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Volumn 11, Issue 15, 2007, Pages 1366-1384

Imidoyl radicals in organic synthesis

Author keywords

Azo bis iso butyronitrile; Benzophenone; Di tert butyl peroxide; Electron withdrawing groups; Isothiocyanates

Indexed keywords

ATOMS; CARBON; CYCLIZATION; REACTION INTERMEDIATES;

EID: 35348914314     PISSN: 13852728     EISSN: None     Source Type: Journal    
DOI: 10.2174/138527207782023120     Document Type: Review
Times cited : (41)

References (135)
  • 2
    • 0002002167 scopus 로고    scopus 로고
    • Useful Traps in Radical Chemistry
    • For a review on the behavior of isonitriles as radical traps, see:, Renaud, P, Sibi, M. P. Eds, Wiley-VCH: Weinheim
    • For a review on the behavior of isonitriles as radical traps, see: Nanni, D. Isonitriles: Useful Traps in Radical Chemistry, in Radicals in Organic Synthesis, Renaud, P.; Sibi, M. P. Eds.; Wiley-VCH: Weinheim, 2001, Vol. 2, pp. 44-61.
    • (2001) Radicals in Organic Synthesis , vol.2 , pp. 44-61
    • Nanni, D.I.1
  • 4
    • 85196434030 scopus 로고    scopus 로고
    • Bishop, R. Ritter-type Reactions, in Comprehensive Organic Synthesis, Trost, B. M.; Fleming, I. Eds.; Pergamon: Oxford, 1991; 6, Chap. 1.9.4.2, Refs. 237-242.
    • Bishop, R. Ritter-type Reactions, in Comprehensive Organic Synthesis, Trost, B. M.; Fleming, I. Eds.; Pergamon: Oxford, 1991; Vol. 6, Chap. 1.9.4.2, Refs. 237-242.
  • 5
    • 85196434552 scopus 로고    scopus 로고
    • Although imidoyl radicals are bona fide intermediates in such processes, and they were also detected and studied by EPR specroscopy see Section 2, Kim suggested that the isonitrile/nitrile isomerization could be a concerted process, occurring through a polar transition state, when a particular stable radical, such as benzyl, can be released by β-fragmentation; see his papers on the addition of phenyl anq tributyltin radicals to benzyl isonitrile: Kim, S. S, Lee, K. S, Hwang, S. B, Kim, H. J. Tetrahedron Lett, 1990, 31, 3575;
    • Although imidoyl radicals are bona fide intermediates in such processes, and they were also detected and studied by EPR specroscopy (see Section 2), Kim suggested that the isonitrile/nitrile isomerization could be a concerted process, occurring through a polar transition state, when a particular stable radical, such as benzyl, can be released by β-fragmentation; see his papers on the addition of phenyl anq tributyltin radicals to benzyl isonitrile: Kim, S. S.; Lee, K. S.; Hwang, S. B.; Kim, H. J. Tetrahedron Lett., 1990, 31, 3575;
  • 15
    • 85196435682 scopus 로고    scopus 로고
    • Additional studies on imidoyls arising from addition of other radicals (silicon- [9e], phosphorus-, and tin-centered radicals) to isonitriles will be dealt with in the next Sections.
    • Additional studies on imidoyls arising from addition of other radicals (silicon- [9e], phosphorus-, and tin-centered radicals) to isonitriles will be dealt with in the next Sections.
  • 16
    • 85196435674 scopus 로고    scopus 로고
    • The only exception is addition of methylsulfanyl radical to tert-butyl isonitrile, which gives methyl thiocyanate and tert-butyl radical instead of tert-butyl isothiocyanate and methyl radical, due to the very strong S-Me bond of the intermediate imidoyl radical (see Ref. 20b below).
    • The only exception is addition of methylsulfanyl radical to tert-butyl isonitrile, which gives methyl thiocyanate and tert-butyl radical instead of tert-butyl isothiocyanate and methyl radical, due to the very strong S-Me bond of the intermediate imidoyl radical (see Ref. 20b below).
