Stereoselective Total Synthesis
of (-)-β-Conhydrine and (+)-α-Conhydrine

Efraim Reyes; Nerea Ruiz; Jose L. Vicario; Dolores Badía; Luisa Carrillo

doi:10.1055/s-0030-1258390

PAPER

Stereoselective Total Synthesis of (-)-β-Conhydrine and (+)-α-Conhydrine

Efraim Reyes, Nerea Ruiz, Jose L. Vicario*, Dolores Badía*, Luisa Carrillo
Departamento de Química Orgánica II, Facultad de Ciencia y Tecnología, Universidad del País Vasco/Euskal Herriko Unibertsitatea, P. O. Box 644, 48080 Bilbao, Spain
Fax: +34(94)6012748; e-Mail: dolores.badia@ehu.es; e-Mail: joseluis.vicario@ehu.es;

Abstract

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Abstract

We have carried out the stereoselective synthesis of (-)-β-conhydrine and (+)-α-conhydrine, two bioactive α-hydroxyalkyl-substituted piperidines, using the commercially available and inexpensive amino alcohol (S,S)-(+)-pseudoephedrine as chiral auxiliary. The key step of this synthesis relies on new methodology previously developed in our group, consisting of the chemo- and diastereoselective addition of Grignard reagents across the C=N bond of α-iminoglyoxylamides derived from (S,S)-(+)-pseudoephedrine followed by the selective monoaddition of organolithium reagents to the carbamoyl group, leading to the formation of enantioenriched α-amino ketones.

Key words

asymmetric synthesis - chiral auxiliaries - piperidines - total synthesis - conhydrine

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References

<A NAME="RT19910SS-1A">1a</A> Michael JP. Nat. Prod. Rep. 1997, 14: 619

<A NAME="RT19910SS-1B">1b</A> Casiraghi G. Zanardi F. Rassu G. Spanu P. Chem. Rev. 1995, 95: 1677

<A NAME="RT19910SS-2">2</A> Wertheim T. Liebigs Ann. Chem. 1856, 100: 328

<A NAME="RT19910SS-3A">3a</A> Wardrop DJ. Bowen EG. Forslund RE. Sussman AD. Weerasekera SL. J. Am. Chem. Soc. 2010, 132: 1188

<A NAME="RT19910SS-3B">3b</A> Beak P. Lee WK. J. Org. Chem. 1993, 58: 1109

<A NAME="RT19910SS-3C">3c</A> Pilard S. Vaultier M. Tetrahedron Lett. 1984, 25: 1555

<A NAME="RT19910SS-3D">3d</A> Shono T. Matsumura Y. Kanazawa T. Tetrahedron Lett. 1983, 24: 4577

<A NAME="RT19910SS-3E">3e</A> Stock G. Jacobson RM. Levitz R. Tetrahedron Lett. 1979, 20: 771

<A NAME="RT19910SS-3F">3f</A> Galinovsky F. Mulley H. Monatsh. Chem. 1948, 79: 426

<A NAME="RT19910SS-4A">4a</A> Shaikh TM. Sudalai A. Eur. J. Org. Chem. 2010, 3437

<A NAME="RT19910SS-4B">4b</A> Bandini E. Corda G. D’Aurizio A. Panunzio M. Tetrahedron Lett. 2010, 51: 933

<A NAME="RT19910SS-4C">4c</A> Kamal A. Vangala SR. Subba Reddy NV. Santhosh Reddy V. Tetrahedron: Asymmetry 2009, 20: 2589

<A NAME="RT19910SS-4D">4d</A> Liu S. Xie J.-H. Li W. Kong W.-L. Wang L.-X. Zhou Q.-L. Org. Lett. 2009, 11: 4994

<A NAME="RT19910SS-4E">4e</A> Venkataiah M. Fadnavis NW. Tetrahedron 2009, 65: 6950

<A NAME="RT19910SS-4F">4f</A> Srivastava AK. Das SK. Panda G. Tetrahedron 2009, 65: 5322

<A NAME="RT19910SS-4G">4g</A> Roy S. Sharma A. Mula S. Chattopadhyay S. Chem. Eur. J. 2009, 15: 1713

<A NAME="RT19910SS-4H">4h</A> Rodriguez D. Pico A. Moyano A. Tetrahedron Lett. 2008, 49: 6866

<A NAME="RT19910SS-4I">4i</A> Saikia PP. Baishya G. Goswami A. Barua NC. Tetrahedron Lett. 2008, 49: 6508

<A NAME="RT19910SS-4J">4j</A> Lebrun S. Couture A. Deniau E. Grandclaudon P. Tetrahedron: Asymmetry 2008, 19: 1245

<A NAME="RT19910SS-4K">4k</A> Jamieson AG. Sutherland A. Org. Lett. 2007, 8: 1609

<A NAME="RT19910SS-4L">4l</A> Voituriez A. Ferreira F. Chemla F. J. Org. Chem. 2007, 72: 5358

<A NAME="RT19910SS-4M">4m</A> Chang M.-Y. Kung Y.-H. Chen S.-T. Tetrahedron 2006, 62: 10843

<A NAME="RT19910SS-4N">4n</A> Pandey SK. Kumar P. Tetrahedron Lett. 2005, 46: 4091

<A NAME="RT19910SS-4O">4o</A> Kandula SV. Kumar P. Tetrahedron: Asymmetry 2005, 16: 3268

<A NAME="RT19910SS-4P">4p</A> Kandula SV. Kumar P. Tetrahedron Lett. 2003, 44: 1957

<A NAME="RT19910SS-4Q">4q</A> Enders D. Nolte B. Raabe G. Runsink J. Tetrahedron: Asymmetry 2002, 13: 285

