Functionalization of λ5-Phosphinines via Metalation Strategies – A New Route towards Fluorescent 3D-Aromatics

We present herein the straightforward functionalization of l ⁵ -phosphinine derivatives using organometallic strategies. Halogen-zinc and -magnesium exchanges were successfully performed employing Et ₂ Zn·2O amyl or i -PrMgCl·LiCl species under smooth reaction conditions. Such method allowed access to a wide range of sophisticated architectures, photophysical studies of which demonstrated interesting fluorescence properties. With the possibility of using such fluorescence in biomarking, l ⁵ -phosphinines were grafted on a few glycosides, nucleosides and pharmaceutically relevant moieties. The concept of “escaping the flatland” that refers to moving beyond simple, planar (two-dimensional) structures allows to explore the rich possibilities of three-dimensional molecular architectures.[1] Many organic compounds containing aromatic rings and conjugated systems are depicted as flat, which can limit their properties and interactions due to a restrained variety of exit vectors (orientation of substituents). However, introducing sp³-hybridized atoms, and non-planar ring systems allows chemists to access greater molecular complexity, which often leads to improved biological activity, selectivity, and physicochemical properties in drug design.[2] In this regard, we have developed methodologies towards the functionalization of four-membered molecular building blocks such as cyclobutanes[3] and azetidines,[4] strained, three-dimensional sp ³ -rich scaffolds that could be used as 3D-surrogates for classical aromatic structures such as phenyl- or pyridyl-moieties.