  • 20
    • 85196433595 scopus 로고    scopus 로고
    • Abstraction of an iminic hydrogen was also observed to occur intramolecululy by 1,5-H transfer to an aryl radical, see: Gioanola, M.; Leardini, R.; Nanni, D.; Pareschi, P.; Zanardi, G. Tetrahedron, 1995, 51, 2039.
    • Abstraction of an iminic hydrogen was also observed to occur intramolecululy by 1,5-H transfer to an aryl radical, see: Gioanola, M.; Leardini, R.; Nanni, D.; Pareschi, P.; Zanardi, G. Tetrahedron, 1995, 51, 2039.
  • 22
    • 85196434647 scopus 로고    scopus 로고
    • for another α-fragmentation of α-(triphenylmethyl)imidoyl radicals, see
    • for another α-fragmentation of α-(triphenylmethyl)imidoyl radicals, see Ref. 47 below.
    • 47 below
    • Ref1
  • 23
    • 85196432880 scopus 로고    scopus 로고
    • 3SiNC and tert-Bu radical has been proposed by Ingold to explain the radicals detected in die addition of trimethylsilyl radicals to pivalonitrile; see: (b) Kaba, R. A.; Griller, D.; Ingold, K. U. J. Am. Chem. Soc., 1974, 96, 6202.
    • 3SiNC and tert-Bu radical has been proposed by Ingold to explain the radicals detected in die addition of trimethylsilyl radicals to pivalonitrile; see: (b) Kaba, R. A.; Griller, D.; Ingold, K. U. J. Am. Chem. Soc., 1974, 96, 6202.
  • 28
    • 85196434990 scopus 로고    scopus 로고
    • For an additional EPR study on radicals generated from imines, see: Nanni, D, Pareschi, P, Walton, J. C. J. Chem. Soc. Perkin Trans. 2, 2002, 1098. In this paper, however, detection of imidoyls was hindered by competing addition of tert-butoxy radicals to the parent imines, giving aminyls and nitroxides. DFT calculations were also performed in order to show that α-scission of imidoyls is strongly endothermic, even when a tert-butyl radical can be released. A C-unsubstituted imidoyl radical was instead observed by Roberts in the reaction of DTBP with N-methylene-tert-butylamine Ref. 20 c below
    • For an additional EPR study on radicals generated from imines, see: Nanni, D.; Pareschi, P.; Walton, J. C. J. Chem. Soc. Perkin Trans. 2, 2002, 1098. In this paper, however, detection of imidoyls was hindered by competing addition of tert-butoxy radicals to the parent imines, giving aminyls and nitroxides. DFT calculations were also performed in order to show that α-scission of imidoyls is strongly endothermic, even when a tert-butyl radical can be released. A C-unsubstituted imidoyl radical was instead observed by Roberts in the reaction of DTBP with N-methylene-tert-butylamine (Ref. 20 c below).
  • 38
    • 85196432836 scopus 로고    scopus 로고
    • For comparison purpose, Roberts generated some imidoyls also by hydrogen abstraction from imidates or imines by photolysis with bis(trimethylsilyl) or dicumyl peroxide (Refs. 20a,b).
    • For comparison purpose, Roberts generated some imidoyls also by hydrogen abstraction from imidates or imines by photolysis with bis(trimethylsilyl) or dicumyl peroxide (Refs. 20a,b).
  • 39
    • 85196433650 scopus 로고    scopus 로고
    • -1 at 300 K). See: Chatgilialoglu, C.; Ingold, K. U.; Scaiano, J. C. J. Am. Chem. Soc., 1983, 105, 3292.
    • -1 at 300 K). See: Chatgilialoglu, C.; Ingold, K. U.; Scaiano, J. C. J. Am. Chem. Soc., 1983, 105, 3292.
  • 42
    • 85196432502 scopus 로고    scopus 로고
    • Some other phosphorus-substituted imidoyls were also reported in Ref. 20b.
    • Some other phosphorus-substituted imidoyls were also reported in Ref. 20b.
