Progressive Coordinative Oligomerization of a Heterocycle Aggregate Directed by Fe(III): Elucidating a 15-Step Inter- and Intramolecular Domino Mechanism

Benzo[d]thiazol-2-ylmethanol undergoes progressive oligomerization when treated under solvothermal condition with FeCl 3 ·6H 2 O to give heterocycle aggregate (1,2,3-tris(benzo-[ d ]thiazol-2-yl)-2,9-dihydrobenzo-[ b ]cyclopenta-[ e ][1,4]-thiazine. Four single-crystal structures analyses have been performed on compounds isolated during the reactions and 15 consecutive steps have been deciphered from ESI-MS of both solid products and the intermediate reaction solutions. These progressive steps involve intermolecular C-C coupling (9 steps) and intramolecular ring expansion (6 steps). Each of the non-carbon atoms (N, O, and S) has its particular function due to their position on the heterocycle: (i) The N and O coordinated with Fe(III) to activate the reaction site, ( ii ) C-O homolytic cleavage promoted C-C coupling reactions, and ( iii ) C-S migration caused intramolecular ring expansion. Importantly, through theoretical calculations, decrease in Gibbs free energy of intramolecular reaction pathways support this mechanism and activation mode, which indicated that the Fe(III) is necessary for the reaction to progress. The investigation of photophysical properties revealed that the heterocyclic aggregates exhibited good luminescent behavior in the wavelength range of 535–610 nm, approaching the near infrared region. This finding underscores the significance of this reaction pathway and the identification of its mechanistic steps in facilitating the synthesis of functional oligomers and polymers from monomers, particularly through the catalytic promotion by inexpensive metal ions. Progressive Coordinative Oligomerization of a Heterocycle Aggregate Directed by Fe(III): Elucidating a 15-Step Inter- and Intramolecular Domino Mechanism Kai-Bin Chen, † Ting-Ting Wang, † Zhi-Wei Xu, Ning Tian, Jin Cai, Wen-Yu Qiu, Mohamedally Kurmoo, Bin Zhang, Zheng Yin, Bin Liu,* Ming-Hua Zeng* Kai-Bin Chen, Ting-Ting Wang, Jin Cai, Bin Liu, Prof. Ming-Hua Zeng Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China. E-mail: [email protected]; [email protected]. Zhi-Wei Xu, Ning Tian, Wen-Yu Qiu, Mohamedally Kurmoo, Bin Zhang, Zheng Yin, Prof. Ming-Hua Zeng State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.

domino reaction, progressive coordinative oligomerization, inter- and intramolecular transformation, heterocyclic aggregates, elucidating reaction mechanism Benzo[d]thiazol-2-ylmethanol undergoes progressive oligomerization when treated under solvothermal condition with FeCl 3 ·6H 2 O to give heterocycle aggregate (1,2,3-tris(benzo-[ d ]thiazol-2-yl)-2,9-dihydrobenzo-[ b ]cyclopenta-[ e ][1,4]-thiazine. Four single-crystal structures analyses have been performed on compounds isolated during the reactions and 15 consecutive steps have been deciphered from ESI-MS of both solid products and the intermediate reaction solutions. These progressive steps involve intermolecular C-C coupling (9 steps) and intramolecular ring expansion (6 steps). Each of the non-carbon atoms (N, O, and S) has its particular function due to their position on the heterocycle: (i) The N and O coordinated with Fe(III) to activate the reaction site, ( ii ) C-O homolytic cleavage promoted C-C coupling reactions, and ( iii ) C-S migration caused intramolecular ring expansion. Importantly, through theoretical calculations, decrease in Gibbs free energy of intramolecular reaction pathways support this mechanism and activation mode, which indicated that the Fe(III) is necessary for the reaction to progress. The investigation of photophysical properties revealed that the heterocyclic aggregates exhibited good luminescent behavior in the wavelength range of 535–610 nm, approaching the near infrared region. This finding underscores the significance of this reaction pathway and the identification of its mechanistic steps in facilitating the synthesis of functional oligomers and polymers from monomers, particularly through the catalytic promotion by inexpensive metal ions. 1. Introduction Exploring the limits of rational chemical synthesis is one of the core issues in chemical science. [1] To achieve this goal, chemists have tried to combine into essentially any molecular configuration they desire by introducing and breaking the covalent bonds. Wherein, synthesis of multi-heterocyclic aggregated compounds using heterocyclic simple compounds as raw materials is the ultimate goals of synthetic chemistry because chemical aggregation is an important reaction mode widely used in fields