Synthesis 2018; 50(20): 3974-3996
DOI: 10.1055/s-0037-1609941
review
© Georg Thieme Verlag Stuttgart · New York

Retaining Alkyl Nucleophile Regiofidelity in Transition-Metal-Mediated Cross-Couplings to Aryl Electrophiles

Matthew O’Neill
,
Josep Cornella*
Department of Organometallic Chemistry, Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany   Email: cornella@kofo.mpg.de
› Author Affiliations
We would like to thank the Max-Planck-Gesellschaft, Max-Planck-Institute für Kohlenforschung, and the Fulbright Kommission (M.J.O).
Further Information

Publication History

Received: 11 June 2018

Accepted after revision: 01 August 2018

Publication Date:
10 September 2018 (online)


Abstract

While the advent of transition-metal catalysis has undoubtedly transformed synthetic chemistry, problems persist with the introduction of secondary and tertiary alkyl nucleophiles into C(sp2) aryl electrophiles. Complications arise from the delicate organometallic intermediates typically invoked by such processes, from which competition between the desired reductive elimination event and the deleterious β-H elimination pathways can lead to undesired isomerization of the incoming nucleophile. Several methods have integrated distinct combinations of metal, ligand, nucleophile, and electrophile to provide solutions to this problem. Despite substantial progress, refinements to current protocols will facilitate the realization of complement reactivity and improved functional group tolerance. These issues have become more pronounced in the context of green chemistry and sustainable catalysis, as well as by the current necessity to develop robust, reliable cross-couplings beyond less explored C(sp2)–C(sp2) constructs. Indeed, the methods discussed herein and the elaborations thereof enable an ‘unlocking’ of accessible topologically enriched chemical space, which is envisioned to influence various domains of application.