  • 44
    • 85196434572 scopus 로고    scopus 로고
    • Imidoyl radicals could also be formed by Group 11 metal atoms addition to isonitriles in a rotating cryostat at 77 K. However, if ever formed, they seem extremely prone to fragmentation and could not be observed even at so low temperatures. See: Howard, J. A.; Sutcliffe, R.; Dahmane, H.; Mile, B. Organometallics, 1985, 4, 697.
    • Imidoyl radicals could also be formed by Group 11 metal atoms addition to isonitriles in a rotating cryostat at 77 K. However, if ever formed, they seem extremely prone to fragmentation and could not be observed even at so low temperatures. See: Howard, J. A.; Sutcliffe, R.; Dahmane, H.; Mile, B. Organometallics, 1985, 4, 697.
  • 53
    • 85196435030 scopus 로고    scopus 로고
    • This rearrangement may involve either 3-exo ring closure of the cyclohexadienyl radical onto the C=N double bond, followed by ring opening, or direct C-N bond fragmentation, followed by cyclization of the resulting iminyl radical. Some results (see Ref. 14a) indicate that the latter mechanism is a viable pathway, although the concomitant occurrence of the former cannot be excluded
    • This rearrangement may involve either 3-exo ring closure of the cyclohexadienyl radical onto the C=N double bond, followed by ring opening, or direct C-N bond fragmentation, followed by cyclization of the resulting iminyl radical. Some results (see Ref. 14a) indicate that the latter mechanism is a viable pathway, although the concomitant occurrence of the former cannot be excluded.
  • 58
    • 85196433285 scopus 로고    scopus 로고
    • Benzoxazoles and biaryls were additional products isolated in trace amounts and symptomatic of the presence of phenoxyl 14: the former are formed by cyclization of the phenoxyl onto the C=N double bond, followed by release of an aryl radical; the latter are the result of attack of that aryl radical onto the solvent benzene
    • Benzoxazoles and biaryls were additional products isolated in trace amounts and symptomatic of the presence of phenoxyl 14: the former are formed by cyclization of the phenoxyl onto the C=N double bond, followed by release of an aryl radical; the latter are the result of attack of that aryl radical onto the solvent benzene.
  • 59
    • 85196432884 scopus 로고    scopus 로고
    • Leardini, R.; Nanni, D.; Santori, M.; Zanardi, G. Tetrahedron, 1992, 48, 3961. For a theoretical study on the competition between imidoyl. radical cyclization onto cyano and sulfide moieties, see Ref. 57c below.
    • Leardini, R.; Nanni, D.; Santori, M.; Zanardi, G. Tetrahedron, 1992, 48, 3961. For a theoretical study on the competition between imidoyl. radical cyclization onto cyano and sulfide moieties, see Ref. 57c below.
  • 60
    • 85196435260 scopus 로고    scopus 로고
    • Hi reaction of imidoyls at the sulfur atom strictly resembles that of akin vinyl radicals, which have been shown to release from sulfur acyl Benati, L.; Calestani, G.; Leardini, R.; Minozzi, M.; Nanni, D.; Spagnolo, P.; Strazzari; S. Org. Lett., 2003, 5, 1313;
    • Hi reaction of imidoyls at the sulfur atom strictly resembles that of akin vinyl radicals, which have been shown to release from sulfur acyl (Benati, L.; Calestani, G.; Leardini, R.; Minozzi, M.; Nanni, D.; Spagnolo, P.; Strazzari; S. Org. Lett., 2003, 5, 1313;
  • 62
    • 85196433697 scopus 로고    scopus 로고
    • carbamoyl (Benati, L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni, D.; Scialpi, R.; Spagnolo, P.; Zanardi, G. J. Org. Chem, 2006, 71, 3192), and even simple, unstabilized alkyl radicals (Bencivenni, G.; Lanza, T.; Leardini, R.; Minozzi, M.; Nanni, D.; Spagnolo, P.; Zanardi, G., paper to be subinitted).
