Synlett 2021; 32(06): 551-560
DOI: 10.1055/s-0040-1706404
account
© Georg Thieme Verlag Stuttgart · New York

Carbenoid-Mediated Homologation Tactics for Assembling (Fluorinated) Epoxides and Aziridines

Laura Ielo
a   University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, 1090 Vienna, Austria   Email: laura.ielo@univie.ac.at
,
Veronica Pillari
a   University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, 1090 Vienna, Austria   Email: laura.ielo@univie.ac.at
,
Margherita Miele
a   University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, 1090 Vienna, Austria   Email: laura.ielo@univie.ac.at
,
Davide Castiglione
a   University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, 1090 Vienna, Austria   Email: laura.ielo@univie.ac.at
,
Vittorio Pace
b   University of Turin, Department of Chemistry, Via P. Giuria 7, 10125 Turin, Italy   Email: vittorio.pace@unito.it
› Author Affiliations
We acknowledge the University of Vienna and the University of Turin for financial support.
Further Information

Publication History

Received: 11 June 2020

Accepted: 10 July 2020

Publication Date:
26 August 2020 (online)


In memory of Professor Hans Reich, a pioneer in organolithium chemistry.

Abstract

Homologation strategies provide highly versatile tools in organic synthesis for the introduction of a CH2 group into a given carbon skeleton. The operation can result in diverse structural motifs by tuning of the reaction conditions and the nature of the homologating agent. In this Account, concisely contextualizing our work with lithium carbenoids (LiCH2X, LiCHXY etc) for homologating carbon-centered electrophiles, we focus on the assembly of three-membered cycles featuring fluorinated substituents. Two illustrative case studies are considered: (1) the development and employment of fluorinated carbenoids en route to rare α-fluoroepoxides and aziridines, and (2) the installation of up to halomethylenic groups on trifluoroimidoylacetyl chlorides (TFAICs) for preparing CF3-containing halo- and halomethylaziridines. Collectively, we demonstrate that the initial homologation event generated by the installation of the carbenoid, upon modulation of the conditions, serves as a tool for creating fluorinated building blocks in a single operation.

