Metalated Chromene and Chromone Complexes: pH Switchable Metal–Carbon Bonding Interaction, Photo‐triggerable Chromone Delivery Application, and Antioxidative Activity

Abstract

The two families of Ru -chromene and -chromone complexes isolated in this work represent the first examples of metalated chromene and chromone complexes synthesized through transition-metal-mediated cyclization of phenol-tethered ynone. These unprecedented metalated heterocyclic compounds exhibit remarkable features, such as pH-switchable metal-carbon bonding interactions, photo-triggerable release of organic chromone upon visible-light irradiation, and superior antioxidative property to their organic analogue (1,4-benzopyrone). These findings not only offer mechanistic insights into metal-induced activation of functionalized alkynes, but also add a new dimension to rational design of antioxidants and photo-responsive drug delivery systems.

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

“…[4] It should be pointed out that the term "indolizine" here actually refers to "1,1-disubstituted 1H-indolizinium-2-yl" zwitterion. The scope of this reaction was later extended to pyrimidine-and quinoline-substituted propargylic alcohols, and another Ru II precursor [Ru( [14]-aneS4)Cl 2 ]( 2a-2c in Scheme 2b; [ 14]aneS4 = 1,4,8,11-tetrathiacyclotetradecane). [5] The X-ray crystal structures of cations 1a, 1b,a nd 2c ( Figure 1) clearly reveal that the propargylic substratesc ycloisomerizei nto indolizines and metalate at the C-2 positions.…”

“…The first metalated indolizinonec omplexes 3-5 were prepared from reactions between [Ru( [9]aneS3)(bpy)(H 2 O)] 2 + or [Ru( [14]aneS4)Cl 2 ]a nd pyridine-substituted ynones RCC(C= O)(2-py) (Scheme4;t he term "indolizinone" here referst o" 3monosubstituted 1-indolizinonium-2-yl" zwitterion). [7] As shown in the crystal structures,t he ynones cycloisomerize into indolizinones and behavea sm onodentate ligands coordinating through the C-2 ( Figure 2).…”

“…Reactions between the Ru II precursors and non-pyridine-substituteda lkyne substrates were performed to gain more mechanistic insight (Scheme6): (a) reaction between [Ru([9]-aneS3)(bpy)(H 2 O)] 2 + and HCCC(OH)Ph 2 in H 2 Oa fforded aR uacyl complex 6; [4] (b) reacting [Ru( [14]aneS4)Cl 2 ]w ithH C CC(OH)Ph 2 in MeOH yieldedaRu-methoxycarbene complex 7; [5] (c) ar uthenafuran complex 8 was obtained from reaction between [Ru( [14]aneS4)Cl 2 ]a nd HCC(C=O)Ph in MeOH. [9] Importantly, these reactions were reported to proceed via vinylidene-involving pathways.…”

“…Therefore, the vinylidene intermediacy should not be taken for granted regarding the mechanism in any Ru-mediated alkyne transformations. Scheme6.Reactions between [Ru( [9]aneS3)(bpy)(H 2 O)] 2 + or [Ru( [14]a-neS4)Cl 2 ]and non-pyridine substituted alkynes reportedw ith vinylidenei ntermediacy.…”

“…The RuÀCd istances (1.944(5)-1.965 (5) )i n10 indicate that the RuÀCb ond possesses partial double-bond character.N otably,s tructurally analogous Ru-N-heterocyclic speciesw ere proposed to be the key intermediates in Ru-catalyzed cyclization of aniline-tether alkynes. [11] Mechanistic studies It is clear from the studies on the Ru-indolizine and -indolizinone complexes 1-5 that there exist non-vinylidene-involving pathways (5-endo-dig cyclization) apart from the conventional vinylidene-involving mechanism regarding the interaction between [Ru( [14]aneS4)Cl 2 ]a nd alkynes. Therefore, two different pathways were considered for the formationo f9-11 from a Ru-alkyne p-intermediate formed between [Ru([14]aneS4)Cl] + and HCC(C 6 H 4 NRR'-2) (Scheme 8): pathway C involves the formationo fR u-vinylidene intermediate through1 ,2-H shift, followed by 5-exo-dig cyclization to give Ru-indole species (isolated as 9 for R = R' = Me);t he N-protonated Ru-indole species (i.e.,f or R = H) undergoes hydrogen-transfer( assisted by solvent) to give Ru-indoline complexes 10 and 11.P athway D represents an on-vinylidene-involving pathway,w hich involves 5-endo-dig cyclization followed by further transformations to give Ru-indole and -indoline species.…”