    • carbamoyl (Benati, L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni, D.; Scialpi, R.; Spagnolo, P.; Zanardi, G. J. Org. Chem, 2006, 71, 3192), and even simple, unstabilized alkyl radicals (Bencivenni, G.; Lanza, T.; Leardini, R.; Minozzi, M.; Nanni, D.; Spagnolo, P.; Zanardi, G., paper to be subinitted).
  • 65
    • 1242343132 scopus 로고    scopus 로고
    • Curiously, formation of imidoyl halides can also be the fate of imidoyl radicals. In fact, when imidoyls are generated by treatment of isonitriles with alkylmercury halides, they undergo electron transfer to the mercury reagent giving a nitriliurn ion which, in benzene solution, is then trapped by the halide ion. See
    • Curiously, formation of imidoyl halides can also be the fate of imidoyl radicals. In fact, when imidoyls are generated by treatment of isonitriles with alkylmercury halides, they undergo electron transfer to the mercury reagent giving a nitriliurn ion which, in benzene solution, is then trapped by the halide ion. See: Russell, G. A.; Rajaratnam, R.; Chen, P. Acta Chem. Scand., 1998, 52, 528.
    • (1998) Acta Chem. Scand , vol.52 , pp. 528
    • Russell, G.A.1    Rajaratnam, R.2    Chen, P.3
  • 68
    • 85196433211 scopus 로고    scopus 로고
    • Some additional examples dealing with the radical chemistry of telluroimidates have been reported: since they involve use of isonitriles, they will be discussed in the next Section (see Refs 66 below).
    • Some additional examples dealing with the radical chemistry of telluroimidates have been reported: since they involve use of isonitriles, they will be discussed in the next Section (see Refs 66 below).
  • 74
    • 0001451085 scopus 로고    scopus 로고
    • For a very nice review on the use of radical carbonylation in synthesis, see
    • For a very nice review on the use of radical carbonylation in synthesis, see: Ryu, I.; Sonoda, N.; Curran, D. P. Chem. Rev., 1996, 96, 177.
    • (1996) Chem. Rev , vol.96 , pp. 177
    • Ryu, I.1    Sonoda, N.2    Curran, D.P.3
  • 79
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    • Isonitriles
    • For a general view on isonitrile chemistry, see: a, Patai, S, Rappoport, Z. Eds, Wiley: London, Chap. 15;
    • For a general view on isonitrile chemistry, see: (a) Hoffmann, P.; Marquarding, D.; Kliimann, H.; Ugi, I. Isonitriles, in The Chemistry of the Cyano Group, Patai, S.; Rappoport, Z. Eds.; Wiley: London, 1970; Chap. 15;
    • (1970) The Chemistry of the Cyano Group
    • Hoffmann, P.1    Marquarding, D.2    Kliimann, H.3    Ugi, I.4
  • 81
    • 0000809496 scopus 로고
    • Synthesis of Pseudohalides, Nitriles and Related Compounds
    • Trost, B. M, Fleming, I. Eds, Pergamon: Oxford, Chap. 1.8.2;
    • (c) Grashey, R. Synthesis of Pseudohalides, Nitriles and Related Compounds, in Comprehensive Organic Synthesis, Trost, B. M.; Fleming, I. Eds.; Pergamon: Oxford, 1991; Vol. 6, Chap. 1.8.2;
    • (1991) Comprehensive Organic Synthesis , vol.6
    • Grashey, R.1
  • 82
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    • Kantlehner, W. Synthesis of Iminium Salts, Orthoesters and Related Compounds, ibid.; 6, Chap. 2.7.2. 1.1;
    • (d) Kantlehner, W. Synthesis of Iminium Salts, Orthoesters and Related Compounds, ibid.; Vol. 6, Chap. 2.7.2. 1.1;
  • 102
    • 85196432451 scopus 로고    scopus 로고
    • A few [4 + 1] annulation strategies involving a cyano group were also used by Curran: see Refs. 56d,g.
    • A few [4 + 1] annulation strategies involving a cyano group were also used by Curran: see Refs. 56d,g.