 
  • References

  • 1 Li JJ. Name Reactions for Homologation . Wiley; Hoboken: 2009
    • 2a Arndt F, Eistert B, Ender W. Ber. Dtsch. Chem. Ges. B 1929; 62: 44
    • 2b Pace V, Verniest G, Sinisterra JV, Alcántara AR, De Kimpe N. J. Org. Chem. 2010; 75: 5760
    • 2c Candeias NR, Paterna R, Gois PM. P. Chem. Rev. 2016; 116: 2937
    • 2d Ford A, Miel H, Ring A, Slattery CN, Maguire AR, McKervey MA. Chem. Rev. 2015; 115: 9981
    • 2e Castoldi L, Ielo L, Holzer W, Giester G, Roller A, Pace V. J. Org. Chem. 2018; 83: 4336
  • 3 Kohlbacher SM, Ionasz V.-S, Ielo L, Pace V. Monatsh. Chem. 2019; 150: 2011
    • 4a Corey EJ, Chaykovsky M. J. Am. Chem. Soc. 1965; 87: 1345
    • 4b Corey EJ, Chaykovsky M. J. Am. Chem. Soc. 1962; 84: 867
    • 4c Gololobov YG, Nesmeyanov AN, lysenko VP, Boldeskul IE. Tetrahedron 1987; 43: 2609
    • 4d Triandafillidi I, Savvidou A, Kokotos CG. Org. Lett. 2019; 21: 5533
  • 5 Maryanoff BE, Reitz AB. Chem. Rev. 1989; 89: 863
  • 6 Pace V. New Perspectives in Homologation Processes for Synthetic Medicinal Chemistry: Lithium Halocarbenoids at the Helm. Habilitation Thesis; University of Vienna: 2016
    • 7a Pace V, Castoldi L, Monticelli S, Rui M, Collina S. Synlett 2017; 28: 879
    • 7b Pace V, Holzer W, De Kimpe N. Chem. Rec. 2016; 16: 2061
    • 7c Castoldi L, Monticelli S, Senatore R, Ielo L, Pace V. Chem. Commun. 2018; 54: 6692
  • 8 Closs GL, Moss RA. J. Am. Chem. Soc. 1964; 86: 4042
  • 11 Monticelli S, Rui M, Castoldi L, Missere G, Pace V. Monatsh. Chem. 2018; 149: 1285
    • 12a Colella M, Tota A, Takahashi Y, Higuma R, Ishikawa S, Degennaro L, Luisi R, Nagaki A. Angew. Chem. Int. Ed. 2020; 59: 10924
    • 12b Musci P, Colella M, Sivo A, Romanazzi G, Luisi R, Degennaro L. Org. Lett. 2020; 22: 3623
    • 12c Degennaro L, Fanelli F, Giovine A, Luisi R. Adv. Synth. Catal. 2015; 357: 21
    • 13a Reeder MR, Anderson RM. Chem. Rev. 2006; 106: 2828
    • 13b Izawa K, Onishi T. Chem. Rev. 2006; 106: 2811
    • 13c Castoldi L, Ielo L, Hoyos P, Hernáiz MJ, De Luca L, Alcántara AR, Holzer W, Pace V. Tetrahedron 2018; 74: 2211
    • 14a Matteson DS. J. Org. Chem. 2013; 78: 10009
    • 14b Matteson DS, Majumdar D. J. Am. Chem. Soc. 1980; 102: 7588
    • 15a Casoni G, Kucukdisli M, Fordham JM, Burns M, Myers EL, Aggarwal VK. J. Am. Chem. Soc. 2017; 139: 11877
    • 15b Balieu S, Hallett GE, Burns M, Bootwicha T, Studley J, Aggarwal VK. J. Am. Chem. Soc. 2015; 137: 4398
    • 15c Burns M, Essafi S, Bame JR, Bull SP, Webster MP, Balieu S, Dale JW, Butts CP, Harvey JN, Aggarwal VK. Nature 2014; 513: 183
    • 15d Collins BS. L, Wilson CM, Myers EL, Aggarwal VK. Angew. Chem. Int. Ed. 2017; 56: 11700
    • 15e Sandford C, Aggarwal VK. Chem. Commun. 2017; 53: 5481
    • 15f Leonori D, Aggarwal VK. Acc. Chem. Res. 2014; 47: 3174
    • 16a Blakemore PR, Marsden SP, Vater HD. Org. Lett. 2006; 8: 773
    • 16b Blakemore PR, Burge MS. J. Am. Chem. Soc. 2007; 129: 3068
    • 16c Barsamian AL, Blakemore PR. Organometallics 2011; 31: 19
    • 16d Emerson CR, Zakharov LN, Blakemore PR. Chem. Eur. J. 2013; 19: 16342
    • 16e Wu Z, Sun X, Potter K, Cao Y, Zakharov LN, Blakemore PR. Angew. Chem. Int. Ed. 2016; 55: 12285
    • 16f Blakemore PR, Hoffmann RW. Angew. Chem. Int. Ed. 2018; 57: 390
  • 17 Pace V, Castoldi L, Holzer W. Adv. Synth. Catal. 2014; 356: 1761
  • 18 Pace V, Castoldi L, Mamuye AD, Langer T, Holzer W. Adv. Synth. Catal. 2016; 358: 172
  • 19 Hesse M. Ring Enlargement in Organic Chemistry . Wiley-VCH; Weinheim: 1991
    • 20a Pace V, Holzer W, Olofsson B. Adv. Synth. Catal. 2014; 356: 3697
    • 20b Pace V, Holzer W. Aust. J. Chem. 2013; 66: 507
    • 21a Pace V, Holzer W, Verniest G, Alcántara AR, De Kimpe N. Adv. Synth. Catal. 2013; 355: 919
    • 21b Monticelli S, Holzer W, Langer T, Roller A, Olofsson B, Pace V. ChemSusChem 2019; 12: 1147
    • 21c Senatore R, Ielo L, Urban E, Holzer W, Pace V. Eur. J. Org. Chem. 2018; 2466
    • 21d Stadler M, Monticelli S, Seidel T, Luger D, Salzer I, Boehm S, Holzer W, Schwarzer C, Urban E, Khom S, Langer T, Pace V, Hering S. J. Med. Chem. 2019; 62: 317
    • 21e Pace V, Vilkauskaite G, Sackus A, Holzer W. Org. Biomol. Chem. 2013; 11: 1085
