Ruthenium‐Induced Alkyne Cycloisomerization: Construction of Metalated Heterocycles, Revelation of Unconventional Reaction Pathways, and Exploration of Functional Applications

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: Discussionmentioning

confidence: 99%

Section: Catalytic Ru II -Mediated Cyclizations Of N/o-functionalizedmentioning

confidence: 99%

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

Chung

Wong

2020

Chemistry A European J

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“…Recently, we have been scrutinizing the reactivity between structurally well‐defined low‐valent transition‐metal complexes and functionalized alkynes, and several classes of interesting and unprecedented metal‐heterocyclic and metallacyclic complexes were isolated . We herein report a series of phosphonium‐bearing bicyclic ruthenafuran and osmafuran complexes prepared from the reactions between cis ‐[Ru/Os(dppm) 2 Cl 2 ] and terminal ynones HC≡C(C=O)R. DFT calculations revealed that the metal‐vinylidene‐involving pathway represents an energetically feasible formation mechanism for these complexes.…”

Section: Methodsmentioning

confidence: 99%

“…[8] To date, the exploration of synthetic approaches that enable the preparation of novel metallafurans remains unabated.Recently,w ehave been scrutinizing the reactivity between structurally well-defined low-valent transition-metal complexes and functionalized alkynes, and several classes of interesting and unprecedented metal-heterocyclic and metallacyclic complexesw ere isolated. [9, 10] We herein report as eries of phosphonium-bearing bicyclicr uthenafuran and osmafuran complexes prepared from the reactions between cis-[Ru/Os(dppm) 2 Cl 2 ] and terminaly nonesH C C(C=O)R. DFT calculationsr evealed that the metal-vinylidene-involving pathway represents an energetically feasible formation mechanism for these complexes. Interestingly,t he metallafurans exhibit stronger cytotoxicity against several human cancer cell lines in comparison with their metal precursors and the classica nticancer drugc isplatin, and have shown ability to induce mitochondrial dysfunction in cells.Phosphonium ring-fused bicyclic metallafuran complexes 1(PF 6 )a nd 2(PF 6 )w ere prepared from reactions between cis-[M(dppm) 2 Cl 2 ]( racemic;o nly one enantiomer is shown in the schemes and figures) and terminal ynones HCC(C=O)R in the presence of NaPF 6 in CH 2 Cl 2 (Scheme 1), during whicht he reaction mixturest urned from yellowishb rown to deep purple.…”

mentioning

confidence: 99%

Phosphonium‐Ring‐Fused Bicyclic Metallafuran Complexes of Ruthenium and Osmium

Chung

et al. 2019

Chemistry A European J

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Metallafuran complexes with a fused five‐membered phosphonium ring were synthesized from reactions between terminal ynones HC≡C(C=O)R and cis‐[Ru/Os(dppm)2Cl2] (dppm=1,1‐bis(diphenylphosphino)methane). A metal–vinylidene‐involving pathway was found to be an energetically feasible formation mechanism for these complexes. These phosphonium‐containing metallafurans, like many phosphonium‐functionalized drugs, have the ability to induce mitochondrial dysfunction. They also exhibit stronger cytotoxicity against several human cancer cell lines in comparison with their metal precursors and the classic anticancer drug cisplatin. Overall, this work provides structural and mechanistic insights for the rational design of functional metallacycles via activation of alkynes by RuII and OsII centers.

“…Our group has recently initiated a paradigm in scrutinizing the reactivity between low-valent transition metal precursors and heteroatom-functionalized alkynes [16][17][18][19][20][21][22][23][24][25][26][27][28][29]. Gratifyingly, several Ru-and Os-heterocyclic complexes reported by our group exhibit interesting biological applications.…”

Section: Introductionmentioning

confidence: 99%

A New Tetradentate Mixed Aza-Thioether Macrocycle and Its Complexation Behavior towards Fe(II), Ni(II) and Cu(II) Ions

Chan

et al. 2020

Molecules

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A new tetradentate mixed aza-thioether macrocyclic ligand 2,6-dithia[7](2,9)-1,10-phenanthrolinophane ([13]ane(phenN2)S2) was successfully synthesized. Reacting metal precursors [Fe(CH3CN)2(OTf)2], Ni(ClO4)2·6H2O, and Cu(ClO4)2·6H2O with one equivalent of [13]ane(phenN2)S2 afforded [Fe([13]ane(phenN2)S2)(OTf)2] (1), [Ni([13]ane(phenN2)S2)](ClO4)2 (2(ClO4)2), and [Cu([13]ane(phenN2)S2)(OH2)](ClO4)2 (3(ClO4)2), respectively. The structures of [13]ane(phenN2)S2 and all of its metal complexes were investigated by X-ray crystallography. The [13]ane(phenN2)S2 was found to behave as a tetradentate ligand via its donor atoms N and S.