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Synlett 2009(9): 1413-1416  
DOI: 10.1055/s-0029-1217165
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioselective Syntheses of 2-Substituted Pyrrolidines from Allylamines by Domino Hydroformylation-Condensation: Short Syntheses of (S)-Nicotine and the Alkaloid 225C

Pierre Dübon, Andreas Farwick, Günter Helmchen*
Organisch-Chemisches Institut der Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax: +49(6221)544205; e-Mail: g.helmchen@oci.uni-heidelberg.de;
Further Information

Publication History

Received 2 February 2009
Publication Date:
13 May 2009 (online)

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Abstract

Short routes to chiral 2-substituted pyrrolidines based on rhodium-catalyzed hydroformylations of allylamines and their N-alkyl and N-acyl derivatives, which were prepared by asymmetric allylic substitutions, are described. The outcome of the hydroformylation reaction was controlled by the substituent at nitrogen, not by the substituent at carbon. In the case of N-alkylallylamines in situ reduction to the pyrrolidines occurred, with N-acyl derivatives hemiaminals and with primary amines cyclic imines were formed. Very short syntheses of (S)-nicotine and the alkaloid 225C are presented.

Key words

domino reactions - hydroformylation - pyrrolidines - ­alkaloids - cyclizations

    References and Notes

  • 1a Helmchen G. In Iridium Complexes in Organic Synthesis   Oro LA. Claver C. Wiley-VCH; Weinheim: 2009.  p.211 
    Google Scholar
  • 1b Helmchen G. Dahnz A. Dübon P. Schelwies M. Weihofen R. Chem. Commun.  2007,  675 
    Google Scholar
  • 1c Takeuchi R. Kezuka S. Synthesis  2006,  3349 
    Google Scholar
  • 1d Miyabe H. Takemoto Y. Synlett  2005,  1641 
    Google Scholar
  • 2a Streiff S. Welter C. Schelwies M. Lipowsky G. Miller N. Helmchen G. Chem. Commun.  2005,  2957 
    Google Scholar
  • 2b Welter C. Moreno RM. Streiff S. Helmchen G. Org. Biomol. Chem.  2005,  3:  3266 
    Google Scholar
  • 2c Böhrsch V. Blechert S. Chem. Commun.  2006,  1968 
    Google Scholar
  • 3 Schelwies M. Dempwolff A. Rominger F. Helmchen G. Angew. Chem. Int. Ed.  2007,  46:  5598;   Angew. Chem. 2007, 119, 5694
    CrossrefGoogle Scholar
  • 4a Allylamines prepared by Ir-catalyzed asymmetric allylic substitution have been used in hydroformylation-indolization sequences: Bondzić BP. Farwick A. Liebich J. Eilbracht P. Org. Biomol. Chem.  2008,  3723 
    Google Scholar
  • 4b For preparation of an indolizine via hydroformylation of an N-allyl-pyrrole, see: Guazzelli G. Lazzaroni R. Settambolo R. Beilstein J. Org. Chem.  2008,  4:  2 
    Google Scholar
  • For a review, see:
  • 5a Eilbracht P. Schmidt AM. Top. Organomet. Chem.  2006,  18:  65 
    Google Scholar
  • 5b Eilbracht P. Bärfacker L. Buss C. Hollmann C. Kitsos-Rzychon BE. Kranemann CL. Roggenbruck R. Schmidt A. Chem. Rev.  1999,  99:  3329 
    Google Scholar
