Aldehyde is one of most synthetically versatile functional groups and can participate in numerous chemical transformations. While a variety of simple aromatic aldehydes are commercially available, those with a more complex substitution pattern are often difficult to obtain. Benzylic oxygenation of methylarenes is a highly attractive method for aldehyde synthesis as the starting materials are easy to obtain and handle. However, regioselective oxidation of functionalized methylarenes, especially those that contain heterocyclic moieties, to aromatic aldehydes remains a significant challenge. Here we show an efficient electrochemical method that achieves site-selective electrooxidation of methyl benzoheterocycles to aromatic acetals without using chemical oxidants or transition-metal catalysts. The acetals can be converted to the corresponding aldehydes through hydrolysis in one-pot or in a separate step. The synthetic utility of our method is highlighted by its application to the efficient preparation of the antihypertensive drug telmisartan.
Cyclopropane
is a prevalent structural unit in natural products
and bioactive compounds. While the transition metal-catalyzed alkene
cyclopropanation of functionalized compounds such as α-diazocarbonyl
derivatives has been well established and provides straightforward
access to cyclopropanes, cyclopropanation directly from the more stable
and simpler methylene compounds has remained an unsolved challenge
despite the highly desirable benefits of minimal prefunctionalization
and increased operational safety. Herein we report an electrocatalytic
strategy for the cyclopropanation of active methylene compounds, employing
an organic catalyst. The method shows a broad substrate scope and
excellent scalability, requires no metal catalyst or external chemical
oxidant, and provides convenient access to several types of cyclopropane-fused
heterocyclic and carbocyclic compounds. Mechanistic investigations
suggest that the reactions proceed through a radical–polar
crossover process to form the two new carbon–carbon bonds in
the nascent cyclopropane ring.
The development of efficient and sustainable methods for carbon-phosphorus bond formation is of great importance due to the wide application of organophosphorus compounds in chemistry, material sciences and biology. Previous C–H phosphorylation reactions under nonelectrochemical or electrochemical conditions require directing groups, transition metal catalysts, or chemical oxidants and suffer from limited scope. Herein we disclose a catalyst- and external oxidant-free, electrochemical C–H phosphorylation reaction of arenes in continuous flow for the synthesis of aryl phosphorus compounds. The C–P bond is formed through the reaction of arenes with anodically generated P-radical cations, a class of reactive intermediates remained unexplored for synthesis despite intensive studies of P-radicals. The high reactivity of the P-radical cations coupled with the mild conditions of the electrosynthesis ensures not only efficient reactions of arenes of diverse electronic properties but also selective late-stage functionalization of complex natural products and bioactive compounds. The synthetic utility of the electrochemical method is further demonstrated by the continuous production of 55.0 grams of one of the phosphonate products.
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