Imidoyl Radicals Research Articles

Stereocontrolled 5-Exo-Trig Cyclization of Imidoyl Radicals in the Synthesis of Substituted (Alkylthio)pyrrolines, Pyroglutamates, and Thiopyroglutamates

Stereocontrolled 5-Exo-Trig Cyclization of Imidoyl Radicals in the Synthesis of Substituted (Alkylthio)pyrrolines, Pyroglutamates, and Thiopyroglutamates

Radical annulations and cyclisations with isonitriles: the fate of the intermediate imidoyl and cyclohexadienyl radicals

The reaction of 4-methoxyphenylisonitrile with phenylacetylene and AIBN produces a novel cyclopenta-fused quinoxaline through addition of 2-cyanoprop-2-yl radical to the alkyne; the resulting vinyl radical attacks isonitrile to afford an imidoyl radical, which gives rise to a tandem 5-exo, 6-endo cyclisation. The whole process entails a new example of a rare 4 + 1 radical annulation. The cyanopropyl radical can also attack isonitrile to yield small amounts of quinolines deriving from 4 + 2 and 3 + 2 annulation between the resulting imidoyl radicals and phenylacetylene. The oxidation step leading to the final aromatic products involves the starting isonitrile, which is converted to an α-unsubstituted imidoyl radical and affords 2-unsubstituted quinolines. This behaviour was also found in cyclisations of biphenyl-2-ylisonitrile under various radical conditions. Finally, the title reaction gives small amounts of an α,β-unsaturated nitrile, which can arise from a spirocyclohexadienyl radical through fragmentation and subsequent β-scission of the resulting iminyl. This could be the first, direct evidence of the intermediacy of iminyl radicals in the rearrangements of the spirocyclohexadienyls obtained by 3 + 2 annulation between imidoyl radicals and alkynes.

Intramolecular addition of aryl radicals to carbon-nitrogen double bonds

Cyclisation of radicals 6a,b is highly regioselective towards a 5-exo process; 6-endo ring closure is a minor route and their ratio depends on the substituents. No ring expansion of the five-membered radical intermediates 7a,b was observed. Radicals 27a,b give rise to 5-exo cyclisation regiospecifically. A competitive 1,5-hydrogen shift leading to imidoyl radicals was noticed. An analogous behaviour is also exhibited by vinyl radicals when allowed to add to carbon-nitrogen double bonds.

N-( ortho-Aryloxyphenyl)arylimidoyl radicals: Novel 1,5-aryl radical translocation from oxygen to carbon

Imidoyl radicals 4a-d, obtained by hydrogen abstraction from imines 1a-d, give 7-membered cyclisation leading to oxazapines 2a-d. The intermediate spirocyclohexadienyl radicals of the competitive 6-membered ring closure ( 6a-d) rearrange to aryloxy radicals, giving benzophenones 3a-d: the whole process entails a novel 1,5-aryl radical translocation from an oxygen to a carbon atom.

EPR studies of the additon of 1,1-bis(alkoxycarbonyl)alkyl radicals and tris(ethoxycarbonyl)methyl radicals to alkenes and to alkyl isocyanides

EPR spectroscopy has been used to monitor the addition of RĊ(CO2Et)2(R = H or Me) and of ˙C(CO2Et)3 to terminal alkenes, furan, MeNC and ButNC in cyclopropane solution at low temperatures. The radical addenda were generated by UV photolysis of di-tert-butyl peroxide in the presence of the corresponding malonate or triethyl methanetricarboxylate and trimethylamine–butylborane complex, which acts as a polarity reversal catalyst for hydrogen-atom abstraction from the electron-deficient α–C–H groups in the esters. For all acceptors, addition of each of the electrophilic α-alkoxycarbonyl(alkyl) radicals is more rapid than the corresponding addition of simple (nucleophilic) alkyl radicals, a result which is attributed to the importance of charge-transfer interactions in the transition states (polar effects). Relative rates of addition of HĊ(CO2Et)2, MeĊ(CO2Et)2 and ˙C(CO2Et)3 to H2CCH2, MeCHCH2, Me2CHCH2 and Me3SiCH2CHCH2 are also governed mainly by polar effects. Approximate absolute rate constants for addition of HĊ(CO2Et)2 and ˙C(CO2Et)3 to ethene at 221 K have been determined to be 7.3 × 103 and 1.4 × 103 dm3 mol–1 s–1, respectively. The radical H2CCH(CH2)3Ċ(CO2Et)2 undergoes rapid 5-exo-cyclisation with a lower activation energy than that for corresponding cyclisation of the unsubstituted hex-5-enyl radical; this is attributed to the electrophilic nature of the radical centre in the former species. Addition of α-alkoxycarbonyl(alkyl) radicals to alkyl isocyanides occurs at the terminal carbon atom to give imidoyl radicals which are strongly bent at Cα. Addition of HĊ(CO2Et)2 to ButNC takes place 16 times faster than its addition to ethene at 220 K.