  • 5c Ahmed M. Seayad AM. Jackstell R. Beller M. J. Am. Chem. Soc.  2003,  125:  10311 
    Google Scholar
  • 5d Ahmed M. Buch C. Routaboul L. Jackstell R. Klein H. Spannenberg A. Beller M. Chem. Eur. J.  2007,  13:  1594 ; and previous work cited there
    Google Scholar
  • 6a Vieira TO. Alper H. Chem. Commun.  2007,  2710 
    Google Scholar
  • 6b Wittmann K. Wisniewski W. Mynott R. Leitner W. Kranemann CL. Rische T. Eilbracht P. Sander S. Ernsting JM. Chem. Eur. J.  2001,  7:  4584 
    Google Scholar
  • 6c Eguchi M. Tzamarioudaki M. Ojima I. J. Org. Chem.  1995,  60:  7078 
    Google Scholar
  • 6d Vidal ES. Ojima I. J. Org. Chem.  1998,  63:  7999 
    Google Scholar
  • 6e Spangenberg T. Airiau E. Bui The Thuong M. Donnard M. Billet M. Mann A. Synlett  2008,  2859 
    Google Scholar
  • 6f Airiau E. Spangenberg T. Girard N. Schoenfelder A. Salvadori J. Taddei M. Mann A. Chem. Eur. J.  2008,  14:  10938 
    Google Scholar
  • 6g Spangenberg T. Breit B. Mann A. Org. Lett.  2009,  11:  261 
    Google Scholar
  • 7 For leading references to asymmetric syntheses of pyrrolidines, including alkaloid 225C, see: Davis FA. Xu H. Wu Y. Zhang J. Org. Lett.  2006,  8:  2273 
    CrossrefGoogle Scholar
  • 8 Rhodium-Catalyzed Hydroformylation   van Leeuwen PWNM. Claver C. Kluwer Academic; Dordrecht: 2000. 
    Google Scholar
  • 9 Kamer PCJ. van Leeuwen PWNM. Reek JNH. Acc. Chem. Res.  2001,  34:  895 
    CrossrefGoogle Scholar
  • 10 Cuny GD. Buchwald SL. J. Am. Chem. Soc.  1993,  115:  2066 
    CrossrefGoogle Scholar
  • 11a Ohmura T. Hartwig JF. J. Am. Chem. Soc.  2002,  124:  15164 
    Google Scholar
  • 11b Welter C. Dahnz A. Brunner B. Streiff S. Dübon P. Helmchen G. Org. Lett.  2005,  7:  1239 
    Google Scholar
  • 11c Gnamm C. Franck G. Miller N. Stork T. Brödner K. Helmchen G. Synthesis  2008,  3331 
    Google Scholar
  • 12 Keränen MD. Eilbracht P. Org. Biomol. Chem.  2004,  2:  1688 
    CrossrefGoogle Scholar
  • For a review, see:
  • 15a Felpin F.-X. Lebreton A. Eur. J. Org. Chem.  2003,  3693 
    Google Scholar
  • 15b Wagner FF. Comins DL. Tetrahedron  2007,  63:  8065 
    Google Scholar
  • 15c Schäfer B. Chem. Unserer Zeit  2008,  42:  330 
    Google Scholar
  • 15d Baxendale IR. Brusotti G. Matsuoka M. Ley SV. J. Chem. Soc., Perkin Trans. 1  2002,  143 
    Google Scholar
  • 15e Welter C. Moreno RM. Streiff S. Helmchen G. Org. Biomol. Chem.  2005,  3:  3266 
    Google Scholar
  • 17 Weihofen R. Tverskoy O. Helmchen G. Angew. Chem. Int. Ed.  2006,  45:  5546 ; Angew. Chem. 2006, 118, 5673
    CrossrefGoogle Scholar
  • 18 Weihofen R. Dahnz A. Tverskoy O. Helmchen G. Chem. Commun.  2005,  3541 
    CrossrefGoogle Scholar
  • 19a Spiess S. Berthold C. Weihofen R. Helmchen G. Org. Biol. Chem.  2007,  5:  2357 
    Google Scholar
  • 19b Pouy MJ. Leitner A. Weix DJ. Ueno S. Hartwig JF. Org. Lett.  2007,  9:  3949 
    Google Scholar
  • 19c Singh OV. Han H. Tetrahedron Lett.  2007,  48:  7094 
    Google Scholar
