Synlett 2019; 30(11): 1275-1288
DOI: 10.1055/s-0037-1612257
account
© Georg Thieme Verlag Stuttgart · New York

Cascades Involving anti-Carbopalladation Steps: From Our Initial Hypothesis to Natural Product Synthesis

Theresa Schitter
,
Andreas Reding
,
Daniel B. Werz*
Technische Universität Braunschweig, Institut für Organische Chemie, Hagenring 30, 38106 Braunschweig, Germany   Email: d.werz@tu-braunschweig.de
› Author Affiliations
This research was supported by the Deutsche Forschungsgemeinschaft (DFG grant WE 2932/7-1 to D.B.W.).
Further Information

Publication History

Received: 10 January 2019

Accepted: 30 January 2019

Publication Date:
19 March 2019 (online)


These authors contributed equally to this work.

Abstract

Our endeavors in the design, realization and application of a formal anti-carbopalladation of alkynes are summarized. Whereas numerous examples of syn-carbopalladation steps embedded in cascade reactions are known, there have been almost no examples of the corresponding anti-carbopalladation steps. From a personal perspective, this account provides insights on the original considerations and hypotheses, and their validation or invalidation by experimental and computational means. This account also aims at clarifying how different ideas have been developed and how novel reaction sequences paving the way to a plethora of different scaffolds have been designed. The reader will recognize the importance of the interplay between elucidating reaction mechanisms and developing novel methodologies. As a result, useful methods to create homo- and heterotetrasubstituted double bonds have been developed. The broad versatility of these methods has been demonstrated by a novel total synthesis of the indole alkaloid (+)-lysergol.

1 Introduction

2 Initial Studies

3 Various Termination Steps

4 Termination with Heteronucleophiles

5 Natural Product Synthesis

6 anti-Carbopalladations Realized by the Lautens Lab

7 Conclusion and Outlook

 
  • References

    • 1a Tietze LF. Chem. Rev. 1996; 96: 115
    • 1b Tietze LF, Brasche G, Gericke KM. Domino Reactions in Organic Synthesis, 1st ed. Wiley-VCH; Weinheim: 2006
    • 1c Tietze LF. Domino Reactions: Concepts for Efficient Organic Synthesis. Wiley-VCH; Weinheim: 2014

      For a general overview on carbopalladation reactions in cascades using alkynes, see:
    • 2a Düfert A, Werz DB. Chem. Eur. J. 2016; 22: 16718
    • 2b Ardkhean R, Caputo DF. J, Morrow SM, Shi H, Xiong Y, Anderson EA. Chem. Soc. Rev. 2016; 45: 1557
    • 2c Blouin S, Blond G, Donnard M, Gulea M, Suffert J. Synthesis 2017; 49: 1767
  • 3 Zhang Y, Negishi E. J. Am. Chem. Soc. 1989; 111: 3454
    • 4a Meyer FE, de Meijere A. Synlett 1991; 777
    • 4b Hulot C, Blond G, Suffert J. J. Am. Chem. Soc. 2008; 130: 5046
    • 4c Tietze LF, Düfert A, Lotz F, Sölter L, Oum K, Lenzer T, Beck T, Herbst-Irmer R. J. Am. Chem. Soc. 2009; 131: 17879
    • 4d Hulot C, Amiri S, Blond G, Schreiner PR, Suffert J. J. Am. Chem. Soc. 2009; 131: 13387
    • 4e Leibeling M, Koester DC, Pawliczek M, Schild SC, Werz DB. Nat. Chem. Biol. 2010; 6: 199
    • 4f Leibeling M, Koester DC, Pawliczek M, Kratzert D, Dittrich B, Werz DB. Bioorg. Med. Chem. 2010; 18: 3656
    • 4g Leibeling M, Milde B, Kratzert D, Stalke D, Werz DB. Chem. Eur. J. 2011; 17: 9888
    • 4h Tietze LF, Hungerland T, Eichhorst C, Düfert A, Maaß C, Stalke D. Angew. Chem. Int. Ed. 2013; 52: 3668
    • 4i Wallbaum J, Neufeld R, Stalke D, Werz DB. Angew. Chem. Int. Ed. 2013; 52: 13243
    • 4j Shan D, Gao Y, Jia Y. Angew. Chem. Int. Ed. 2013; 52: 4902
    • 4k Goh SS, Chaubet G, Gockel B, Cordonnier M.-CA, Baars H, Phillips AW, Anderson EA. Angew. Chem. Int. Ed. 2015; 54: 12618
    • 4l Milde B, Leibeling M, Pawliczek M, Grunenberg J, Jones PG, Werz DB. Angew. Chem. Int. Ed. 2015; 54: 1331
    • 4m Milde B, Leibeling M, Hecht A, Visscher A, Stalke D, Jones PG, Grunenberg J, Werz DB. Chem. Eur. J. 2015; 21: 16136
    • 4n Bai L, Yuan Y, Liu J, Wu J, Han L, Wang H, Wang Y, Luan X. Angew. Chem. Int. Ed. 2016; 55: 6946
    • 4o Blouin S, Gandon V, Blond G, Suffert J. Angew. Chem. Int. Ed. 2016; 55: 7208
    • 4p Zuo Z, Wang H, Fan L, Liu J, Wang Y, Luan X. Angew. Chem. Int. Ed. 2017; 56: 2767