4 + 1 Radical annulations with isonitriles: a simple route to cyclopenta-fused quinolines

Sunlamp irradiation of 1-substituted 5-iodo-1-pentynes, 5 equiv of phenyl isocyanide, and 1.5 equiv of hexamethylditin in tert-butylbenzene (0.01-0.025 M) at 150 o C produces 9-substituted 2,3-dihydro-1H-cyclopenta [b] quinolines in 36-70% yields. A mechanistic proposal for this first example of a 4+1 radical annulation includes the following: (1) radical addition to an isonitrile, (2) cyclization of the resulting imidoyl radical to the alkyne, (3) addition of the so-formed vinyl radical to the aromatic ring, and (4) rearomatization. When substituted isonitriles (p-F p-OMe, m-F) are employed, the major unrearranged products are accompanied by 7-30% or rearranged products. Independent generation of a proposed intermediate suggests that the rearranged products arise by initial closure of the vinyl radical to form a five-membered ring, followed by C-N bond cleavage and recyclization

ChemInform Abstract: Reaction of Imidoyl Radicals with Multiple Carbon‐Carbon Bonds.

AbstractA general view on the reaction between imidoyl radicals, e.g. (III), and alkenes and alkynes is given.

ChemInform Abstract: Homolytic Annulation by Reaction of Imidoyl Radicals with Diethyl Azodicarboxylate: A New Route to Nitrogen Heterocycle Derivatives.

An easily effected aromatic annulation is described, involving the reaction of arylimidoyl radicals with diethyl azodicarboxylate to give 1,2-dihydro-1,2-dihydro-1,2-diethoxycarbonyl-benzo- and -pyrido-1,2,4-triazines.

ChemInform Abstract: Cyclizations of Ene Radicals. Imidoyl Radicals as Intermediates in the Synthesis of Heterocyclic Compounds.

AbstractThe cyclizations of the selenoimidates (I) or (V) affording the chroman (II) along with the cyanide (III) or, after aromatization, the chromanoquinolines (V), resp., proceed via imidoyl radical intermediates.

Cyclizations of ene radicals. Imidoyl radicals as intermediates in the synthesis of heterocyclic compounds

Cyclizations of ene radicals. Imidoyl radicals as intermediates in the synthesis of heterocyclic compounds

Homolytic annulation by reaction of imidoyl radicals with diethyl azodicarboxylate: a new route to nitrogen heterocycle derivatives

An easily effected aromatic annulation is described, involving the reaction of arylimidoyl radicals with diethyl azodicarboxylate to give 1,2-dihydro-1,2-dihydro-1,2-diethoxycarbonyl-benzo- and -pyrido-1,2,4-triazines.

Homolytic reactions of ligated boranes. Part 4. Electron spin resonance studies of radicals derived from secondary phosphine–boranes

Radicals produced by reaction of photochemically or thermally generated t-butoxyl radicals with dimethyl-, diethyl-, and diphenyl-phosphine–boranes have been studied in solution by e.s.r. spectroscopy. Hydrogen abstraction from R2PH→BH3 appears to yield the phosphinyl–borane radical R2Ṗ→BH3 as the major product, although its e.s.r. spectrum is difficult to detect. Evidence for the competitive formation of an isomeric phosphoranyl radical [R2P(BH2)H]˙ was found for dimethylphosphine–borane. No phosphine–boryl radical R2PH→ḂH2, analogous to R3P→ḂH2 obtained from the reaction of ButO˙ with a trialkylphosphine–borane, was detected. Like the isoelectronic silyl and phosphonyl radicals, R2Ṗ→BH3 abstracts halogen from alkyl bromides and adds readily to alkenes and isocyanides to give alkyl and imidoyl radical adducts, respectively. Spin-trapping of R2Ṗ→BH3 with 2-methyl-2-nitrosopropane or phenyl-N-t-butylnitrone affords the appropriate nitroxides, whilst with 1-nitroso-2,4,6-tri-t-butylbenzene addition takes place exclusively at oxygen to give an oxyaminyl radical.

Conformational analysis of imidoyl radicals by electron spin resonance spectroscopy

A series of N-t-butylimidoyl radicals, RĊNBut, have been prepared by the reaction of t-butoxyl radicals with the parent imines, RCHNBut, and their e.s.r. spectra have been recorded. The n.m.r. coupling constants, 3J(CH–CHNBut), in the imines are related to the e.s.r. hyperfine coupling constants, a(Hβ), in the imidoyl radicals by the expression a(Hβ)/G = 3.53 3J(CHCHNBut)/Hz – 8.48. A similar relationship has been identified previously between the aldehydes and the acyl radicals.These results are rationalised on the assumption that the radicals have a σ-electronic configuration, and that similar intramolecular interactions in the imines and imidoyl radicals impose on them similar conformations.

