The importance of chain conformational mobility during 5-exo-cyclizations of C-, N- and O-centred radicals

Abstract

The reaction coordinates of an archetypical set of 5-exo cyclizations of C-, N-and O-centred radicals were investigated by computational methods. G4 theory, and DFT with the um062x functional, were able to rationalise counterintuitive factors such as the 'normal' order of rate constants being: N-centred < C-centred < O-centred radicals. The access angle between the radical centre and the double bond was identified as a key factor. Examination of its evolution during ring closure implied that rigidity at the N-ends of the chains, and the consequent extra energy needed to attain chair-like transition states, might be the reason for slow aminyl cyclizations. A novel linear correlation between cyclization activation energies and the access angles was discovered. The preference for cis-1,2-disubstituted product formation was also accounted for in terms of interaction between the hyperconjugatively delocalized SOMO and the alkene * orbital.

Photocatalysis with TiO2 Applied to Organic Synthesis

“…Apart from the reduction potential of the conduction band, conformational mobility in the intermediate 145 plays an important role in the competition between these two reactions. [96] The same reaction was also observed under UV irradiation and without a photoredox catalyst. [97] Under these conditions, only tandem addition cyclization products were obtained.…”

The Baldwin rules: revised and extended

“…The computational investigation of these trends suggested that increased rigidity of reacting nitrogen species can be the reason for this counterintuitive order . Interestingly, the computational data suggest that carbon centered radicals engage in the bond forming interactions with the target π‐bond at the larger distances than their nitrogen and oxygen analogues.…”

Photoredox Imino Functionalizations of Olefins

“…[9] While facing the difficulties of developing cascade photoredox imino functionalizations of electron-poor O-aryl oximes, [6] we realized that an inherent chemical reactivity issue was associated with the envisaged catalytic cycle.T he nitrogen radicals A are electrophilic species and undergo facile exo-trig cyclizations (Scheme 1C). [10] However,u pon ring closure,they generate the nucleophilic carbon radical B, which benefits from polar effects [11] in the reaction with SOMOphiles X À Y. This process leads to the formation of the imino-functionalized product C and the radical YC.T his radical, even though it is not involved in any bond-forming event, controls the fate of our photoredox manifold.…”