Synthesis 2023; 55(22): 3759-3776
DOI: 10.1055/a-2111-9910
feature

Titanium-Catalyzed Intermolecular Hydroaminoalkylation of Terminal Alkynes

Hermann Thye
,
Felix Fornfeist
,
Dennis Geik
,
Levi L. Schlüschen
,
Marc Schmidtmann
,
Sven Doye
We thank the Research Training Group ‘Chemical Bond Activation’ (GRK 2226) funded by the Deutsche Forschungsgemeinschaft for financial support of this project.


Abstract

Terminal alkynes undergo intermolecular hydroaminoalkylation reactions with secondary amines in the presence of titanium catalysts and depending on the catalyst and the structure of the substrates, allylic amines and/or imines are formed as products in moderate yields. In addition, the desired allylamines can also be obtained from a convenient reaction sequence consisting of an initial hydroaminoalkylation of trimethylsilyl-protected alkynes and a subsequent protodesilylation that selectively delivers γ-unsubstituted allylamines.

Supporting Information



Publikationsverlauf

Eingereicht: 17. Mai 2023

Angenommen nach Revision: 16. Juni 2023

Accepted Manuscript online:
16. Juni 2023

Artikel online veröffentlicht:
27. Juli 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References


    • For selected reviews on hydroaminoalkylation chemistry, see:
    • 1a Roesky PW. Angew. Chem. Int. Ed. 2009; 48: 4892
    • 1b Chong E, Garcia P, Schafer LL. Synthesis 2014; 46: 2884
    • 1c Edwards PM, Schafer LL. Chem. Commun. 2018; 54: 12543
    • 1d Hannedouche J, Schulz E. Organometallics 2018; 37: 4313
    • 1e Schafer LL, Manßen M, Edwards PM, Lui EK. J, Griffin SE, Dunbar CR. Adv. Organomet. Chem. 2020; 74: 405
    • 1f Manßen M, Schafer LL. Chem. Soc. Rev. 2020; 49: 6947
    • 1g Manßen M, Schafer LL. Trends Chem. 2021; 3: 428

      For selected pioneering studies in the field of hydroaminoalkylation chemistry, see:
    • 2a Clerici MG, Maspero F. Synthesis 1980; 305
    • 2b Nugent WA, Ovenall DW, Holmes SJ. Organometallics 1983; 2: 161
    • 2c Herzon SB, Hartwig JF. J. Am. Chem. Soc. 2007; 129: 6690
    • 2d Kubiak R, Prochnow I, Doye S. Angew. Chem. Int. Ed. 2009; 48: 1153
    • 2e Bexrud JA, Eisenberger P, Leitch DC, Payne PR, Schafer LL. J. Am. Chem. Soc. 2009; 131: 2116
    • 2f Prochnow I, Zark P, Müller T, Doye S. Angew. Chem. Int. Ed. 2011; 50: 6401
    • 2g Nako AE, Oyamada J, Nishiura M, Hou Z. Chem. Sci. 2016; 7: 6429
    • 2h Geik D, Rosien M, Bielefeld J, Schmidtmann M, Doye S. Angew. Chem. Int. Ed. 2021; 60: 9936
    • 3a Kubiak R, Prochnow I, Doye S. Angew. Chem. Int. Ed. 2010; 49: 2626
    • 3b Dörfler J, Preuß T, Brahms C, Scheuer D, Doye S. Dalton Trans. 2015; 44: 12149
    • 3c Dörfler J, Preuß T, Schischko A, Schmidtmann M, Doye S. Angew. Chem. Int. Ed. 2014; 53: 7918
    • 3d Warsitz M, Doye S. Chem. Eur. J. 2020; 26: 15121
    • 3e Lühning LH, Brahms C, Nimoth JP, Schmidtmann M, Doye S. Z. Anorg. Allg. Chem. 2015; 641: 2071
    • 4a Bielefeld J, Mannhaupt S, Schmidtmann M, Doye S. Synlett 2019; 30: 967
    • 4b Kaper T, Fischer M, Warsitz M, Zimmering R, Beckhaus R, Doye S. Chem. Eur. J. 2020; 26: 14300
    • 4c Kaper T, Elma A, Thye H, Knupe-Wolfgang P, Zimmering R, Schmidtmann M, Doye S. Eur. J. Org. Chem. 2022; e202200991
    • 4d Kaper T, Fischer M, Thye H, Geik D, Schmidtmann M, Beckhaus R, Doye S. Chem. Eur. J. 2021; 27: 6899
    • 4e Nuñez Bahena E, Griffin SE, Schafer LL. J. Am. Chem. Soc. 2020; 142: 20566
    • 4f Kaper T, Geik D, Fornfeist F, Schmidtmann M, Doye S. Chem. Eur. J. 2022; 28: e202103931
    • 5a Jensen T, Pedersen H, Bang-Andersen B, Madsen R, Jørgensen M. Angew. Chem. Int. Ed. 2008; 47: 888
    • 5b Shafi S, Kędziorek M, Grela K. Synlett 2011; 124
    • 5c Li W, Liu C, Zhang H, Ye K, Zhang G, Zhang W, Duan Z, You S, Lei A. Angew. Chem. Int. Ed. 2014; 53: 2443
    • 5d Bower JF, Jumnah R, Williams AC, Williams JM. J. J. Chem. Soc., Perkin Trans. 1 1997; 1411
    • 6a Stütz A. Angew. Chem. Int. Ed. Engl. 1987; 26: 320
    • 6b Handal KA, Schauben JL, Salamone FR. Ann. Emerg. Med. 1983; 12: 438
    • 6c Rains CP, Bryson HM, Fitton A. Drugs 1995; 49: 255
  • 7 Prochnow I. Präparative und mechanistische Studien zur titankatalysierten Hydroaminoalkylierung von Alkenen. PhD Thesis. Carl von Ossietzky Universität Oldenburg; Germany: 2014
  • 8 CCDC 2263621 (2), CCDC 2263618 (10·HCl), CCDC 2263620 (15·HCl), and CCDC 2263619 (24) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
  • 9 For details, see the Supporting Information.
    • 10a Yao W, Li R, Jiang H, Han D. J. Org. Chem. 2018; 83: 2250
    • 10b Xi Z, Liu X, Lu J, Bao F, Fan H, Li Z, Takahashi T. J. Org. Chem. 2004; 69: 8547
    • 10c Nicolaou KC, Sorensen EJ. Classics in Total Synthesis: Targets, Strategies, Methods . WILEY-VCH; Weinheim: 2008: 384
  • 11 Lau PW.-K. Reactions of Vinylsilanes and Allylsilanes . PhD Thesis. McGill University; Montreal, Canada: 1978
  • 12 Ross JH, Preuß T, Brahms C, Doye S. Z. Anorg. Allg. Chem. 2014; 640: 118
  • 13 Elkin T, Kulkarni NV, Tumanskii B, Botoshansky M, Shimon LJ. W, Eisen MS. Organometallics 2013; 32: 6337
  • 14 Mills LR, Zhou C, Fung E, Rousseaux SA. L. Org. Lett. 2019; 21: 8805