Mechanistic and Catalytic Studies on Cyclization of Nucleophile Tethered Alkynes Induced by Iron(II) and Ruthenium(II) Complexes Bearing Thiamacrocycles

Abstract

The cyclization of heteroatom-functionalized alkynes induced by d⁶-transition-metal centers has traditionally been associated with the vinylidene pathway. However, recent evidence suggests that d⁶-transition-metal centers can also activate alkynes through non-vinylidene pathways. In this study, we conducted comprehensive experimental and theoretical investigations into the reactions between the Ru(II) complex [Ru([9]‍aneS3)(bpy)(OH₂)]²⁺ and 2-alkynylanilines. Our study revealed that the selectivity between the vinylidene and non-vinylidene pathways can be tuned by reaction temperature, substrate, and solvent polarity. This strategic control allows for the preferential formation of either C2- or C3-metalated indole zwitterion complexes. Additionally, we identified a rare decyclization mechanism that enables the conversion of C2-metalated indoles to C3-metalated indoles, underscoring the significance of product stability in these pathways. These findings demonstrate practical approaches to control the preference between vinylidene and non-vinylidene pathways, which is crucial for the design of new catalysts and metalated heterocyclic complexes.

Meanwhile, N-alkyl/alkenyl-2-pyridones are privileged motifs in pharmaceuticals, natural products, and functional materials, yet their synthesis often requires costly, unsustainable catalysts or suffers from a narrow scope. Harnessing iron’s natural abundance, low toxicity, and tuneable reactivity, we explored the stoichiometric and catalytic chemistry of a rigid, low-spin stabilizing Fe(II) macrocyclic complex, [Fe([15]ane(phenN₂)S₃)(NCMe)](OTf)₂, with 2-propargyloxypyridine (HC≡C(CH₂)O(2-py)) and heteroatom-substituted analogues. Selective Fe-mediated 5-exo-dig cyclization affords isolable Fe(II) alkenyl heterocycles; uniquely, the oxygen analogue undergoes quantitative alkenyl-to-alkyl isomerization to a rare Fe(II)-alkyl complex, featuring an unprecedentedly upfield Fe–C ¹³C NMR signal (–9.00 ppm) indicative of exceptional electron richness. Crystallographic and multinuclear NMR characterization, supported by theoretical calculations, reveal that this alkyl species is the thermodynamic product of the lowest-barrier cyclization pathway. Translating this reactivity, the Fe(II) complex catalyses rearrangements of 2 propargyloxypyridines and 2 propargyloxyquinolines to N-alkenyl-2-pyridones and N-alkenyl-2 quinolinones with high efficiency and predictable electronic/steric control. These findings expand the known reactivity space of Fe-alkyne chemistry into structurally characterized alkyl territory, establish a mechanistically elucidated sustainable route to valuable heterocycles, and highlight the design potential of macrocyclic Fe(II) platforms for green, practical catalysis in organometallic synthesis.

Date of Award	3 Sept 2026
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Chun Yuen Alex WONG (Supervisor)