Radical iminyl

The 5-dig-mode of cyclization has been applied in the synthesis of N-heterocycles. For example, treatment of the /i-allenyl dithiosemicarbazide 37 with Bu3SnH and AIBN in hot benzene furnishes the substituted 3H-pyrrole 38 in 41% yield and the isomeric heterocycle 39 in 30% yield (Scheme 11.13) [68], Iminyl radical 40 is formed via Bu3Sn addition to the thiocarbonyl group of the radical precursor 37 and fragmentation of the adduct (not shown). Nitrogen-centered radical 40 adds 5-dig-selectively to provide substituted allyl radical 41. The latter intermediate is trapped by Bu3SnH to furnish preferentially product 38 with an endocydic double bond. 

Scheme 11.13 Formation of pyrrole derivatives via iminyl radical cyclization on to a cumulated Jt-bond [68]. a X = S-C(NCH3)(SCH3).

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. 

Various transition metals have been used in redox processes. For example, tandem sequences of cyclization have been initiated from malonate enolates by electron-transfer-induced oxidation with ferricenium ion Cp2pe+ (51) followed by cyclization and either radical or cationic termination (Scheme 41). ° Titanium, in the form of Cp2TiPh, has been used to initiate reductive radical cyclizations to give y- and 5-cyano esters in a 5- or 6-exo manner, respectively (Scheme 42). The Ti(III) reagent coordinates both to the C=0 and CN groups and cyclization proceeds irreversibly without formation of iminyl radical intermediates.The oxidation of benzylic and allylic alcohols in a two-phase system in the presence of r-butyl hydroperoxide, a copper catalyst, and a phase-transfer catalyst has been examined. The reactions were shown to proceed via a heterolytic mechanism however, the oxidations of related active methylene compounds (without the alcohol functionality) were determined to be free-radical processes. 

These data should allow us to derive the desired enthalpy of formation of the iminyl radical. The problem is that the two results differ by ca 100 kJmol M The effect of substituents on the thermochemistry of oximes, their ethers and related imines are not so well-established for us to attempt deciding between these two bond energies. 

A simple route to furo[3,2-6]pyridine is based upon the one-step generation of the pyridine ring by gas-phase cyclization of conjugated iminyl radicals <80JCS(Pi)2200). O-Alkyloximes have proved to be suitable precursors (Scheme 18) (81S464). 

In the PES-studied gas-phase thermolysis of the azines 72 and 73 (96T1965) methacrylonitrile and propene were found in addition to molecular nitrogen, which is in accord with a [5 - 2 + 2+ 1] fragmentation of the five-membered rings. The primary process is the cleavage of the N-N single bond, which is followed by the decay of the iminyl radicals thus formed. 

As an extension of the known radical additions to isonitriles [87], aryl radical cyclizations to /V-acyl cyanamides provide new access to pyrrolo-quinazolines (Scheme 16) [88]. In a tandem process, the iminyl radical 41 resulting from the 5-exo cyclization onto the nitrile was used for a second cyclization step. In this way, the alkaloid luotonin A (42) was synthesized from cyanamide 43 in a single reaction. 

The photocatalytic radical generation was also used in additions to methyl cyanoformate 143 [240]. The product distribution was dependent on the reaction temperature. At room temperature ot-imino esters 144 were formed in 51-99% yield, while at 90 °C nitriles 145 were isolated in 59-76% yield. At low temperature, the iminyl radical 140C generated by the radical addition, abstracts a hydrogen atom from the substrate to continue a chain reaction, while its fragmentation to the nitrile prevails at high temperature, generating carbon dioxide and a methyl radical 146, which acts as a chain carrier. 

Another oddity is that the NHR group can act as an iminyl radical ... 

Recently, radical species have attracted much attention as useful intermediates for carbon-carbon bond formations. By contrast, in organic synthesis, radicals centered on heteroatoms have not been widely utilized for construction of molecular skeletons with carbon-heteroatom bond formation. In this section we will discuss the generation of alkylideneaminyl radicals, conventionally called iminyl radicals from oxime derivatives by electron transfer reactions. AU -lideneaminyl radicals thus created are utilized for making nitrogen-containing heterocycles. 

Generation of the iminyl radical 184 in the above experiment was confirmed by an intramolecular radical trapping experiment. Reaction of l-phenylhept-6-en-3-one 0-2,4-dinitrophenyloxime (87) with m-cresol and NaH afforded 2-methyl-5-(l-phenylethyl)-3,4-dihydro-2H-pyrrole (88), which is the addition product of iminyl radical 187, obtained in 27% yield (Scheme 40). 

The quinoline formation from 2,4-dinitrophenyl oximes suggested to us the possibility of generating radical intermediates and prompted us to study the synthesis of cyclic imines by iminyl radical addition to an internal olefinic moiety as shown in Scheme 44. 

Zard SZ (1996) Iminyl Radicals a Fresh Look at a Forgotten Species (and Some of its Relatives). Synlett 1148... 

The reaction was assumed to proceed via homolysis of the intermediate 0-vinyl oxime 32 followed by an uptake of the rearranged iminyl radical by a second molecule of acetylene (Scheme 5). 

N-centered radicals such as iminyl radicals can also be generated from a radical cyclization step onto nitrile groups. The fate of the iminyl radical depends on the nature of the a-substituent. When this latter is an alkyl group, further cychzation can take place [45]. A combination of both processes has been achieved addition of a staimyl radical onto an azide moiety generated a N-stannylaminyl radical that cyclized onto a nitrile and underwent further cyclization, thus opening access to pyrrolopyrroles and pyrrolopyridines derivatives [46]. 

Other fragmentation approaches have involved the intramolecular addition of alkenyl radicals to furans. The resulting spiro radical intermediate then opens to a new o, 5-unsaturated carbonyl radical intermediate [102]. An interesting cascade process based on 2-cyanophenyl isothiocyanate, promoted by Mn(OAc)3 and featuring the previously unknown addition of an iminyl radical to a thioureido group has been disclosed by Calestani etal. [103]. 

Iminyl radicals are generated by the addition of tributylstannane to N-chloro25 or, more conveniently, A -arylthio imines26,27 , 32. These radicals display considerable reactivity towards unactivated C—C double bonds in intramolecular reactions. 3,4-Dihydro-2//-pyrroles were obtained in good yield with variable stereoselectivity by the slow addition (4-5 h) of tributylstannane to a refluxing cyclohexane solution of suitable unsaturated jV-(2-benzo-thiazolylthio) and Ar-phenylthio imines (Table 2). 

Boivin, J., Fouquet, E., Zard, S. Z. A new and synthetically useful source of iminyl radicals. Tetrahedron Lett. 1991, 32,4299-4302. 

A free radical can add to CO or an isocyanide (RNC) in the course of a free-radical cyclization reaction, too, to give an acyl radical (RC=0) or an iminyl radical (RC=NR), either of which can undergo further reactions. In the following example, an alkyl radical adds to the terminal C of f-BuNC to give an iminyl radical. The iminyl radical then fragments to give t-Bu- and an alkyl cyanide N=CR. In a different substrate, the iminyl radical may undergo an addition or an abstraction reaction instead. 

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