      Representative examples for syn-carbopalladations:
    • 5a Leibeling M, Werz DB. Chem. Eur. J. 2012; 18: 6138
    • 5b Leibeling M, Pawliczek M, Kratzert D, Stalke D, Werz DB. Org. Lett. 2012; 14: 346
    • 5c Charpenay M, Boudhar A, Blond G, Suffert J. Angew. Chem. Int. Ed. 2012; 51: 4379
    • 5d Monks BM, Cook SP. J. Am. Chem. Soc. 2012; 134: 15297
    • 5e Leibeling M, Werz DB. Beilstein J. Org. Chem. 2013; 9: 2194
    • 5f Castanheiro T, Donnard M, Gulea M, Suffert J. Org. Lett. 2014; 16: 3060
    • 5g Campbell CD, Greenaway RL, Holton OT, Walker PR, Chapman HA, Russell CA, Carr G, Thomson AL, Anderson EA. Chem. Eur. J. 2015; 21: 12627
    • 5h Li L, Yang Q, Wang Y, Jia Y. Angew. Chem. Int. Ed. 2015; 54: 6255
    • 5i Yoon H, Rölz M, Landau F, Lautens M. Angew. Chem. Int. Ed. 2017; 56: 10920
    • 6a Zhang Y, Wu G, Agnel G, Negishi E. J. Am. Chem. Soc. 1990; 112: 8590
    • 6b Marek I, Chinkov N, Banon-Tenne D. Carbometallation Reactions . In Metal-Catalyzed Cross-Coupling Reactions . de Meijere A, Diederich F. Wiley-VCH; Weinheim: 2004
    • 6c Salem B, Suffert J. Angew. Chem. Int. Ed. 2004; 43: 2826
    • 6d Negishi E, Wang G, Zhu G. Top. Organomet. Chem. 2006; 19: 1
  • 7 Pawliczek M, Schneider TF, Maaß C, Stalke D, Werz DB. Angew. Chem. Int. Ed. 2015; 54: 4119
    • 8a Nakhla JS, Kampf JW, Wolfe JP. J. Am. Chem. Soc. 2006; 128: 2893
    • 8b Fujino D, Yorimitsu H, Oshima K. J. Am. Chem. Soc. 2011; 133: 9682
    • 9a Harayama H, Kuroki T, Kimura M, Tanaka S, Tamaru Y. Angew. Chem. Int. Ed. 1997; 36: 2352
    • 9b Terao Y, Wakui H, Satoh T, Miura M, Nomura M. J. Am. Chem. Soc. 2001; 123: 10407
    • 9c Nishimura T, Araki H, Maeda Y, Uemura S. Org. Lett. 2003; 5: 2997
    • 10a Arcadi A, Cacchi S, Fabrizi G, Marinelli F, Parisi LM. J. Organomet. Chem. 2003; 687: 562
    • 10b Yoshida M, Gotou T, Ihara M. Tetrahedron Lett. 2004; 45: 5573
    • 10c Wei L.-M, Wei L.-L, Pan W.-B, Wu M.-J. Synlett 2005; 2219
    • 11a Dyker G, Kellner A. Tetrahedron Lett. 1994; 35: 7633
    • 11b Abdur Rahman SM, Sonoda M, Itahashi K, Tobe Y. Org. Lett. 2003; 5: 3411
    • 11c Amatore J, Bensalem S, Ghalem S, Jutand A. J. Organomet. Chem. 2004; 689: 4642
    • 11d Le CM, Menzies PJ. C, Petrone DA, Lautens M. Angew. Chem. Int. Ed. 2015; 54: 254
  • 12 For a general overview on Heck reactions, see: Beletskaya IP, Cheprakov AV. Chem. Rev. 2000; 100: 3009
  • 13 Pawliczek M, Jones PG, Werz DB. Eur. J. Org. Chem. 2015; 6278
  • 14 Pawliczek M, Milde B, Jones PG, Werz DB. Chem. Eur. J. 2015; 21: 12303
  • 15 Milde B, Reding A, Geffers FJ, Jones PG, Werz DB. Chem. Eur. J. 2016; 22: 14544

    • For a general overview on Stille reactions, see:
    • 16a Stille JK. Angew. Chem. Int. Ed. 1986; 6: 508
    • 16b Espinet P, Echavarren AM. Angew. Chem. Int. Ed. 2004; 43: 4704
  • 18 Tsui GC, Lautens M. C–H Activation Reactions in Domino Processes. In Domino Reactions: Concepts for Efficient Organic Synthesis. Tietze LF. Wiley-VCH; Weinheim: 2014: 67-103
  • 19 Reding A, Jones PG, Werz DB. Angew. Chem. Int. Ed. 2018; 57: 10610
  • 20 Schitter T, Jones PG, Werz DB. Chem. Eur. J. 2018; 24: 13446
  • 21 Schitter T, Roy NJ, Jones PG, Werz DB. Org. Lett. 2019; 21: 640
  • 22 Reding A, Jones PG, Werz DB. Org. Lett. 2018; 20: 7266
  • 24 Milde B, Pawliczek M, Jones PG, Werz DB. Org. Lett. 2017; 19: 1914
  • 25 Inuki S, Oishi S, Fujii N, Ohno H. Org. Lett. 2008; 10: 5239
  • 26 Yuan H, Guo Z, Luo T. Org. Lett. 2017; 19: 624
    • 27a Le CM, Sperger T, Fu R, Hou X, Lim YH, Schoenebeck F, Lautens M. J. Am. Chem. Soc. 2016; 138: 14441
    • 27b Sperger T, Le CM, Lautens M, Schoenebeck F. Chem. Sci. 2017; 8: 2914
  • 28 Le CM, Hou X, Sperger T, Schoenebeck F, Lautens M. Angew. Chem. Int. Ed. 2015; 54: 15897
  • 29 Petrone DA, Franzoni I, Ye J, Rodríguez JF, Poblador-Bahamonde AI, Lautens M. J. Am. Chem. Soc. 2017; 139: 3546