An unexpected rhodium-catalyzed regioselective C–H chlorination of 7-azaindoles was developed using 1,2-dichloroethane (DCE) as a chlorinating agent and 7-azaindole as the directing group. This ...protocol provides an efficient access to ortho-chlorinated azaindoles with operational simplicity, good functional group tolerance, and a wide substrate scope.
An efficient rhodium-catalyzed regioselective C–H bond cyanation of arenes was developed using tert-butyl isocyanide as the cyanide source. A wide range of (hetero)aryl and cycloalkenyl nitriles ...could be afforded with high regioselectivity and good functional group tolerance.
An efficient and mild synthesis of imidazo1,2‐apyrimidine derivatives has been developed from readily available pyrimidyl arylamines or enamines through a hypervalent iodine‐promoted intramolecular ...C–H bond cycloamination reaction. This protocol allows for the facile construction of biologically active bicyclic imidazo1,2‐apyrimidine skeletons as well as other imidazo1,2‐a‐type fused heterocycles.
Imidazo1,2‐a‐type fused heterocycles are prevalent structural motifs in pharmaceutically and biologically active compounds. In this paper, an efficient and mild synthesis of imidazo1,2‐apyrimidine skeletons was developed from readily available pyrimidyl arylamines or enamines through a hypervalent iodine‐promoted intramolecular C–H bond cycloamination reaction.
Reported is a modular one‐step three‐component synthesis of tetrahydroisoquinolines using a Catellani strategy. This process exploits aziridines as the alkylating reagents, through ...palladium/norbornene cooperative catalysis, to enable a Catellani/Heck/aza‐Michael addition cascade. This mild, chemoselective, and scalable protocol has broad substrate scope (43 examples, up to 90 % yield). The most striking feature of this protocol is the excellent regioselectivity and diastereoselectivity observed for 2‐alkyl‐ and 2‐aryl‐substituted aziridines to access 1,3‐cis‐substituted and 1,4‐cis‐substituted tetrahydroisoquinolines, respectively. Moreover, this is a versatile process with high step and atom economy.
A modular synthesis of tetrahydroisoquinolines was developed. Aziridines act as the alkylating reagents to enable a Catellani/Heck/aza‐Michael addition cascade by palladium/norbornene (NBE) cooperative catalysis. This mild, chemoselective, and scalable protocol is compatible with a wide range of readily available aryl iodides, aziridines, and olefins. Excellent regio‐ and diastereoselectivities are observed for 1,3‐cis‐substituted and 1,4‐cis‐substituted tetrahydroisoquinolines.
We report a cooperative catalytic system comprising a PdII complex, XPhos, and the potassium salt of 5‐norbornene‐2‐carboxylic acid that enables the use of epoxides as alkylating reagents in the ...Catellani reaction, thereby expanding the existing paradigm of this powerful transformation. The potassium salt of inexpensive 5‐norbornene‐2‐carboxylic acid acts as both mediator and base in the process. This mild, chemoselective, scalable, and atom‐economical protocol is compatible with a wide variety of readily available functionalized aryl iodides and epoxides, as well as terminating olefins. The resulting products undergo facile oxa‐Michael addition to furnish ubiquitous isochroman scaffolds.
A little cooperation can go a long way: A cooperative catalytic system comprising a PdII/XPhos complex and the potassium salt of 5‐norbornene‐2‐carboxylic acid, which serves dual roles as a mediator and a base, enabled the use of epoxides as alkylating reagents in the Catellani reaction (see scheme). The products could also undergo oxa‐Michael addition to furnish valuable isochroman scaffolds.
