Introduction

Organic synthesis experiments are generally designed around a predetermined transformation: substrates and reagents are selected, the temperature and reaction time are controlled, and the target product is then isolated. Unknown peaks or unexpected products observed in an actual reaction may arise from impurities in the starting materials, fluctuations in reaction conditions, or transformations during workup, but they may also indicate an unrecognized consecutive reaction pathway.

This article was inspired by two studies. The first study reported that a reaction system composed of trimethylsilyl chloride (TMSCl) and N,N-dimethylformamide (DMF) promoted the annulative condensation of pyrazine-2-carboxamide with aldehydes to generate 3-substituted imidazo[1,5-a]pyrazin-1(7H)-ones [1]. The second study reported that copper(I) cyanide (CuCN) mediated the cyanation and subsequent cascade transformation of ortho-haloacetophenones, providing 3-methyleneisoindolin-1-ones in a single operation [2].

The two reactions begin with an amide–aldehyde reaction and aryl cyanation, respectively, and both can be understood from the perspective of consecutive reaction pathways: reactive intermediates formed during the initial transformation undergo further intramolecular cyclization and ultimately furnish heterocyclic products. Their common features can be summarized in three stages:

① The reaction conditions generate intermediates capable of undergoing subsequent transformations;

② Adjacent reactive sites within the substrate promote intramolecular cyclization;

③ Cyclization, dehydration, or tautomerization continues to consume the intermediates, directing the reaction toward the formation of heterocyclic products.

1 Core Questions Revealed by the Two Studies

1.1 Initial Transformations and Final Products

In the first reaction, the aldehyde serves not only as a condensation substrate but also as the source of the carbon atom required to construct the new five-membered ring. The pyrazine-ring nitrogen and the amide nitrogen subsequently participate in bond formation, generating the imidazopyrazinone framework.

In the second reaction, aryl cyanation is not the endpoint of the reaction. The newly introduced nitrogen-containing functional group undergoes a further intramolecular reaction with the adjacent ketone carbonyl group, ultimately forming a lactam ring and an exocyclic carbon–carbon double bond.

The two reactions raise three central questions:

① How do the reaction conditions generate reactive intermediates capable of undergoing further transformation?

② Which structural features of the substrates control intramolecular cyclization?

③ Why do the initial intermediates not accumulate, but instead continue to undergo conversion into heterocyclic products?

2 TMSCl/DMF-Promoted Formation of Imidazopyrazinones

2.1 Reaction Overview

The study employed pyrazine-2-carboxamide and aldehydes as substrates. TMSCl was added in anhydrous DMF, and the reaction mixture was heated under sealed conditions to afford 3-substituted imidazo[1,5-a]pyrazin-1(7H)-ones [1].

Representative reaction conditions were as follows:

① Pyrazine-2-carboxamide: 1.0 equiv;

② Aldehyde: 1.0 equiv;

③ TMSCl: 3.0 equiv;

④ Solvent: anhydrous DMF;

⑤ Reaction temperature: 100 °C.

Proposed Reaction Pathway

Pyrazine-2-carboxamide + R—CHO

                │ TMSCl, DMF, 100 °C

                ↓

N-Acyl hemiaminal, iminium ion, or a corresponding silylated intermediate

                ↓

Possible intramolecular attack by the adjacent pyrazine ring nitrogen

                ↓

Cyclic oxygen-containing intermediate

                ↓

Dehydration, desilylation, and tautomerization

                ↓

3-R-Imidazo[1,5-a]pyrazin-1(7H)-one

The pathway shown above is proposed primarily on the basis of the atomic connectivity observed in the product. The exact site of silylation and the sequence of the individual steps have not yet been established.

Based on the product connectivity, the newly formed five-membered ring is composed of the amide carbonyl carbon, the amide nitrogen, the carbon atom derived from the aldehyde, and the adjacent atoms of the pyrazine ring. The reaction therefore combines intermolecular condensation with intramolecular fused-ring formation.

2.2 Role of the TMSCl/DMF System

Condition screening in the study showed that the common strong acids examined did not achieve the same reaction performance as the TMSCl/DMF combination [1]. This indicates that simply adding a strong acid is insufficient to reproduce the behavior of this system, although the specific active species generated by TMSCl/DMF cannot be determined from this result alone. Silylation, consumption of water, in situ formation of acidic species, and activation of intermediates may all participate in the reaction.

