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Author
Rulli, Federica
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Abstract
In recent years, very novel strategies have emerged within the area of isosterism applied not only to drug design meant to improve the drug pharmacokinetic and pharmacodynamic profile but also to material science. Particularly, the isosterism aimed at replacing an arene double bond with an isosteric and isoelectronic boron-nitrogen unit, so called BN/CC isosterism, modifies the optoelectronic properties in polyaromatic hydrocarbons (PAHs). The presence of BN fragments in these conjugated systems considerably modifies the energy levels of their frontier orbitals (HOMO and LUMO), thus changing their conductive behaviour, their reactivity and their regioselectivity towards common organic reactions.
Among different types of BN-arenes, the present work has been focused on the synthesis and regioselective functionalization of BN-4a,8a-naphthalene 10, which is isoelectronic and isostructural to naphthalene. The synthesis of BN-4a,8a-naphthalene has been accomplished following two currently available synthetic routes described by A. J. Ashe and X. Fang. Both methodologies are time-demanding and characterized by low reaction efficiencies: the dehydrogenation step is the critical reaction in this synthesis, which provides the final product in 20% and 17% yield, respectively. In this work, a remarkable improvement has been developed using Pd/C as the catalyst and norbornene as
the hydrogen acceptor solvent, achieving a very good 68% yield. Regarding selective functionalization of BN-arenes, electrophilic aromatic borylation and halogenation, in combination with cross-coupling methodologies, may unlock a collection of functionalized BN-derivatives. Direct intermolecular borylation on a pre-formed BN-arene is not yet
reported in the literature; in this sense, the Ingleson strategy has been applied on BN-4a,8a-naphthalene and a selective borylation at C-4 position was achieved in 58% yield.
While different examples of chlorination and bromination of BN doped arenes are described in the area of BN isosterism, electrophilic aromatic iodination reported by Fang is currently the unique protocol available. For this reason, the Fang iodination procedure described on BN-4a,8a-naphthalene has been reproduced, obtaining the C-4 iodinated product accompanied by several by-products. Hence, the previously described electrophilic borylation was applied to selectively achieve the 4-iodo-BN-4a,8a-naphthalene species (48% yield).
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