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Author
Martínez Fernández, Nina
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Abstract
Currently applied isosterism is a versatile tool for the implementation of innovative strategies not only in the design of drugs, improving their pharmacokinetic and pharmacodynamic profile, but also in the area of materials science. In particular, BN / CC isotericism replaces an arene double bond with an isosteric and isoelectronic boron-nitrogen unit, thus modifying the optoelectronic properties in polyaromatic hydrocarbons. (PAHs). The presence of BN fragments in these conjugated systems considerably modifies the energy levels of their boundary orbitals (HOMO and LUMO), thus changing their reactivity and regioselectivity in common organic chemistry reactions.
Among all the types of BN-arens, the present work focuses on the synthesis and regioselective functionalization of BN-4a, 8a-naphthalene 1, an isoelectronic and isostructural compound in naphthalene. The synthesis of BN-4a, 8a-naphthalene 1, has been carried out following two synthetic routes previously described by A. J. Ashe and X. Fang. Both methodologies are time consuming and characterized by poor performance. Specifically, the dehydrogenation step is the most critical of the synthesis, which provides the final product with a yield of 20% and 17% respectively. On the basis of the previous work carried out by our group, in the following project the optimization and scaling of this oxidative step has been developed using Pd / C as a catalyst and norborneo as a hydrogen-accepting solvent, thus obtaining a better performance.
Regarding the selective functionalization of BN-arens, C ‒ H borylation followed by “cross-coupling” methodologies would allow access to a collection of functionalized BN derivatives. Specifically, metal-catalyzed C ‒ H borylation was not previously described for BN-arene 1, therefore in this work this strategy has been applied to BN-4a, 8a-naphthalene 1 obtaining a selective borylation at the C2 position ( β at the nitrogen atom) with 34% yield. Likewise, the present work investigates the possibility of carrying out a Suzuki-type coupling reaction with the borylated BN-naphthalene product. This methodology has been applied to introduce an aromatic group in the C2 position of BN-naphthalene 1, thus developing a solution for the late functionality of this azaborine position, thus expanding the set of synthetic tools of this family of compounds. Furthermore, during the performance of this methodology, a homocoupling reaction took place where the final product was isolated and characterized.
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