Radical amidyl

In intermolecular reactions, neutral aminyl radicals, R2N", react with n systems preferably by HAT. N-protonation increases the electrophUicity of the radical center, and successful addition of aminium radicals, R2NH, to 7t systems, usually alkenes, has been reported in the hterature." Compared to aminium radicals, amidyl and imidyl radicals, for example, RN C(0)R and [RC(0)]2N , are less electrophilic. Although they are delocahzed 7t-allyl radicals, they react exclusively at nitrogen." Only very few examples for radical cascades that are initiated by addition of A-centered radicals to alkynes have been reported. 

The attacking radical need not always be at carbon. Amidyl radical are known and give cyclization reactions. Aminyl radical cyclizations have been reported. Oxygen radical can be generated under photochemical conditions, and they add to alkenes in a normal manner. ... 

The limited kinetic data for reactions of tin hydride with nitrogen-centered radicals apparently demonstrates the combined effects of the enthalpies of the reactions and polarization in the transition states for H-atom transfer. The aminyl and iminyl radicals are electron-rich, and the N-H bonds formed are relatively weak these radicals react relatively slowly with tin hydride. On the other hand, the electrophilic amidyl and aminium cation radicals form strong N-H bonds and react rapidly with the tin hydride reagents. 

Cyclizations of amidyl radicals have been studied both synthetically and kinetically. A detailed study on the rates of a variety of amidyl radical reactions was determined by both LFP and indirect competition methods (Table l) In addition, the rate constants for reactions with BusSnH and PhSH were also reported (thus giving a range of simple amidyl radical clocks). The results obtained will be useful in synthetic sequenceplanning involving amidyl radicals. 

In synthetic work, amidyl radicals, prepared by BusSnH/AIBN-mediated homolysis of O-benzoylhydroxamic acid derivatives, have been shown to cyclize in a A-exo fashion to give -lactams (Scheme 10). In addition, radicals generated in this way have also been reported to undergo 5-exo cyclization to give mixtures of cis- and Iranx-pyrrolidinones with the steric nature of the Al-substituent having little effect on the stereochemical outcome (Scheme 11). The major products detected were those predicted by application of the Beckwith rule. ... 

Anchimeric assistance by the aUcoxyl oxygen lone pair promotes heterolytic S v 1 and reactions at nitrogen as well as homolysis of the N—Cl bond. A-Haloamides are also amidyl radical sources" but their heterolytic reactivity is known to involve positive, rather than negative, halogen ... 

For amidyl radicals carrying a 6-hydrogen in the alkyl chain (e.g., XVII or N-pentyl, N-butyl, N-phenylbutyl analogues) intramolecular abstraction of the 6-hydrogen as in XVII and the collapse to 6-nitroso compound XVIII are very facile and occur preferentially within the radical pair (vide infra) over other... 

We have demonstrated that intermolecularly, amidyl radicals preferentially abstract an allylic hydrogen rather than add to a TT bond of olefins such as cyclohexene and 1,3-pentadiene (33). This reactivity pattern is completely reversed in intramolecular reactions as shown in the following examples of alkenyl mitro-samide photolysis. In every case, the amidyl radicals generated from photolysis preferentially attack the ir bonds intramolecu-... 

Stereochemical probes of intramolecular H-abstraction leads to a conclusion not in contradiction with the II electronic configuration and also reveals that simple amidyl radicals react exclusively as the N-radical but not the 0-radical (25). Scarcity of data in this area does not allow a definitive discussion on stereochemical controls of amidyl radical reactions that are being studied in our group. 

Direct flash excitation (>400 nm) or the triplet-acetone-sensitization of nitrosamide X in degassed water or benzene solutions gives the amidyl radical transient exhibiting lax 335-350 nm. This transient is not observed with undegassed solution of X, indicating that oxygen has intercepted the precursor of the amidyl radical at least, with the diffusion controlled rate... 

Radical cyclization is an effective approach to the synthesis of isoquinolines (Scheme 8). In some cases these offer an alternative to the palladium-catalyzed reactions with aryl halide intermediates <99EJOC1925, 99TL1125>. For example, the radical cyclization of the iodide 37 onto the vinylsulfide moiety was followed by a cascade cyclization to form the benzo[n]quinolizidine system <99TL1149>. In some cases the radical cyclization can take place without the need for a halo intermediate. The reactive intermediate of 38 was formed on the nitrogen as an amidyl radical, which underwent tandem cyclizations to the lycorane system <99TL2125, 99SL441>. 

Figure 4.12. Second-order rate constants for reactions of hydrogen atom donors with various radical types at ambient temperature. Data sources group 14 (IV A) hydrides (15) aminyl radicals (69) amidyl radicals (70) alkyl radials with group 16 (VI A) hydrides (71) acyl radical with PhSeH (72).

To facilitate the cyclizations of nitrogen-centered radicals, one need only increase the electronegativity at nitrogen. This makes the radical more electrophilic (which accelerates the cyclization), and strengthens the forming bonds (which shifts the equilibrium to the cyclic product). Amminium radical cations are more well-behaved in cyclizations than aminyl radicals, and these radical cations can either be formed directly from ammonium salts, or by protonation of aminyl radicals (which are relatively weak bases and require strong acids for protonation). Metal-complexed aminyl radicals are highly reactive, and amidyl radicals are also useful.178... 

Photolysis of PTOC imidate esters generated amidyl radicals which can undergo intramolecular homolytic substitution reactions (Scheme 29).152 The ratio of exo to endo products observed for die reaction of each of die diiocarbonylimidazolide diastereomers (70) and (71) with B113S11H was found to be different indicating tiiat die intermediate radical (72) produced in each case was generated and reacted in a different conformation, respectively (Scheme 30).153... 

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