Synthesis of conjugated polyynes by alkyne metathesis – SyCoPAM
Synthesis of conjugated polyynes by alkyne metathesis
Conjugated polyynes are an important class of molecules, both in the field of materials and the field of biochemistry. The synthesis of polyynes bearing an odd number of conjugated triple bonds is challenging. Preliminary results suggested that alkyne metathesis could be very helpful for the synthesis of conjugated triynes and longer polyynes.
This project aims to develop this methodology to access highly challenging molecules containing an odd number of conjugated triple bonds.
The word "polyynes" refers to molecules that contain several conjugated C≡C triple bonds. This is an important family of compounds found in nature as well as in the interstellar medium. Strictly speaking, a polymer of alkyne is called "carbyne", and it represents a yet unknown allotrope of carbon. It is predicted to have exceptional properties, particularly in terms of conductivity, strength, elasticity, and stiffness, which are expected to exceed those of all known materials. However, it has never been isolated due to its instability. It has only been stabilized inside carbon nanotubes. Analogues have been synthesized by the research teams of R. Tykwinski and J. Gladysz, containing up to 26 conjugated triple bonds. Over the past decades, several strategies have been developed to connect two C≡C triple bonds, thus enabling the formation of conjugated diynes. The most well-known method is probably the Glaser coupling, which uses copper salts to induce the formation of Csp–Csp bonds from terminal alkynes. This reaction is particularly useful for homocoupling. The Cadiot-Chodkiewicz coupling, on the other hand, is used for heterocoupling, connecting a terminal alkyne to a brominated alkyne. More recently, scientists have developed new strategies to synthesize unsymmetrical conjugated diynes, in order to improve yields or overcome the limitations of the aforementioned methods. The formation of conjugated triynes is much more complex, as the introduction of a third triple bond can compromise the stability of the precursors or the resulting compounds. Nevertheless, some methods have been developed to access these molecules. Glaser-type couplings are not suitable, since they require the reaction of two types of alkynes (a diyne and a simple alkyne), which generates multiple products without selectivity. Moreover, terminal diynes are generally unstable and should be avoided. Cadiot-Chodkiewicz couplings are therefore preferred, although brominated diynes themselves can also be unstable. The Fritsch-Buttenberg-Wiechell rearrangement is often used to build symmetrical or unsymmetrical conjugated triynes, and provides a convenient protocol applicable to a range of alkynes. Nevertheless, the use of a strong base such as n-butyllithium limits the scope of this method. Thus, the development of new methods for the synthesis of conjugated triynes is clearly in high demand. Furthermore, access to longer polyynes such as pentaynes is even more difficult, as the stability of precursors or products decreases with the number of C≡C triple bonds.
In the early 2010s, the Tamm group attempted to use alkyne metathesis to access conjugated triynes. This reaction is the equivalent of alkene metathesis, but with C=C double bonds replaced by C≡C triple bonds. It requires a catalyst, generally based on molybdenum or tungsten, and more recently rhenium.
Importantly, no base is required, and the reaction proceeds without heating or under mild heating conditions, which limits the potential degradation of the reactants or products.
However, contrary to expectations, the Tamm group was unable to isolate any conjugated triynes from conjugated diynes. Only new conjugated diynes were formed, along with 2,4-hexadiyne.
Although the group successfully exploited this reaction to propose an innovative and simple route to diynes, triynes remained inaccessible via alkyne metathesis at that time.
To overcome this limitation, the Mauduit and Trolez groups hypothesized that conjugated triynes could still be formed by protecting one of the two C≡C triple bonds of the precursors. Following this idea, they reacted 1,3-diynes bearing a bulky group at one end and a methyl group at the other.
A molybdenum-based catalyst developed by Alois Fürstner's group was used. They thus succeeded, for the first time, in synthesizing a variety of symmetrical and unsymmetrical conjugated triynes.
Furthermore, they demonstrated that the bulkier the terminal group, the higher the selectivity in favor of triyne formation (over diyne), as anticipated. This selectivity can reach 95% with a group such as tri(isopropyl)silyl (TIPS).
Following these initial results, a collaboration was established between the Mauduit, Trolez, and Tamm groups.
As preliminary results, they managed to increase the selectivity toward triynes using TIPS and mesityl derivatives. Indeed, they observed complete selectivity in favor of triynes with the molybdenum catalysts when using TIPS- or mesityl-substituted diynes, along with better yields than those obtained with Fürstner’s catalyst. This success encourages them to continue improving the methodology.
The ultimate goal is therefore to develop this methodology and ideally control selectivity through the catalyst rather than the substrate.
This project aims to achieve several objectives:
1) Synthesis and design of new catalysts for the preparation of polyynes via alkyne metathesis
2) Evaluation of the efficiency of these new catalysts
3) Use of the best catalysts for the synthesis of target polyynes.
A number of catalysts were synthesized and developed by Matthias Tamm’s group. On one hand, previously known and proven catalysts from this laboratory were synthesized and sent to the Rennes team for methodology development, with very promising results. On the other hand, new catalysts were also developed. Some of them have a structure very similar to those previously used in the preliminary results (siloxy series). One of these catalysts exhibited exceptional catalytic activity and remarkable selectivity for triyne formation. A second series (iminato series) was also developed, but did not yield the expected results. Although these catalysts were active in alkyne metathesis, they did not show promising activity for the selective formation of triynes.
The most efficient catalysts were subsequently sent to Rennes to support the development of the triyne synthesis methodology. This made it possible to evaluate the scope and limitations of the method by synthesizing variously substituted new triynes. Among other things, this helped identify which substituents were necessary to achieve total selectivity. In particular, aryl groups substituted at least once in the ortho position relative to the triple bond were compatible with this method, while those with only meta substitutions (and no ortho substitution) were not.
Then, this method was applied to the synthesis of various original polyynes. It enabled the straightforward synthesis of triyne precursors of [7]cumulenes, whose synthesis had previously been reported as long and difficult. New [7]cumulenes were thus obtained and characterized. In addition, this method was also applied to cobalt complexes used to mask alkyne functions, also acting as a bulky group in the context of metathesis. With an appropriate functionalization of the resulting triynes, a pentayne and a heptayne were isolated after removal of the protective cobalt complex. These two types of compounds, although already described in the literature, previously required long and tedious synthetic routes. Once again, alkyne metathesis offers a much shorter pathway to access these compounds.
Lastly, two triangular macrocycles containing three conjugated triyne units were isolated and characterized. Macrocycles containing such triyne motifs are extremely rare in the literature, and no isolated macrocycles of this type had ever been described. Alkyne metathesis thus represents a unique method to obtain compounds that are otherwise very difficult to synthesize by conventional routes.
The results obtained during this project have thus demonstrated the scope of this method for the synthesis of polyynes with an odd number of conjugated triple bonds. This opens the way for the future synthesis of even longer polyynes, bringing us closer to the carbyne model. The successful formation of macrocyclic compounds also paves the way for the synthesis of new macrocyclic carbon allotropes. Finally, the ease of synthesis of [7]cumulenes makes it possible to envision the development of new materials with unique optoelectronic properties in the future.
The synthesis of conjugated polyynes is a genuine scientific challenge nowadays. Although several methods have been reported over the last decades, diverse and efficient methods for the synthesis of compounds bearing more than two conjugated CC triple bonds remain inadequate. In this project, we propose to use alkyne metathesis as a new "soft" and expedient method for the synthesis of triynes, tetraynes, pentaynes and beyond. On the basis of promising preliminary results obtained with triynes, we proposed new catalysts that are designed to control the selectivity towards the targeted polyynes. After evaluating the scope and limitations of our methodology, it will be applied to the synthesis of polyynes that are currently inaccessible with known methods in the field of physical organic chemistry. An ultimate goal of the project is the synthesis of C24, a cyclic allotrope of carbon.
Project coordination
Yann TROLEZ (INSTITUT DES SCIENCES CHIMIQUES DE RENNES)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Partnership
ISCR INSTITUT DES SCIENCES CHIMIQUES DE RENNES
Technische Universität Braunschweig / Institut für Anorganische und Analytische Chemie
University of Alberta
Help of the ANR 276,080 euros
Beginning and duration of the scientific project:
January 2022
- 36 Months
