*3.2. Sequential Growth Based on the Coordination Polymer/Glaser Coupling Combination*

Still implying intermediate organometallic structures in multistep reactions, a surprising example has been reported in 2018 where the monomer, i.e., 2,5-diethynyl-1,4-*bis*(4-bromophenyl-ethynyl) benzene (2Br-DEBPB) could theoretically react according to the Ullmann and Glaser coupling mechanisms (see Figure 22A) [124].

**Figure 22.** (**A**) Polymerization of 2,5-diethynyl-1,4-*bis*(4-bromophenyl-ethynyl)benzene (2Br-DEBPB) on Ag(111) substrates and chemical structures of 1-((4-bromophenyl)ethynyl)-2,5-diethynyl-4- (phenylethynyl)benzene (1Br-DEBPB) and ((2,5-diethynyl-1,4-phenylene)bis(ethyne-2,1-diyl))dibenzene (DEBPB). (**B**) STM images of the supramolecular phases obtained by annealing the surface at RT temperature for 30 min. (**C**) STM images of the coordination polymer obtained by annealing the surface at RT temperature for 10.5 hours. 4) Covalent polymer chains obtained by annealing the Ag(111) surface at 410K. Reproduced from [124] with permission from The Royal Society of Chemistry.

However, only one type of coupling was observed on Ag(111) surfaces. To get this discrimination between the two possible types of coupling, the experiments were carried out at low temperature. Thus, coexistence of two supramolecular phases consisting in a chevron-type structure and a honeycomb arrangement could be found on a Ag(111) surface after a thermal evaporation of 2Br-DEBPB on a

surface held at −123 ◦C (see Figure 22B). After annealing this surface for 1.5 h at room temperature and subsequent cooling of the surface at low temperature (see Figure 22C), a newly ordered structure could be found on Ag (111) surfaces, consisting of parallel rows of molecules where intact molecules and monobrominated 1-((4-bromophenyl)ethynyl)-2,5-diethynyl-4-(phenylethynyl)benzene (1Br-DEBPB) (2% of the total molecules) were coassembled in a densely packed structure. Presence of a large number of bromine adatoms (higher than the 2% resulting from the debromination reaction) on the surface was assigned to the desorption of the fully debrominated molecules. This fact was confirmed by annealing the supramolecular phase for 30 min instead of 1.5 h at room temperature. Twenty-one percent of fully reduced molecules could be found on the surface. However, it has to be noticed that the temperature was insufficient to initiate an Ullmann coupling. Molecular chains corresponding to the formation of coordination polymers could only be obtained by annealing the surface for 10 hours at RT. In these conditions, an activation of the C–H bonds of terminal alkynes could be obtained, resulting in the formation of polymer chains. Finally, conversion of the coordination polymers to covalently bonded polymers was achieved at the relatively low temperature of 137 ◦C (See Figure 22D). By the abundant presence of bromine adatoms on the Ag(111) surface, interactions between the electron-rich bromines and the electron-deficient hydrogens of terminal alkynes could occur, reducing the BDE, and weakening the C–H bond. As a result of this, Glaser coupling, assisted by both the surface and the presence of halogen adatoms, could occur.

## *3.3. Sequential Growth Based on the Glaser Coupling/Dehydrogenative Coupling Combination*

Convincing results concerning the benefits of a sequential procedure were also obtained by combining a Glaser coupling with a dehydrogenative polymerization [125]. Use of carboxylic acid derivatives for on-surface syntheses of supramolecular networks is not new and this is notably due to the ability of the carboxylic functional groups to form hydrogen bonds or to interact with the metal substrates, giving rise to metal–ligand coordination networks [126,127]. The carboxylic functional groups can also be deprotonated by the metal surface, drastically modifying the structure of the final network. A clear evidence of this influence was provided with trimesic acid deposited onto a Cu(100) surface [128]. Deprotonation of the carboxylic functions modified the adsorption geometry of the network by inducing a rotation of 90◦ relative to the substrate so that the deprotonated form of trimesic acid stands upright and perpendicular to the surface. With aim at generating covalent bonds, only few articles have been reported in the literature and the decarboxylation of 2,6-naphthalenedicarboxylic acid to form carbon–carbon bonds can be cited as the unique example [129]. Parallel to this, on-surface Glaser coupling of terminal alkynes was reported prior to this work but examples in the literature are scarce [42]. Orthogonality of these two reactions is clear so that their combination was examined for the polymerization of 6-ethynyl-2-naphthoic acid (ENA). Interestingly, influence of the surface topography as well as the density of molecules on surface were determined as controlling the reaction outcome. Upon deposition of ENA on Au(111) substrates at low surface coverage and upon annealing of the surface at 124 ◦C, a 2D network formed, resulting from the dimerization of ENA, i.e., 6,6 -(buta-1,3-diyne-1,4-diyl)*bis*(2-naphthoic acid) (DBNA) and the formation of a metal–carboxylate coordination network (see Figure 23). Differing from this first arrangement, the same experiments carried out at high surface coverage resulted in the coexistence of two distinct phases on the surface (See Figure 24A). The first one corresponds to an intermediate state of the Glaser dimerization where two ENA molecules are arranged in a linear fashion with Au adatoms ensuring the connection with two ENA units. In the second phase and contrarily to what was expected, the product resulting from the Glaser coupling, i.e., DBNA was detected on the surface, but coexisting with an unexpected compound resulting from an oxidative dehydrogenation. In fact, disordered polymer chains could be detected in this second phase, resulting from the formation of bisacylperoxides (see Figure 24B).

