Mechanistic insight into organic and industrial transformations: general discussion

Wong

2020

Chemistry A European J

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Metal-induced cyclization of functionalized alkynes represents one of the most general approaches to prepare organic heterocycles. AlthoughR u II centers are well-established to promote alkyne to vinylidener earrangements and many Ru II -mediated alkyne cyclizations have been rationalized to be the resultso fp ost-vinylidene transformations, recent discoveries indicate that Ru II centers can serve as electrophiles and induce alkyne cyclizationsw ithoutv inylidene intermediacy. In this Minireview,a no verview of the Ru II -induced cyclization of heteroatom-functionalized alkynes in the last decadei sp rovided, with an emphasis on the discoveries and validations of the unconventional "non-vinylidene-involving" pathways. Recent Progress of Ruthenium-Induced Cyclization of AlkynesResearcho nt he activation of heteroatom-functionalizeda lkynes by Ru II complexes for oxygen-and nitrogen-containing heterocycles of different ring sizes (5-to 8-membered) continues unabated. Most reported Ru complexes ares upported by Cp (Cp = cyclopentadienyl) or structurally analogous h 5 -ligands, amine-or mixed amine/phosphine-basedc helates. In general, the catalyst loadings are almost lower than 10 mol %a nd can be as low as 0.5 mol %. Although the cyclizations are mostly demonstrated with terminala lkynes, there are increasing number of successful reports on cyclizing internal alkynes.T he use of proton shuttles( internal or external bases which facilitate protont ransfer) has been found to be critical in many of these catalytic reactions. Noteworthy,s everal recent studies clearly indicatet hat the "vinylidene-involving" and "non-vinylidene-involving" pathwaysd epicted in Scheme 1are competing mechanisms. In this section, Ru-catalyzedc yclization of heteroatom-functionalized alkynes in the last decade is discussed in chronological order,e xcept in the cases of certain serial or outlying works. Catalytic Ru II -mediated cyclizations of N/O-functionalized alkynesthrough "vinylidene-involving" pathwaysThe successful isolations of Fe-, Ru-, and Os-oxacarbene complexesf rom the reactions between homopropargylic/bis-ho-Scheme1.(a) Established mechanisms for the formation of Ru-vinylidene species. (b) Electrophilic cyclizationso fheteroatom-functionalized alkynes induced by Ru.[a] Dr.Scheme8.Ru-catalyzed cycloisomerizations of alkynols into 5-, 6-and 7membered oxacycles developed by Jia and co-workers. [13,14] Scheme7.Ru-catalyzed cyclizationso fa niline-and phenol-tethered alkynes into indoles and benzofurans, respectively developed by Grotjahn and coworkers. [11,12] Scheme9.Ru-catalyzed cycloisomerizations of hydroxyl-and amine-substituteda lkynes into isochromenes, indolesa nd isoquinolinones developedby Blacquiereand co-workers. [15][16][17] Scheme10. Ru-catalyzed cycloisomerizations of alcohol-tethered alkynes developedb yWen and co-workers. [18] Chem.E ur.Scheme20. Isolation of, and proposed formation mechanism for 4a.The synthesis of 4b is also depictedf or reference [31].Scheme21. Isolation of, and proposed formation mechanism for...

Section: Validating “Non‐vinylidene‐involving” Pathways Through Isolamentioning

confidence: 99%

Ruthenium‐Induced Cyclization of Heteroatom‐Functionalized Alkynes: Progress, Challenges and Perspectives

Chung

Wong

2020

Chemistry A European J

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“…With the hope to offer more comprehensive understanding regarding the activation of alkynes by d6‐transition‐metal centers for a broader audience of organometallic chemists, we recently utilized cis ‐[Ru(dppm) 2 Cl 2 ] and cis ‐[Os(dppm) 2 Cl 2 ] (dppm=1,2‐bis(diphenylphosphino)methane) in our investigations [2d,e,4] . These precursors have been extensively studied in the activation of alkynes, resulting in a diverse array of Ru/Os‐vinylidene, ‐allenylidene, and ‐alkynyl complexes over the past 40 years [5] .…”

Section: Introductionmentioning

confidence: 99%

Cyclization, Decyclization, and Metallacyclization of Pyridine‐Substituted Homopropargylic Alcohols on Ruthenium(II) and Osmium(II) Centers

Shek

Chung

et al. 2023

Chemistry A European J

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Systematic investigations on the reactions between cis-[M(dppm) 2 Cl 2 ](M = Ru/Os; dppm = 1,1bis(diphenylphosphino)methane) and pyridine/quinoline substituted homopropargylic alcohols uncovered the diverse Ru(II)/Os(II)-induced alkyne activation pathways. The alkynes underwent cyclization on M via a "non-vinylidene" pathway at lower temperatures, resulting in alkenyl intermediates which might further metallacyclize to give metallapyrroloindolizines. Conversely, reactions at higher temperatures induced alkyne cyclization on M via a "vinylidene" pathway, affording cyclic oxacarbene complexes. Additionally, a rare decyclization mechanism was observed during the transformation of a metallacyclization-resistant alkenyl complex into a cyclic oxacarbene complex. DFT calculations were employed to validate the experimental findings. Overall, these results not only provide insights into controlling alkyne activation pathways, but also offer new strategies for preparing metalated heterocyclic and metallacyclic complexes.

“…Recently, we initiated a paradigm in preparing an array of transition-metalated heterocyclic complexes from heteroatom-functionalized alkynes and low-valent transition metal precursors. Gratifyingly, with this “metal-induced alkyne cyclization” strategy, several series of unprecedented ruthenated and osmated heterocyclic complexes were successfully isolated . Herein, we report the preparation of ruthenium(II)/osmium(II)–chromene and −chromone complexes supported by the diphosphine ancillary ligand 1,1-bis(diphenylphosphino)methane (dppm), from the reactions between cis -[Ru/Os(dppm) 2 Cl 2 ] and HCC(CO)( o -C 6 H 4 OH).…”

Section: Introductionmentioning

confidence: 99%

Ru(II)- and Os(II)-Induced Cycloisomerization of Phenol-Tethered Alkyne for Functional Chromene and Chromone Complexes

Tse

et al. 2020

Organometallics

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Diphosphine-containing Ru(II)/Os(II)–chromene and −chromone complexes were synthesized from reactions between phenol ynone HCC(CO)(o-C6H4OH) and cis-[Ru/Os(dppm)2Cl2] (dppm = 1,1-bis(diphenylphosphino)methane). The structures of these complexes in the solid state along with their pH-dependent chromene/chromone equilibrium behavior in aqueous medium were investigated. The cis–trans equilibration in solution demonstrated by chloride-ligated Ru–chromene and −chromone series represents a rare example for Ru complexes bearing dppm auxiliary ligands. More importantly, these metalated chromene and chromone complexes exhibit moderate to strong cytotoxicity against several human cancer cell lines and stronger antioxidative activities in comparison with their organic counterpart. Overall, these findings highlight the potential applications of metalated chromenes and chromones as anticancer agents and antioxidants.