A mild light-driven protocol for the direct alkylation of phenols is reported. The process is driven by the photochemical activity of a halogen-bonded complex formed upon complexation of the in situ generated electron-rich phenolate anion with the α-iodosulfone. The reaction proceeds rapidly (10 min) under microfluidic conditions, delivering a wide variety of ortho-alkylated products (27 examples, up to 97% yield, >20:1 regioselectivity, on a gram scale), including densely functionalized bioactive phenol derivatives
We describe an efficient photocatalytic procedure for the direct iodosulfonylation of terminal olefins 3 with α-iodo phenylsulfones 4. Specifically, the process uses the simple, robust, and fully recyclable phenol derivative 6e as the precatalytic system and occurs with visible-light irradiation (450 nm). Mechanistic investigations proved the key role of the in situ generated photocatalyst, namely phenolate anion 7e, which has shown high catalytic activity and considerable stability toward the operating conditions. Importantly, this photocatalytic transformation provides a wide variety of densely functionalized alkyl iodides 5 (23 examples, up to 95% yield). Finally, the synthetic potential of this photochemical transformation was demonstrated by scaling up the process under microfluidic conditions (up to 0.67 mmol h–1) while accessing a series of relevant product manipulations.
Here, we report a general approach to the synthesis of the difluoroalkyl bicycloalkanes (CF 2 -BCAs), as structural surrogates of aryl ketones and ethers. The chemistry is driven by a dihydrobenzoacridine photocatalyst, that engages in a catalytic electrondonor acceptor (EDA) complex, or directly reduces the fluorinated substrate. These two convergent manifolds lead to the generation of the R-CF 2 radical, that reacts with the [1.1.1]-or [3.1.1.]-propellane. The method is extremely general, and extendable to complex bioactive molecules (30 examples, up to 87 % yield). The structural features of the CF 2 -BCP hybrid bioisostere were investigated by single crystal X-ray. Finally, we synthesised a CF 2 -BCP analogue of a Leukotriene A 4 hydrolase inhibitor, replacing the original aryl ether motif. In silico docking studies indicated that this new analogue maintains the same arrangement within the enzyme pocket, profiling the use of the CF 2 -BCA hybrid bioisostere in medicinal chemistry settings.
Here, we report a general approach to the synthesis of the difluoroalkyl bicycloalkanes (CF2‐BCAs), as structural surrogates of aryl ketones and ethers. The chemistry is driven by a dihydrobenzoacridine photocatalyst, that engages in a catalytic electron‐donor acceptor (EDA) complex, or directly reduces the fluorinated substrate. These two convergent manifolds lead to the generation of the R‐CF2 radical, that reacts with the [1.1.1]‐ or [3.1.1.]‐propellane. The method is extremely general, and extendable to complex bioactive molecules (30 examples, up to 87 % yield). The structural features of the CF2‐BCP hybrid bioisostere were investigated by single crystal X‐ray. Finally, we synthesised a CF2‐BCP analogue of a Leukotriene A4 hydrolase inhibitor, replacing the original aryl ether motif. In silico docking studies indicated that this new analogue maintains the same arrangement within the enzyme pocket, profiling the use of the CF2‐BCA hybrid bioisostere in medicinal chemistry settings.
Here, we report a mild approach to the construction of the difluoroalkyl bicyclopentane and bicycloheptane (CF2-BCP and CF2-BCHep) units, as the structural surrogates of para- and meta-substituted aryl ketones and aryl ethers. The chemistry is orchestrated by the key activity of a dihydrobenzoacridine photocatalyst (PC). Depending by the nature of the substrate, the PC engages in catalytic electron-donor acceptor (EDA) complex or promotes the direct reduction of the substrate (Ered up to -1.9 V vs SCE) through a single-electron transfer (SET) mechanism. These two convergent manifolds leads to the generation of the reactive R-CF2 radical that reacts trough a strain-release atom-transfer-radical addition (ATRA) process with the [1.1.1]- or [3.1.1]-propellane. The method is general and tolerant of a variety of functional groups, such as sulfones, amines, amides or alkynes (30 examples, yields up to 90%), and extendable to complex bioactive molecules, including aminoacids, dipeptides or carbohydrates. The structural features of the CF2-BCP hybrid bioisostere were investigated in the solid state by single crystal X-ray analysis. Finally, we synthesised a CF2-BCP analogue of a Leukotriene A4 (LTA4) hydrolase inhibitor, replacing the original aryl ether motif. Interestingly, in-silico docking studies indicated that this new molecule maintains the same arrangement and key interactions within the enzyme pocket.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.