A Mild Synthetic Procedure for the Preparation of N-Alkylated Sulfoximines

Abstract

N-Alkylated sulfoximines have been synthesized in good yields by acylation of NH-sulfoximines followed by carbonyl reduction with complexed boranes. Enantiopure substrates react without racemization, and stereogenic centers originating from the acylating component are retained. If the acylation is performed by DCC coupling, this two-step procedure represents a rare example of a formal N-alkylation of sulfoximines under base-free conditions.

Keywords

acylation - borane - chirality - reduction - sulfoximine

References and Notes

• 1a Johnson CR. Aldrichimica Acta  1985,  18:  3 
• 1b Johnson CR. Acc. Chem. Res.  1973,  6:  341 
• 1c Johnson CR. In Comprehensive Organic Chemistry   Vol. 3:  Barton D. Ollis WD. Pergamon Press; Oxford: 1979.  p.223 
• 1d Pyne SG. Sulfur Rep.  1992,  12:  57 
• 1e Reggelin M. Zur C. Synthesis  2000,  1 
• For representative examples see:
• 2a Pyne SG. Dong Z. Skelton BW. White AH. J. Org. Chem.  1997,  62:  2337 
• 2b Reggelin M. Heinrich T. Angew. Chem. Int. Ed.  1998,  37:  2883 ; Angew. Chem. 1998, 110, 3005
• 2c Bosshammer S. Gais H.-J. Synthesis  1998,  919 
• 2d Hachtel J. Gais H.-J. Eur. J. Org. Chem.  2000,  1457 
• 2e Gais H.-J. Loo R. Das P. Raabe G. Tetrahedron Lett.  2000,  41:  2851 
• 2f Paquette LA. Gao Z. Ni Z. Smith GF. J. Am. Chem. Soc.  1998,  120:  2543 
• 2g Harmata M. Kahraman M. Jones DE. Pavri N. Weatherwax SE. Tetrahedron  1998,  54:  9995 
• 2h Harmata M. Pavri N. Angew. Chem. Int. Ed.  1999,  38:  2419 ; Angew. Chem. 1999, 111, 2577
• 2i Bolm C. Muñiz K. Aguilar N. Kesselgruber M. Raabe G. Synthesis  1999,  1251 
• 2j Bolm C. Kesselgruber M. Muñiz K. Raabe G. Organometallics  2000,  19:  1648 
• 3a Bolm C. Felder M. Müller J. Synlett  1992,  439 
• 3b Bolm C. Felder M. Tetrahedron Lett.  1993,  34:  6041 
• 3c Bolm C. Müller J. Schlingloff G. Zehnder M. Neuburger M. J. Chem. Soc., Chem. Commun.  1993,  182 
• 3d Bolm C. Seeger A. Felder M. Tetrahedron Lett.  1993,  34:  8079 
• 3e Bolm C. Felder M. Synlett  1994,  655 
• 3f Bolm C. Müller P. Tetrahedron Lett.  1995,  36:  1625 
• 3g Bolm C. Müller P. Acta Chem. Scand.  1996,  50:  305 
• 3h Bolm C. Kaufmann D. Zehnder M. Neuburger M. Tetrahedron Lett.  1996,  37:  3985 
• 3i Bolm C. Simić O. J. Am. Chem. Soc.  2001,  123:  3830 
• 3j Harmata M. Ghosh SK. Org. Lett.  2001,  3:  3321 
• 4a Bolm C. Kahmann JD. Moll G. Tetrahedron Lett.  1997,  38:  1169 
• 4b Bolm C. Moll G. Kahmann JD. Chem.-Eur. J.  2001,  7:  1118 
• 4c Bolm C. Müller D. Hackenberger CPR. Org. Lett.  2002,  4:  893 
• 5a Fusco R. Tericoni F. Chim. Ind.  1965,  47:  61 
• 5b Johnson CR. Schroeck CW. J. Am. Chem. Soc.  1973,  95:  7418 
• 5c Shiner CS. Berks AH. J. Org. Chem.  1988,  53:  5542 
• 5d Mori K. Toda F. Chem. Lett.  1988,  1997 
• 5e Brandt J. Gais H.-J. Tetrahedron: Asymmetry  1997,  6:  909 
• 6a Tamura Y. Sumoto K. Minamikawa J. Ikeda M. Tetrahedron Lett.  1972,  37:  4137 
• 6b Johnson CR. Kirchhoff RA. Corkins HG. J. Org. Chem.  1974,  39:  2458 
• 6c Müller JFK. Vogt P. Tetrahedron Lett.  1998,  39:  4805 