A cooperative catalytic system comprising a palladium/XPhos complex and 5-norbornene-2-carboxylic acid was developed. This system promotes a two-component annulation reaction, allowing the ...construction of tetrahydronaphthalenes and indanes that contain quaternary centers through consecutive Catellani-type C–H activation and redox-relay Heck reaction. Inexpensive 5-norbornene-2-carboxylic acid acts as a catalytic mediator (20 mol %) in this process. This mild, scalable, and chemoselective protocol is compatible with a wide variety of readily available aryl iodides and alkylating reagents. Application of this method in a 4-step synthesis of opioid analgesic eptazocine is demonstrated. Preliminary studies underscore the future promise of rendering this Catellani/redox-relay Heck cascade enantioselective.
Ramelteon is the first medicine in human history that treat insomnia as a melatonin receptor agonist. Herein, we report an efficient three‐step synthetic route to access it from commercially ...available 2,3‐dihydrobenzofuran‐4‐amine, which represents as the shortest racemic synthesis to date with a 26 % overall yield. Key to the success is the application of the intermolecular Catellani‐type alkylation and intramolecular redox‐relay Heck cyclization cascade for preparation of the key indane‐containing aldehyde. The unique primary amide‐involved reductive amination of aldehyde is another feature of this route. New process of ramelteon can be developed based on this chemistry.
Taking the shorter path: An efficient three‐step synthetic route to access the anti‐insomnia medicine ramelteon from commercially available 2,3‐dihydrobenzofuran‐4‐amine was developed, which represents as the shortest racemic synthesis to date.
Mediators play a central role in Catellani-type reactions. Herein we reported the discovery of inexpensive 5-norbornene-2-carboxylic acid (N4) as a general catalytic mediator (20 mol%) to facilitate ...ortho C–H activation and the following C–C bond formation of aryl iodides. Firstly, a cooperative catalytic system comprising N4 and a palladium/XPhos complex was developed for the novel Catellani/redox-relay Heck cascade to construct tetrahydronaphthalenes and indanes that contain a quaternary carbon stereogenic center. The striking feature of this work was the avoidance of stoichiometric NBE mediator that are usually required for Catellani-type reactions. Then, preliminary results demonstrated that N4 could act as a general catalytic mediator to replace NBE for other Catellani-type reactions, which will undoubtedly inspire future developments in the field of cooperative catalysis. Finally, control experiments indicated that the carboxylic acid moiety of N4 plays an essential role in its ability to serve as a superior mediator.
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Epoxides are highly challenging alkylating reagents for the Catellani reaction. In their Communication on page 3444, Q. Zhou and co‐workers report a cooperative catalytic system comprising of a ...PdII/XPhos complex and the potassium salt of 5‐norbornene‐2‐carboxylic acid to enable the use of epoxides as alkylating reagents in the Catellani reaction. The picture shows the key elements of this novel transformation, with representative buildings of Wuhan University in the background. Cover design by Jun Deng, Wuhan University.
Reported is a modular one‐step three‐component synthesis of tetrahydroisoquinolines using a Catellani strategy. This process exploits aziridines as the alkylating reagents, through ...palladium/norbornene cooperative catalysis, to enable a Catellani/Heck/aza‐Michael addition cascade. This mild, chemoselective, and scalable protocol has broad substrate scope (43 examples, up to 90 % yield). The most striking feature of this protocol is the excellent regioselectivity and diastereoselectivity observed for 2‐alkyl‐ and 2‐aryl‐substituted aziridines to access 1,3‐cis‐substituted and 1,4‐cis‐substituted tetrahydroisoquinolines, respectively. Moreover, this is a versatile process with high step and atom economy.
Eine modulare Synthese von Tetrahydroisochinolinen wurde entwickelt. Aziridine fungieren als Alkylierungsreagentien in einer Kaskade aus Catellani‐, Heck‐ und Aza‐Michael‐Reaktion unter kooperativer Palladium/Norbornen‐Katalyse. Dieses milde, chemoselektive und skalierbare Protokoll ist kompatibel mit einer breiten Spanne von Aryliodiden, Aziridinen und Olefinen. Exzellente Regio‐ und Diastereoselektivitäten werden für die 1,3‐cis‐ und 1,4‐cis‐substituierten Tetrahydroisochinoline beobachtet.
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