Synlett 2016; 27(14): 2051-2064
DOI: 10.1055/s-0035-1562095
account
© Georg Thieme Verlag Stuttgart · New York

Direct Imine Acylation: A Versatile Method for the Synthesis of Nitrogen-Containing Heterocycles, Spirocycles and Natural Products

William P. Unsworth*
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK   eMail: william.unsworth@york.ac.uk   eMail: richard.taylor@york.ac.uk
,
Richard J. K. Taylor*
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK   eMail: william.unsworth@york.ac.uk   eMail: richard.taylor@york.ac.uk
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Accepted: 25. Februar 2016

Accepted after revision: 25. März 2016

Publikationsdatum:
10. Mai 2016 (online)


Abstract

Diverse nitrogen-containing heterocyclic compounds can be synthesised by the N-acylation of imines using functionalised carboxylic acids (Direct Imine Acylation, DIA). The carboxylic acids are activated in situ using the coupling agent propylphosphonic acid anhydride (T3P), before reacting with the imine coupling partner to generate N-acyl­iminium ions in situ, that can then be trapped by oxygen-, nitrogen-, sulfur- or carbon-based nucleophiles built into the carboxylic acid. This versatile, convergent method has been used to generate a wide range of products, including aromatic and aliphatic heterocycles, β-lactams, azaspirocycles and natural products.

1 Introduction

2 DIA in the Total Synthesis of ‘Upenamide

3 DIA with Benzoic Acid Derivatives

4 DIA with Aliphatic Carboxylic Acids

5 DIA in the Synthesis of β-Lactams

6 DIA in the Synthesis of Azaspirocycles

7 Mechanistic Studies

8 Conclusion

 
  • References

    • 1a Horton DA, Bourne GT, Smythe ML. Chem. Rev. 2003; 103: 893
    • 1b Comprehensive Heterocyclic Chemistry III . Katritzky AR, Ramsden CA, Scriven EF. V, Taylor RJ. K. Elsevier; Oxford: 2008. ; and references therein.
  • 2 Unsworth WP, Kitsiou C, Taylor RJ. K. Org. Lett. 2013; 15: 258
  • 3 Unsworth WP, Gallagher KA, Jean M, Schmidt JP, Diorazio LJ, Taylor RJ. K. Org. Lett. 2013; 15: 262
  • 4 Unsworth WP, Taylor RJ. K. Org. Biomol. Chem. 2013; 11: 7241
  • 5 Unsworth WP, Coulthard G, Kitsiou C, Taylor RJ. K. J. Org. Chem. 2014; 79: 1368
  • 6 Kitsiou C, Unsworth WP, Coulthard G, Taylor RJ. K. Tetrahedron 2014; 70: 7172
  • 7 Coulthard G, Unsworth WP, Taylor RJ. K. Tetrahedron Lett. 2015; 56: 3113
  • 8 Chambers SJ, Coulthard G, Unsworth WP, O’Brien P, Taylor RJ. K. Chem. Eur. J. 2016; 22: 6496
    • 9a Speckamp WN, Hiemstra H. Tetrahedron 1985; 41: 4367
    • 9b Speckamp WN, Moolenaar MJ. Tetrahedron 2000; 56: 3817
    • 9c Maryanoff BE, Zhang H.-C, Cohen JH, Turchi IJ, Maryanoff CA. Chem. Rev. 2004; 104: 1431
    • 9d Yazici A, Pyne SG. Synthesis 2009; 339
    • 9e Yazici A, Pyne SG. Synthesis 2009; 513
    • 9f Le Quement ST, Petersen R, Meldal M, Nielsen TE. Biopolymers (Pept. Sci.) 2010; 94: 242
    • 9g Daïch A, Ghinet A, Rigo B. Addition to N-Acyliminium Ions of Heteroatoms such as Oxygen Nitrogen Sulfur and Selenium as Internal Nucleophiles. In Comprehensive Organic Synthesis. Molander GA, Knochel P. Elsevier; Oxford: 2014. 2nd ed., Vol. 2 682
  • 10 For the paper on the isolation of ‘upenamide, see: Jiménez JI, Goetz G, Mau CM. S, Yoshida WY, Scheuer PJ, Williamson RT, Kelley M. J. Org. Chem. 2000; 65: 8465