• 6d Bach T. Körber C. Eur. J. Org. Chem.  1999,  1033 
• 6e Lacote E. Amatore M. Fensterbank L. Malacria M. Synlett  2002,  116 
• 7a Kagan HB. Diter P. In Organosulfur Chemistry   Vol. 2:  Page PCB. Academic Press; New York: 1998.  p.1 
• 7b Kagan HB. Luukas T. In Transition Metals for Organic Synthesis   Vol. 2:  Beller M. Bolm C. Wiley-VCH; Weinheim: 1998.  p.361 
• 7c Kagan HB. In Catalytic Asymmetric Synthesis   2nd Ed.:  Ojima I. VCH Publisher; New York: 2000.  p.327 
• 7d Bolm C. Muñiz K. In Comprehensive Asymmetric Catalysis   Jacobsen EN. Pfaltz A. Yamamoto H. Springer Verlag; Berlin: 1999.  p.697 
• 8a Andersen KK. Tetrahedron Lett.  1962,  3:  93 
• 8b Andersen KK. J. Org. Chem.  1964,  29:  1952 
• 8c Solladié G. Hutt J. Girardin A. Synthesis  1987,  173 
• 8d Fernandez I. Khiar N. Llera JM. Alcudia F. J. Org. Chem.  1992,  57:  6789 
• 8e Fernandez I. Llera JM. Alcudia F. Tetrahedron Lett.  1991,  32:  7299 
• 8f Guerrero-de la Rosa V. Ordonez M. Llera JM. Alcudia F. Synthesis  1995,  761 
• 8g Capozzi MAM. Cardellicchio C. Naso F. Tortorella P. J. Org. Chem.  2001,  66:  5933 
• 9a Williams TR. Booms RE. Cram DJ. J. Am. Chem. Soc.  1971,  93:  7338 
• 9b Schmidbaur H. Kammer G. Chem. Ber.  1971,  104:  3234 
• 9c Johnson CR. Schroeck CW. Shanklin JR. J. Am. Chem. Soc.  1973,  95:  7424 
• N-Methyl and N-ethyl sulfoximines can also be obtained by alkylations with trialkyloxonium salts:
• 10a Johnson CR. Rigan JJ. Haake M. McCants D. Keiser JE. Gertsema A. Tetrahedron Lett.  1968,  3719 
• 10b Johnson CR. Haake M. Schroeck CW. J. Am. Chem. Soc.  1970,  92:  6594 
• 11a Bolm C. Hildebrand JP. Tetrahedron Lett.  1998,  39:  5731 
• 11b Bolm C. Hildebrand JP. J. Org. Chem.  2000,  65:  169 
• 11c Bolm C. Hildebrand JP. Rudolph J. Synthesis  2000,  911 
• 12 Johnson CR. Lavergne OM. J. Org. Chem.  1993,  58:  1922 
• 13 The NH proton has a pKa value of 243 (compare ref.). For a list of related values see: Bordwell FG. Brance JC. Johnson CR. Vanier NR. J. Org. Chem.  1980,  45:  3884 
• 14 For N-trifluoromethanesulfonations of sulfoximines see: Craig D. Geach NJ. Synlett  1993,  481 
• 15 Brown HC. Heim P. J. Org. Chem.  1973,  38:  912 
• 18 Bolm C. Bienewald F. Harms H. Synlett  1996,  775 
• 19 Bolm C. Simić O. Martin M. Synlett  2001,  1878 
• 22 N-β-Aminoalkylated diarylsulfoximines have been shown for example to be spasmolytically highly active compounds. Satzinger G. Stoss P. Arzneim.-Forsch.  1970,  20:  1214 

16

Both enantiomers of S-methyl-S-phenyl-sulfoximine (1a) are commercially available (Lancaster). To prepare 1a on a large scale we recommend the improved protocol described in ref. [5e]

17

The reaction was monitored by TLC after 4, 8, 16 and 36 hours and quenched when the product formation was complete.

20

For a discussion on this analogy see ref. [18]

21

The sulfoximines mentioned in entries 2 and 3 of Table [2] were prepared from TMS-protected (S)-S-methyl-S-phenyl-sulfoximine by metalation/alkylation sequence. Those shown in entries 4-8 (Table [2] ) were obtained by the procedure described in ref. [6] (MSH imination of the corresponding enantiopure sulfoxide).