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: [email protected];
Further Information

Publication History

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

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.

    References and Notes

  • 1a Helmchen G. In Iridium Complexes in Organic Synthesis   Oro LA. Claver C. Wiley-VCH; Weinheim: 2009.  p.211 
  • 1b Helmchen G. Dahnz A. Dübon P. Schelwies M. Weihofen R. Chem. Commun.  2007,  675 
  • 1c Takeuchi R. Kezuka S. Synthesis  2006,  3349 
  • 1d Miyabe H. Takemoto Y. Synlett  2005,  1641 
  • 2a Streiff S. Welter C. Schelwies M. Lipowsky G. Miller N. Helmchen G. Chem. Commun.  2005,  2957 
  • 2b Welter C. Moreno RM. Streiff S. Helmchen G. Org. Biomol. Chem.  2005,  3:  3266 
  • 2c Böhrsch V. Blechert S. Chem. Commun.  2006,  1968 
  • 3 Schelwies M. Dempwolff A. Rominger F. Helmchen G. Angew. Chem. Int. Ed.  2007,  46:  5598;   Angew. Chem. 2007, 119, 5694
  • 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 
  • 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: 
  • For a review, see:
  • 5a Eilbracht P. Schmidt AM. Top. Organomet. Chem.  2006,  18:  65 
  • 5b Eilbracht P. Bärfacker L. Buss C. Hollmann C. Kitsos-Rzychon BE. Kranemann CL. Roggenbruck R. Schmidt A. Chem. Rev.  1999,  99:  3329 
  • 5c Ahmed M. Seayad AM. Jackstell R. Beller M. J. Am. Chem. Soc.  2003,  125:  10311 
  • 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
  • 6a Vieira TO. Alper H. Chem. Commun.  2007,  2710 
  • 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 
  • 6c Eguchi M. Tzamarioudaki M. Ojima I. J. Org. Chem.  1995,  60:  7078 
  • 6d Vidal ES. Ojima I. J. Org. Chem.  1998,  63:  7999 
  • 6e Spangenberg T. Airiau E. Bui The Thuong M. Donnard M. Billet M. Mann A. Synlett  2008,  2859 
  • 6f Airiau E. Spangenberg T. Girard N. Schoenfelder A. Salvadori J. Taddei M. Mann A. Chem. Eur. J.  2008,  14:  10938 
  • 6g Spangenberg T. Breit B. Mann A. Org. Lett.  2009,  11:  261 
  • 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 
  • 8 Rhodium-Catalyzed Hydroformylation   van Leeuwen PWNM. Claver C. Kluwer Academic; Dordrecht: 2000. 
  • 9 Kamer PCJ. van Leeuwen PWNM. Reek JNH. Acc. Chem. Res.  2001,  34:  895 
  • 10 Cuny GD. Buchwald SL. J. Am. Chem. Soc.  1993,  115:  2066 
  • 11a Ohmura T. Hartwig JF. J. Am. Chem. Soc.  2002,  124:  15164 
  • 11b Welter C. Dahnz A. Brunner B. Streiff S. Dübon P. Helmchen G. Org. Lett.  2005,  7:  1239 
  • 11c Gnamm C. Franck G. Miller N. Stork T. Brödner K. Helmchen G. Synthesis  2008,  3331 
  • 12 Keränen MD. Eilbracht P. Org. Biomol. Chem.  2004,  2:  1688 
  • For a review, see:
  • 15a Felpin F.-X. Lebreton A. Eur. J. Org. Chem.  2003,  3693 
  • 15b Wagner FF. Comins DL. Tetrahedron  2007,  63:  8065 
  • 15c Schäfer B. Chem. Unserer Zeit  2008,  42:  330 
  • 15d Baxendale IR. Brusotti G. Matsuoka M. Ley SV. J. Chem. Soc., Perkin Trans. 1  2002,  143 
  • 15e Welter C. Moreno RM. Streiff S. Helmchen G. Org. Biomol. Chem.  2005,  3:  3266 
  • 17 Weihofen R. Tverskoy O. Helmchen G. Angew. Chem. Int. Ed.  2006,  45:  5546 ; Angew. Chem. 2006, 118, 5673
  • 18 Weihofen R. Dahnz A. Tverskoy O. Helmchen G. Chem. Commun.  2005,  3541 
  • 19a Spiess S. Berthold C. Weihofen R. Helmchen G. Org. Biol. Chem.  2007,  5:  2357 
  • 19b Pouy MJ. Leitner A. Weix DJ. Ueno S. Hartwig JF. Org. Lett.  2007,  9:  3949 
  • 19c Singh OV. Han H. Tetrahedron Lett.  2007,  48:  7094 
  • 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 
  • 21a Tissot-Croset K. Polet D. Gille S. Hawner C. Alexakis A. Synthesis  2004,  2586 
  • 21b Polet D. Alexakis A. Tissot-Croset K. Corminboeuf C. Ditrich K. Chem. Eur. J.  2006,  12:  3596 
  • 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 
  • For previous syntheses, see:
  • 23a Pedder DJ. Fales HM. Jaouni T. Blum M. MacConnell J. Crewe RM. Tetrahedron  1976,  32:  2275 
  • 23b Tufariello JJ. Puglis JM. Tetrahedron Lett.  1986,  27:  1489 
  • 23c Wistrand L.-G. Skinjar M. Tetrahedron  1991,  47:  573 
  • 23d Oppolzer W. Bochet CG. Merifield E. Tetrahedron Lett.  1994,  35:  7015 
  • 23e Arredondo VM. Tian S. McDonald FE. Marks T. J. Am. Chem. Soc.  1999,  121:  3633 
  • 24a Tang TP. Volkman SK. Ellman JA. J. Org. Chem.  2001,  66:  8772 
  • 24b Côtè A. Charette AB. J. Am. Chem. Soc.  2008,  130:  2771 
  • For a review, see:
  • 25a Alvaro G. Savoia D. Synlett  2002,  651 
  • 25b Yamada H. Kawate T. Nishida A. Nakagawa M. J. Org. Chem.  1999,  64:  8821 
  • 25c Takemoto Y. Takeuchi J. Iwata C. Tetrahedron Lett.  1993,  34:  6069 
  • 25d Bandini M. Cozzi PG. Umani-Ronchi A. Villa M. Tetrahedron  1999,  55:  8103 
  • 26 We used apparatus described in: Bartels B. Garcia-Yebra C. Helmchen G. Eur. J. Org. Chem.  2003,  1097 
  • 27 Our procedure complements Buchwald’s similarly short asymmetric hydrogenation route: Willoughby CA. Buchwald SL. J. Am. Chem. Soc.  1994,  116:  8952 
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.