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Synthesis 2011(23): 3827-3838  
DOI: 10.1055/s-0030-1260260
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Asymmetric Syntheses of S,S-Dialkyl-Substituted Sulfoximines and Related Heterocycles

Ankur G. Pandey, Matthew J. McGrath, Olga García Mancheño, Carsten Bolm*
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52056 Aachen, Germany
Fax: +49(241)8092391; e-Mail: Carsten.Bolm@oc.rwth-aachen.de;
Further Information

Publication History

Received 30 August 2011
Publication Date:
17 October 2011 (online)

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Abstract

Enantiomerically enriched forms of a sulfoximine-based myristic acid analogue are prepared using either an asymmetric desymmetrization with a chiral base, or an enantioselective oxidation procedure as key steps. Additionally, a variety of 2-oxa-2-alkyl 3,4-dihydro 2,1-benzothiazines are synthesized via intramolecular metal­-catalyzed N-arylation of appropriately functionalized sulfoximines with tethered 2-bromoaryl substituents. In turn, the sulfoximines are prepared by lithiation-alkylation sequences including enantioselective deprotonation steps or the use of an optically active sulfoxide. Using this methodology, the range of accessible 3,4-dihydro 2,1-benzothiazine derivatives is expanded.

Key words

alkyl sulfoximines - dihydro benzothiazines - desymmetrization - cyclizations - copper

    References

  • For reviews, see:
  • 1a Reggelin M. Zur C. Synthesis  2000,  1 
    Google Scholar
  • 1b Harmata M. Chemtracts  2003,  16:  660 
    Google Scholar
  • 1c Okamura H. Bolm C. Chem. Lett.  2004,  33:  482 
    Google Scholar
  • 1d Bolm C. In Asymmetric Synthesis with Chemical and Biological Methods   Enders D. Jaeger K.-E. Wiley-VCH; Weinheim: 2007.  p.149 
    Google Scholar
  • 1e Worch C. Mayer AC. Bolm C. In Organosulfur Chemistry in Asymmetric Synthesis   Toru T. Bolm C. Wiley-VCH; Weinheim: 2008.  p.209 
    Google Scholar
  • 1f Bentley R. Chem. Soc. Rev.  2005,  34:  609 
    Google Scholar
  • 2 For recent patents involving sulfoximines, see references 3 and 4 in: García Mancheño O. Dallimore J. Plant A. Bolm C. Adv. Synth. Catal.  2010,  352:  309 
    Google Scholar
  • 3a Bentley HR. McDermott EE. Pace J. Whitehead JK. Moran T. Nature  1950,  165:  150 
    Google Scholar
  • 3b Bentley HR. McDermott EE. Whitehead JK. Nature  1950,  165:  735 
    Google Scholar
  • 4 For a key publication in this area, see: Brandt J. Gais H.-J. Tetrahedron: Asymmetry  1997,  8:  909 
    Google Scholar
  • For early reports on the inhibitory activity of methionine sulfoximine, see:
  • 5a Pace J. McDermott EE. Nature  1952,  169:  415 
    Google Scholar
  • 5b Meister A. Science  1983,  220:  472 
    Google Scholar
  • From these and subsequent studies it is known that for this particular dialkyl sulfoximine the (S,S)-diastereoisomer is the most active.
  • 6 For a recent example, where a mixture of stereoisomers of buthionine sulfoximine (BSO) was used to study induced apoptotic cell death, see: Takahashi K. Tatsunami R. Oba T. Tampo Y. Biol. Pharm. Bull.  2010,  33:  556 
    Google Scholar
  • 7 McDonald IA. Nyce PL. Ku GS. Bowlin TL. Bioorg. Med. Chem. Lett.  1993,  3:  1717 
    Google Scholar
  • 8 Jackson TE. inventors; (Sandoz-Wander, Inc., USA) US Patent  4031227.  ; Chem. Abstr. 1977, 87, 102318
  • 9 McGrath MJ. Bolm C. Beilstein J. Org. Chem.  2007,  3:  33 
    Google Scholar
  • 10a Kagan HB. Dunach E. Nemecek C. Pitchen P. Samuel O. Zhao S.-H. Pure Appl. Chem.  1985,  1911 
    Google Scholar
  • 10b Capozzi MAM. Cardellicchio C. Naso F. Tortorella P. J. Org. Chem.  2000,  65:  2843 
    Google Scholar
  • 10c For a review, see: Capozzi MAM. Cardellicchio C. Naso F. Eur. J. Org. Chem.  2004,  1855 
    Google Scholar
  • For syntheses of structurally related 2,1-benzothiazine and 1,2-benzoisothiazole derivatives by alternative pathways, see:
  • 11a Harmata M. Kahraman M. J. Org. Chem.  1998,  63:  6845 
    Google Scholar
  • 11b Harmata M. Pavri N. Angew. Chem. Int. Ed.  1999,  38:  2419 
    Google Scholar
  • 11c Hong X. Harmata M. J. Am. Chem. Soc.  2003,  125:  5754 
    Google Scholar
  • 11d Harmata M. Rayanil K.-o. Gomes MG. Zheng P. Calkins NL. Kim S.-Y. Fan Y. Bumbu V. Lee DR. Wacharasindhu S. Hong X. Org. Lett.  2005,  7:  143 
    Google Scholar
  • 11e Harmata M. Calkins NL. Baughman RG. Barnes CL. J. Org. Chem.  2006,  71:  3650 
    Google Scholar
  • 11f Harmata M. Chen Y. Barnes CL. Org. Lett.  2007,  9:  4701 
    Google Scholar
  • 11g Harmata M. Ying W. Hong X. Barnes CL. Synthesis  2008,  594 
    Google Scholar
  • 11h Harmata M. Rayanil K.-o. Espejo VR. Barnes CL. J. Org. Chem.  2009,  74:  3214 
    Google Scholar
  • 11i Harmata M. Cai Z. Chen Y. J. Org. Chem.  2009,  74:  5559 
    Google Scholar
  • 11j For a review, see: Harmata M. Hong X. Prog. Heterocycl. Chem.  2008,  19:  1 
    Google Scholar
  • 12 For the synthesis of isomeric dihydro benzothiazines by intramolecular α-arylation of sulfoximines, see: Bolm C. Okamura H. Verrucci M. J. Organomet. Chem.  2003,  687:  444 
    Google Scholar
  • 13 For the possible precision of such data, see: Wernerova M. Hudlicky T. Synlett  2010,  2701 
    Google Scholar
  • 14a García Mancheño O. Dallimore J. Plant A. Bolm C. Org. Lett.  2009,  11:  2429 
    Google Scholar
  • 14b