2.2.1 Heteroatom Silylation and Carbonyl Activation

TMSCl can interact with oxygen- or nitrogen-containing functional groups, thereby altering the electronic properties of aldehydes, amides, and nitrogen-containing sites in the heteroaromatic ring.

In this reaction, TMSCl may alter the resonance and charge distribution of the amide through silylation of the amide oxygen or through other heteroatom-activation processes. Direct evidence is still lacking as to whether this process increases the effective nucleophilicity of the amide nitrogen. TMSCl may also activate the aldehyde or oxygen- and nitrogen-containing condensation intermediates that have already formed, thereby facilitating the formation of a new C—N bond. These effects may favor the formation of a new C—N bond between an amide-related nitrogen-containing site and an aldehyde-derived electrophilic carbon center.

The specific site of silylation and the sequence in which the various intermediates are formed still require further investigation by in situ spectroscopy, intermediate trapping, or computational chemistry.

2.2.2 Condensation Equilibrium and Dehydration

Condensation between an aldehyde and a nitrogen-containing compound is generally accompanied by the formation of water, and the reaction may be affected by the reverse hydrolysis process. Condensation between an aldehyde and a nitrogen-containing compound is generally accompanied by the formation of water, and the reaction may be affected by the reverse hydrolysis process. TMSCl is sensitive to water, and its silicon center is electrophilic and can react with water and oxygen-containing nucleophiles. Accordingly, TMSCl may reduce the effect of the reverse hydrolysis reaction by consuming water in the system or by promoting silylation of oxygen-containing intermediates, while also facilitating subsequent dehydration. It should be noted that the reaction of TMSCl with water may also generate HCl; therefore, acidic species formed in situ may also influence the reaction, although their specific role has not yet been determined.

2.2.3 Regulation of the Reaction Environment by DMF

DMF is a polar aprotic solvent that can dissolve organic substrates and stabilize certain polar intermediates. Interactions between TMSCl and DMF may also generate species with enhanced activating ability, further affecting carbonyl reactivity and the formation of ionic intermediates.

Condition screening indicates that the combination of TMSCl and DMF produces a pronounced reaction-condition effect. This combination may influence the reaction in the following ways:

① Regulating the reactivity of the aldehyde and amide;

② Promoting the formation of nitrogen-containing condensation intermediates;

③ Reducing the effects of water on the condensation equilibrium and intermediate stability;

④ Promoting subsequent ring closure, dehydration, or desilylation.

The effectiveness of the reaction arises from the combined influence of these effects.

2.3 Substrate Preorganization Controls Fused-Ring Cyclization

Pyrazine-2-carboxamide has an arrangement of atoms suitable for the construction of a five-membered ring. The carboxamide group is located at the 2-position of the pyrazine ring, and the spatial distance between the amide nitrogen and the adjacent pyrazine-ring nitrogen is relatively short.

After a new linkage is formed between the aldehyde and the amide nitrogen, the aldehyde-derived carbon is positioned near the pyrazine-ring nitrogen. Intramolecular attack by the pyrazine-ring nitrogen on this carbon center can then form a new five-membered ring.

This process can be divided into three stages:

① Condensation stage: the aldehyde and an amide-related site form a nitrogen-containing condensation intermediate;

② Ring-closure stage: the adjacent pyrazine-ring nitrogen undergoes intramolecular attack to form a new C—N bond;

③ Product-formation stage: the cyclic intermediate undergoes dehydration and tautomerization to generate the fused lactam.

The two reactive sites involved in the intramolecular reaction are already connected by the pyrazine framework, eliminating the need for two independent molecules to collide and adopt the correct orientation. This structural arrangement increases the likelihood of five-membered-ring formation and reduces the opportunity for the intermediate to participate in other intermolecular side reactions.

2.4 Reaction-Control Factors Reflected by the Substrate Scope

The reaction is compatible with aromatic aldehydes, certain aliphatic aldehydes, and various heteroaromatic aldehydes [1]. The reaction outcomes obtained with different aldehyde substrates do not display a simple linear electronic effect, indicating that the final yield is determined by multiple steps.

The principal factors that may affect the reaction outcome include:

① Initial condensation efficiency

The electrophilicity of the aldehyde carbonyl group affects the rate of its reaction with an amide-related nitrogen-containing site.

