{
  "abstracts": [
    {
      "content": "Rolf Huisgen hat vor 60 Jahren das Konzept der 1,3-dipolaren Cycloaddition vorgestellt und dabei bis dahin unbekannte reaktive Zwischenstufen, wie z.B. Azomethinylide, in die organische Chemie eingeführt. Danach entwickelten sich die (3+2)-Cycloadditionen von 1,3-Dipolen an Mehrfachbindungssysteme zu einer der vielseitigsten Synthesemethoden in der Heterocyclen-chemie. In diesem Aufsatz gehen wir auf die geschichtliche Entwicklung dieses Arbeitsgebietes ein, führen die relevanten Vorläuferarbeiten auf und schildern das Entstehen des Konzeptes und seine Weiterentwicklung. Die wichtigsten mechanistischen und präparativen Befunde werden diskutiert. Quantenmechanische Berechnungen stützen den von R. Huisgen immer favorisierten konzertierten Reaktionsmechanismus, aber in Extremfällen können auch zwitterionische Zwischenstufen durchlaufen werden. Die Bedeutung der 1,3-dipolaren Cycloaddition für die experimentelle Umsetzung des Click-Chemie-Konzept von K. B. Sharpless wird ebenfalls diskutiert.",
      "lang": "en",
      "mimetype": "text/plain",
      "sha1": "bb7891bd4132c96d1aa39ee00f8eeeb381614d8a"
    }
  ],
  "container_id": "yvxuqnndanecfkaawvplfvqzdi",
  "contribs": [
    {
      "extra": {},
      "given_name": "Hans-Ulrich",
      "index": 0,
      "raw_affiliation": "Freie Universität Berlin, Institut für Chemie und Biochemie, Takustr. 3, 14195, Berlin, GERMANY.",
      "raw_name": "Hans-Ulrich Reissig",
      "role": "author",
      "surname": "Reissig"
    },
    {
      "extra": {},
      "given_name": "Martin",
      "index": 1,
      "raw_affiliation": "Universitat zu Koln, Department Chemie, GERMANY.",
      "raw_name": "Martin Breugst",
      "role": "author",
      "surname": "Breugst"
    }
  ],
  "ext_ids": {
    "doi": "10.1002/anie.202003115",
    "pmid": "32255543"
  },
  "extra": {
    "pubmed": {
      "pub_types": [
        "Journal Article"
      ]
    }
  },
  "ident": "s7mpon5havhx3eil563hcz6anu",
  "language": "en",
  "refs": [
    {
      "extra": {
        "unstructured": " "
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    },
    {
      "extra": {
        "unstructured": "R. Huisgen, in Zehnjahresfeier des Fonds der Chemischen Industrie, Düsseldorf, 1960, pp. 73-102 (Reprint in Naturwiss. Rundschau 1961, 1914, 1963);"
      },
      "index": 1
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, Proc. Chem. Soc. London 1961, 357-369."
      },
      "index": 2
    },
    {
      "extra": {
        "unstructured": "Looking back, Huisgen was not happy about the choice of the name because it may be misleading. The name 1,3-dipole may imply high dipole moments of these compounds which is not the case for many 1,3-dipoles."
      },
      "index": 3
    },
    {
      "extra": {
        "unstructured": "In the first reviews (e.g., in ref. [33]) reactions of 1,3-dipoles without octet stabilization were included, for instance those of keto carbenes. Later it was recognized that they are better regarded as 2π components in cycloadditions."
      },
      "index": 4
    },
    {
      "extra": {
        "unstructured": "In our opinion and that of many colleagues, all 1,3-dipolar cycloadditions should be called Huisgen reactions. Occasionally, the cycloadditions of organic azides with alkynes are given the name Huisgen reaction. This is incorrect since this variation of the 1,3-dipolar cycloaddition was not discovered by Huisgen but by Arthur Michael already in 1893 (see ref. [14]). However, the Huisgen group investigated this reaction for the first time in detail and included it in the concept of 1,3-dipolar cycloadditions."
      },
      "index": 5
    },
    {
      "extra": {
        "unstructured": " "
      },
      "index": 6
    },
    {
      "extra": {
        "unstructured": "1,3-Dipolar Cycloaddition Chemistry, Vol. 1 and 2, (Ed.: A. Padwa), Wiley, New York, 1984;"
      },
      "index": 7
    },
    {
      "extra": {
        "unstructured": "Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products (Eds.: A. Padwa, W. H. Pearson), Wiley, New York, 2002."
      },
      "index": 8
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, in 1,3-Dipolar Cycloaddition Chemistry, Vol. 1 (Ed.: A. Padwa), Wiley, New York, 1984, pp. 1-176."
      },
      "index": 9
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, The Adventure Playground of Mechanisms and Novel Reactions in Profiles, Pathways, and Dreams (Ed.: J. I. Seeman), American Chemical Society, Washington, DC, 1994."