1 Introduction

2 Mechanistic Considerations

3 Magnesium Nucleophiles

4 Zinc Nucleophiles

5 Boron Nucleophiles

6 Other Nucleophiles

7 Tertiary Nucleophiles

8 Reductive Cross-Coupling with in situ Organometallic Formation

9 Conclusion

 
  • References

  • 1 Gerry CJ. Schreiber SL. Nat. Rev. Drug Discovery 2018; 17: 333
  • 2 Newhouse T. Baran PS. Hoffmann RW. Chem. Soc. Rev. 2009; 38: 3010
    • 5a Whitesides GM. Angew. Chem. Int. Ed. 2015; 54: 3196
    • 5b Whitesides GM. Isr. J. Chem. 2018; 58: 142
    • 6a Rudolph A. Lautens M. Angew. Chem. Int. Ed. 2009; 48: 2656
    • 6b Hammann JM. Hofmayer MS. Lutter FH. Thomas L. Knochel P. Synthesis 2017; 49: 3887
  • 7 For an early review, see: Organotransition Metal Chemistry: A Mechanistic Approach. Heck RF. Academic Press; New York: 2004
  • 8 Science of Synthesis: Cross Coupling and Heck-Type Reactions . Molander GA. Wolfe JP. Larhed M. Georg Thieme Verlag KG; Stuttgart: 2013. Vol: 1-3
  • 9 Cherney AH. Kadunce NT. Reisman SE. Chem. Rev. 2015; 115: 9587
  • 10 O’Reilly ME. Dutta S. Veige AS. Chem. Rev. 2016; 116: 8105
  • 11 Heck RF. Organotransition Metal Chemistry: A Mechanistic Approach. Academic Press; New York: 1974
    • 12a Vasseur A. Bruffaerts J. Marek I. Nat. Chem. 2016; 8: 209
    • 12b Sommer H. Julia-Hernandez F. Martin R. Marek I. ACS Cent. Sci. 2018; 4: 153
  • 13 Labadie JW. Stille JK. J. Am. Chem. Soc. 1983; 105: 6129
  • 14 Levin MD. Kim S. Toste FD. ACS Cent. Sci. 2016; 2: 293
  • 15 Ni- and Fe-Based Cross-Coupling Reactions . In Topics in Current Chemistry . Correa A. Springer International Publishing; Cham: 2017
  • 16 Kagan HB. Angew. Chem. Int. Ed. 2012; 51: 7376
  • 17 Kharasch MS. Reinmuth O. Grignard Reactions of Nonmetallic Substances . Prentice-Hall; Englewood Cliffs (NJ): 1954: 122-137
  • 18 Tamao K. J. Organomet. Chem. 2002; 653: 23
  • 19 Tamao K. Sumitani K. Kumada M. J. Am. Chem. Soc. 1972; 94: 4374
  • 20 Corriu RJ. P. Masse JP. J. Chem. Soc., Chem. Commun. 1972; 144
  • 21 Tamao K. Kiso Y. Sumitani K. Kumada M. J. Am. Chem. Soc. 1972; 94: 9268
  • 22 Hayashi T. Konishi M. Kobori Y. Kumada M. Higuchi T. Kirotsu K. J. Am. Chem. Soc. 1984; 106: 158
    • 23a Fürstner A. ACS. Cent. Sci. 2016; 2: 778
    • 23b Piontek A. Bisz E. Szostak M. Angew. Chem. Int. Ed. 2018; 130: 2
  • 24 Fürstner A. Leitner A. Mendez M. Krause H. J. Am. Chem. Soc. 2002; 124: 13856
  • 25 Kanemura S. Kondoh A. Yorimitsu H. Oshima K. Synthesis 2008; 2659
  • 26 Kranenburg M. Kamer PC. J. van Leewen PW. N. M. Eur. J. Inorg. Chem. 1998; 155
  • 27 Perry M. Gillett AN. Law TC. Tetrahedron Lett. 2012; 53: 4436
  • 28 Agrawal T. Cook SP. Org. Lett. 2013; 15: 96
  • 29 Guo W.-J. Wang Z.-X. Tetrahedron 2013; 69: 9580
  • 30 Agata R. Iwamoto T. Nakagawa N. Isozaki K. Hatakeyama T. Takaya H. Nakamura M. Synthesis 2015; 47: 1733
  • 31 Chen X. Quan Z.-J. Wang X.-C. Appl. Organomet. Chem. 2015; 29: 296
  • 32 Li Z. Liu L. Sun H.-m. Shen Q. Zhang Y. Dalton Trans. 2016; 45: 17739
  • 33 Sanderson JN. Dominey AP. Percy JM. Adv. Synth. Catal. 2017; 359: 1007
  • 34 Piontek A. Szostak M. Eur. J. Org. Chem. 2017; 7271
  • 35 Bisz E. Szostak M. Green Chem. 2017; 19: 5361
  • 36 O’Neill MJ. Riesebeck T. Cornella J. Angew. Chem. Int. Ed. 2018; 57: 9103
  • 37 Haas D. Hammann JM. Greiner R. Knochel P. ACS Catal. 2016; 6: 1540
  • 38 Negishi E. Valente LF. Kobayashi M. J. Am. Chem. Soc. 1980; 102: 3298
  • 39 For a comprehensive coverage of alkylzinc reagents in cross-couplings, see: Li L. Biscoe MR. Alkylzinc Cross-Coupling Reactions . In Science of Synthesis: Cross-Coupling and Heck-Type Reactions 1 . Molander GA. Georg Thieme Verlag KG; Stuttgart: 2013: 795-838
  • 40 McCann LC. Organ MG. Angew. Chem. Int. Ed. 2014; 53: 4386
  • 41 Schlosser M. Organometallics in Synthesis: A Manual . Wiley-VCH; New York: 2002
  • 42 McCann LC. Hunter HN. Clyburne JA. C. Organ MG. Angew. Chem. Int. Ed. 2012; 124: 7130
    • 43a Thaler T. Haag B. Gavryushin A. Schober K. Hartmann E. Gschwind RM. Zipse H. Mayer P. Knochel P. Nat. Chem. 2010; 2: 125
    • 43b Moriya K. Knochel P. Org. Lett. 2014; 16: 924
  • 44 Melzig L. Gavryushin A. Knochel P. Org. Lett. 2007; 9: 5529
  • 45 Nataoka N. Shelby Q. Stambuli JP. Hartwig JF. J. Org. Chem. 2002; 67: 5553
  • 46 Han C. Buchwald SL. J. Am. Chem. Soc. 2009; 131: 7532
  • 47 Yang Y. Niedermann K. Han C. Buchwald SL. Org. Lett. 2014; 16: 4638
  • 48 Phapale VB. Guisan-Ceinos M. Bunuel E. Cardenas DJ. Chem. Eur. J. 2009; 15: 12681
  • 49 Joshi-Pangu A. Ganesh M. Biscoe MR. Org. Lett. 2011; 13: 1218
  • 50 Froese RD. J. Lombardi C. Pompeo M. Rucker RP. Organ MG. Acc. Chem. Res. 2017; 50: 2244
  • 51 Pompeo M. Froese RD. J. Hadei N. Organ MG. Angew. Chem. Int. Ed. 2012; 124: 11516
  • 52 Atwater B. Chandrasoma N. Mitchell D. Rodriguez MJ. Organ MG. Chem. Eur. J. 2016; 22: 14531
  • 53 Price GA. Hassan A. Chandrasoma N. Bogdan AR. Djuric SW. Organ MG. Angew. Chem. Int. Ed. 2017; 56: 13347
  • 54 Kalvet I. Sperger T. Scattolin T. Magnin G. Schoenebeck F. Angew. Chem. Int. Ed. 2017; 56: 7078
  • 55 Brown DG. Boström J. J. Med. Chem. 2016; 59: 4443
  • 56 Lennox AJ. J. Lloyd-Jones GC. Chem. Soc. Rev. 2014; 43: 412

