Synlett 2014; 25(20): 2819-2826
DOI: 10.1055/s-0034-1379304
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© Georg Thieme Verlag Stuttgart · New York

Proton-Coupled Electron Transfer in Organic Synthesis: Novel Homolytic Bond Activations and Catalytic Asymmetric Reactions with Free Radicals

Hatice G. Yayla
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA   Email: rknowles@princeton.edu
,
Robert R. Knowles*
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA   Email: rknowles@princeton.edu
› Author Affiliations
Further Information

Publication History

Received: 15 August 2014

Accepted after revision: 20 September 2014

Publication Date:
16 October 2014 (online)


Abstract

Proton-coupled electron transfers (PCET) are unconventional redox processes in which an electron and proton are exchanged together in a concerted elementary step. While these mechanisms are recognized to play a central role in biological redox catalysis, their applications in synthetic organic chemistry have yet to be widely established. In this Account, we highlight two recent examples from our group outlining the use of concerted PCET as a platform for the development of catalytic and enantioselective reactions of neutral ketyl radicals. Central to this work was the recognition that PCET provides a mechanism for independent proton and electron donors to function jointly as a formal hydrogen atom donor competent to activate organic π systems that are energetically inaccessible using conventional H-atom transfer technologies. In addition, we found that neutral ketyls formed in the PCET event are remarkably strong hydrogen-bond donors and remain strongly associated to the conjugate base of the proton donor following the PCET event. When chiral proton donors are used, these successor H-bond complexes provide a basis for asymmetric induction in subsequent reactions of the ketyl radical.

1 Introduction

2 Concerted PCET and Effective Bond Strengths

3 Concerted PCET Activation of Ketones: A Catalytic Protocol for Ketyl–Olefin Coupling and Mechanistic Investigations

4 Enantioselective PCET Catalysis: Development of Catalytic Asymmetric Aza-pinacol Cyclizations

5 Conclusions

Supporting Information

 
  • References and Notes

    • 1a Meyer TJ, Huynh MH. V, Thorp HH. Angew. Chem. Int. Ed. 2007; 46: 5284
    • 1b Stubbe J, Nocera DG, Yee C, Chang M. Chem. Rev. 2003; 103: 2167
    • 1c Kaila VR. I, Verkhovsky MI, Wikström M. Chem. Rev. 2010; 110: 7062
    • 1d Hatcher E, Soudachov A, Hammes-Schiffer S. J. Am. Chem. Soc. 2004; 126: 5763
    • 1e Migliore A, Polizzi NF, Therien MJ, Beratan DN. Chem. Rev. 2014; 114: 3381
    • 1f Smith KW, Stroupe ME. Biochemistry 2012; 51: 9857
    • 1g Kennis JT. M, Mathes T. Interface Focus 2013; 3: 20130005
    • 1h Reece SY, Hodgkiss JM, Stubbe J, Nocera DG. Philos. Trans. R. Soc., B 2006; 361: 1351
    • 1i Barry BA. J. Photochem. Photobiol. B 2011; 104: 60
    • 1j Lehnert N, Solomon EI. J. Biol. Inorg. Chem. 2003; 8: 294
    • 1k Neidig ML, Wecksler AT, Schenk G, Holman TR, Solomon EI. J. Am. Chem. Soc. 2007; 129: 7531
    • 1l Moiseyev N, Rucker J, Glickman MK. J. Am. Chem. Soc. 1997; 119: 3853
    • 1m Derat E, Shaik S. J. Am. Chem. Soc. 2006; 128: 13940
    • 1n Wang Y, Chen H, Makino M, Shiro Y, Nagano S, Asamizu S, Onaka H, Shaik S. J. Am. Chem. Soc. 2009; 131: 6748
    • 1o Wang H, Hirao H, Chen H, Onaka H, Nagano S, Shaik S. J. Am. Chem. Soc. 2008; 130: 7170
    • 2a Weinberg DR, Gagliardi CJ, Hull JF, Murphy CF, Kent CA, Westlake BC, Paul A, Ess DH, McCafferty DG, Meyer TJ. Chem. Rev. 2012; 112: 4016
    • 2b Huynh MH. V, Meyer TJ. Chem. Rev. 2007; 107: 5004
    • 2c Costentin C. Chem. Rev. 2008; 108: 2145
    • 2d Hammes-Schiffer S, Stuchebrukhov AA. Chem. Rev. 2010; 110: 6939
    • 2e Dempsey JL, Winkler JR, Gray HB. Chem. Rev. 2010; 110: 7024
    • 2f Warren JJ, Tronic TA, Mayer JM. Chem. Rev. 2010; 110: 6961
    • 2g Hammes-Schiffer S, Hatcher E, Ishikita H, Skone JH, Soudackov AV. Coord. Chem. Rev. 2008; 252: 384
    • 2h Costentin C. Chem. Rev. 2008; 108: 2145
    • 2i Reece SY, Nocera DG. Annu. Rev. Biochem. 2009; 78: 673
    • 2j Gagliardi CJ, Westlake BC, Kent CA, Paul JJ, Papanikolas JM, Meyer TJ. Coord. Chem. Rev. 2010; 254: 2459
    • 2k Hammarstrom L, Styring S. Philos. Trans. R. Soc., B 2008; 363: 1283
    • 3a Rosenthal J, Luckett TD, Hodgkiss JM, Nocera DG. J. Am. Chem. Soc. 2006; 128: 6546
    • 3b Yang JY, Nocera DG. J. Am. Chem. Soc. 2007; 129: 8192
    • 4a Evans MG, Polanyi M. Trans. Faraday Soc. 1938; 34: 11
    • 4b Ingold KU In Free Radicals . Vol. 1. Kochi JK. Wiley; New York: 1973: 283
    • 4c Russell GA In Free Radicals . Vol. 1. Kochi JK. Wiley; New York: 1973: 69
    • 4d Roth JP, Yoder JC, Won T.-J, Mayer JM. Science 2001; 294: 2524
    • 4e Warren JJ, Mayer JM. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 5282
    • 5a Zhang X.-M. J. Org. Chem. 1998; 63: 1872
    • 5b Tang L, Papish ET, Abramo GP, Norton JR, Baik M.-H, Friesner RA, Rappe A. J. Am. Chem. Soc. 2003; 125: 10093
    • 5c Brown RL, Stein SE. J. Am. Chem. Soc. 1991; 113: 787
    • 5d Gou Y, Grabowski JJ. J. Am. Chem. Soc. 1991; 113: 5923
  • 6 BDFE from CBS-QB3 calculations. For details, see the Supporting Information.
  • 7 The given O–H bond strength for isopropanol is a bond-dissociation enthalpy (BDE): Blanksby SJ, Ellison GB. Acc. Chem. Res. 2003; 36: 255
    • 8a Choi JW, Pulling ME, Smith DM, Norton JR. J. Am. Chem. Soc. 2008; 130: 4250
    • 8b Estes DP, Vannucci AK, Hall AR, Lichtenberger DL, Norton JR. Organometallics 2011; 30: 3444
    • 8c Uddin J, Morales CM, Maynard JH, Landis CR. Organometallics 2006; 25: 5566