    • For synthetic work towards the synthesis of ‘upenamide prior to the development of DIA, see:
    • 11a Reid M, Taylor RJ. K. Tetrahedron Lett. 2004; 45: 4181
    • 11b Mons S, Malves Maia A, Mons S, Pereira de Freitas Gil R, Marazano C. Eur. J. Org. Chem. 2004; 1057
    • 11c Kiewel K, Luo Z, Sulikowski GA. Org. Lett. 2005; 7: 5163
    • 11d Han JL, Ong CW. Tetrahedron 2007; 63: 609
    • 11e Cayley AN, Cox RJ, Ménard-Moyon C, Schmidt JP, Taylor RJ. K. Tetrahedron Lett. 2007; 48: 6556
    • 11f Ménard-Moyon C, Taylor RJ. K. Eur. J. Org. Chem. 2007; 3698
    • 11g Schmidt JP, Beltran-Rodil S, Cox RJ, McAllister GD, Reid M, Taylor RJ. K. Org. Lett. 2007; 20: 4041
    • 11h Luo Z, Peplowski K, Sulikowski GA. Org. Lett. 2007; 9: 5051
  • 12 Cayley AN, Gallagher KA, Ménard-Moyon C, Schmidt JP, Diorazio LJ, Taylor RJ. K. Synthesis 2008; 3846
    • 13a Ziegler E, Hanus HD. Monatsh. Chem. 1965; 96: 411
    • 13b Ziegler E, Kollenz G, Kappe T. Monatsh. Chem. 1968; 99: 804
    • 13c Kametani T, Higa T, Van Loc C, Ihara M, Koizumi M, Fukumoto K. J. Am. Chem. Soc. 1976; 98: 6186
    • 13d Castagnioli Jr N. J. Org. Chem. 1969; 34: 3187
    • 13e Wang H, Ganesan A. Tetrahedron Lett. 1997; 38: 4327
    • 13f Wang H, Ganesan A. Org. Lett. 1999; 1: 1647
    • 13g Strumberg D, Pommier Y, Paull K, Jayaraman M, Nagafuji P, Cushman M. J. Med. Chem. 1999; 42: 446
    • 13h Sieck O, Ehwald M, Liebscher J. Eur. J. Org. Chem. 2005; 663
    • 13i Chen Z, Hu G, Chen J, Li D, Chen J, Li Y, Zhou H, Xie Y. Bioorg. Med. Chem. 2009; 17: 2351
    • 13j Johannes K, Martens J. Tetrahedron 2010; 66: 242
    • 13k Zarei M. Tetrahedron Lett. 2014; 55: 5354

      For related processes involving the coupling of imines with in situ activated carboxylic acids, see:
    • 14a Smith MW, Hunter R, Patten DJ, Hinz W. Tetrahedron Lett. 2009; 50: 6342
    • 14b Pin F, Comesse S, Daϊch A. Tetrahedron 2011; 67: 5564
  • 15 Successful coupling was also achieved using HATU {1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate} or DCC (N,N'-dicyclohexylcarbodiimide) under the same conditions albeit in lower yield.
  • 16 Wissmann H, Kleiner H.-J. Angew. Chem. Int. Ed. 1980; 19: 133
    • 17a Nakasato T, Asada S, Murai K. J. Pharm. Soc. Jpn. 1962; 82: 619
    • 17b Kobayashi Y, Nakano Y, Kizaki M, Hoshikuma K, Yokoo Y, Kamiya T. Planta Med. 2001; 67: 628
    • 17c Dong G, Sheng CS, Wang S, Miao Z, Yao J, Zhang W. J. Med. Chem. 2010; 53: 7521
  • 18 For a related total synthesis of dievodiamine, see: Unsworth WP, Kitsiou C, Taylor RJ. K. Org. Lett. 2013; 15: 3302
  • 19 Böhme H, Hartke K. Chem. Ber. 1963; 96: 600
    • 20a Schöpf C, Komzak A, Braun F, Jacobi E, Bormuth M.-L, Bullnheimer M, Hagel I. Justus Liebigs Ann. Chem. 1948; 559: 1
    • 20b Barker G, McGrath JL, Klapars A, Stead D, Zhou G, Campos KR, O’Brien P. J. Org. Chem. 2011; 76: 5936
  • 21 For a similar synthesis of related scaffolds by a dearomatisation approach, see: Dannhardt G, Bauer A, Nowe U. J. Prakt. Chem. 1998; 340: 256
  • 22 Surygina O, Ehwald M, Liebscher J. Tetrahedron Lett. 2000; 41: 5479

