Indole-tethered ynones form an intramolecular electron donor–acceptor complex that can undergo visible-light-induced charge transfer to promote thiyl radical generation from thiols.

Astrategy for the synthesis of medium-sized lactones and lactams from linear precursors is described in whicha n amine acts as an internal nucleophilic catalyst to facilitate an ovel cyclisation/ring expansion cascade sequence.T his method obviates the need for the high-dilution conditions usually associated with medium-ring cyclisation protocols,a s the reactions operate exclusively via kinetically favourable "normal"-sized cyclic transition states.T his same feature also enables biaryl-containing medium-sized rings to be prepared with complete atroposelectivity by point-to-axial chirality transfer.

The outcomeo fr ing-expansion reactions based on amino/hydroxyacid side-chain insertion is strongly dependent on ring size. This manuscript, which builds upon our previousw ork on Successive Ring Expansion (SuRE) methods, detailse fforts to betterd efine the scope andl imitations of these reactions on lactam and b-ketoester ring systems with respecttoring size and additional functionality. The synthetic resultsp rovide clear guidelines as to which substrate classes are more likely to be successful and are supported by computational results, using ad ensity functional theory(DFT) approach. Calculating the relative Gibbs free energies of the three isomeric speciest hat are formed reversibly duringr ing expansion enables the viability of new synthetic reactions to be correctly predicted in most cases. The new synthetic and computational resultsa re expected to support the design of new lactam-a nd b-ketoester-based ring-expansion reactions. Scheme1.Side-chain insertion ring-expansion reactionsand Successive Ring Expansion (SuRE).

A method to ring expand lactams into macrocyclic thiolactones is reported that can be incorporated into successive ring expansion sequences.

Two new ring expansion strategies are reported for the synthesis of medium sized ring and macrocyclic sulfonamides. Both methods can be performed without using classical protecting groups, with the key ring expansion step initiated by nitro reduction and amine conjugate addition respectively. Each method can be used to make diversely functionalised cyclic sulfonamides in good to excellent yields, in a range of ring sizes. The ring size dependency of the synthetic reactions is in good agreement with the outcomes modelled by Density Functional Theory calculations.