② Conformation and stability of the cyclization intermediate

The size and spatial orientation of the aldehyde substituent affect the ease with which the pyrazine-ring nitrogen can approach the reaction center.

③ Interactions between heteroatoms and TMSCl

Nitrogen, oxygen, or sulfur atoms in heteroaromatic aldehydes may interact with the silicon reagent, altering the effective concentration of TMSCl and the reactivity of the intermediates.

④ Efficiency of dehydration and tautomerization

Different substituents may affect the relative rates of dehydration of the cyclic intermediate and tautomerization of the product.

⑤ Product stability and recovery during isolation

The isolated yield may also be affected by product stability, solubility, and recovery efficiency during purification, and therefore may not necessarily be identical to the actual conversion.

Both electron-rich and electron-deficient aromatic aldehydes can participate in the reaction, indicating that the electronic properties of the aromatic aldehyde are not the sole controlling factor. The yields obtained from heteroaromatic aldehydes are relatively sensitive to heteroatom position and substitution pattern, possibly because of heteroatom coordination, competitive silylation, and intermediate stability.

For pyrazine carboxamides bearing hydroxyl groups or other readily silylated functional groups, reactivity may be affected by competitive silylation, hydrogen bonding, and proton transfer. The specific effects require confirmation through experiments with the corresponding substrates.

3 CuCN-Mediated Formation of 3-Methyleneisoindolinones

3.1 From Aryl Cyanation to Cascade Cyclization

In the second study, the original plan was to prepare ortho-acetylbenzonitriles from ortho-haloacetophenones through a Rosenmund–von Braun-type reaction. The reaction was carried out using CuCN in a DMF/tert-butanol/water system, and the major products were 3-methyleneisoindolin-1-ones [2].

Representative reaction conditions were as follows:

① Substrate: ortho-haloacetophenone;

② Cyanating reagent: CuCN;

③ Mixed solvent: DMF/tert-butanol (t-BuOH)/water, volume ratio 3:3:2;

④ Reaction temperature: 110 °C;

⑤ Reaction time: 20 h.

For a representative substrate, the target product was isolated in 92% yield, and no residual nitrile intermediate was observed at the reaction endpoint [2].

Proposed Reaction Pathway

ortho-Haloacetophenone

       │ CuCN-mediated aryl cyanation

       ↓

ortho-Acetylbenzonitrile or a related copper-bound nitrogen-containing intermediate

       │ Hydration or amidation

       ↓

An amide or a nitrogen-containing intermediate with equivalent reactivity

       ↓

Possible intramolecular attack of the nitrogen-containing site on the ketone carbonyl

       ↓

Cyclic hydroxy intermediate

       ↓

Dehydration to form an exocyclic C=C double bond

       ↓

3-Methyleneisoindolin-1-one

This reaction links aryl cyanation, nitrogen-containing functional-group transformation, intramolecular cyclization, and dehydration into a continuous sequence.

3.2 Role of the Aryl Nitrile in the Consecutive Reaction

Rosenmund–von Braun-type reactions generally target aryl nitriles as the final products. In this system, the aryl nitrile is more appropriately understood as a precursor to the subsequent cyclization.

Ortho-acetylbenzonitrile contains both a nitrile group and an adjacent ketone carbonyl group. Based on the atomic connectivity of the product, the nitrile carbon and nitrogen must be further transformed into the lactam carbonyl carbon and nitrogen. A possible pathway can therefore be proposed: the aryl nitrile is converted into an amide in the aqueous reaction medium, or into a nitrogen-containing intermediate with subsequent reactivity similar to that of an amide; this nitrogen-containing site then undergoes an intramolecular reaction with the adjacent ketone carbonyl group.

Based on the product structure, the reaction may proceed in the following sequence:

① The aryl halide may first be converted by CuCN into an aryl nitrile or a copper-bound cyanide-containing species;

② This cyanide-containing species may then undergo hydration or amidation;

③ The resulting nitrogen-containing site may undergo intramolecular nucleophilic addition to the adjacent ketone carbonyl group;

④ The cyclic hydroxy intermediate subsequently undergoes dehydration to form the exocyclic methylene group.