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      "extra": {
        "unstructured": "R. Huisgen, M. Christl, Angew. Chem. Int. Ed. Engl. 1967, 6, 456-457;"
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      "index": 14
    },
    {
      "extra": {
        "unstructured": "Angew. Chem. 1967, 79, 471-472;"
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    {
      "extra": {
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      },
      "index": 21
    },
    {
      "extra": {
        "unstructured": "T. Curtius, Ber. Dtsch. Chem. Ges. 1884, 17, 953-959."
      },
      "index": 22
    },
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    },
    {
      "extra": {
        "unstructured": "E. Buchner, Ber. Dtsch. Chem. Ges. 1888, 21, 2637-2647;"
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      "extra": {
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    {
      "extra": {
        "unstructured": "O. Dimroth, G. Fester, Ber. Dtsch. Chem. Ges. 1910, 43, 2219-2223."
      },
      "index": 33
    },
    {
      "extra": {
        "unstructured": "C. Harries, Justus Liebigs Ann. Chem. 1915, 410, 1-21."
      },
      "index": 34
    },
    {
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    },
    {
      "extra": {
        "unstructured": "R. Criegee, Justus Liebigs Ann. Chem. 1953, 583, 1-36;"
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    },
    {
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        "unstructured": "R. Criegee, G. Schröder, Chem. Ber. 1960, 93, 689-700."
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      "index": 37
    },
    {
      "extra": {
        "unstructured": "K. von Auwers, F. König, Justus Liebigs Ann. Chem. 1932, 496, 27-51."
      },
      "index": 38
    },
    {
      "extra": {
        "unstructured": "J. C. Earl, A. W. Mackney, J. Chem. Soc. 1935, 899-900."
      },
      "index": 39
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, R. Grashey, H. Gotthardt, R. Schmidt, Angew. Chem. Int. Ed. Engl. 1962, 1, 48-49;"
      },
      "index": 40
    },
    {
      "extra": {
        "unstructured": "Angew. Chem. 1962, 74, 29-30."
      },
      "index": 41
    },
    {
      "extra": {
        "unstructured": "At about the same time, a group in the Soviet Union investigated cycloadditions of “Sydnones”: V. F. Vasiléva, V. G. Yashunskii, M. N. Shchukina, J. Gen. Chem. USSR (Engl. Transl.) 1961, 31, 1390."
      },
      "index": 42
    },
    {
      "extra": {
        "unstructured": "L. I. Smith, Chem. Rev. 1938, 23, 193-285."
      },
      "index": 43
    },
    {
      "extra": {
        "unstructured": "Smith provided only few original contributions to the 1,3-additions; in the 1930s and 1940s he published a few reports concerning diazoalkane cycloadditions to α,β-unsaturated carbonyl compounds. He apparently lost interest in this research area later."
      },
      "index": 44
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, R. Fleischmann, H. Stangl, München, unpublished results, 1957-1959; reported in Huisgen′s reviews."
      },
      "index": 45
    },
    {
      "extra": {
        "unstructured": "A. Quilico, G. Speroni, Gazz. Chim. Ital. 1946, 76, 148-166."
      },
      "index": 46
    },
    {
      "extra": {
        "unstructured": "T. Mukaiyama, T. Hoshino, J. Am. Chem. Soc. 1960, 82, 5339-5342."
      },
      "index": 47
    },
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      "extra": {
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      "extra": {
        "unstructured": "N. A. LeBel, J. J. Whang, J. Am. Chem. Soc. 1959, 81, 6334-6335;"
      },
      "index": 49
    },
    {
      "extra": {
        "unstructured": "N. A. LeBel, M. E. Post, J. J. Whang, J. Am. Chem. Soc. 1964, 86, 3759-3767;"
      },
      "index": 50
    },
    {
      "extra": {
        "unstructured": "A. Padwa, Angew. Chem. Int. Ed. Engl. 1976, 15, 123-136;"
      },
      "index": 51
    },
    {
      "extra": {
        "unstructured": "Angew. Chem. 1976, 88, 131-144."
      },
      "index": 52
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, R. Grashey, E. Steingruber, Tetrahedron Lett. 1963, 4, 1441-1445."
      },
      "index": 53
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, A. Eckell, Tetrahedron Lett. 1960, 1, 5-8."
      },
      "index": 54
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, H. Stangl, H. J. Sturm, H. Wagenhofer, Angew. Chem. Int. Ed. Engl. 1962, 1, 50;"
      },
      "index": 55
    },
    {
      "extra": {
        "unstructured": "Angew. Chem. 1962, 74, 31."
      },
      "index": 56
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, M. Seidel, G. Wallbillich, H. Knupfer, Tetrahedron 1962, 17, 3-29."
      },
      "index": 57
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, R. Knorr, Naturwissenschaften 1961, 48, 716."
      },
      "index": 58
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, Angew. Chem. Int. Ed. Engl. 1963, 2, 565-598;"
      },
      "index": 59
    },
    {
      "extra": {
        "unstructured": "Angew. Chem. 1963, 75, 604-637."
      },
      "index": 60
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, H. Gotthardt, H. O. Bayer, F. C. Schaefer, Angew. Chem. Int. Ed. Engl. 1964, 3, 136-137;"
      },
      "index": 61
    },
    {
      "extra": {
        "unstructured": "Angew. Chem. 1964, 76, 185-186."
