The direct arylation of aliphatic aldehydes has been established via Pd-catalyzed sp3 C–H bond functionalization in the presence of 3-aminopropanoic acids as transient directing groups. The reaction ...showed excellent functional group compatibility and chemoselectivity in which a predominant preference for functionalizing unactivated β-C–H bonds of methyl groups over others was achieved. In addition, C–H bonds of unactivated secondary sp3 carbons can also be functionalized. The extreme popularity and importance of aliphatic aldehydes would result in broad applications of this novel method in organic chemistry and medicinal sciences.
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We report a method for the electrochemical deuteration of α,β‐unsaturated carbonyl compounds under catalyst‐ and external‐reductant‐free conditions, with deuteration rates as high as 99 % and yields ...up to 91 % in 2 h. The use of graphite felt for both the cathode and the anode was key to ensuring chemoselectivity and high deuterium incorporation under neutral conditions without the need for an external reductant. This method has a number of advantages over previously reported deuteration reactions that use stoichiometric metallic reductants. Mechanistic experiments showed that O2 evolution at the anode not only eliminates the need for an external reductant but also regulates the pH of the reaction mixture, keeping it approximately neutral.
It's a D‐all! The first catalyst‐free and chemical‐reductant‐free deuteration of alkene and alkynes was achieved through an electrochemical approach with graphite felt electrodes and deuterated water in an undivided cell under neutral conditions. Up to 99 % D incorporation and 91 % yield can be obtained, and the method is compatible with electron‐rich alkenes, heterocycles, epoxides, and protecting groups. A series of deuterated pharmaceutical compounds was prepared.
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Arylation of carbonyls, one of the most common approaches toward alcohols, has received tremendous attention, as alcohols are important feedstocks and building blocks in organic synthesis. Despite ...great progress, there is still a great gap to develop an ideal arylation method featuring mild conditions, good functional group tolerance, and readily available starting materials. We now show that electrochemical arylation can fill the gap. By taking advantage of synthetic electrochemistry, commercially available aldehydes (ketones) and benzylic alcohols can be readily arylated to provide a general and scalable access to structurally diverse alcohols (97 examples, >10 gram‐scale). More importantly, convergent paired electrolysis, the ideal but challenging electrochemical technology, was employed to transform low‐value alcohols into more useful alcohols. Detailed mechanism study suggests that two plausible pathways are involved in the redox neutral α‐arylation of benzylic alcohols.
Electrochemical approaches to the direct arylation of carbonyls and alcohols through less‐explored cathodic reduction and convergent paired electrolysis are presented. This protocol features: excellent functional group (including ester, amide, amine, thioether, borate) tolerance, mild conditions (metal catalyst‐ and external reductant‐free), good scalability (>10 gram‐scale), and site‐selectivity.
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The first direct aziridination of triaryl‐substituted alkenes was achieved by means of an electrochemical process that could extend to multisubstituted styrenes. Specifically, hexafluoroisopropanol ...sulfamate was used as a nucleophilic nitrogen source. Mechanistic experiments suggest that this electrochemical process proceeds by stepwise formation of two C−N bonds through reactions between cationic carbon species and the sulfamate.
Az is: An electrochemical aziridination of triaryl ethylene was achieved by an alkene activation pathway with sulfamate as a nitrogen source. Two stepwise electron transfers were key to the construction of C−N bonds from congested and conjugation‐stabilized alkenes. With this approach, tri‐ and tetrasubstituted styrenes were also converted into the corresponding aziridines.
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The development of environmentally benign, operationally simple, and economically viable synthetic methodologies has been a great challenge in organic synthesis. Group-assisted purification (GAP) ...chemistry was established to enable the synthesis of organic compounds without using traditional purification technologies, such as column chromatography and recrystallization. This concept/technology should encourage the synthetic community to make more efforts on searching for environmentally benign reagents and reactions to reduce the waste generated from silica and solvents, particularly toxic solvents; also, to reduce production/synthesis expenses, manpower, and energy. This review will discuss the GAP concept/technology and related reactions that were mainly conducted in the PI's laboratories after 2010.
