Synthesis of Iron(II)- and Ruthenium(II)-Heterocyclic Complexes via Metal-Induced Cycloisomerization of Phenol-/Pyridine-Tethered Alkynes

Abstract

Ruthenium(II)-chromene and -chromone complexes (1-3) were synthesized by reacting phenol ynone HC≡C(C=O)(o-C₆H₄OH) and Ru(II) precursors cis-[Ru([14]aneS4)Cl₂], cis-[Ru(bpy)₂Cl₂] and cis-[Ru(dppm)₂Cl₂] (racemic) respectively ([14]aneS4 = 1,4,8,11-tetrathiacyclotetradecane, bpy = 2,2'-bipyridine, dppm = 1,1-bis(diphenylphosphino)methane) through Ru-mediated cyclization of phenol-tethered ynone. These unprecedented metalated heterocyclic compounds deriving from Ru-vinylidene intermediacy exhibit remarkable features, such as pH-dependent chromene/chromone equilibrium behavior in aqueous medium, photo-triggerable release of organic chromone upon visible-light irradiation, and superior antioxidative property in comparison with their organic analog (1,4-benzopyrone). More importantly, the cis-trans equilibration in solution demonstrated by chloride-ligated Ru-chromene and -chromone series represents a rare example for Ru complexes bearing dppm ancillary ligands. 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.

Two series of isolable and structurally characterized ruthenium(II)-indolizinone complexes (4-6) were prepared by reacting pyridyl-ynone RC≡C(C=O)(2-py) with [Ru([9]aneS3)(bpy)(H₂O)]²⁺ and cis-[Ru([14]aneS4)Cl₂] respectively ([9]aneS3 = 1,4,7-trithiacyclononane). These complexes deriving from Ru-induced cycloisomerization of pyridine-tethered alkynes represent the first examples of metalated indolizinone complexes. Joint experimental-theoretical investigation suggests an unconventional 5-endo-dig cyclization pathway as their formation mechanism. The cycloisomerization of pyridine-tethered ynones on the Ru center represents a general synthetic strategy for stable metal-indolizinone complexes. Most of these complexes also exhibit moderate cytotoxicity against several human cancer cell lines.

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 precursor [Fe(CH₃CN)₂(OTf)₂] with 1 equivalent of [13]ane(phenN₂)S₂ afforded high-spin [Fe([13]ane(phenN₂)S₂)(OTf)₂] (8). The solid-state structures of [13]ane(phenN₂)S₂ and its metal complex were investigated by X-ray crystallography. The possible low-energy conformers of [13]ane(phenN₂)S₂ were also explored by theoretical calculations. The [13]ane(phenN₂)S₂ was found to behave as a tetradentate ligand via its donor atoms N and S. Although 8 suffered from ligand dissociation upon activation of pyridine-tethered alkynes, reacting a low-spin metal precursor Fe([15]ane(phenN₂)S₃)(H₂O)](OTf)₂ (9) ([15]ane(phenN₂)S₃ = 2,5,8-trithia[9](2,9)-1,10-phenanthrolinophane) supported by a structurally robust pentadentate macrocycle with pyridyl ynone RC≡C(C=O)(2-py) under ambient condition enables the preparation of structurally well-defined and low-spin iron(II)-indolizinone complexes, [Fe([15]ane(phenN₂)S₃)(indolizinone)]²⁺ (10). A 5-endo-dig cyclization mechanism is suggested for the formation of these Fe(II)-indolizinone species. The success of preparing these macrocyclic Fe-heterocycles undoubtedly provides insight into the role of Fe(II) in the cycloisomerizations and broadens the spectrum of metalated heterocycles.

Date of Award	16 Sept 2020
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Chun Yuen Alex WONG (Supervisor)