The stability of nitrogen-centered radicals

Abstract

Radical stabilization energies (RSEs) for a wide variety of nitrogen-centered radicals and their protonated counterparts have been calculated at G3(MP2)-RAD and G3B3 level. The calculated RSE values can be rationalized through the combined effects of resonance delocalization of the unpaired spin, electron donation through adjacent alkyl groups or lone pairs, and through inductive electron donation/electron withdrawal. The influence of ring strain effects as well as the synergistic combination of individual substituent effects (captodatively stabilized N-radicals) have also been explored. In symmetric N-radicals the substituents may also affect the relative ordering of electronic states. In most cases the π-type radical (unpaired spin distribution perpendicular to the plane of the N-radical) is found to be most stable. Closed shell precursors of biological and pharmaceutical relevance, for which neither experimental nor theoretical results on radical stabilities exist, have been included.

A Type of Auxiliary for Native Chemical Peptide Ligation beyond Cysteine and Glycine Junctions

“…According to our hypothesis the thiyl radical 12 would, in analogy to the radical desulfurization procedure, [6] form the benzyl radical 13 upon treatment with phosphine.I nt he absence of ar eactive hydrogen donor, bfragmentation would deliver the amide radical 14 along with styrene which may react further under the cleavage conditions.Weexpected that the nitrogen-centered amide radical should be readily scavenged by amines such as morpholine which are not reactive enough to quench the benzyl radical 13. [7] Since the auxiliary is removed after ligation, its chirality does not affect the final product. Therefore,t he 2-mercapto-2-phenethyl auxiliary lends itself to af acile introduction by reductive amination of the racemic alkyl aldehyde with the peptide N-terminus in the last step of solid-phase peptide synthesis (Scheme 3).…”

γ‐Functionalizations of Amines through Visible‐Light‐Mediated, Redox‐Neutral C−C Bond Cleavage

“…Analogously,the use of BrCCl 3 furnished g-brominated products 27-28 b in synthetically useful yields. [18,19] Acarbon-to-nitrogen aryl migration with concomitant C(sp 3 )-C(sp 2 )c leavage via spiro radical s-complex III takes place producing aC -centred radical IV.U nder the redoxneutral conditions,a ddition of IV to the Michael acceptor delivers intermediate V which undergoes further reduction to produce Ir III together with the observed products thus restarting the catalytic cycle.T he formation of aza-Michael product 2' ' as well as the lack of reactivity of substrates bearing less electron-withdrawing groups on the Natom supports the idea of amidyl anion being present in these transformations. [5] Further, Michael-type additions onto the acrylate moieties (19)(20)(21)26), deprotonation in C a of the corresponding electron-withdrawing groups (22-25)o rs ubstitution reactions on 27-28 b highlight the synthetic potential of the building blocks obtained in these transformations.…”

“…Para-substituted arenes proved to be efficient migration partners delivering compounds 3-6 (R = Me, tBu, F, Ph) in moderate to excellent yields whereas more electronically biased substrates (e.g. Significant selectivities in favour of the migration of the more electron-rich aromatic ring [5] were observed even in the case of electronically similar arenes as demonstrated by the productive reactions yielding compounds 13-15.I nt he case of highly electronically differentiated substrates,only products stemming the migration of the electron rich aromatic could be identified and isolated in moderate yield from the reaction media (16)(17)(18). Meta-substituted derivatives were also well tolerated as demonstrated by the reactions to form 7 and 8.…”

Synthesis of Arylamines via Aminium Radicals

“…This lack of synthetic application can be explained by the intrinsic nucleophilic nature of aminyls, which causes repulsive interactions between their lone pair and the aromatic ring 13. However, upon protonation, aminyl radicals are converted into aminium radicals10d,10i, 14 that are isoelectronic to alkyl radicals but carry a formal positive charge (Scheme 1 B). This makes them powerful electrophiles that undergo highly polarized radical processes.…”