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

Abstract

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...

Controlled Activation of Dipicolinyl-Substituted Propargylic Alcohol by Ru(II) and Os(II) for Unprecedented Indolizine-Fused Metallafuran Complexes

“…While the formation of M–allenylidene complexes from alkyl- and aryl-substituted propargylic alcohols and Fe­(II)/Ru­(II)/Os­(II) precursors is well-documented, we discovered that pyridyl-substituted propargylic alcohols could be activated via non-vinylidene pathways to give M–indolizine complexes (Scheme ). , More recently, we reported the formation of 2-methylpyridinium-functionalized metallafuran and M–quinolizinium complexes from the reactions between Ru­(II)/Os­(II) precursors and picolinyl-substituted propargylic alcohol HCCC­(OH)­(Ph)­(CH 2 (2-py)), in which the former complexes were derived from non-vinylidene pathways . Evidently, the presence and the nature of nucleophilic functionality on alkynes diversify the mode of Fe­(II)/Ru­(II)/Os­(II)–alkyne interactions, and it is essential to control the selectivity of these modes (vinylidene vs non-vinylidene pathways) for rational molecular and catalytic designs.…”

“…Our group has been investigating the reaction mechanisms between d 6 transition metal complexes and functional alkynes − and reported the isolation of monocyclic or bicyclic metallafurans from the reactions between terminal ynone HCC­(C=O)­R and d 6 transition metal precursors including cis -[Ru­([14]­aneS4)­Cl 2 ], cis -[M­(bpy) 2 Cl 2 ], and cis -[M­(dppm) 2 Cl 2 ] (M = Ru and Os; [14]­aneS4 = 1,4,8,11-tetrathiacyclotetradecane; bpy = 2,2′-bipyridine; dppm = 1,1-bis­(diphenylphosphino)­methane). ,,, We herein report the isolation of indolizine-fused ruthenafuran and osmafuran complexes from the one-pot reactions between cis -[Ru II /Os II (dppm) 2 Cl 2 ] and dipicolinyl-substituted propargylic substrates HCCC­(OR)­(CH 2 (2-py)) 2 . Notably, these complexes not only represent an unprecedented class of metallafurans but also provide insights via their formation mechanism into Ru/Os-induced alkyne transformations.…”

Ruthenafuran Complexes Supported by the Bipyridine-Bis(diphenylphosphino)methane Ligand Set: Synthesis and Cytotoxicity Studies

“…Activation of alkynes by transition-metal complexes has recently gained increasing research interest in the field of organometallic chemistry [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Although the formation of metal–vinylidene species via alkyne–vinylidene rearrangement has been regarded as a key step in Ru(II)-induced alkyne transformations, a number of our synthetic studies revealed that Ru(II) can also activate alkynes via “non-vinylidene” pathways [ 31 , 32 ]. With the aim to gain control on the modes of alkyne activation, we initiated research activities on probing and isolating intermediates and products from the reactions between functionalized alkynes and a variety of Fe(II), Ru(II) and Os(II) complexes [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , …”

“…Although the formation of metal–vinylidene species via alkyne–vinylidene rearrangement has been regarded as a key step in Ru(II)-induced alkyne transformations, a number of our synthetic studies revealed that Ru(II) can also activate alkynes via “non-vinylidene” pathways [ 31 , 32 ]. With the aim to gain control on the modes of alkyne activation, we initiated research activities on probing and isolating intermediates and products from the reactions between functionalized alkynes and a variety of Fe(II), Ru(II) and Os(II) complexes [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. In 2015, we reported the synthesis of metallafuran complexes in the form of [M(bpy) 2 (C^O)] + from the reactions between cis -[M(bpy) 2 Cl 2 ] (M = Ru, Os; bpy = 2,2′-bipyridine) and ynone HC≡C(C=O)Ph in MeOH ( Scheme 1 a; C^O represents an anionic bidentate [ C (OMe)CHC(Ph) O ] − chelate, coordinating atoms in italics) [ 38 ].…”

Recent Advances in Silver‐Catalyzed Transformations of Electronically Unbiased Alkenes and Alkynes

“…Alkenes and alkynes, as abundant and versatile feedstocks employed in the synthesis of natural products, pharmaceutical molecules and agricultural chemicals, represent one of the most significant classes of unsaturated organic compounds. Owning to their easy availability and rich reactivity, numerous elegant examples have been successfully established for the construction of an array of functionalized and useful molecular scaffolds over the past several years . However, in contras t to the extensive explorations of electron‐biased alkenes or alkynes, the straightforward transformations of alkenes or alkynes without any electron‐withdrawing or electron‐donating functional groups generally receive less attention from chemists.…”