    • For general considerations on berberine alkaloids, see:
    • 23a Gear JR, Spenser ID. Can. J. Chem. 1963; 41: 783
    • 23b Beecher CW. W, Kelleher WJ. Tetrahedron Lett. 1984; 25: 4595
    • 23c Kobayashi M, Frenzel T, Lee JP, Zenk MH, Floss HG. J. Am. Chem. Soc. 1987; 109: 6184
    • 23d Jendrzejewski S. Phytochemistry 1990; 29: 135
    • 23e Amann M, Nagakura N, Zenk MH. Eur. J. Biochem. 1988; 175: 17
    • 23f Kametani T, Takemura M, Ihara M, Takahashi K, Fukumoto K. J. Am. Chem. Soc. 1976; 98: 1956
    • 23g Jeffs PW, Scharver JD. J. Am. Chem. Soc. 1976; 98: 4301
    • 23h Bhakuni DS, Gusta S, Jain S. Tetrahedron 1983; 39: 4003
    • 23i Grycova L, Dostal J, Marek R. Phytochemistry 2007; 68: 150
    • 23j Niu X.-F, Xu H.-B, Liu X, Fan T, Qi L. Chem. Nat. Compd. 2013; 49: 187
    • 23k Hughes DW, Holland HL, MacLean DB. Can. J. Chem. 1976; 54: 2252

      For the isolation structural assignment and previous syntheses of cavidine, see:
    • 24a Taguchi H, Imaseki I. Yakugaku Zasshi 1964; 84: 955
    • 24b Yu CK, MacLean DB, Rodrigo RG. A, Manske RH. F. Can. J. Chem. 1970; 48: 3673
    • 24c Ninomiya I, Takasugi H, Naito T. Heterocycles 1973; 1: 17
    • 24d Ninomiya I, Naito T, Takasugi H. J. Chem. Soc., Perkin Trans. 1 1975; 1791
    • 24e Iwasa K, Gupta YP, Cushman M. J. Org. Chem. 1981; 46: 4744
    • 24f Bhakuni DS, Jain S, Gupta S. Tetrahedron 1986; 42: 675
  • 25 For a recent publication of similar scaffolds by a Redox-Mannich approach, see: Ma L, Seidel D. Chem. Eur. J. 2015; 21: 12908
  • 26 For a more recent synthesis of similar N,O-acetal scaffolds by a similar approach, see: Shymanska NV, An IH, Pierce JG. Angew. Chem. Int. Ed. 2014; 53: 540
  • 27 Ohno K, Ueki T, Fushikida K, Okita T, Komori S, Tazawa Y, Kumakura Y, Izakura K. WO Patent 2013/061973, 2013
  • 28 Verma A, Saraf SK. Eur. J. Med. Chem. 2008; 43: 897

    • For alternative syntheses of similar scaffolds, see:
    • 29a Johnson MR, Fazio MJ, Ward DL, Sousa LR. J. Org. Chem. 1983; 48: 494
    • 29b Jarvis CL, Richers MT, Breugst M, Houk KN, Seidel D. Org. Lett. 2014; 16: 3556
    • 29c Wen L.-R, Yuan W.-K, Li MI. J. Org. Chem. 2015; 50: 4942
    • 30a Iwasa K, Gupta YP, Cushman M. J. Org. Chem. 1981; 46: 4744
    • 30b Herlé B, Wanner MJ, van Maarseveen JH, Hiemstra H. J. Org. Chem. 2011; 76: 8907
    • 30c Cao M, Muganga R, Tits M, Angenot L, Frederich M. Planta Med. 2011; 77: 2050
  • 31 Negoro T, Murata M, Ueda S, Fujitani B, Ono Y, Kuromiya A, Komiya M, Suzuki K, Matsumoto J. J. Med. Chem. 1998; 41: 4118
    • 32a The Organic Chemistry of β-Lactams . Georg GI. Verlag Chemie; New York: 1993
    • 32b Broccolo F, Cainelli G, Caltabiano G, Cocuzza CE. A, Fortuna CG, Galletti P, Giacomini D, Musumarra G, Musumeci R, Quintavalla A. J. Med. Chem. 2006; 49: 2804
  • 33 King AM, Reid-Yu SA, Wang W, King DT, De Pascale G, Strynadka NC, Walsh TR, Coombes BK, Wright GD. Nature 2014; 510: 503
    • 34a D’hooghe M, Dekeukeleire S, Mollet K, Lategan C, Smith PJ, Chibale K, De Kimpe N. J. Med. Chem. 2009; 52: 4058
    • 34b D’hooghe M, Mollet K, De Vreese R, Jonckers TH. M, Dams G, De Kimpe N. J. Med. Chem. 2012; 55: 5637