No aryl nitrile was detected at the reaction endpoint, indicating that no significant amount of aryl nitrile remained at the end of the reaction. This observation does not exclude the possibility that the aryl nitrile formed transiently during the early or middle stages of the reaction and was subsequently consumed. At least two possible explanations can be considered:

① The aryl nitrile did not accumulate to a detectable extent as a free intermediate, but instead entered the subsequent reaction through a copper-bound cyanide- or nitrogen-containing species;

② The free aryl nitrile formed and then rapidly underwent subsequent hydration and cyclization, resulting in a low steady-state concentration.

Independent transformation experiments using pre-synthesized ortho-acetylbenzonitrile could be used to determine whether the free aryl nitrile is an actual reaction intermediate.

3.3 The Ortho Arrangement Promotes Lactam-Ring Formation

The ortho-acetyl group performs two structural functions in the reaction.

3.3.1 Providing the Carbonyl Group for Intramolecular Addition

The nitrile group or its hydrated product is positioned ortho to the acetyl group. The nitrogen atom of the amide or related nitrogen-containing intermediate and the adjacent ketone carbonyl group are geometrically arranged in a manner suitable for constructing a five-membered ring and are therefore capable of undergoing intramolecular addition.

If the two functional groups were positioned meta or para to one another, formation of a five-membered ring by the same pathway would be difficult. This indicates that the ortho arrangement is an important structural basis for the consecutive reaction.

3.3.2 Providing the Carbon Framework of the Exocyclic Methylene Group

The methyl carbon of the acetyl group is ultimately converted into the exocyclic methylene group. After intramolecular addition forms a 3-hydroxy cyclic intermediate, a hydrogen atom on the original acetyl methyl group and the hydroxy group at the 3-position undergo formal dehydrative elimination to generate the exocyclic C=C bond.

Nitrogen-containing site + adjacent ketone carbonyl ⟶ intramolecular addition and ring closure ⟶ 3-hydroxy cyclic intermediate ⟶ dehydrative elimination⟶ exocyclic methylene product

Formation of the lactam ring and formation of the exocyclic double bond are two consecutive but distinguishable steps.

3.4 Substrates Lacking an α-Hydrogen Support a Stepwise Reaction Pathway

When diaryl ketone substrates lacking a suitable α-hydrogen were used, stable cyclic hydroxy addition products were obtained instead of the corresponding exocyclic alkenes [2].

This experimental result supports the following reaction sequence:

① The nitrogen-containing intermediate can still undergo intramolecular attack on the adjacent ketone carbonyl group;

② Intramolecular addition generates a cyclic hydroxy or amino alcohol intermediate;

③ Because the substrate lacks an α-hydrogen capable of participating in elimination, subsequent dehydration is restricted;

④ The reaction stops at the hydroxy-intermediate stage.

This result distinguishes “intramolecular cyclization” from “dehydration to form the exocyclic double bond” as two separate steps and provides structural support for a stepwise pathway involving ring closure before dehydration.

3.5 Key Role of CuCN in the Reaction

When zinc cyanide, Zn(CN)₂, was used instead of CuCN, the same overall transformation was not obtained [2], indicating that another cyanide source cannot simply reproduce the effect of CuCN. This control experiment is simultaneously influenced by factors such as cyanide-transfer ability, solubility, the metal center, and the nature of the reactive species, and therefore cannot by itself prove that copper participates in subsequent nitrile hydration or intramolecular cyclization.

The clearest role of CuCN, consistent with its classical reactivity, is to mediate the cyanation of the aryl halide. Whether copper continues to participate in hydration of the cyanide-containing species, activation of the ketone carbonyl group, or intramolecular cyclization requires further investigation through control experiments.

Experiments that could be used to distinguish the respective roles of copper and cyanide include:

① Using combinations of other copper salts and independent cyanide sources;

② Using a soluble cyanide source that does not contain copper;

③ Investigating the transformation of pre-synthesized ortho-acetylbenzonitrile under copper-free conditions;

④ Investigating the independent cyclization of pre-synthesized ortho-acetylbenzamide;

⑤ Comparing the proportions of nitrile, amide, and cyclized products at different water contents.

3.6 Regulation of the Consecutive Reaction by the Mixed Solvent

DMF, t-BuOH, and water together constitute the mixed-solvent system used in this reaction.

