Recyclable organocatalysts : The first chiral DMAP analogue immobilized on magnetic nanoparticles is a highly active catalyst that is capable of the acylation of racemic sec‐alcohols under convenient, process‐scale friendly conditions (room temperature, 5 mol % loading, with acetic anhydride as the acylating agent) with excellent enantiodiscrimination. The catalyst is easily recovered and possesses unprecedented recyclability—in this study it was demonstrated to retain excellent activity and selectivity over 32 iterative cycles.

     

Organocatalytic enantioselective acyl transfer onto racemic as well as meso alcohols, amines, and thiols

Acyl transfer is at the heart of functional-group transfers utilized both in nature and in the chemical laboratory. Acylations are part of the natural assembly machinery for the generation of complex molecules and for energy transport in biological systems. The recognition of covalent acyl-enzyme intermediates led to both mechanistic studies as well as the development of biomimetic approaches. Consequently, chemists first used the tools of nature in the form of enzymes and naturally occurring alkaloids as catalysts, before eventually developing a large variety of synthetic small molecules for selective acyl transfer. In contrast to nature, chemists utilize acylation reactions as a practical way for stereoselection and functional-group protection. Indeed, the number of studies concerning acyl transfer has significantly increased over the last 15 years. This Review examines and highlights these recent developments with the focus as given in the title.     

Formamides as Lewis Base Catalysts in SN Reactions—Efficient Transformation of Alcohols into Chlorides,Amines, and Ethers

A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium‐activated alcohols as intermediates. The novel method, which can be even performed under solvent‐free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste‐balance (E‐factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee). In a practical one‐pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac‐Clopidogrel and S‐Fendiline.     

Structure–Activity Relationship of Palladium Phosphanesulfonates: Toward Highly Active Palladium‐Based Polymerization Catalysts

Palladium phosphanesulfonate [R₂P(C₆H₄‐o‐SO₃)PdMeL] catalysts permit the copolymerization of an exceptional large number of functional olefins with ethylene. However, these catalysts usually have reduced activity. We here have conducted a systematic study on the influence of the phosphane substituent, R, on activity and molecular weight. Phosphanes with strong σ‐donating character are shown to lead to the most active catalysts. Thus, the catalyst based on phosphane bis‐tert‐butyl‐phosphanyl‐benzenesulfonic acid (R=tBu) exhibits unprecedented high activity, rapidly polymerizing ethylene at room temperature to yield a linear polymer of high molecular weight (M_w=116 000 g mol^?1). The influence of the R group on the catalyst ability to incorporate methyl acrylate is also investigated.     

Chiral Sulfinamide Bisphosphine Catalysts: Design,Synthesis, and Application in Highly Enantioselective Intermolecular Cross‐Rauhut–Currier Reactions

A novel type of highly efficient chiral sulfinamide bisphosphine catalysts (Wei‐Phos) were developed. These could be easily prepared from commercially available starting materials. Wei‐Phos has shown good performance in the very challenging intermolecular cross‐Rauhut–Currier reactions of vinyl ketones and 3‐acyl acrylates or 2‐ene‐1,4‐diones, leading to the R‐C products in high yields with up to 99 % ee under 2.5–5 mol% catalyst loading. The highly regio‐ and enantio‐selective cross‐Rauhut–Currier reactions of 2‐ene‐1,4‐diones and vinyl ketone have yet reported so far.     

Controllable 1D and 2D Cobalt Oxide and Cobalt Selenide Nanostructures as Highly Efficient Electrocatalysts for the Oxygen Evolution Reaction

The relationship between controllable morphology and electrocatalytic activity of Co₃O₄ and CoSe₂ for the oxygen evolution reaction (OER) was explored in alkaline medium. Based on the time‐dependent growth process of cobalt precursors, 1D Co₃O₄ nanorods and 2D Co₃O₄ nanosheets were successfully synthesized through a facile hydrothermal process at 180 °C under different reaction times, followed by calcination at 300 °C for 2 h. Subsequently, 1D and 2D CoSe₂ nanostructures were derived by selenization of Co₃O₄, which achieved the controllable synthesis of CoSe₂ without templating agents. By comparing the electrocatalytic behavior of these cobalt‐based catalysts in 1 m KOH electrolyte toward the OER, both 2D Co₃O₄ and 2D CoSe₂ nanocrystals have lower overpotentials and better electrocatalytic stability than that of 1D nanostructures. The 2D CoSe₂ nanosheets require overpotentials of 372 mV to reach a current density of 50 mA cm⁻² with a small Tafel slope of 74 mV dec⁻¹. A systematic contrast of the electrocatalytic performances for the OER increase in the order: 1D Co₃O₄<2D Co₃O₄<1D CoSe₂<2D CoSe₂. This work provides fundamental insights into the morphology–performance relationships of both Co₃O₄ and CoSe₂, which were synthesized through the same approach, providing a solid guide for designing OER catalysts.     

Ionic Liquids as Organocatalysts for Nucleophilic Fluorination: Concepts and Perspectives

Besides their extremely useful properties as solvent, ionic liquids (ILs) are now considered to be highly instructive tools for enhancing the rates of chemical reactions. The ionic nature of the IL anion and cation seems to be the origin of this fascinating function of ILs as organocatalyst/promoter through their strong Coulombic forces on other ionic species in the reaction and also through the formation of hydrogen bonds with various functional groups in substrates. It is now possible to tailor-make ILs for specific purposes as solvent/promoters in a variety of situations by carefully monitoring these interactions. Despite the enormous potentiality, it seems that the application of ILs as organocatalysts/promoters for chemical reactions have not been fully achieved so far. Herein, we review recent developments of ILs for promoting the nucleophilic reactions, focusing on fluorination. Various aspects of the processes, such as organocatalytic capability, reaction mechanisms and salt effects, are discussed.     

Vaulted Biaryls in Catalysis: A Structure–Activity Relationship Guided Tour of the Immanent Domain of the VANOL Ligand

The active site in the BOROX catalyst is a chiral polyborate anion (boroxinate) that is assembled in situ from three equivalents of B(OPh)₃ and one of the VANOL ligand by a molecule of substrate. The substrates are bound to the boroxinate by H bonds to oxygen atoms O1–O3. The effects of introducing substituents at each position of the naphthalene core of the VANOL ligand are systematically investigated in an aziridination reaction. Substituents in the 4,4′‐ and 8,8′‐positions have a negative effect on catalyst performance, whereas, substituents in the 7‐ and 7′‐positions have the biggest impact in a positive direction.     

Metal–Organic Frameworks as Catalysts for Oxidation Reactions

This Concept is aimed at describing the current state of the art in metal–organic frameworks (MOFs) as heterogeneous catalysts for liquid‐phase oxidations, focusing on three important substrates, namely, alkenes, alkanes and alcohols. Emphases are on the nature of active sites that have been incorporated within MOFs and on future targets to be set in this area. Thus, selective alkene epoxidation with peroxides or oxygen catalyzed by constitutional metal nodes of MOFs as active sites are still to be developed. Moreover, no noble metal‐free MOF has been reported to date that can act as a general catalyst for the aerobic oxidation of primary and secondary aliphatic alcohols. In contrast, in the case of alkanes, a target should be to tune the polarity of MOF internal pores to control the outcome of the autooxidation process, resulting in the selective formation of alcohol/ketone mixtures at high conversion.     

Horseradish Peroxidase Catalyzed Hydrogelation for Biomedical,Biopharmaceutical, and Biofabrication Applications

Horseradish peroxidase (HRP)‐catalyzed hydrogelation has attracted much attention owing to the ease of handling, high biocompatibility, and processability. This review summarizes recent developments, including cutting‐edge research into the use of HRP‐mediated hydrogelation toward biomedical, biopharmaceutical, and biofabrication applications. From the viewpoint of polymer chemistry, the basic chemistry behind hydrogelation, the structure–property relationship, and hybridization of multiple materials by using HRP‐catalyzed hydrogelation are summarized. From the chemical engineering perspective, strategies for controlling hydrogelation kinetics, hydrogel characteristics, and hydrogelation processes are summarized and discussed in detail. Strategies for obtaining biomaterials for medical and pharmaceutical use, and biofabrication for tissue engineering and regenerative medicine emerge by unifying the aspects of HRP‐mediated hydrogelation.     

Chiral DMAP‐N‐oxides as Acyl Transfer Catalysts: Design,Synthesis, and Application in Asymmetric Steglich Rearrangement

A DMAP‐N‐oxide, featuring an α‐amino acid as the chiral source, was developed, synthesized and applied in asymmetric Steglich rearrangement. A series of O‐acylated azlactones afforded C‐acylated azlactones possessing a quaternary stereocenter in high yields (up to 97 % yield) and excellent enantioselectivities (up to 97 % ee). Compared to the widespread use of pyridine nitrogen, which serves as the nucleophilic site in the asymmetric acyl transfer reaction, we discovered that chiral DMAP‐N‐oxides, in which the oxygen now acts as the nucleophilic site, are efficient acyl transfer catalysts. Our finding might open a new door for the development of chiral DMAP‐N‐oxides for asymmetric acyl transfer reactions.     

Reactions of a Ruthenium Complex with Substituted N‐Propargyl Pyrroles

In an investigation into the chemical reactions of N‐propargyl pyrroles 1 a – c , containing aldehyde, keto, and ester groups on the pyrrole ring, with [Ru]?Cl ([Ru]=Cp(PPh₃)₂Ru; Cp=C₅H₅), an aldehyde group in the pyrrole ring is found to play a crucial role in stimulating the cyclization reaction. The reaction of 1 a , containing an aldehyde group, with [Ru]?Cl in the presence of NH₄PF₆ yields the vinylidene complex 2 a , which further reacts with allyl amine to give the carbene complex 6 a with a pyrrolizine group. However, if 1 a is first reacted with allyl amine to yield the iminenyne 8 a , then the reaction of 8 a with [Ru]?Cl in the presence of NH₄PF₆ yields the ruthenium complex 9 a , containing a cationic pyrrolopyrazinium group, which has been fully characterized by XRD analysis. These results can be adequately explained by coordination of the triple bond of the propargyl group to the ruthenium metal center first, followed by two processes, that is, formation of a vinylidene intermediate or direct nucleophilic attack. Additionally, the deprotonation of 2 a by R₄NOH yields the neutral acetylide complex 3 a . In the presence of NH₄PF₆, the attempted alkylation of 3 a resulted in the formation the Fischer‐type amino–carbene complex 5 a as a result of the presence of NH₃, which served as a nucleophile. With KPF₆, the alkylation of 3 a with ethyl and benzyl bromoacetates afforded the disubstituted vinylidene complexes 10 a and 11 a , containing ester groups, which underwent deprotonation reactions to give the furyl complexes 12 a and 13 a , respectively. For 13 a , containing an O‐benzyl group, subsequent 1,3‐migration of the benzyl group was observed to yield product 14 a with a lactone unit. Similar reactivity was not observed for the corresponding N‐propargyl pyrroles 1 b and 1 c , which contained keto and ester groups, respectively, on the pyrrole ring.