Synlett 2017; 28(16): 2057-2065
DOI: 10.1055/s-0036-1589077
synpacts
© Georg Thieme Verlag Stuttgart · New York

Regioselective Hydroamination Using a Directed Nucleopalladation/Protodepalladation Strategy

John A. Gurak Jr, Keary M. Engle*
  • Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA   Email: keary@scripps.edu
We gratefully acknowledge TSRI and Pfizer, Inc. for financial support, as well as the Donald E. and Delia B. Baxter Foundation and the National Science Foundation (NSF/DGE-1346837) for predoctoral fellowships (J.A.G.)
Further Information

Publication History

Received: 15 May 2017

Accepted after revision: 21 June 2017

Publication Date:
02 August 2017 (eFirst)

Abstract

Alkene hydroamination is an attractive approach for converting alkenes into structurally complex amine products. Several different strategies have been pursued over the past few decades to achieve this historically challenging reaction. One of the key issues associated with this transformation is control of regioselectivity, which is particularly difficult for internal non-conjugated alkenes. Our group has recently found success using a removable bidentate auxiliary to control regioselectivity and stabilize the key nucleopalladated intermediate in a palladium(II)-catalyzed alkene hydroamination with N–H nucleophiles. This article describes the historical context for this work, the underlying conceptual logic, our results to date, and the future outlook.

 
  • References and Notes


    • For reviews on alkene hydroamination, see:
    • 1a Müller TE. Beller M. Chem. Rev. 1998; 98: 675
    • 1b Müller TE. Hultzsch KC. Yus M. Foubelo F. Tada M. Chem. Rev. 2008; 108: 3795
    • 1c Hesp KD. Stradiotto M. ChemCatChem 2010; 2: 1192
    • 1d Nishina N. Yamamoto Y. Top. Organomet. Chem. 2013; 43: 115
    • 1e Bernoud E. Lepori C. Mellah M. Schulz E. Hannedouche J. Catal. Sci. Technol. 2015; 5: 2017
    • 1f Huang L. Arndt M. Gooßen K. Heydt H. Gooßen LJ. Chem. Rev. 2015; 115: 2596
    • 1g Lepori C. Hannedouche J. Synthesis 2017; 49: 1158
  • 2 Johns AM. Sakai N. Ridder A. Hartwig JF. J. Am. Chem. Soc. 2006; 128: 9306

    • For selected examples of alkene hydroamination reactions catalyzed by CuH species, see:
    • 3a Miki Y. Hirano K. Satoh T. Miura M. Angew. Chem. Int. Ed. 2013; 52: 10830
    • 3b Zhu S. Niljianskul N. Buchwald SL. J. Am. Chem. Soc. 2013; 135: 15746
    • 3c Zhu S. Buchwald SL. J. Am. Chem. Soc. 2014; 136: 15913
    • 3d Yang Y. Shi S.-L. Niu D. Liu P. Buchwald SL. Science 2015; 349: 62
    • 3e Pirnot MT. Wang Y.-M. Buchwald SL. Angew. Chem. Int. Ed. 2016; 55: 48
    • 3f Xi Y. Butcher TW. Zhang J. Hartwig JF. Angew. Chem. Int. Ed. 2016; 55: 776

    • For related examples with Pd, see:
    • 3g Xu T. Qiu S. Liu G. J. Organomet. Chem. 2011; 696: 46
    • 3h Yu F. Chen P. Liu G. Org. Chem. Front. 2015; 2: 819

      For selected examples of hydrogen atom transfer (HAT) alkene hydroamination reactions, see:
    • 4a Kato K. Mukaiyama T. Chem. Lett. 1992; 1137
    • 4b Waser J. Nambu H. Carreira EM. J. Am. Chem. Soc. 2005; 127: 8294
    • 4c Leggans EK. Barker TJ. Duncan KK. Boger DL. Org. Lett. 2012; 14: 1428
    • 4d Gui J. Pan C.-M. Jin Y. Qin T. Lo JC. Lee BJ. Spergel SH. Mertzman ME. Pitts WJ. La Cruz TE. Schmidt MA. Darvatkar N. Natarajan SR. Baran PS. Science 2015; 348: 886

      For selected examples of intermolecular alkene hydroamination reactions involving aminometalation using metals other than palladium, see:
    • 5a Beller M. Trauthwein H. Eichberger M. Breindl C. Herwig J. Müller TE. Thiel OR. Chem. Eur. J. 1999; 5: 1306
    • 5b Utsunomiya M. Kuwano R. Kawatsura M. Hartwig JF. J. Am. Chem. Soc. 2003; 125: 5608
    • 5c Utsunomiya M. Hartwig JF. J. Am. Chem. Soc. 2004; 126: 2702
    • 5d Wang X. Widenhoefer RA. Organometallics 2004; 23: 1649
    • 5e Karshtedt D. Bell AT. Tilley TD. J. Am. Chem. Soc. 2005; 127: 12640
    • 5f Pan S. Endo K. Shibata T. Org. Lett. 2012; 14: 780
    • 5g Sevov CS. Zhou J. Hartwig JF. J. Am. Chem. Soc. 2012; 134: 11960
    • 5h Sevov CS. Zhou J. Hartwig JF. J. Am. Chem. Soc. 2014; 136: 3200
    • 6a Nishina N. Yamamoto Y. Angew. Chem. Int. Ed. 2006; 45: 3314
    • 6b Timmerman JC. Robertson BD. Widenhoefer RA. Angew. Chem. Int. Ed. 2015; 54: 2251
    • 6c Blieck R. Bahri J. Taillefer M. Monnier F. Org. Lett. 2016; 18: 1482
    • 6d Perego LA. Blieck R. Groué A. Monnier F. Taillefer M. Ciofini I. Grimaud L. ACS Catal. 2017; 7: 4253