  • 20 This has only been observed previously with derivatives of the parent allylamine using Ph3P as ligand, see: Dong Y. Busacca CA. Tetrahedron Lett.  1996,  37:  3947 
    CrossrefGoogle Scholar
  • 21a Tissot-Croset K. Polet D. Gille S. Hawner C. Alexakis A. Synthesis  2004,  2586 
    Google Scholar
  • 21b Polet D. Alexakis A. Tissot-Croset K. Corminboeuf C. Ditrich K. Chem. Eur. J.  2006,  12:  3596 
    Google Scholar
  • 22 We have found only one report on such a reaction, the hydroformylation of the parent allylamine, see: Lin JJ. Larkin JM. Knifton JF. In Catalysis of Organic Reactions   Augustine RL. Dekker; New York: 1988.  p.29 
    Google Scholar
  • For previous syntheses, see:
  • 23a Pedder DJ. Fales HM. Jaouni T. Blum M. MacConnell J. Crewe RM. Tetrahedron  1976,  32:  2275 
    Google Scholar
  • 23b Tufariello JJ. Puglis JM. Tetrahedron Lett.  1986,  27:  1489 
    Google Scholar
  • 23c Wistrand L.-G. Skinjar M. Tetrahedron  1991,  47:  573 
    Google Scholar
  • 23d Oppolzer W. Bochet CG. Merifield E. Tetrahedron Lett.  1994,  35:  7015 
    Google Scholar
  • 23e Arredondo VM. Tian S. McDonald FE. Marks T. J. Am. Chem. Soc.  1999,  121:  3633 
    Google Scholar
  • 24a Tang TP. Volkman SK. Ellman JA. J. Org. Chem.  2001,  66:  8772 
    Google Scholar
  • 24b Côtè A. Charette AB. J. Am. Chem. Soc.  2008,  130:  2771 
    Google Scholar
  • For a review, see:
  • 25a Alvaro G. Savoia D. Synlett  2002,  651 
    Google Scholar
  • 25b Yamada H. Kawate T. Nishida A. Nakagawa M. J. Org. Chem.  1999,  64:  8821 
    Google Scholar
  • 25c Takemoto Y. Takeuchi J. Iwata C. Tetrahedron Lett.  1993,  34:  6069 
    Google Scholar
  • 25d Bandini M. Cozzi PG. Umani-Ronchi A. Villa M. Tetrahedron  1999,  55:  8103 
    Google Scholar
  • 26 We used apparatus described in: Bartels B. Garcia-Yebra C. Helmchen G. Eur. J. Org. Chem.  2003,  1097 
    CrossrefGoogle Scholar
  • 27 Our procedure complements Buchwald’s similarly short asymmetric hydrogenation route: Willoughby CA. Buchwald SL. J. Am. Chem. Soc.  1994,  116:  8952 
    CrossrefGoogle Scholar
13

All new compounds described were fully characterized by elemental analysis and spectroscopic data. Yields always refer to isolated products.

14

General Procedure for the Rh-Catalyzed Hydroformylation-Reduction (cf. Conditions B, Scheme 4) A cylindrical glass vessel (2.5 × 7 cm) with a perforated snap on lid was charged with Rh(acac)(CO)2 (2.3 mg, 9.0 µmol), Biphephos (18 µmol), and a soln of the allylic amine (1.0 mmol) in CHCl3 (10 mL/mmol). The vessel was placed in an autoclave, which was pressurized (30 bar) with H2/CO (5:1); oxygen was removed by flushing twice with the gas mixture. The autoclave was then heated for 18-24 h at 50 ˚C. The resulting brown mixture was analyzed by GC-MS. The solvent was removed in vacuo and the residue subjected to flash chromatography on SiO2.

16

Very recently, a short synthesis of (S)-nicotine via hydroformylation of a homoallylazide has been reported,
cf. ref. 6g.