      For selected relevant examples and stereochemical studies, see:
    • 35a Staudinger H. Justus Liebigs Ann. Chem. 1907; 356: 51
    • 35b Cossío FP, Arrieta A, Sierra MA. Acc. Chem. Res. 2008; 41: 925
    • 35c Crichfield KS, Hart JE, Lampert JT, Vaid RK. Synth. Commun. 2000; 30: 3737
    • 35d Zarei M. Monatsh. Chem. 2014; 145: 1495
    • 35e Jiao L, Liang Y, Xu J. J. Am. Chem. Soc. 2006; 128: 6060
    • 36a Carreira EM, Fessard TC. Chem. Rev. 2014; 114: 8257
    • 36b Hung AW, Ramek A, Wang Y, Kaya T, Wilson JA, Clemons PA, Young DW. Proc. Natl. Acad. Sci. U. S. A. 2011; 108: 6799
    • 36c Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
    • 36d Zheng Y, Tice CM, Singh SB. Bioorg. Med. Chem. Lett. 2014; 24: 3673
    • 36e James MJ, O’Brien P, Taylor RJ. K, Unsworth WP. Chem. Eur. J. 2016; 22: 2856
    • 37a Reymond J.-L, van Deursen R, Blum LC, Ruddigkeit L. MedChemComm 2010; 1: 30
    • 37b Reymond J.-L, Awale M. ACS Chem. Neurosci. 2012; 3: 649
    • 37c Hung W, Ramek A, Wang Y, Kaya T, Wilson JA, Clemons PA, Young DW. Proc. Natl. Acad. Sci. U. S. A. 2011; 108: 6799

      For recent dearomatisation reactions, see:
    • 38a Wu Q.-F, Zheng C, You S.-L. Angew. Chem. Int. Ed. 2012; 51: 1680
    • 38b Gao RD, Liu C, Dai L.-X, Zhang W, You S.-L. Org. Lett. 2014; 16: 3919
    • 38c Zhu Y, Rawal VH. J. Am. Chem. Soc. 2012; 134: 111
    • 38d James MJ, Cuthbertson JD, O’Brien P, Taylor RJ. K, Unsworth WP. Angew. Chem. Int. Ed. 2015; 54: 7640
    • 38e James MJ, Clubley RE, Palate KY, Procter TJ, Wyton AC, O’Brien P, Taylor RJ. K, Unsworth WP. Org. Lett. 2015; 17: 4372
    • 38f Liddon JT. R, James MJ, Clarke AK, O’Brien P, Taylor RJ. K, Unsworth WP. Chem. Eur. J. 2016; DOI: 10.1002/chem.201601836.
  • 39 For a recent example of a spirocyclisation method using N-acyliminium ion intermediates, see: Ledovskaya MS, Stepakov AV, Molchanov AP, Kostikov RR. Tetrahedron 2015; 71: 7562
  • 40 Dömling A, Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168
  • 41 Kitsiou C, Hindes JJ, I’Anson P, Jackson P, Wilson TC, Daly EK, Felstead HR, Hearnshaw P, Unsworth WP. Angew. Chem. Int. Ed. 2015; 54: 15794
  • 42 Efforts towards the total synthesis of berberine alkaloid pallimamine (Sheng-Teh, L.; Jeng-Fen, H.; Tian-Shung, W.; McPhail, D. R.; McPhail, A. T.; Lee, K-H. Phytochemistry 1989, 28, 1245) have recently been accepted for publication: Synthetic Approaches to Pallimamine and Analogues using Direct Imine Acylation; Ronson, T. O.; Kitsiou, C.; Taylor, R. J. K.; Unsworth, W. P. Tetrahedron, in press.