      Several examples of intermolecular hydroamination of conjugated alkenes catalyzed by palladium–phosphine complexes have been described. A commonly invoked mechanistic paradigm for these transformations involves oxidative addition of Pd(0) to HX, followed by hydropalladation to generate a π-allyl (or analogous) intermediate, and finally attack of the nitrogen nucleophile:
    • 7a Al-Masum M. Meguro M. Yamamoto Y. Tetrahedron Lett. 1997; 38: 6071
    • 7b Kawatsura M. Hartwig JF. J. Am. Chem. Soc. 2000; 122: 9546
    • 7c Johns AM. Utsunomiya M. Incarvito CD. Hartwig JF. J. Am. Chem. Soc. 2006; 128: 1828
    • 7d Johns AM. Liu Z. Hartwig JF. Angew. Chem. Int. Ed. 2007; 46: 7259
    • 7e Banerjee D. Junge K. Beller M. Org. Chem. Front. 2014; 1: 368
  • 8 For a two-step catalytic approach involving Wacker oxidation followed by reductive amination, see: Bronner SM. Grubbs RH. Chem. Sci. 2014; 5: 101

    • For selected examples of photoredox alkene hydroamination reactions, see:
    • 9a Yasuda M. Kojima R. Tsutsui H. Utsunomiya D. Ishii K. Jinnouchi K. Shiragami T. Yamashita T. J. Org. Chem. 2003; 68: 7618
    • 9b Nguyen TM. Nicewicz DA. J. Am. Chem. Soc. 2013; 135: 9588
    • 9c Musacchio AJ. Nguyen LQ. Beard GH. Knowles RR. J. Am. Chem. Soc. 2014; 136: 12217
    • 9d Nguyen TM. Manohar N. Nicewicz DA. Angew. Chem. Int. Ed. 2014; 53: 6198
    • 9e Davies J. Svejstrup TD. Reina DF. Sheikh NS. Leonori D. J. Am. Chem. Soc. 2016; 138: 8092
    • 9f Musacchio AJ. Lainhart BC. Zhang X. Naguib SG. Sherwood TC. Knowles RR. Science 2017; 355: 727
    • 9g For a related radical approach, see: Guin J. Mück-Lichtenfeld C. Grimme S. Studer A. J. Am. Chem. Soc. 2007; 129: 4498

      For selected examples of Cope type hydroamination reactions, see:
    • 10a Gravestock MB. Knight DW. Thornton SR. J. Chem. Soc., Chem. Commun. 1993; 169
    • 10b Bell KE. Coogan MP. Gravestock MB. Knight DW. Thornton SR. Tetrahedron Lett. 1997; 38: 8545
    • 10c Gravestock MB. Knight DW. Abdul Malik KM. Thornton SR. J. Chem. Soc., Perkin Trans. 1 2000; 3292
    • 10d Beauchemin AM. Moran J. Lebrun M.-E. Séguin C. Dimitrijevic E. Zhang L. Gorelsky SI. Angew. Chem. Int. Ed. 2008; 47: 1410
    • 10e Moran J. Gorelsky SI. Dimitrijevic E. Lebrun M.-E. Bédard A.-C. Séguin C. Beauchemin AM. J. Am. Chem. Soc. 2008; 130: 17893
    • 10f MacDonald MJ. Schipper DJ. Ng PJ. Moran J. Beauchemin AM. J. Am. Chem. Soc. 2011; 133: 20100
    • 10g Zhao S.-B. Bilodeau E. Lemieux V. Beauchemin AM. Org. Lett. 2012; 14: 5082
    • 10h Beauchemin AM. Org. Biomol. Chem. 2013; 11: 7039
    • 10i Brown AR. Uyeda C. Brotherton CA. Jacobsen EN. J. Am. Chem. Soc. 2013; 135: 6747

      For reviews on nucleopalladation, see:
    • 11a Jensen KH. Sigman MS. Org. Biomol. Chem. 2008; 6: 4083
    • 11b McDonald RI. Liu G. Stahl SS. Chem. Rev. 2011; 111: 2981