**Figure 23.** Polymerization of 6-ethynyl-2-naphthoic acid (ENA) by a domino reaction based on the Glaser coupling/dehydrogenative coupling combination. Depending of the density of molecules onto the Au(111) substrates, different structures are obtained.

**Figure 24.** Polymerization of 6-ethynyl-2-naphthoic acid (ENA) by a domino reaction based on the Glaser coupling/dehydrogenative coupling combination. (**A**) STM topographs obtained at low density of molecules after Glaser coupling and formation of the Au-carboxylate complex on Au(111) substrates (left: 42 nm × 38 nm, right: 21 nm × 17 nm, bottom: 5.9 nm × 5.0 nm). (**B**) STM topographs obtained at high density of molecules on Au(111) substrates (top left: 72 nm × 88 nm, top right: 2.6 nm × 1.2 nm, bottom left: 17 nm × 12 nm, bottom right: 5 nm × 4 nm). Reprinted with permission from Held et al. [125]. Copyright © 2016 John Wiley & Sons, Inc.

Interestingly, the starting point of these different polymer chains was still a gold–carboxylate complex. As a result of this, the direction of the chains growth is thus predetermined by the geometry of the Au-complex and the number of "ligands" around the Au center. To verify the role of the substrate in the growth direction, similar experiments were carried out onto Au(100) substrates with a structured surface and these latter revealed the Glaser coupling as well as the dehydrogenative coupling to produce chains aligned along with the channels direction, without the formation of ramifications. Polymers extending over 100 nm could be thus prepared, with a thermal stability higher than 160 ◦C. In this work, the crucial role of the first step, i.e., the formation of the butadiyne groups, was determined as being primordial to activate the formation of bisacylperoxides. Indeed, despite numerous aromatic acids having been examined for on-surface synthesis prior to this work, formation of peroxides from carboxylic groups has never been reported. Finally, XPS experiments confirmed the formation of both Au–carboxylate complexes as well as bisacylperoxide groups.

## **4. Conclusions**

In this review, a series of eight combinations of orthogonal reactions enabling the successful realization of 1D and 2D macromolecular organic structures on surface have been reported. The development of efficient chemistries in a vacuum environment is an important challenge conditioning the future of numerous applications. For these reasons, it is of high importance to continue to acquire knowledge and know-how on the growth of macromolecular organic structures in vacuum environment. Based on the different works devoted to the hierarchical or sequential construction of 1D and 2D structures, the possibility to elaborate extended covalent organic structures on surface was brilliantly demonstrated with STM images of scan area sizes larger than <sup>60</sup> × 60 nm2. Comparison between the macromolecular structures obtained by sequential or hierarchical growth on surface and those obtained by the classical one-step approach would be of crucial interest for the future development of this approach and the optimization of the reaction conditions. However, the comparison between the two approaches remains extremely difficult with regards to the multiparametric character (metal, crystallographic plane, formation or not of an intermediate supramolecular phase, density of molecules on-surface, etc.) of the delicate growth. This is notably the reason why the comparison between the two models is not established in the different studies. With regards to the large number of reactions existing in organic chemistry and the infinite of combinations, there is still room for improvement and numerous unexplored combinations will be reported in the future.

**Author Contributions:** Writing—Original Draft Preparation, C.P. and F.D.; Writing—Review & Editing, C.P. and F.D.

**Funding:** This research was funded by Aix Marseille University and the Centre National de la Recherche Scientifique (CNRS).

**Conflicts of Interest:** The authors declare no conflicts of interest.

#### **References**


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