    • For excellent reviews, see:
    • 57a Crudden CM. Glasspoole BW. Lata CJ. Chem. Commun. 2009; 6704
    • 57b Doucet H. Eur. J. Org. Chem. 2008; 2013
    • 57c Leonori D. Aggarwal VK. Angew. Chem. Int. Ed. 2015; 54: 1082

      For examples not involving transition metals, see:
    • 58a Bonet A. Odachowski M. Leonori D. Essafi S. Aggarwal V. Nat. Chem. 2014; 6: 584
    • 58b Matsui JK. Primer DN. Molander GA. Chem. Sci. 2017; 8: 3512
  • 59 Rygus JP. G. Crudden CM. J. Am. Chem. Soc. 2017; 139: 18124
  • 60 Hildebrand JP. Marsden SP. Synlett 1996; 893
  • 61 Wang X.-Z. Deng M.-Z. J. Chem. Soc., Perkin Trans. 1 1996; 2663
  • 62 Rubina M. Rubin M. Gevorgyan V. J. Am. Chem. Soc. 2003; 125: 7198
  • 63 Imao D. Glasspoole BW. Laberge VS. Crudden CM. J. Am. Chem. Soc. 2009; 131: 5024
  • 64 Littke AF. Dai C. Fu GC. J. Am. Chem. Soc. 2000; 122: 4020
  • 65 Kataoka N. Shelby Q. Stambuli JP. Hartwig JF. J. Org. Chem. 2002; 67: 5553
  • 66 van den Hoogenband A. Lange JH. M. Terpstra JW. Koch M. Visser GM. Visser M. Korstanje TJ. Jastrzebski JT. B. H. Tetrahedron Lett. 2008; 49: 4122
  • 67 Dreher SD. Dormer PG. Sandrock DL. Molander GA. J. Am. Chem. Soc. 2008; 130: 9257
  • 68 Sandrock DL. Jean-Gerard L. Chen C.-y. Dreher SD. Molander GA. J. Am. Chem. Soc. 2010; 132: 17108
  • 69 Li L. Zhao S. Joshi-Pangu A. Diane M. Biscoe MR. J. Am. Chem. Soc. 2014; 136: 14027
  • 70 Li C. Xiao G. Zhao Q. Liu H. Wang T. Tang W. Org. Chem. Front. 2014; 1: 225
  • 71 Li C. Chen T. Li B. Xiao G. Tang W. Angew. Chem. Int. Ed. 2015; 54: 3792
  • 72 Si T. Li B. Xiong W. Xu B. Tang W. Org. Biomol. Chem. 2017; 15: 9903
  • 73 Tellis JC. Kelly CB. Primer DN. Jouffroy M. Patel NR. Molander GA. Acc. Chem. Res. 2016; 49: 1429
  • 74 Tellis JC. Primer DN. Molander GA. Science 2014; 345: 6195
  • 75 Primer DN. Karakaya I. Tellis JC. Molander GA. J. Am. Chem. Soc. 2015; 137: 2195
  • 76 Giannerini M. Fananas-Mastral M. Feringa BL. Nat. Chem. 2013; 5: 667
  • 77 Vila C. Giannerini M. Hornillos V. Fananas-Mastral M. Feringa BL. Chem. Sci. 2014; 5: 1361
  • 78 Heijnen D. Gualtierotti JB. Hornillos V. Feringa BL. Chem. Eur. J. 2016; 22: 3991
  • 79 Denmark S. Chang W.-TT. Alkylsilicon Cross-Coupling Reactions . In Science of Synthesis: Cross-Coupling and Heck-Type Reactions 1 . Molander GA. Georg Thieme Verlag KG; Stuttgart: 2013: 495-510
  • 80 Nakao Y. Takeda M. Matsumoto T. Hiyama T. Angew. Chem. Int. Ed. 2010; 49: 4447
  • 81 Corce V. Chamoreau L.-M. Derat E. Goddard J.-P. Ollivier C. Fensterbank L. Angew. Chem. Int. Ed. 2015; 54: 11414