    • For selected examples of catalytic reactions involving nucleopalladation, see:
    • 11c Jensen KH. Pathak TP. Zhang Y. Sigman MS. J. Am. Chem. Soc. 2009; 131: 17074
    • 11d Martínez C. Muñiz K. Angew. Chem. Int. Ed. 2012; 51: 7031
    • 11e Weinstein AB. Stahl SS. Angew. Chem. Int. Ed. 2012; 51: 11505
    • 11f Joosten A. Persson AK. Å. Millet R. Johnson MT. Bäckvall J.-E. Chem. Eur. J. 2012; 18: 15151
    • 11g Dong JJ. Harvey EC. Fañanás-Mastral M. Browne WR. Feringa BL. J. Am. Chem. Soc. 2014; 136: 17302
    • 11h Fornwald RM. Fritz JA. Wolfe JP. Chem. Eur. J. 2014; 20: 8782
    • 11i White DR. Hutt JT. Wolfe JP. J. Am. Chem. Soc. 2015; 137: 11246

      For reviews on Wacker oxidation, see:
    • 12a Takacs JM. Jiang X. Curr. Org. Chem. 2003; 7: 369
    • 12b Keith JA. Henry PM. Angew. Chem. Int. Ed. 2009; 48: 9038
    • 12c Dong JJ. Browne WR. Feringa BL. Angew. Chem. Int. Ed. 2015; 54: 734
    • 13a Paiaro G. De Renzi A. Palumbo R. Chem. Commun. 1967; 1150
    • 13b Åkermark B. Bäckvall JE. Hegedus LS. J. Organomet. Chem. 1974; 72: 127

      For reviews on aza-Wacker reactions, see:
    • 14a Kotov V. Scarborough CC. Stahl SS. Inorg. Chem. 2007; 46: 1910
    • 14b Minatti A. Muñiz K. Chem. Soc. Rev. 2007; 36: 1142

    • For pioneering reports on intermolecular aza-Wacker reactions, see:
    • 14c Liu G. Stahl SS. J. Am. Chem. Soc. 2006; 128: 7179
    • 14d Liu G. Stahl SS. J. Am. Chem. Soc. 2007; 129: 6328
    • 15a Bozell JJ. Hegedus LS. J. Org. Chem. 1981; 46: 2561
    • 15b Hegedus LS. McKearin JM. J. Am. Chem. Soc. 1982; 104: 2444
    • 15c McDonald RI. White PB. Weinstein AB. Tam CP. Stahl SS. Org. Lett. 2011; 13: 2830
  • 16 For early work towards a protodepalladation approach to alkene hydroamination, see: Seligson AL. Trogler WC. Organometallics 1993; 12: 744
    • 17a Gaunt MJ. Spencer JB. Org. Lett. 2001; 3: 25
    • 17b Pei T. Widenhoefer RA. J. Am. Chem. Soc. 2001; 123: 11290
    • 17c Qian H. Widenhoefer RA. J. Am. Chem. Soc. 2003; 125: 2056
    • 17d Michael FE. Cochran BM. J. Am. Chem. Soc. 2006; 128: 4246
    • 17e Cochran BM. Michael FE. J. Am. Chem. Soc. 2008; 130: 2786
  • 18 Hoveyda AH. Evans DA. Fu GC. Chem. Rev. 1993; 93: 1307
    • 19a Ickes AR. Ensign SC. Gupta AK. Hull KL. J. Am. Chem. Soc. 2014; 136: 11256
    • 19b Ensign SC. Vanable EP. Kortman GD. Weir LJ. Hull KL. J. Am. Chem. Soc. 2015; 137: 13748
    • 20a Zaitsev VG. Shabashov D. Daugulis O. J. Am. Chem. Soc. 2005; 127: 13154
    • 20b Shabashov D. Daugulis O. J. Am. Chem. Soc. 2010; 132: 3965
    • 20c Rouguet G. Chatani N. Angew. Chem. Int. Ed. 2013; 52: 11726
    • 20d Daugulis O. Roane J. Tran LD. Acc. Chem. Res. 2015; 48: 1053
  • 21 Gurak JA. Jr. Yang KS. Liu Z. Engle KM. J. Am. Chem. Soc. 2016; 138: 5805
  • 22 Gurak JA. Jr. Tran VT. Sroda MM. Engle KM. Tetrahedron 2017; 73: 3636
  • 23 Yang KS. Gurak JA. Jr. Liu Z. Engle KM. J. Am. Chem. Soc. 2016; 138: 14705
  • 24 At this stage, we have not confirmed whether all of the examples in this manuscript proceed via anti-nucleopalladation or whether the mechanism of this step is dependent on the identity of the alkene and/or amine.
  • 25 Liu Z. Zeng T. Yang KS. Engle KM. J. Am. Chem. Soc. 2016; 138: 15122
    • 26a Liu Z. Derosa J. Engle KM. J. Am. Chem. Soc. 2016; 138: 13076
    • 26b Derosa J. Cantu AL. Boulous MN. O’Duill ML. Turnbull JL. Liu Z. De La Torre DM. Engle KM. J. Am. Chem. Soc. 2017; 139: 5183