An electron spin resonance study of the generation and reactions of borane radical anions in solution

Photochemically or thermally generated t-butoxyl radicals rapidly abstract hydrogen from borohydride or cyanoborohydride anions to form H3B–˙ or H2[graphic omitted]CN–, respectively, which can be detected and their reactions studied in fluid solution using e.s.r. spectroscopy. The spectroscopic parameters confirm that the equilibrium geometry of H3B–˙ is planar, as is that of the isoelectronic H3C·, and the temperature dependences of a(11B) and a(3H) result from Boltzmann population of out-of-plane vibrational states. The extent of conjugative delocalisation of the unpaired electron onto nitrogen is similar in H2[graphic omitted]CN– and in the isoelectronic H2ĊCN. H3B–˙ adds to ethylene, trimethylvinylsilane, benzene, and pyridine, but H2[graphic omitted]CN– is less reactive and addition to only Me3SiCHCH2 was detected. The B–C bond eclipses the orbital of the unpaired electron in the preferred conformation of the ethylene adduct H3H2ĊH2, in contrast to the staggered conformation adopted by the isoelectronic propyl radical. Addition of H3B–˙ to electron deficient arenes is faster than to benzene, and the regioselectivities of these reactions also show that the borane radical anion is highly nucleophilic. Both H3B–˙ and H2[graphic omitted]CN– add to alkyl azides and cyanides to give triazenyl and iminyl radical adducts, respectively, and both borane radical anions displace alkyl radicals from alkyl isocyanides, perhaps through the intermediacy of a transient imidoyl radical adduct. H3B–˙ abstracts a halogen atom from alkyl chlorides, bromides, and iodides, while H2[graphic omitted]CN– reacts rapidly with only bromides and iodides; neither reacts with alkyl fluorides. The reactivities of H3B–˙ and H2[graphic omitted]CN– resemble those of H3Si· and R3Si· much more than those of H3C· and R3C·.

An electron spin resonance study of trialkylsilyl radical addition to alkyl isocyanates

Addition of photochemically-generated trialkylsilyl radicals to alkyl isocyanates to give imidoyl radicals (A) has been studied in cyclopropane solution using e.s.r. spectroscopy. The rate of addition of trimethylsilyl radicals to R13Si˙+ R2NCO [graphic omitted] alkyl isocyanates has been determined relative to that of addition to methyl trifluoroacetate or ethylene and kadd(R1= Me) was found to decrease in the order R2= Me > Et > Pri > But at 164 K. It is proposed that this trend is steric in origin and that the Me3Si group is closer to the N-alkyl group in the transition state for addition than in the product imidoyl radical. The palladium chloride catalysed addition of triethylsilane to n-butyl isocyanate gives the imidate BunNC(H)OSiEt3 rather than the isomeric C-silylamide BunN(H)C(O)SiEt3, as previously reported.

An electron spin resonance study of radical addition to alkyl isocyanides

Using e.s.r. spectroscopy, a variety of types of free radical (Z·) have been shown to add to the terminal carbon of alkyl isocyanides (RNC) to form imidoyl radical adducts (RNĊZ). At 253 K the rate constants for radical addition to ButNC are in the order k(Ph˙) > k(ButO˙) > k(Me˙), and k(ButO˙)= 6 × 105 l mol–1 s–1. The imidoyl adducts are σ-radicals in which the unpaired electron occupies an orbital orthogonal to the NC π-orbital. The magnitudes of a(13Cα) and a(Nβ) are markedly dependent upon the nature of Z, and a(13Cα) increases with the electronegativity of Z. The radical ButNĊSiEt3 appears to be close to linear at Cα, whilst ButNĊOR is bent. There appear to be two contributions, of opposite sign, to a(Nβ), a positive one resulting from direct overlap of the orbital of the unpaired electron with that of the lone pair on nitrogen, and a negative one resulting from spinpolarisation of the Nβ–Cασ-bonding orbital. The β-scission of some imidoyl radicals has also been studied using e.s.r. spectroscopy. Radicals of the type RNĊXBut(X = O or S) undergo X–C cleavage to form RNCX and But˙, whilst the radicals RNĊY (Y = MeS, Et3Si, or Ph) undergo cleavage to produce R˙ and NCY. At 243 K the rate constants for β-scission were ca. 1.4 × 105(ButNĊSiEt3), 3.1 × 105(ButNĊSBut), and 3.6 × 103 s–1(ButNĊOBut).

Electron spin resonance study of radical addition to alkyl isocyanides

The e.s.r. spectra of a number of imidoyl radicals, generated in solution by radical addition to alkyl isocyanides, have been detected and the fragmentation of these radicals has been studied.