      },
      "index": 62
    },
    {
      "extra": {
        "unstructured": "Short review: H.-U. Reissig, R. Zimmer, Angew. Chem. Int. Ed. 2014, 53, 9708-9710;"
      },
      "index": 63
    },
    {
      "extra": {
        "unstructured": "Angew. Chem. 2014, 126, 9864-9866. Arndtsen's phosphorus-containing “Montréalones” were also discussed here (D. J. St. Cyr, B. A. Arndtsen, J. Am. Chem. Soc. 2007, 129, 12366-12367 and subsequent publications)."
      },
      "index": 64
    },
    {
      "extra": {
        "unstructured": "Selected reviews for synthetic applications of azomethine ylide cycloadditions:"
      },
      "index": 65
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      "index": 91
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      },
      "index": 95
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    {
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      },
      "index": 98
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    {
      "extra": {
        "unstructured": "J. Zhang, Q. Chen, R. J. Mayer, J.-D. Yang, A. R. Ofial, J.-P. Cheng, H. Mayr, Angew. Chem. Int. Ed. 2020, https://doi.org/10.1002/anie.202003029;"
      },
      "index": 99
    },
    {
      "extra": {
        "unstructured": "Angew. Chem. 2020, https://doi.org/10.1002/ange.202003029."
      },
      "index": 100
    },
    {
      "extra": {
        "unstructured": "Reactions between diazoalkanes and highly reactive Michael acceptors such as 1,1-bis(phenylsulfonyl)ethene can be described very well with the reactivity parameters developed by Mayr et al. (H. Mayr, M. Patz, Angew. Chem. Int. Ed. Engl. 1994, 33, 938-957;"
      },
      "index": 101
    },
    {
      "extra": {
        "unstructured": "Angew. Chem. 1994, 106, 990-1010. In contrast, less reactive Michael acceptors such as methyl acrylate react much faster than predicted based on their reactivity parameters. However, the analysis relying on nucleophilicity and electrophilicity parameters is only valid when only one bond is formed in the rate-limiting transition state. This also means that the investigated (3+2) cycloadditions with less reactive Michael acceptors must proceed via a concerted mechanism with the formation of two bonds."
      },
      "index": 102
    },
    {
      "extra": {
        "unstructured": " "
      },
      "index": 103
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, G. Mloston, E. Langhals, J. Am. Chem. Soc. 1986, 108, 6401-6402;"
      },
      "index": 104
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, G. Mloston, E. Langhals, J. Org. Chem. 1986, 51, 4085-4087;"
      },
      "index": 105
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, E. Langhals, G. Mloston, T. Oshima, Heterocycles 1989, 29, 2069-2074;"
      },
      "index": 106
    },
    {
      "extra": {
        "unstructured": "R. Huisgen, G. Mlostoń, E. Langhals, T. Oshima, Helv. Chim. Acta 2002, 85, 2668-2685."
      },
      "index": 107
    },
    {
      "extra": {
        "unstructured": "The observation of (4+3) cycloadducts by H. Mayr and colleagues indicate that stepwise reactions can also play an important role in cycloadditions to 1,3-dienes:"
      },
      "index": 108
    },
    {
      "extra": {
        "unstructured": "J. Baran, H. Mayr, J. Am. Chem. Soc. 1987, 109, 6519-6521;"
      },
      "index": 109
    },
    {
      "extra": {
        "unstructured": "J. Baran, H. Mayr, J. Org. Chem. 1989, 54, 5012-5016;"
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      "index": 110
    },
    {
      "extra": {
        "unstructured": "J. Baran, H. Mayr, J. Org. Chem. 1989, 54, 5774-5783;"
      },
      "index": 111
    },
    {
      "extra": {
        "unstructured": "H. Mayr, J. Baran, U. W. Heigl, Gazz. Chim. Ital. 1991, 121, 373-381."
      },
      "index": 112
    },
    {
      "extra": {
        "unstructured": "O. E. Polansky, P. Schuster, Tetrahedron Lett. 1964, 5, 2019-2022."
      },
      "index": 113
    },
    {
      "extra": {
        "unstructured": " "
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      "index": 114
    },
    {
      "extra": {
        "unstructured": "R. Sustmann, Tetrahedron Lett. 1971, 12, 2717-2720;"
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      "index": 115
    },
    {
      "extra": {
        "unstructured": "R. Sustmann, H. Trill, Angew. Chem. Int. Ed. Engl. 1972, 11, 838-840;"
      },
      "index": 116
    },
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  "release_date": "2020-04-07",
  "release_stage": "published",
  "release_type": "article-journal",
  "release_year": 2020,
  "revision": "5536158c-f03e-44c5-9e28-e6a456b62506",
  "state": "active",
  "title": "Die Huisgen-Reaktion - Meilensteine der 1,3-Dipolaren Cycloaddition",
  "work_id": "h54zh2d6uffcxda2dkj7qbpozq"
}