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

Objective

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.

Field of science

  • /natural sciences/chemical sciences/organic chemistry/heterocyclic compounds
  • /medical and health sciences/basic medicine/medicinal chemistry
  • /natural sciences/chemical sciences/physical chemistry/photochemistry
  • /natural sciences/chemical sciences/organic chemistry/ketones
  • /natural sciences/chemical sciences/inorganic chemistry/inorganic compounds

Call for proposal

H2020-MSCA-IF-2020
See other projects for this call

Funding Scheme

MSCA-IF-EF-ST - Standard EF

Coordinator

UNIVERSITY OF BRISTOL
Address
Beacon House Queens Road
BS8 1QU Bristol
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 212 933,76