      For selected examples of HAT to olefins from metal hydrides, see:
    • 9a Halpern J. Pure Appl. Chem. 1986; 58: 575 ; and references cited therein
    • 9b Iwasaki K, Wan KK, Oppedisano A, Crossley SW. M, Shenvi RA. J. Am. Chem. Soc. 2014; 136: 1300
    • 9c King SM, Ma X, Herzon SB. J. Am. Chem. Soc. 2014; 136: 6884
    • 9d Lo JC, Yabe Y, Baran PS. J. Am. Chem. Soc. 2014; 136: 1304
    • 10a Wiberg KB, Foster G. J. Am. Chem. Soc. 1961; 83: 423
    • 10b Breslow R, Balasubramanian K. J. Am. Chem. Soc. 1969; 91: 5182
    • 10c Breslow R, Chu W. J. Am. Chem. Soc. 1973; 95: 411
    • 10d Jaun B, Schwarz J, Breslow R. J. Am. Chem. Soc. 1980; 102: 5741
    • 10e Bordwell FG, Cheng J.-P, Harrelson JA. Jr. J. Am. Chem. Soc. 1988; 110: 1229
    • 10f Wayner DM, Parker VD. Acc. Chem. Res. 1993; 26: 287
    • 10g Tilset M, Parker VD. J. Am. Chem. Soc. 1989; 111: 6711
    • 10h Tilset M, Parker VD. J. Am. Chem. Soc. 1990; 112: 2843
    • 10i Parker VD, Handoo KL, Roness F, Tilset M. J. Am. Chem. Soc. 1991; 113: 7493
  • 11 Waidmann CR, Miller AJ. M, Ng AC.-W, Scheuermann ML, Porter TR, Tronic TA, Mayer JM. Energy Environ. Sci. 2012; 5: 7771
    • 12a Mayer JM. Acc. Chem. Res. 2001; 44: 36
    • 12b Costeintin C, Robert M, Saveant J.-M. J. Am. Chem. Soc. 2007; 129: 9953
    • 12c Sjodin M, Styring S, Wolpher H, Xu Y, Sun L, Hammarstrom L. J. Am. Chem. Soc. 2005; 127: 3855
    • 12d Osako T, Ohkubo K, Taki M, Tachi Y, Fukuzumi S, Itoh S. J. Am. Chem. Soc. 2003; 125: 11027
    • 12e Schrauben JN, Cattaneo M, Day TC, Tenderholt AL, Mayer JM. J. Am. Chem. Soc. 2012; 134: 16635
  • 13 Tarantino KT, Liu P, Knowles RR. J. Am. Chem. Soc. 2013; 135: 10022

    • For examples of ketyl reactions in synthesis, see:
    • 14a Edmonds DJ, Johnston D, Procter DJ. Chem. Rev. 2004; 104: 3371
    • 14b Nicolaou KC, Ellery SP, Chen JS. Angew. Chem. Int. Ed. 2009; 48: 7140
  • 15 This analysis does not include the thermochemical impact of the H-bonding interactions, which can play a substantive role in the overall thermochemistry of PCET reactions in the low-driving force regime. See also ref. 22.