N‐Atom Deletion in Nitrogen Heterocycles Qin, Haitao; Cai, Wangshui; Wang, Shuang ...
Angewandte Chemie International Edition,
September 13, 2021, Volume:
60, Issue:
38
Journal Article
Peer reviewed
Excising the nitrogen in secondary amines, and coupling the two residual fragments is a skeletal editing strategy that can be used to construct molecules with new skeletons, but which has been ...largely unexplored. Here we report a versatile method of N‐atom excision from N‐heterocycles. The process uses readily available N‐heterocycles as substrates, and proceeds by N‐sulfonylazidonation followed by the rearrangement of sulfamoyl azide intermediates, providing various cyclic products. Examples are provided of deletion of nitrogen from natural products, synthesis of chiral O‐heterocycles from commercially available chiral β‐amino alcohols, formal inert C−H functionalization through a sequence of N‐directed C−H functionalization and N‐atom deletion reactions in which the N‐atom can serve as a traceless directing group.
N‐atom deletion from N‐heterocycles via N‐sulfonylazidonation, Curtius‐type rearrangement and rearrangement of 1,2‐diazene intermediates is described. It provides a unique opportunity to achieve ring contraction of (n+1)‐membered N‐heterocycles to n‐membered cycles.
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The enantioselective copper-catalyzed borylacylation of aryl olefins with acyl chlorides and bis-(pinacolato)diboron is reported. This three-component reaction involves an enantioselective ...syn-borylcupration of the aryl olefin, followed by a nucleophilic attack on the acyl chloride. This reaction proceeds with a 2 mol % catalyst loading and is generally completed within 30 min at room temperature. Because the boron moiety can be converted into versatile functional groups and the carbonyl group is a ubiquitous functional group, the resulting chiral β-borylated ketones are versatile intermediates in organic synthesis.
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Transition metal-catalyzed direct C-H bond functionalization enabled by transient ligands has become an attractive topic. Here we report a palladium-catalyzed site-selective arylation of β-C(sp
)-H ...bonds in aliphatic ketones with β-alanine as the transient ligand.
Chemodivergent asymmetric synthesis was achieved by tuning the metal‐to‐ligand ratio in an organometallic catalytic system. Using N‐(aroyloxy)phthalimide as the precursor of either an oxygen‐centered ...aroyloxy radical or a nitrogen‐centered phthalimidyl radical, enantioselective oxocyanation or aminocyanation of alkenes was achieved separately through a dual photoredox and copper catalysis. The metal‐to‐ligand ratio can exert chemoselective control while retaining the high enantiopurity of divergent products. Both reactions proceed efficiently with catalyst loading as low as 0.2 mol % and can be performed on a gram scale without loss of chemoselectivity or enantioselectivity. Chemodivergent asymmetric 1,5‐aminocyanation or 1,5‐oxocyanation of vinylcyclopropane can also be realized by this protocol. Mechanistic investigations involving electron paramagnetic resonance (EPR) experiments were performed to shed light on the stereochemical and chemodivergent results.
A chemodivergent asymmetric synthesis can be achieved by tuning the metal‐to‐ligand ratio in an organometallic catalytic system.
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Stereoselective synthesis of trisubstituted alkenes is a long-standing challenge in organic chemistry, due to the small energy differences between E and Z isomers of trisubstituted alkenes (compared ...with 1,2-disubstituted alkenes). Transition metal-catalyzed isomerization of 1,1-disubstituted alkenes can serve as an alternative approach to trisubstituted alkenes, but it remains underdeveloped owing to issues relating to reaction efficiency and stereoselectivity. Here we show that a novel cobalt catalyst can overcome these challenges to provide an efficient and stereoselective access to a broad range of trisubstituted alkenes. This protocol is compatible with both mono- and dienes and exhibits a good functional group tolerance and scalability. Moreover, it has proven to be a useful tool to construct organic luminophores and a deuterated trisubstituted alkene. A preliminary study of the mechanism suggests that a cobalt-hydride pathway is involved in the reaction. The high stereoselectivity of the reaction is attributed to both a π–π stacking effect and the steric hindrance between substrate and catalyst.
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