    • 21f Parisi G, Degennaro L, Carlucci C, de Candia M, Mastrorilli P, Roller A, Holzer W, Altomare CD, Pace V, Luisi R. Org. Biomol. Chem. 2017; 15: 5000
    • 21g Miele M, Citarella A, Micale N, Holzer W, Pace V. Org. Lett. 2019; 21: 8261
    • 21h Senatore R, Castoldi L, Ielo L, Holzer W, Pace V. Org. Lett. 2018; 20: 2685
    • 21i Senatore R, Ielo L, Monticelli S, Castoldi L, Pace V. Synthesis 2019; 51: 2792
  • 22 Castoldi L, Holzer W, Langer T, Pace V. Chem. Commun. 2017; 53: 9498
  • 23 Monticelli S, Urban E, Langer T, Holzer W, Pace V. Adv. Synth. Catal. 2019; 361: 1001
    • 24a Gilman H, Breuer F. J. Am. Chem. Soc. 1933; 55: 1262
    • 24b Schäfer G, Matthey C, Bode JW. Angew. Chem. Int. Ed. 2012; 51: 9173
    • 24c Pace V, Monticelli S, de la Vega-Hernandez K, Castoldi L. Org. Biomol. Chem. 2016; 14: 7848
    • 24d Serrano E, Martin R. Eur. J. Org. Chem. 2018; 3051
    • 26a Pace V, Castoldi L, Monticelli S, Safranek S, Roller A, Langer T, Holzer W. Chem. Eur. J. 2015; 21: 18966
    • 26b Pace V, de la Vega-Hernández K, Urban E, Langer T. Org. Lett. 2016; 18: 2750
    • 26c de la Vega-Hernández K, Senatore R, Miele M, Urban E, Holzer W, Pace V. Org. Biomol. Chem. 2019; 17: 1970
    • 27a Mamuye AD, Monticelli S, Castoldi L, Holzer W, Pace V. Green Chem. 2015; 17: 4194
    • 27b Monticelli S, Castoldi L, Touqeer S, Miele M, Urban E, Pace V. Chem. Heterocycl. Compd. 2018; 54: 389
  • 28 Pace V, Castoldi L, Mazzeo E, Rui M, Langer T, Holzer W. Angew. Chem. Int. Ed. 2017; 56: 12677
  • 29 Pace V, Pelosi A, Antermite D, Rosati O, Curini M, Holzer W. Chem. Commun. 2016; 52: 2639
  • 30 Touqeer S, Castoldi L, Langer T, Holzer W, Pace V. Chem. Commun. 2018; 54: 10112
  • 31 Singh GS, Desta ZY. Chem. Rev. 2012; 112: 6104
  • 32 Suero MG, Bayle ED, Collins BS. L, Gaunt MJ. J. Am. Chem. Soc. 2013; 135: 5332
    • 33a Campbell MG, Ritter T. Chem. Rev. 2015; 115: 612
    • 33b Wang J, Sánchez-Roselló M, Aceña JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H. Chem. Rev. 2014; 114: 2432
    • 33c Zhu Y, Han J, Wang J, Shibata N, Sodeoka M, Soloshonok VA, Coelho JA. S, Toste FD. Chem. Rev. 2018; 118: 3887
    • 33d Gillis EP, Eastman KJ, Hill MD, Donnelly DJ, Meanwell NA. J. Med. Chem. 2015; 58: 8315
    • 33e Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
  • 34 Kail DC, Krizkova PM, Wieczorek A, Hammerschmidt F. Chem. Eur. J. 2014; 20: 4086
  • 35 Parisi G, Colella M, Monticelli S, Romanazzi G, Holzer W, Langer T, Degennaro L, Pace V, Luisi R. J. Am. Chem. Soc. 2017; 139: 13648
    • 36a Monticelli S, Pace V. Aust. J. Chem. 2018; 71: 473
    • 36b Senatore R, Malik M, Spreitzer M, Holzer W, Pace V. Org. Lett. 2020; 22: 1345
    • 36c Colella M, Tota A, Großjohann A, Carlucci C, Aramini A, Sheikh NS, Degennaro L, Luisi R. Chem. Commun. 2019; 55: 8430
  • 37 Singh GS, Mollet K, D’hooghe M, De Kimpe N. Chem. Rev. 2013; 113: 1441
  • 38 Blanksby SJ, Ellison GB. Acc. Chem. Res. 2003; 36: 255
    • 39a Kazia A, Melngaile R, Mishnev A, Veliks J. Org. Biomol. Chem. 2020; 18: 1384
    • 39b Veliks J, Kazia A. Chem. Eur. J. 2019; 25: 3786
    • 39c Melngaile R, Sperga A, Baldridge KK, Veliks J. Org. Lett. 2019; 21: 7174
    • 39d Boultwood T, Affron DP, Bull JA. Tetrahedron 2015; 71: 4949
    • 39e Boultwood T, Affron DP, Trowbridge AD, Bull JA. J. Org. Chem. 2013; 78: 6632
    • 39f Bull JA, Boultwood T, Taylor TA. Chem. Commun. 2012; 48: 12246
  • 40 Monticelli S, Colella M, Pillari V, Tota A, Langer T, Holzer W, Degennaro L, Luisi R, Pace V. Org. Lett. 2019; 21: 584
  • 41 Shimizu M, Hata T, Hiyama T. Heterocycles 2000; 52: 707
  • 42 Fasano V, Winter N, Noble A, Aggarwal VK. Angew. Chem. Int. Ed. 2020; 59: 8502
  • 43 Bloch R. Chem. Rev. 1998; 98: 1407
  • 45 Meyer F. Chem. Commun. 2016; 52: 3077
    • 46a Ielo L, Touqeer S, Roller A, Langer T, Holzer W, Pace V. Angew. Chem. Int. Ed. 2019; 58: 2479
    • 46b During the peer-review of this Account, we reported that by simply switching the homologating carbenoid to iodomethyllithium, bis-trifluoromethyl-β-diketiminates can be prepared from TFAICs. See: Ielo L, Castoldi L, Touqeer S, Lombino J, Roller A, Prandi C, Holzer W, Pace V. Angew. Chem. Int. Ed. 2020; DOI: doi: 10.1002/anie.202007954.
  • 47 Chen Z, Hu S, Wu X.-F. Org. Chem. Front. 2020; 7: 223