  • 103
    • 85196432389 scopus 로고    scopus 로고
    • For another example of tandem cyclization triggered by attack of an alkylsulfanyl radical to an isonitrile, see Ref. 73below
    • For another example of tandem cyclization triggered by attack of an alkylsulfanyl radical to an isonitrile, see Ref. 73below.
  • 104
    • 85196434109 scopus 로고    scopus 로고
    • For another example of attack to aromatic rings of imidoyl radicals generated from isonitriles, see Ref. 35b. In that case, 2-(phenoxy)phenyl isonitrile, when treated with dibenzoyl peroxide, gave 2-phenyloxazole through presumable 1,5-phenyl radical migration (in analogy to what shown in Scheme 15) followed by ring closure of the resulting phenoxyl with expulsion of benzoyloxy radicals.
    • For another example of attack to aromatic rings of imidoyl radicals generated from isonitriles, see Ref. 35b. In that case, 2-(phenoxy)phenyl isonitrile, when treated with dibenzoyl peroxide, gave 2-phenyloxazole through presumable 1,5-phenyl radical migration (in analogy to what shown in Scheme 15) followed by ring closure of the resulting phenoxyl with expulsion of benzoyloxy radicals.
  • 110
    • 85196434636 scopus 로고    scopus 로고
    • Another convenient enantioselective total synthesis of (-)α-kainic acid was obtained by tin radical addition to an alkenyl thioformamide, see Ref 49a. Similar cyclizations to thiolactams were also carried by tin radical additions to alkenyl isothiocyanates, see Ref. 76below.
    • Another convenient enantioselective total synthesis of (-)α-kainic acid was obtained by tin radical addition to an alkenyl thioformamide, see Ref 49a. Similar cyclizations to thiolactams were also carried by tin radical additions to alkenyl isothiocyanates, see Ref. 76below.
  • 122
    • 85196434885 scopus 로고    scopus 로고
    • In some cases, also α-scission of thioimidoyls affording isonitriles can become a competing, dangerous process, see
    • In some cases, also α-scission of thioimidoyls affording isonitriles can become a competing, dangerous process, see: Refs. 52a, 76, and 77a.
    • 52a, 76, and 77a
    • Refs1
  • 123
    • 85196434368 scopus 로고    scopus 로고
    • The first instances of reactions between isocyanates and isothiocyanates with organostannanes date back to the beginning of the 1960s Lorenz, D. H, Becker, E. I. J. Org. Chem, 1963, 28, 1707;
    • The first instances of reactions between isocyanates and isothiocyanates with organostannanes date back to the beginning of the 1960s (Lorenz, D. H.; Becker, E. I. J. Org. Chem., 1963, 28, 1707;
  • 124
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    • but in those papers no evidence is reported about the intermediacy of radical species
    • Noltes, J. G.; Janssen, M. J. J. Organomet. Chem., 1964, 1, 346), but in those papers no evidence is reported about the intermediacy of radical species.
    • (1964) J. Organomet. Chem , vol.1 , pp. 346
    • Noltes, J.G.1    Janssen, M.J.2
  • 125
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    • See also:, 1413 Section III, Refs. 140-143
    • See also: Crich, D.; Quintero, L. Chem. Rev., 1989, 89, 1413 (Section III, Refs. 140-143).
    • (1989) Chem. Rev , vol.89
    • Crich, D.1    Quintero, L.2
  • 129
    • 85196435943 scopus 로고    scopus 로고
    • An analogous process was observed starting from an alkynylaryl isonitrile and cyclohexylsulfanyl radicals
    • An analogous process was observed starting from an alkynylaryl isonitrile and cyclohexylsulfanyl radicals.
  • 135
    • 85196432966 scopus 로고    scopus 로고
    • In these reactions even α-fragmentation with loss of a sulfanyl radical does not seem a drawback, since isonitriles and disulfides were only detected in few cases and just in trace amounts
    • In these reactions even α-fragmentation with loss of a sulfanyl radical does not seem a drawback, since isonitriles and disulfides were only detected in few cases and just in trace amounts.


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