such as materials science and pharmaceutical research. In order to accurately synthesize heterocyclic aggregates, studying complex reaction process to understand the mechanism that gives rise to each constitutional step is necessary. [2] Domino reaction is one of the complex chemical reactions that process involving two or more consecutive reactions in which subsequent reactions result as a consequence of the functionality formed by bond formation or fragmentation in the previous step. [3] The high step efficiency of the reaction, as well as its convenience of operation, foster its wide use in the synthesis of heterocyclic aggregate, natural products, macrocycles, polymers, and other target molecules. [4] Wherein, transition-metal-catalyzed domino reactions is the typical reactions, often used for synthesizing complex multi heterocyclic compounds by metal ions facilitating C-X/H bond insertion via oxidative addition or metal ions coordinate with heteroatoms such as N or O, altering the charge distribution on the substrate and enabling further aggregation. [5, 6] However, revealing the role of metal ions and heteroatoms in domino reaction to elucidating the mechanism is a significant challenge because domino sequence consists of numerous steps making it is hard to set up appropriate process tracking strategy and study methods. [7] To solve this challenge, new concepts and methods are needed to facilitate the fast detection of active intermediates and elucidation of their possible structures. The combined application of single-crystal crystallography and mass spectroscopy of both the isolated crystals and the intermediate reaction solutions provides a reliable strategy to tackle the above-mentioned problem. This strategy has been exemplary in the development of our understanding of some complex sequences of domino reactions for aggregates synthesis. [8] In addition, DFT calculations of the energetics have allowed the most plausible mechanism to be delineated. The results stand-out in studies of complex reaction involving multiple covalent bonds breaking and forming to building-up of molecular diversity which represents an important research frontier of synthetic chemistry. [9] In this venture, our group has taken two directions in elucidating solvothermal reaction processes and defining their mechanisms; One is studying the formation of step-by-step coordination assembly of metal ions in solutions to clusters in crystals and their chemical properties. [10, 11] The other is studying the PCO reaction of organic heterocycles induced by metal ions. [12] The first direction has led to the most logical mechanism for the sequential assembly of the largest chiral cobalt cluster Co 16 as well as elucidating the self-assembly of a highly stable Zn 5 cluster. [13, 14] The second branch of this work has revealed a novel 14-step domino reaction of benzo[ d ]imidazole-2-methylamine in the presence of Fe(III) leading to a highly stable purely organic radical tris(4-methyl-1-(1-methyl-1 H -benzo[ d ]imidazol-2-yl)-4 H -benzo-[ d ]imidazo[1,5- a ]imidazol-3-yl)methyl hydrochloride. [15] Through the crystallography the step-by-step assembly is revealed while identifying an exceptional formation of twelve covalent bonds and three five-membered heterocycles in this domino reaction. This reaction also includes consecutive intermolecular transformation of C=N bond and C-C bonds as well as C-O bond homolytic cleavage between benzimidazol-2-methylamine and the methanol solvent which becomes the site of the radical. Importantly, not only did the terminal amino group participate in the reaction, but also the nitrogen atoms of the heterocycles took part. Based on this, we speculated that non-carbon atoms play an important role to synthesis poly- heterocycle aggregates in the PCO reaction. Introducing more kinds of hetero atoms into the substrate may result in more fascinating transformations. we speculated that using heterocyclic substrates, poly- heterocycle aggregates can be obtained by progressive coordinative oligomerization (PCO) reaction and key intermediates can be observed by the solid-state/solution structure information correlation. Inspired by the above observations, we decided to explore what consequence the presence of a S on the cycle and an OH in place of the amine will have on the oligomerization due to their different coordination ability with Fe(III). To explore this possibility, benzo[ d ]thiazol-2-ylmethanol ( L1 ) was selected to react with 3d transition metal ions. To our delight, the heterocyclic aggregate with AIE effect 1,2,3-tris(benzo-[ d ]thiazol-2-yl)-2,9-dihydrobenzo-[ b ]cyclopenta-[ e ][1,4]-thiazine ( 1 ) represents the first 2,9-isomer of dihydrobenzo-[ b ]cyclopenta-[ e ][1,4]-thiazine was been obtained. Affirmingly, a 15-step domino sequence is proposed including intermolecular triple C-C coupling and intramolecular C-S migration. It is the only example of consecutive change of C-C, C-O, and C-S bonds (Scheme 1). Scheme 1 Coordination directed inter/intramolecular C-C coupling and C-S migration domino reaction between FeCl 3 ∙6H 2 O and chelating substrate L1 leading to the 2,9-dihydrobenzo[ b ]cyclopenta[ e ][1,4]thiazine core. 2. Results and discussion Benzo[d]thiazol-2-ylmethanol in the presence of the iron(III) salt undergoes a transformation to form compound 1 and dehydrogenated 2 (1,2,3-tris(benzo[ d ]thiazol-2-yl)benzo[ b ]cyclopenta[ e ][1,4]thiazine) (Figure 1) under solvothermal conditions (120 °C), with ethanol as solvent. 1 crystallizes from the solution obtaining a yield of 32% after the reaction and belongs to the triclinic crystal system with the P -1 space group (Table S1a). The smallest asymmetric unit consists of a tricyclic system containing two six-membered rings and one five-membered ring A, which consists of five carbon atoms C1-C5. The bond lengths and angles of the newly formed rings suggest that C3 is sp 3 hybridized and ring A has a cyclopentadiene structure. Combined with the position and type of the heteroatom of L1, the six-membered ring fused with A is a [1,4]-thiazine ring and this tricyclic system is a trisubstituted 2,9-dihydrobenzo-[b]cyclopenta-[e][1,4]thiazine (Table S1b). The NMR of the protons attached to C3 and N1 are at 6.01 ppm and 11.06 ppm (Figure S1a), respectively, which further support the proposed structure. Three benzo[ d ]thiazolyl groups are attached to C2, C3, and C4 atoms, respectively. Compound 2 was separated from the solution by column chromatography and recrystallizes from chloroform. It crystallized in the monoclinic crystal system, P 2 1 /n space group (Table S1a) and its smallest asymmetric unit is similar to 1 . In contrast to 1, the C3 in 2 is sp 2 hybridized, which is supported by the bond lengths and angles around C3 (Table S1b). In 1 H NMR, the two protons attached to C3 and N1 in 1 are absent in 2 (Figure S2a). They are rare heterocyclic aggregates that contain four heterocycles and eight heteroatoms (four N atoms and four S atoms). These heteroatoms are distributed around the newly formed ring A / A’ and distance between the centre of the rings are less than 4 Å. When the L1-Cl [(5-chlorobenzo[ d ]thiazol-2-yl)methanol] is used, the corresponding tricyclic products 3 (7-chloro-1,2,3-tris(5-chlorobenzo[ d ]thiazol-2-yl)-2,9-dihydrobenzo[ b ]cyclopenta[ e ][1,4]thiazine) and its dehydrogenated derivative 4 (7-chloro-1,2,3-tris(5-chlorobenzo[ d ]thiazol-2-yl)benzo[ b ]cyclopenta[ e ][1,4]thiazine) are also obtained. The structures had been characterized by X-ray single crystal diffraction (Figure 1, Table S2). This fact implies that this synthetic method has a potential application in heterocycle synthesis. In addition, dihydrobenzo-cyclopenta-thiazine core has eight possible isomers, [16] only two types of isomers with only five molecules had been reported (Figure S4). 1 is the third isomer to be synthesized. It is notable that the starting material of the reaction is different from all those reported to synthesize this core. (Table S3). Compound 2 is the first compound that three aryl groups substituted derivative of benzo[ b ]-cyclopenta[ e ][1,4]thiazine. Previously, there was only one report for the framework which is substituted by ester groups. (Table S4). Figure 1 The crystal structures of 1-4 and the localized aggregation of heteroatoms. The red atom highlights the proton on C3. (The chemical structures see figure S3) To get reference for the MS fragment assignment, the ESI-MS of compounds 1 and 2 were recorded. The molecular ion peak of 1 and 2 is found at m/z 585.0318 and ascribed to fragment [ 1 +H] + or [ 2 -H] + (Figure S1c and S2c). Then, the reaction mechanism is studied via control experiments firstly (Figure 2 and S5). When the reaction was carried out without FeCl 3 ·6H 2 O, the hydroxyl group of L1 underwent dehydrogenation to form a carbonyl group and generated to L1’ ( L1’ = benzo[d]thiazole-2-carbaldehyde). When the reaction is carried out under reflux conditions, the same result was obtained. In addition, when reacting at 80°C under solvothermal conditions, L1’ also obtained. At the same time, a diol intermediate L2 (1,2-bis(benzo[ d ]thiazol-2-yl)ethane-1,2-diol) could be detected. It is worth noting that the crystal of L2 appear in the reaction system (Figure S6 and