Synlett 2016; 27(07): 1051-1055
DOI: 10.1055/s-0035-1561199
cluster
© Georg Thieme Verlag Stuttgart · New York

Organocatalysis Intermediates as Platforms to Study Noncovalent Interactions: Integrating Fluorine Gauche Effects in Iminium Systems to Facilitate Acyclic Conformational Control

István Gábor Molnár
a  Institute for Organic Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster, Germany, Email: ryan.gilmour@uni-muenster.de
,
Mareike C. Holland
a  Institute for Organic Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster, Germany, Email: ryan.gilmour@uni-muenster.de
b  Department of Chemistry and Biochemistry, University of California Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095-1569, USA
,
Constantin Daniliuc
a  Institute for Organic Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster, Germany, Email: ryan.gilmour@uni-muenster.de
,
K. N. Houk
b  Department of Chemistry and Biochemistry, University of California Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA 90095-1569, USA
,
Ryan Gilmour*
a  Institute for Organic Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster, Germany, Email: ryan.gilmour@uni-muenster.de
c  Excellence Cluster EXC 1003, Cells in Motion, Westfälische Wilhelms-Universität Münster, Waldeyerstrasse 15, 48149 Münster, Germany   Email: ryan.gilmour@uni-muenster.de
› Author Affiliations
Further Information

Publication History

Received: 14 December 2015

Accepted: 28 December 2015

Publication Date:
18 January 2016 (online)


X-ray crystallographer

Dedicated to Prof. Dr. Dieter Seebach

Abstract

Achieving acyclic conformational control over several bonds has been realized by the strategic installation of a vicinal difluoroethane bridge in a generic proline-derived organocatalyst. The torsion angle ϕFCCF is governed by stabilizing hyperconjugative interactions (σ→σ*), thus ensuring a 60° relationship. This effect has been telescoped by positioning a stereogenic fluorine center proximal to the nucleophilic amine. Upon iminium formation, this center is rendered electron deficient, thus triggering a dynamic fluorine iminium ion gauche effect. Consequently, conformational control over five atoms and four bonds can be achieved by reversible formation of an iminium π-bond.

Supporting Information

 
  • References and Notes

  • 2 Holland MC, Gilmour R. Angew. Chem. Int. Ed. 2015; 54: 3862
  • 3 Bertelsen S, Jørgensen KA. Chem. Soc. Rev. 2009; 38: 2178
  • 4 For the example of cyclopropyliminium activation, see: Sparr C, Gilmour R. Angew. Chem. Int. Ed. 2011; 50: 8391

    • For selcted examples see:
    • 5a Holland MC, Paul S, Schweizer WB, Bergander K, Mück-Lichtenfeld C, Lakhdar S, Mayr H, Gilmour R. Angew. Chem. Int. Ed. 2013; 52: 7967
    • 5b Holland MC, Metternich JB, Mück-Lichtenfeld C, Gilmour R. Chem. Commun. 2015; 51: 5322
    • 5c Seebach D, Gilmour R, Grošelj U, Deniau G, Sparr S, Ebert MO, Beck A, McCusker LB, Šišak D, Uchimaru T. Helv. Chim. Acta 2010; 93: 603
    • 5d Grošelj U, Schweizer WB, Ebert M.-O, Seebach D. Helv. Chim. Acta 2009; 92: 1
  • 6 MacMillan DW. C. Nature 2008; 455: 304
  • 7 Knowles RR, Jacobsen EN. Proc. Natl. Acad. Sci. U.S.A. 2010; 107: 20678
  • 8 Congreve M, Murray CW, Blundell TL. Drug Discovery Today 2005; 10: 895
  • 9 Sparr C, Schweizer WB, Senn HM, Gilmour R. Angew. Chem. Int. Ed. 2009; 48: 3065
  • 10 O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
    • 11a Tanzer E.-M, Zimmer LE, Schweizer WB, Gilmour R. Chem. Eur. J. 2012; 18: 11334
    • 11b Molnár IG, Tanzer E.-M, Daniliuc C, Gilmour R. Chem. Eur. J. 2014; 20: 794
  • 12 Tsou C.-L. Science 1993; 262: 380
  • 13 For beautiful applications of this motif in modulating peptide conformation, see: Schüler M, O’Hagan D, Slawin AM. Z. Chem. Commun. 2005; 4324
    • 14a Donner BG. Tetrahedron Lett. 1995; 36: 1223
    • 14b Reed PE, Katzenellenbogen JA. J. Org. Chem. 1991; 56: 2624
  • 15 Crystallographic data: CCDC 1441597 (HClO4), 1441598 (15), 1441599 (11·HClO4), 1441601 (12) and 1441600 (13) contain the supplementary crystallographic data. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
  • 16 Gooseman NE. J, O’Hagan D, Slawin AM. Z, Teale AM, Tozer DJ, Young RJ. Chem. Commun. 2006; 3190
  • 17 MacroModel, version 10.6. Schrödinger LLC; New York: 2014
  • 18 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA. Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam MJ, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ. Gaussian 09, Revision D.01. Gaussian Inc; Wallingford (CT, USA): 2013
    • 19a Vosko SH, Wilk L, Nusair M. Can. J. Phys. 1980; 58: 1200
    • 19b Lee C, Yang W, Parr RG. Phys. Rev. B: Condens. Matter Mater. Phys. 1988; 37: 785
    • 19c Becke AD. J. Chem. Phys. 1993; 98: 5648
    • 19d Stephens PJ, Devlin FJ, Chabalowski CF, Frisch MJ. J. Phys. Chem. 1994; 98: 11623
  • 20 Cancès E, Mennucci B, Tomasi J. J. Chem. Phys. 1997; 107: 3032
    • 21a Grimme S, Antony J, Ehrlich S, Krieg H. J. Chem. Phys. 2010; 132: 154104
    • 21b Grimme S, Ehrlich S, Goerigk L. J. Comput. Chem. 2011; 32: 1456
    • 21c Johnson ER, Becke AD. J. Chem. Phys. 2006; 124: 174104
    • 21d Johnson ER, Becke AD. J. Chem. Phys. 2005; 123: 024101
    • 21e Goerigk L, Grimme S. Phys. Chem. Chem. Phys. 2011; 13: 6670
  • 22 Weigend F, Ahlrichs R. Phys. Chem. Chem. Phys. 2005; 7: 3297
    • 23a Ribeiro RF, Marenich AV, Cramer CJ, Truhlar DG. J. Phys. Chem. B 2011; 115: 14556
    • 23b Zhao Y, Truhlar DG. Phys. Chem. Chem. Phys. 2008; 10: 2813
  • 24 Dennington R, Keith T, Millam J. GaussView, version 5.0. Semichem Inc; Shawnee Mission (KS, USA): 2009
  • 25 Legault CY. CYLview, version 1.0b. Université de Sherbrooke; Sherbrooke (QC, CA): 2009
  • 26 Vesely J, Ibrahem I, Zhao G.-L, Rios R, Córdova A. Angew. Chem. Int. Ed. 2007; 46: 778