Novel Scaffolds by Mild Photochemical Rearrangement of Reactive Enolate and Organolithium Anions

We propose to develop new photochemical reactions of conjugated anions with lithium counterions (organolithiums and enolates) to construct functionalized, fused heterocyclic frameworks of use in medicinal chemistry development.

N-Allyl/N-benzyllithiums tethered to aromatic and heteroaromatic carboxamides will be employed in dearomatizing cyclizations for the construction of partially saturated fused ring systems, generating extended lithium enolates.

Irradiation with visible light at low temperature will induce a series of photochemical rearrangements, delivering – in an operationally simple way - structurally demanding unusual products containing various heterocycles and hetero-fused skeletons based on norcaradienes, cycloheptatrienes, and cyclic ketones.

Trapping the reactive cyclopropane units of the products with dipolarophiles such alkynes and olefins will extend the method to dearomatized polycycles via a [3+2] cycloaddition strategy.

The method will then be extended from enolates to coloured, conjugated organolithiums more generally, promoting an electron from the HOMO (the C–Li bond of metalated carboxamides) to a new higher energy SOMO.

This excited state takes the form of an anion-diradical which may be expected to undergo further interesting inter- or intramolecular reactions to furnish biologically relevant structures.