Table S1a). The dimerization of aryl-methanol to give diol derivatives have been reported by the catalysis of FeCl 3 in protonic solvent [17] or at photo irradiation condition. [18] When the reaction was performed in the presence of 1,1-diphenylethylene (C 14 H 12 ), no product was detected. However, the peaks at m/z 344.1100 and 346.5533 were found and assigned to the fragments derived from [(C 14 H 12 ) L1 ] + and [Fe(C 14 H 12 ) L3 ] 2+ ( L3 = 1,2,3-tris(benzo[d]thiazol-2-yl)propan-1-one), suggesting that free radical pathways were involved. When the reaction was performed with FeCl 2 ∙4H 2 O, L1’ was also obtained but L2 was not observed. This reflects that Fe(III) is the key for this reaction. To investigate the intermediates involved in the reaction, L1’ and L2 as starting materials to react under the same conditions, respectively. To our delight, L2 was transformed via an aggregation process to the product 1 with the product a single crystalline structures. This result confirmed that L2 could be the reaction intermediate. On the contrast, when L1’ was used as the starting material, no product was observed, suggesting that the aldehyde which could be produced by the oxidation of L1 is not the reaction intermediate. The time-dependent ESI-MS was applied to track the reaction process at 80°C, 100°C, 120°C and 140°C to check the influence of reaction temperature on the aggregation process. Selected key fragments which represent L1 - L4 are presented to show the possible reaction pathway (Figure 3 and Figure S7a-c). Wherein, the peaks at m/z 255.9278, 311.0307, 327.9854, 345.9961, 418.9368, 457.0337, 493.0107, 535.0212, 565.0679 and 692.9401 are assigned to fragments [ FeClL1 ] +, [ HL2” ] + ( L2” = 1,2-bis(benzo[d]thiazol-2-yl)ethan-1-one), [ (HCl)L2’-H 2 O ] • + ( L2’ = 1,2-bis(benzo[d]thiazol-2-yl)ethen-1-ol), [ (HCl)L2’ ] • + , [ FeClL2 ] • + , [ L3 ] • + , [ (HCl)HL3 ] • + , [ (L3-2H)Cl(EtOH) ] • + , [ (HCl)HL 3 (4H 2 O) ] • + and [ FeClL4 ] + [ L4 = (1,2,3,4-tetrakis(benzo[ d ]thiazol-2-yl)but-2-en-1-one)], respectively (Figure S7d and Table S5). From the appearance time of the key fragments, when the reaction temperature rises from 80°C to 120°C, the reaction rate and yield increase, the time to obtain the product decreases. Yet, when the reaction temperature reached 140°C, the reaction rate no longer decreases and the yield no longer increases. Combining the screening of reaction conditions (Table S6), 120°C is used as the reaction temperature and the reaction process is further studied (Figure 4). Figure 2 Observing the progress of reactions by ESI-MS at 80°C, 100°C, 120°C and 140°C. When the reaction mixture is heated at 120 °C for 0.5 h, the peaks represent L1 - L3 were observed. [ FeClL1 ] + indicates the coordination of Fe(III) with L1, which could activate the ligand for the subsequent transformations. L2 can be obtained by in-situ coupling of L1 and easily transform to L2’ by dehydrated. L2’ could transform to its ketone tautomer L2 ” . Recently, the formation of deoxy benzoin from diol intermediate has been realized by using visible light at photo irradiation catalyzed by ZnIn sulfides semiconductors. [19] L3 is probably produced from the aldol condensation between L2” and L1 . The Fe(III) catalyzed aldol condensation of aldehyde has been reported. [20] After 1 h, the fragment [ FeClL4 ] + appeared. Base on control experiment, this fragment is probably produced from the free radical C-C coupling between L1 and L3 . [19, 21] From 1 h to 5 h, the intensities of these eight fragments gradually increase and then decrease, indicating their intermediate feature. From 5 to 24 h the intensities of those peaks were gradually decreases, indicating that 1 and 2 are formed gradually. Based on above data and analysis, a plausible mechanism of Fe(III) coordination directed intermolecular mechanism was proposed (Figure 5a), including triple C-C coupling and leads the aggregation of four heterocycles. Figure 3 Relative intensities of the MS fragments corresponding key intermediates and compound 1 during the reaction process (Fragment information see Table S5). By comparing the structures of L4 and 1, we propose plausible mechanism whereby L4 undergoes a series of intramolecular reaction directed by Fe(III) coordination involving the fourth C-C coupling and S-migration (Figure 5b). The H atom of γ -C migrates to N by Fe(III) induced charge transfer to give X . It has been reported that through protonation or alkylation of the N atom of the thiazole ring, the neighboring C atom ( a’ -C) gets activated, and attacked by nucleophilic reagents. [22] Next, the γ -C atom attacks the a’ -C, breaking the C-S bond to produce a new five-membered carbon ring in XI . The carbonyl carbon ( a -C) undergoes an intramolecular nucleophilic reaction with S to produce a 1,4-thiazine ring ( XII ). The opening of the thiazole ring to produce 1,4-thiazide has been reported, which usually needs reactive alkyne derivatives [23] or strong bases [24] to activate the thiazole ring. After H-migration, XIII is formed. Then, dissociation of the coordinated [FeCl 3 H 2 O] group together with the proton attached on N results in 2 . Finally, 2 is reduced by the in-situ generated H 2 molecule to give 1 . In total there are 15 steps in this reaction which is the longest domino sequence. Figure 4 Plausible mechanism for the formation of compounds 1 and 2 ([Fe] = FeCl 3 ): (a) intermolecular C-C coupling reaction; (b) intramolecular reaction. Each step in this domino sequence had been independently reported, but no report of the continuous reaction (Table S7). The realization of domino sequence of reactions is attributed to the unique spatial arrangement of the N, O, S atoms within the substrate and their effect on the heterocycle upon coordination to Fe(III). The N and O atoms often act as a chelating unit enforcing coordination to Fe(III), [25] which activate the α -C leading to free radical. O atoms were removed in the form of water easily, and the adjacent carbons undergo C-C coupling reactions. [23] This coupling induces the aggregation of four heterocycles. In the intramolecular reaction, the γ -C atom of IX acts as good nucleophile to realize the intramolecular nucleophilic reaction after coordinated by Fe(III). The released γ -H is then attached to the N atom of the thiazole to activate the α -C which is prone to attack by γ -C, yielding the cyclopentadiene ring. [26] The formal C-S bond migration resulting in the ring expansion of thiazole to thiazine is achieved by the cleavage of the C-S and the intramolecular nucleophilic attack of -S - ion by the adjacent carbonyl group. [27] Because of the migration of C-S bond, this transformation finally forms a tricyclic ring and constructs a heterocyclic aggregate with three others substituted phenylpropyl thiazole. It should be noted that from IX to 1 is a series of intramolecular transformations, involving intermediates with the same chemical formula (The molecular weight is same as [ FeClL4 ] + ). This makes the assignment of the MS peaks of these intermediates inaccessible. At the same time, it is without x-ray structures from IX to XII . To verify the process of the reaction, density functional theoretical (DFT) calculation was performed. High spin state in the calculation of iron complexes was considered because the four coordinated iron complexes with weak field ligands (Cl-) calculated are highly likely to be in a reasonable state. The Gibbs free energy changes (-16.6 kcal/mol) from IX to 2 had been studied (Figure 6a). This study indicated that the reaction sequence is plausible from thermodynamic. The highest energy barrier is for TS -3, indicating that the rate-determining step could be the H-transfer on the five-membered ring. To explore Fe(III) can promote the reaction, we compared the energies and structural changes of two key steps γ- H migration and C-S migration in intramolecular reactions in both the presence and absence of Fe(III) (Figure 6b). Obviously, the Gibbs free energy without Fe(III) is higher, 14.6 kcal/mol, than with Fe(III) at 10.5 kcal/mol. Additionally, in the presence of Fe(III), the distant between reacting atoms and reaction sites (2.23 and 1.91 Å) are shorter than those of without Fe(III) (2.75 and 2.66 Å). Those differences can be attributed to the coordination of Fe(III) with the ligands changes the spatial structure and the active reaction sites. [28] Figure 5 (a) DFT calculated reaction pathway and Gibbs free energy profile for the intramolecular transformation (in kcal/mol) at the M06L/(def2-SVP)/SMD(ethanol)//M06-L/(def2-TZVP) level of theory; (b) Key intermediates IX and XI leading to X and XII . Preliminary study on photophysical properties of 1 - 4 is performed. Using the maximum absorption wavelength of the compound as the excitation wavelength, the maximum fluorescence emission wavelength is obtained. Fluorescence lifetime and quantum yield show that they have good luminescence performance (Figure 6, S9-S10). Compare with 1 and 3 or 2 and 4, Cl atoms act as chromophores on the benzene rings, and their electron withdrawing effect increases the conjugation of compound electrons, causing both absorption and emission peaks to red shift. The red shift of the maximum emission from 1 and 3 to 2 and 4 could be attributed to the conjugated system. At the same time, the quantum yield increase. These results indicated that the products have the potential for development and application in the field of luminescence. Figure 6 UV-Vis absorption spectrum (red line) and fluorescence spectrum (blue dotted line) at 10 -5 M in CH 2 Cl 2 (r.t.) of (a) compound 1 (E x = 424 nm); (b) compound 2 (Ex = 445 nm) (c) compound 3 (E x = 438 nm) and (d) compound 4 (Ex = 464 nm). 