The individual components may exert the following effects:

① DMF may improve the dissolution or dispersion of the organic substrate and certain copper species and may favor the existence of polar intermediates;

② Water may participate in the hydration of cyanide-containing species and provide a proton source for related proton-transfer processes;

③ t-BuOH primarily serves as a cosolvent that regulates medium polarity, the dissolution or dispersion of the substrate and inorganic species, and water activity; there is no direct evidence that it participates directly in key proton-transfer steps.

The role of the mixed solvent is reflected in the coordination of the rates of the individual steps. If cyanation is rapid but nitrile hydration is slow, the aryl nitrile may accumulate; if hydration and cyclization are rapid, the isoindolinone will predominate at the reaction endpoint.

4 Common Cyclization Principles in the Two Reactions

4.1 Reaction Conditions Determine Whether Intermediates Can Undergo Further Transformation

Both the TMSCl/DMF system and the CuCN mixed-solvent system involve multiple interconnected chemical processes.

In the TMSCl/DMF reaction, the conditions simultaneously affect carbonyl activation, heteroatom silylation, the condensation equilibrium, and dehydration.

In the CuCN reaction, the conditions successively affect aryl cyanation, hydration of the nitrogen-containing functional group, intramolecular addition, and dehydrative elimination.

The reaction outcome is jointly determined by the relative rates of the individual steps. Once a particular step has occurred, whether the intermediate can proceed promptly to the next step directly affects the final product composition.

4.2 The Arrangement of Reactive Sites in the Substrate Determines Its Cyclization Ability

Both reactions depend on an arrangement of functional groups suitable for five-membered-ring formation.

① In pyrazine-2-carboxamide, the amide nitrogen and the adjacent pyrazine-ring nitrogen can be connected through the aldehyde-derived carbon to form a fused five-membered ring;

② In ortho-acetyl aryl nitriles or aryl amides, the nitrogen-containing site can undergo intramolecular addition to the adjacent ketone carbonyl group to form the five-membered isoindolinone ring.

This spatial relationship, predetermined by the molecular framework, can reduce the conformational adjustment required for cyclization and improve the competitiveness of the intramolecular reaction relative to intermolecular side reactions.

4.3 Subsequent Reactions Continuously Consume Precursor Intermediates

Some candidate intermediates are not observed or do not remain in significant amounts at the reaction endpoint, possibly because they are continuously consumed by subsequent cyclization and dehydration processes.

In the TMSCl/DMF system, the aldehyde–amide condensation intermediate continues to undergo intramolecular C—N bond formation and dehydration, ultimately being converted into a fused lactam.

In the CuCN system, cyanide-containing or amide intermediates continue to undergo hydration, lactamization, and dehydration, ultimately forming 3-methyleneisoindolin-1-one.

The proportion of the major product depends not only on the rate of the first reaction step but also on how readily the intermediate undergoes reversal after entering the subsequent reaction pathway. If subsequent cyclization and dehydration are sufficiently rapid relative to the reverse reactions, they may continuously consume the precursor intermediate and drive the overall reaction toward the cyclic product.

5 Validation of Reaction Pathways Leading to Unexpected Products

5.1 Determining the Stage at Which the Product Is Formed

An unexpected product may form during the heated reaction, but it may also be generated during concentration, acid–base treatment, or column chromatography.

Time-resolved sampling during the reaction can answer the following questions:

① When does the target heterocycle first appear?

② Is there an intermediate that first increases and then decreases?

③ Are starting-material consumption and product formation synchronized?

④ Do the workup conditions alter the product composition?

For the CuCN system, if the aryl nitrile increases during the early stage of the reaction and subsequently decreases while the amount of isoindolinone continues to increase, this would provide relatively direct evidence for a pathway involving an aryl nitrile intermediate.

5.2 Deconstructing the Consecutive Reaction Using Pre-Synthesized Intermediates

Potential intermediates can be independently synthesized and then resubjected to the reaction conditions to determine whether they are capable of undergoing subsequent transformation.

Experiments with relatively high validation value include:

① Subjecting an aldehyde–amide condensation product to TMSCl/DMF and observing whether it can continue to form an imidazopyrazinone;

② Subjecting ortho-acetylbenzonitrile to an aqueous mixed-solvent system and observing whether it can form an isoindolinone;

③ Subjecting ortho-acetylbenzamide to CuCN-free conditions to determine whether it can cyclize independently;

④ Varying the water content and comparing the proportions of nitrile, amide, and cyclized products;

⑤ Attempting to capture the cyclic hydroxy intermediate at low temperature or with a shortened reaction time.