<A NAME="RT19910SS-4R">4r</A> Agami C. Couty F. Rabasso N. Tetrahedron 2001, 57: 5393

<A NAME="RT19910SS-4S">4s</A> Comins DL. Williams AL. Tetrahedron Lett. 2000, 41: 2839

<A NAME="RT19910SS-4T">4t</A> Guerreiro P. Ratovelomanana-Vidal V. Genêt J.-P. Chirality 2000, 12: 408

<A NAME="RT19910SS-4U">4u</A> Masaki Y. Imaeda T. Nagata K. Oda H. Ito A. Tetrahedron Lett. 1989, 30: 6393

<A NAME="RT19910SS-5">5</A> Ruiz N. Vicario JL. Badía D. Carrillo L. Alonso B. Org. Lett. 2008, 10: 2613

For the first use of pseudoephedrine as chiral auxiliary, see:

<A NAME="RT19910SS-6A">6a</A> Myers AG. Yang BH. Chen H. Gleason JL. J. Am. Chem. Soc. 1994, 116: 9361

<A NAME="RT19910SS-6B">6b</A> Myers AG. Chen H. McKinstry L. Kopecky DJ. Gleason JL. J. Am. Chem. Soc. 1997, 119: 6496

For a review, see:

<A NAME="RT19910SS-6C">6c</A> Myers AG. Charest MG. Handbook of Reagents for Organic Synthesis: Chiral Reagents for Asymmetric Synthesis Paquette LA. Wiley Interscience; New York: 2003. p.485

For other examples, see:

<A NAME="RT19910SS-6D">6d</A> Iza A. Vicario JL. Badía D. Carrillo L. Synthesis 2006, 4065

<A NAME="RT19910SS-6E">6e</A> Reyes E. Vicario JL. Badía D. Carrillo L. Iza A. Uria U. Org. Lett. 2006, 8: 2535

<A NAME="RT19910SS-6F">6f</A> Reyes E. Vicario JL. Badía D. Carrillo L. Uria U. Iza A. J. Org. Chem. 2006, 71: 7763

<A NAME="RT19910SS-6G">6g</A> Etxeberria J. Vicario JL. Badía D. Carrillo L. Ruiz N. J. Org. Chem. 2005, 70: 8790

<A NAME="RT19910SS-6H">6h</A> Etxebarria J. Vicario JL. Badía D. Carrillo L. J. Org. Chem. 2004, 69: 2588

<A NAME="RT19910SS-6I">6i</A> Smitrovich JH. Boice GN. Qu C. Dimichelle L. Nelson TD. Huffman MA. Murry J. McNamara J. Reider PJ. Org. Lett. 2002, 4: 1

<A NAME="RT19910SS-6J">6j</A> Hutchison PC. Heightman TD. Procter DJ. Org. Lett. 2002, 4: 4583

<A NAME="RT19910SS-6K">6k</A> Vicario JL. Badía D. Carrillo L. J. Org. Chem. 2001, 66: 5801

<A NAME="RT19910SS-6L">6l</A> Vicario JL. Badía D. Carrillo L. J. Org. Chem. 2001, 66: 9030

<A NAME="RT19910SS-6M">6m</A> Anakabe E. Vicario JL. Badía D. Carrillo L. Yoldi V. Eur. J. Org. Chem. 2001, 4343

<A NAME="RT19910SS-6N">6n</A> Myers AG. Barbay JK. Zhong B. J. Am. Chem. Soc. 2001, 123: 7207

<A NAME="RT19910SS-6O">6o</A> Vicario JL. Badía D. Domínguez E. Carrillo M. J. Org. Chem. 1999, 64: 4610

<A NAME="RT19910SS-6P">6p</A> Vicario JL. Badía D. Domínguez E. Rodríguez M. Carrillo L. J. Org. Chem. 2000, 65: 3754

<A NAME="RT19910SS-6Q">6q</A> Myers AG. McKinstry L. J. Org. Chem. 1996, 61: 2428

For a detailed study, see ref. 6b. For other related examples, see:

<A NAME="RT19910SS-7A">7a</A> Zhou X.-T. Lu L. Furkert DP. Wells CE. Carter RG. Angew. Chem. Int. Ed. 2006, 45: 7622

<A NAME="RT19910SS-7B">7b</A> Robertson J. Dallimore JWP. Meo P. Org. Lett. 2004, 6: 3857

<A NAME="RT19910SS-7C">7c</A> White JD. Xu Q. Lee C.-S. Valeriote FA. Org. Biomol. Chem. 2004, 2: 2092

<A NAME="RT19910SS-7D">7d</A> Vicario JL. Rodriguez M. Badía D. Carrillo L. Reyes E. Org. Lett. 2004, 6: 3171

<A NAME="RT19910SS-7E">7e</A> Vicario JL. Badía D. Carrillo L. Tetrahedron: Asymmetry 2002, 13: 745

<A NAME="RT19910SS-7F">7f</A> Smith AB. Adams CM. Kozmin SA. Paone DV. J. Am. Chem. Soc. 2001, 123: 5925 ; see also ref. 6n

<A NAME="RT19910SS-8">8</A> See, for example: Trnka TN. Grubbs RH. Acc. Chem. Res. 2001, 34: 18 ; see also ref. 10

<A NAME="RT19910SS-9A">9a</A> Fraser DS. Park SB. Chong JM. Can. J. Chem. 2004, 82: 87

<A NAME="RT19910SS-9B">9b</A> Ordonez M. De la Cruz-Cordero R. Quinones C. Gonzalez-Morales A. Chem. Commun. 2004, 672