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Why is the Thiol-ene reaction known as the "click reaction" in chemistry? What is the secret behind it?
In the chemistry of organic sulfur compounds, the Thiol-ene reaction (also known as the hydration sulfidation reaction of olefins) is an important organic reaction. This reaction is carried out between a sulfur-containing compound (R−SH, thiol) and an alkene (R2C=CR2), ultimately forming a thioether (R−S−R'). Although this reaction was first reported as early as 1905, it began to receive attention in the late 1990s and early 2000s due to its feasibility and widespread application. Today, the Thiol-ene reaction is generally accepted as one of the "click reactions" mainly because of its high yield, stereoselectivity, fast reaction rate, and thermodynamic driving force.
Due to the anti-Markovnikov addition properties of the reaction, thiol compounds can be added to alkenes in a specific manner.
Reaction mechanism
Free radical addition
The Thiol-ene reaction is thought to proceed via two mechanisms: radical addition and catalytic Michaelis-Menten addition. Radical addition can be initiated by light, heat, or a radical initiator to form sulfanyl radicals. This radical then reacts with the ene group via anti-Markonnikov addition to form a carbon-centered radical. The chain transfer step in this process removes hydrogen radicals from the thiol, which can participate in multiple propagation steps. Thiol-ene reactions using free radicals are particularly advantageous for synthesis because these steps effectively produce a uniform polymer network.
Michaelis Addition
In addition, the Thiol-ene reaction can also be carried out through the Michaelis-Menten addition pathway. This type of reaction is generally catalyzed by a base or a nucleophile. The final product is consistent with a free radical addition and is still an anti-Markonikov addition. successful result.
Dynamics
Click chemical reactions generally have high efficiency and fast reaction rates, but the reaction rate depends heavily on the functionality of the olefin. In the process of studying the kinetics of the Thiol-ene reaction, calculations and experiments were conducted on the transition states and reaction enthalpies of various alkenes, and it was found that the reactivity and structure of the alkenes will determine whether the reaction path is step growth or chain growth. Studies have shown that more electronegative alkenes, such as vinyl or allyl ethers, are more reactive than norbornenes, while conjugated or electron-poor alkenes are less reactive.
Kinetic models show that the overall rate of a reaction (RP) can be described by the ratio of the propagation rate (kP) to the strand transfer rate (kCT).
Applications of synthetic fields
Start cascade cyclization
The Thiol-ene reaction (and the similar Thiol-yne reaction) is widely used in reactions to generate unsaturated groups. By hydrating the free radicals of unsaturated groups, carbon-centered free radicals can be indirectly generated, and then internal cyclization reactions can be performed. These reactions can not only generate reaction intermediates, but can also be used to synthesize a variety of natural products.
Internal cyclization reaction
The Thiol-ene reaction of internal cyclization provides the opportunity to create sulfur-containing heterocycles, which is very important in the synthesis of four- to eight-membered rings and macrocycles. The radical-initiated Thiol-ene reaction tends to generate anti-Markonnikov products.
Surface Patterning
Surface functionalization of Thiol-ene has been extensively studied in materials science and biotechnology. Attachment of molecules with stereoaccessible olefin or thiol groups to a solid surface enables the construction of the desired polymer through subsequent Thiol-ene reactions. The advantage of this approach is that it allows for a high level of spatial specificity and precise control through photomasking.
Potential applications
The Thiol-ene reaction has also shown great application potential in the fields of dendritic polymer synthesis, polymer synthesis and electron beam resists. The properties of these reactions make it possible to synthesize biocompatible, high-performance materials in medicine, materials science, and nanoengineering.
The charm of the Thiol-ene reaction lies in its diversity and high efficiency, making it an important technology in chemical synthesis. In the future, what new materials or biomedical applications might scientists use this reaction technology to develop?