These experiments can divide the overall reaction into individual steps such as condensation, cyanation, hydration, cyclization, and dehydration.

It should be noted that the ability of a pre-synthesized compound to undergo conversion into the product only demonstrates its chemical feasibility as an intermediate. Confirmation that it lies on the actual major reaction pathway also requires time-course data, in situ detection, kinetic studies, or isotope-labeling results.

5.3 Using Structurally Diagnostic Substrates to Identify Key Functional Groups

In addition to evaluating the applicability of a method, substrate-scope studies can also be used to determine the roles of individual functional groups in the reaction.

For the TMSCl/DMF system, the following comparisons may be particularly informative:

① Substrates in which the position of the pyrazine-ring nitrogen is changed;

② Substrates lacking the heterocyclic nitrogen that may participate in ring closure;

③ Substrates in which the relative positions of the carboxamide group and the ring nitrogen are altered;

④ Substrates bearing hydroxyl groups or other readily silylated functional groups;

⑤ Substrates in which the pyrazine ring is replaced by another nitrogen-containing heteroaromatic ring.

For the CuCN system, the following comparisons may be particularly informative:

① Moving the acetyl group from the ortho position to the meta or para position;

② Using ketone substrates lacking an α-hydrogen;

③ Replacing the ketone carbonyl group with an aldehyde, ester, or amide;

④ Independently using pre-synthesized aryl nitriles and aryl amides;

⑤ Changing the type of aryl halogen and the electronic properties of the aromatic ring.

Substrates that can block a particular step are generally more useful for determining the reaction sequence than structurally similar substrates that all furnish the product.

5.4 Gram-Scale Experiments for Evaluating Scale-Up Operability

The CuCN reaction afforded the target product in approximately 89% yield in a 1 g-scale experiment [2]. In a single experiment conducted on an approximately 1 g scale, the CuCN reaction afforded the target product in approximately 89% isolated yield [2], preliminarily demonstrating its operability on the gram scale and providing an experimental basis for further scale-up studies. Subsequent process evaluation should also examine:

① The charging method and safety controls for cyanide reagents;

② Calorimetric assessment of reaction heat, gas generation, pressure changes, and the potential risk of thermal runaway;

③ Copper residues and product purification;

④ Treatment of cyanide-containing and copper-containing waste liquids;

⑤ Recovery of DMF and t-BuOH;

⑥ The effects of water content, agitation, and mass transfer on the reaction outcome;

⑦ CuCN and cyanide-containing waste should be handled in accordance with dedicated cyanide safety procedures, and uncontrolled acidification of cyanide-containing systems should be avoided, CuCN is highly toxic, and there is a risk of HCN release under acidic conditions;

⑧ TMSCl has a boiling point below the reaction temperature and can generate HCl upon contact with water. Therefore, sealed reactions at 100 °C should be conducted in suitable pressure-rated equipment, with assessment of vapor pressure, corrosion, and pressure-relief risks.

The gram-scale yield reflects the operability of laboratory-scale enlargement. The feasibility of larger-scale processing requires comprehensive evaluation of safety, impurity control, equipment compatibility, and waste treatment.

6 Representative Chemicals Related to TMSCl/DMF Annulative Condensation and CuCN-Mediated Cascade Cyclization

Table 1. Core Reaction Reagents and Solvents

Table 2. Key Heterocyclic and Ortho-Haloaryl Ketone Substrates

Table 3. Aldehyde Substrates and Studies of Reaction Applicability

Note: The aldehydes listed in the table include representative substrates reported in the literature as well as candidate compounds that may be used for substrate-scope studies. Not all of them have been individually validated in the reaction described in Reference [1]. Specific reaction applicability, conversion, and product yield should be determined on the basis of the original literature or actual experimental results. Product catalog numbers, specifications, purity, certificates of analysis, and other information should be confirmed using the Aladdin website or the latest product documentation.

References

[1] ChemRxiv preprint. DOI: 10.26434/chemrxiv.15005744/v1.

[2] Banik T, Kaliappan K P. A serendipitous one-pot cyanation/hydrolysis/enamide formation: Direct access to 3-methyleneisoindolin-1-ones[J]. Chemistry—A European Journal, 2021, 27(2): 628–633. DOI: 10.1002/chem.202003209.

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