    See also reference 2.

  • 15 Taylor S. Gullick J. McMorn P. Bethell D. Page PCB. Hancock EF. King F. Hutchings GJ. Top. Catal.  2003,  24:  43 
    Google Scholar
  • 16a For pioneering work on the use of the nosyl group, see: Fukuyama T. Jow C.-K. Cheung M. Tetrahedron Lett.  1995,  36:  6373 
    Google Scholar
  • 16b Here the N-nosyl deprotection was performed following procedures reported in: Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   3rd ed.:  John Wiley & Sons; New York: 1999.  p.603 
    Google Scholar
  • 17 Johnson CR. Kirchoff RA. Reischer RJ. Katekar GF. J. Am. Chem. Soc.  1973,  95:  4287 
    Google Scholar
  • 18a N-Cyano sulfoximine 7d was prepared following reported procedures, see: García Mancheño O. Bistri O. Bolm C. Org. Lett.  2007,  9:  3809 
    Google Scholar
  • 18b See also in: Pandey A. Bolm C. Synthesis  2010,  2922 
    Google Scholar
  • 19a Bolm C. Hildebrand JP. Tetrahedron Lett.  1998,  39:  5731 
    Google Scholar
  • 19b Bolm C. Hildebrand JP. J. Org. Chem.  2000,  65:  169 
    Google Scholar
  • 19c Bolm C. Hildebrand JP. Rudolph J. Synthesis  2000,  911 
    Google Scholar
  • 19d Bolm C. Martin M. Gibson L. Synlett  2002,  832 
    Google Scholar
  • See also:
  • 19e Harmata M. Hong X. Ghosh SK. Tetrahedron Lett.  2004,  45:  5233 
    Google Scholar
  • 19f Harmata M. Hong X. Synlett  2007,  969 
    Google Scholar
  • 20a Bolm C. Sedelmeier J. J. Org. Chem.  2005,  70:  6904 
    Google Scholar
  • 20b For a related copper-mediated N-arylation, see: Cho G.-Y. Rémy P. Jansson J. Moessner C. Bolm C. Org. Lett.  2004,  6:  3293 
    Google Scholar
  • For the synthesis of tert-butylthiosulfinate, see:
  • 22a Weix DJ. Ellman JA. Org. Lett.  2003,  5:  1317 
    Google Scholar
  • 22b Blum SA. Bergman RG. Ellman JA. J. Org. Chem.  2003,  68:  150 
    Google Scholar
  • 22c Cogan DA. Liu G. Kim K. Backes BJ. Ellman JA. J. Am. Chem. Soc.  1998,  120:  8011 
    Google Scholar
  • 22d Liu G. Cogan DA. Ellman JA. J. Am. Chem. Soc.  1997,  119:  9913 
    Google Scholar
  • 22e Weix DJ. Ellman JA. Org. Synth.  2005,  82:  157 
    Google Scholar
  • 24a García Mancheño O. Bolm C. Org. Lett.  2006,  8:  2349 
    Google Scholar
  • 24b See also: García Mancheño O. Bolm C. Chem. Eur. J.  2007,  13:  6674 
    Google Scholar
21

The relative configuration of diastereoisomeric 4-methyl substituted benzothiazines 9b and 9b′ was assigned by comparison with the NMR patterns of reported 4-alkyl substituted analogues (see reference 11a). Accordingly, the relative configuration of their precursors 8b and 8b′ was also established.

23

The enantiomeric ratio of 19 was determined by HPLC: Daicel Chiralpack AS, heptane-i-PrOH, 97:3, 0.9 mL˙min-¹, 254 nm, t R1 = 6.3 min, t R2 = 7.7 min.

25

The absolute configuration of 7e could be deduced by considering that the nucleophilic substitution of 19 proceeded with inversion of configuration and that the imination occurred under retention. For respective details, see references 22 and 24.