  • 82 Jouffroy M. Primer DN. Molander GA. J. Am. Chem. Soc. 2016; 138: 475
  • 83 Lin K. Wiles RJ. Kelly CB. Davies GH. M. Molander GA. ACS Catal. 2017; 7: 5129
  • 84 Giustra ZX. Liu S.-Y. J. Am. Chem. Soc. 2018; 140: 1184
  • 85 Juoffroy M. Davies GH. M. Molander GA. Org. Lett. 2016; 18: 1606
  • 86 Cordovilla C. Bartolome C. Martiney-Ilarduza JM. Espinet P. ACS Catal. 2015; 5: 3040
  • 87 For an excellent overview of organotin cross-couplings, see Pitaval A. Echavarren AM. Organotin Cross-Coupling Reactions . In Cross Coupling and Heck-Type Reactions 1 . Molander GA. Georg Thieme Verlag KG; Stuttgart: 2013: 527-622
  • 88 Milstein D. Stille JK. J. Am. Chem. Soc. 1979; 101: 4992
  • 89 Vedejs E. Haight AR. Moss WO. J. Am. Chem. Soc. 1992; 114: 6556
  • 90 Li L. Wang C.-Y. Huang R. Biscoe MR. Nat. Chem. 2013; 5: 607
  • 91 Shrestha B. Thapa S. Gurung SK. Pike RA. S. Giri R. J. Org. Chem. 2016; 81: 787
  • 92 Liu X. Hsiao C.-C. Kalvet I. Leiendecker M. Guo L. Schoenebeck F. Rueping M. Angew. Chem. Int. Ed. 2016; 55: 6093
  • 93 Zhao K. Shen L. Shen Z.-L. Loh T.-P. Chem. Soc. Rev. 2017; 46: 586
  • 94 Thapa S. Gurung SK. Dickie DA. Giri R. Angew. Chem. Int. Ed. 2014; 53: 11620
  • 95 Joshi-Pangu A. Biscoe MR. Synlett 2012; 23: 1103
  • 96 Hintermann L. Xiao L. Labonne A. Angew. Chem. Int. Ed. 2008; 47: 8246
  • 97 Lohre C. Dröge T. Wang C. Glorius F. Chem. Eur. J. 2011; 17: 6052
    • 98a Yoshikai N. Matsuda H. Nakamura E. J. Am. Chem. Soc. 2009; 131: 9590
    • 98b Yoshikai N. Matsuda H. Nakamura E. J. Am. Chem. Soc. 2008; 130: 15258
  • 99 Joshi-Pangu A. Wang C.-Y. Biscoe MR. J. Am. Chem. Soc. 2011; 133: 8478
  • 100 Ando S. Mawatari M. Matsunaga H. Ishizuka T. Tetrahedron Lett. 2016; 57: 3287
  • 101 Tasker SZ. Standley EA. Jamison TF. Nature 2014; 509: 299
  • 102 Harris MR. Li Q. Lian Y. Xiao J. Londregan AT. Org. Lett. 2017; 19: 2450
  • 103 Thapa S. Kafle A. Gurung SK. Montoya A. Riedel P. Giri R. Angew. Chem. Int. Ed. 2015; 54: 8236
  • 104 Primer DN. Molander GA. J. Am. Chem. Soc. 2017; 139: 9847
  • 105 Everson DA. Weix DJ. J. Org. Chem. 2014; 79: 4793
  • 106 Hansen EC. Li C. Yang S. Pedro D. Weix DJ. J. Org. Chem. 2017; 82: 7085
  • 107 Czaplik WM. Mayer M. von Wangelin AJ. Angew. Chem. Int. Ed. 2009; 48: 607
  • 108 Bogdanovic B. Schwickardi M. Angew. Chem. Int. Ed. 2000; 39: 4610
  • 109 Krasovskiy A. Duplais C. Lipshutz BH. J. Am. Chem. Soc. 2009; 131: 15592
  • 110 Duplais C. Krasovskiy A. Lipshutz BH. Organometallics 2011; 30: 6090
  • 111 Zhang K.-F. Christoffel F. Baudoin O. Angew. Chem. Int. Ed. 2018; 57: 1982