3. Conclusions In summary, FeCl 3 ·6H 2 O promoting oligomerization of (benzo[ d ]thiazol-2-ylmethanol, L1) has been successful under solvothermal condition. Poly-heterocycle aggregates 1 and 2 and their Cl-substitution compounds 3 and 4 have been produced. The reaction process was studied by ESI-MS, solid products and the intermediate reaction solutions. A domino sequence was proposed involving intermolecular triple C-C coupling (9 steps) and intramolecular C-S migration (6 steps), achieving the longest consecutive transformation (15 steps). In addition, calculations of the energetics using DFT favor the intramolecular ring expansion. This reaction reflects the induced PCO reaction of N, O, S and other heteroatoms compounds under the coordination of metals. The role of metal ions and heteroatoms in the reaction was revealed. When N, O, S are present in the heterocycle, N and O coordination to Fe(III) induces the departure of O atoms, leading to the generation of more reaction sites, and migration of C-S bonds can occur more interesting reactions and obtain new heterocycles. This shows heteroatoms are potentially interesting alternatives for domino reaction. This work demonstrated the combination of crystallography with ESI-MS can elucidate the mechanism of complex and numerous steps in domino reactions accurately by key intermediate structures. On the other hand, reactions between heteroatom containing chelating substrates and transition metal salts could provide great potential to manipulate the length of domino sequence, elucidate mechanism, and obtain complex aggregates which are difficult or even inaccessible by traditional stepwise method. Moreover, the heterocyclic aggregates exhibit luminescent properties within the visible light spectrum, suggesting that investigating diverse domino reactions involving related multi-heteroatom chelating substrates with 3d transition metal ions represents a promising avenue for the synthesis of functional heterocyclic aggregates.

This work was financially supported by the BAGUI Talent Program (2019AC26001), and the Natural Science Foundation of China (22171075, U23A2080). † These authors contributed equally Conflict of Interests The authors declare no conflict of interests. Supporting Information Supporting Information is available from the Wiley Online Library or from the author. Received: ((will be filled in by the editorial staff)) Revised: ((will be filled in by the editorial staff)) Published online: ((will be filled in by the editorial staff))

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A domino reaction sequence has been realized between benzo[d]thiazol-2-ylmethanol and FeCl 3 ·6H 2 O, leading to heterocyclic aggregate 2,9-dihydrobenzo[b]cyclopenta[e][1,4]thiazine is synthesized. The reaction process has been studied and the longest 15-step domino sequence involving intermolecular C-C coupling and intramolecular expansion has been proposed. Five new C-C bonds, one C-S bond, and a tricyclic system are involved in the domino reaction.

Keywords: domino reaction, progressive coordinative oligomerization, inter- and intramolecular transformation, heterocyclic aggregates, elucidating reaction mechanism, AIE Kai-Bin Chen, † Ting-Ting Wang, † Zhi-Wei Xu, Ning Tian, Jin Cai, Wen-Yu Qiu, Mohamedally Kurmoo, Bin Zhang, Zheng Yin, Bin Liu,* Ming-Hua Zeng* Progressive Coordinative Oligomerization of a Heterocycle Aggregate Directed by Fe(III): Elucidating a 15-Step Inter- and Intramolecular Domino Mechanism ToC figure Supplementary Material File (image5.emf) - Download - 610.77 KB Information & Authors Information Version history Copyright This work is licensed under a Non Exclusive No Reuse License.

Authors Metrics & Citations Metrics Article Usage 259views 118downloads Citations Download citation Kai-Bin Chen, Ting-Ting Wang, Zhi-Wei Xu, et al. Progressive Coordinative Oligomerization of a Heterocycle Aggregate Directed by Fe(III): Elucidating a 15-Step Inter- and Intramolecular Domino Mechanism. Authorea. 09 January 2025. DOI: https://doi.org/10.22541/au.173641501.13995715/v1 DOI: https://doi.org/10.22541/au.173641501.13995715/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu.