Length-controlled oligomerization with synthetic oligoproline-based templates Bartosz Lewandowski, R. Schäfer, S. Loosli, D. Harangozo, H. Wennemers ETH Zürich, Switzerland Templated synthesis is a highly valuable strategy for length-controlled preparation of oligomers. 1,2 Such reactions, however, typically require stoichiometric amounts of the template with respect to the product. 3 Recently, we reported catalytic macrocyclic templates which promote the formation of oligomers of a small molecule substrate with a remarkable degree of length-control. 4 The templates consist of rigid oligoproline moieties decorated with catalytic sites at defined distances on both sides of the macrocyclic cavity. The dimension of the macrocycle and the number of catalytic moieties thereon determine the number of monomers that are incorporated into the growing oligomer in the templated process. Building on these findings we wanted to develop linear templates for catalytic length-controlled oligomerization. Such linear templates would be less complex and thus easier to access and modify, e.g. by extension of the length, than macrocyclic templates. We envisioned that the linear template for length-controlled oligomerization needs to contain a recognition site for an “ initiator ” building block and activation sites that allow for the activation of the initiator and incoming “ propagator ” building blocks (Fig.1a). The initiator should contain a binding site (Fig.1a, green) that binds to the recognition site of the template. Additionally, the initiator needs a functional group (Fig.1a, blue) that can be activated by the activation site on the template for reaction with the reactive site of the propagator. The propagator should contain the reactive site (Fig.1a, brown) as well as the same activatable functional group as the initiator. Upon binding of the initiator to the template (step 1) a series of propagation reactions (steps 2,3) will allow for incorporation of propagator building blocks to the growing oligomer. These reactions will continue until the last activation site at the end of the template is reached. Consequently, the length of formed oligomer will correlate with the number of activation sites on the template (Fig.1b).
Fig.1a) Design of linear templates; b) Theoretical correlation between the length of the template and the formed oligomer. We will present our initial efforts towards the development of linear oligomerization templates, following the above design considerations. Specifically we will discuss systems were the initiator is bound to the template by a dynamic covalent bond thus preventing the dissociation of the oligomer and allowing us to focus on optimizing the propagation reactions. References 1. K. Josephson, M. C. T. Hartman, J. W. Szostak, J. Am. Chem. Soc. , 2005, 127 , 11727–11735; 2. J. Niu, R. Hili, D. Liu, Chem. , 2013, 5 , 282–292. 3. M. C. O'Sullivan, J. K. Sprafke, D. V. Kondratuk, C. Rinfay, T. D. W. Claridge, A. Saywell, M. O. Blunt, J. N. O’Shea, P. H. Beton, M. Malfois, H. L. Anderson, Nature , 2011, 469 , 72-75; 4. D. Núñez-Villanueva, M. Ciaccia, G. Iadevaia, E. Sanna, C. A. Hunter, Chem. Sci. , 2019, 10 , 5258–5266. 5. X. Li, D. Liu, Angew. Chem. Int. Ed. , 2004, 43 , 4848–4870.B. Lewandowski, D. Schmid, R. Borrmann, D. Zetschok, M. Schnurr, H. Wennemers, Nat. Synth ., in press .
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