    • For pioneering studies of on the activation of aryl ketones towards electron transfer using strong Brønsted acids, see:
    • 16a Fukuzumi S, Chiba M, Tanaka T. Chem. Lett. 1989; 18: 31
    • 16b Fukuzumi S, Ishikawa K, Hironaka K, Tanaka T. J. Chem. Soc., Perkin Trans. 2 1987; 751

      For the pK a value of protonated acetophenone in MeCN, see:
    • 17a Kolthoff IM, Chantooni MK. J. Am. Chem. Soc. 1973; 95: 8539

    • For pK a values of phosphoric acids in MeCN, see:
    • 17b Kaupmees K, Tolstoluzhsky N, Raja S, Rueping M, Leito I. Angew. Chem. Int. Ed. 2013; 52: 11569
  • 18 Dixon IM, Collin J, Sauvage J, Flamigni L, Encinas S, Barigelletti F. Chem. Soc. Rev. 2000; 29: 385

    • For synthetic examples of hydrogen bonding interactions with open shell species, see:
    • 19a Curran DP, Kuo LH. J. Org. Chem. 1994; 59: 3259
    • 19b Bach T, Bergmann H, Harms K. Angew. Chem. Int. Ed. 2000; 39: 2302
    • 19c Bach T, Bergmann H, Grosch B, Harms K. J. Am. Chem. Soc. 2002; 124: 7982
    • 19d Aechtner T, Dressel M, Bach T. Angew. Chem. Int. Ed. 2004; 43: 5849
    • 19e Bauer A, Westkämper F, Grimme S, Bach T. Nature (London, U.K.) 2005; 436: 1139
    • 19f Müller C, Bauer A, Bach T. Angew. Chem. Int. Ed. 2009; 48: 6640
    • 19g Müller C, Bauer A, Maturi MM, Cuquerella MC, Miranda MA, Bach T. J. Am. Chem. Soc. 2011; 133: 16689
  • 20 For an alternative approach using chiral Lewis acid activation, see: Du J, Skubi KL, Schultz DM, Yoon TP. Science 2014; 344: 392
  • 21 For a discussion of the energetic role of precursor and successor H bonds in PCET reactions, see: Mader EA, Mayer JM. Inorg. Chem. 2010; 49: 3685
  • 22 Rono LJ, Yayla HG, Wang DY, Armstrong MF, Knowles RR. J. Am. Chem. Soc. 2013; 135: 17735

    • For examples of asymmetric photoredox catalysis, see:
    • 23a Nicewicz DA, MacMillan DW. C. Science 2008; 322: 77
    • 23b Nagib DA, Scott ME, MacMillan DW. C. J. Am. Chem. Soc. 2009; 131: 10875
    • 23c Shih H.-W, Vander Wal MN, Grange RL, MacMillan DW. C. J. Am. Chem. Soc. 2010; 132: 13600
    • 23d DiRocco DA, Rovis T. J. Am. Chem. Soc. 2012; 134: 8094
    • 23e Pirnot MT, Rankic DA, Martin DB, MacMillan DW. C. Science 2013; 339: 1593
    • 23f Cecere G, König CM, Alleva JL, MacMillan DW. C. J. Am. Chem. Soc. 2013; 135: 11521
    • 23g Bergonzini G, Schindler C, Wallentin C.-J, Jacobsen EN, Stephenson CR. J. Chem. Sci. 2013; 5: 112

      For examples of H-bond activation in asymmetric radical additions to imine derivatives, see:
    • 24a Cho DH, Jang DO. Chem. Commun. 2006; 5045
    • 24b Kim SY, Kim SJ, Jang DO. Chem. Eur. J. 2010; 16: 13046
  • 25 For a recent example of catalytic asymmetric ketyl reactivity, see: Streuff J, Feurer M, Bichovski P, Frey G, Gellrich U. Angew. Chem. Int. Ed. 2012; 51: 8661
  • 26 Burchak ON, Py S. Tetrahedron 2009; 65: 7333

    • For selected examples of aza-pinacol reactions in synthesis, see:
    • 27a Nicolaou KC, Hao J, Reddy M, Rao P, Rassias G, Snyder S, Huang X, Chen D, Brenzovich W, Giuseppone N, Giannakakou P, O’Brate A. J. Am. Chem. Soc. 2004; 126: 12897
    • 27b Riber D, Hazell R, Skrydstrup T. J. Org. Chem. 2000; 65: 5382

      The pK a values of neutral ketyl radicals in MeCN can be estimated from the BDFE of the ketyl O–H bond (26 kcal mol–1) and the reduction potential of acetophenone in MeCN (–2.48 V vs. Fc). See:
    • 28a Arnett EM. Prog. Phys. Org. Chem. 1963; 1: 223
    • 28b Hayon E, Ibata T, Lichtin NN, Simic M. J. Phys. Chem. 1972; 76: 2072