Development of a Tandem Base-Catalyzed, Triphenylphosphine-Mediated Disulfide Reduction-Michael Addition

Abstract

A tandem disulfide reduction-Michael addition was developed using both free and polymer-bound triphenylphosphine as the reducing agent. The procedure was applied to intermolecular systems for the synthesis of arylsulfanyl- and alkylsulfanyl-substituted propanoates and related ketones, and to an intramolecular system for the synthesis of a benzothiazepinone derivative.

Key words

Michael additions - reductions - thiols - triphenylphosphine - benzothiazepinones

References

• 1a Kanda Y. Ashizawa T. Kawashima K. Ikeda S. Tamaoki T. Bioorg. Med. Chem. Lett.  2003,  13:  455 
• 1b Cai Z. Zhou W. Sun L. Bioorg. Med. Chem.  2007,  15:  7809 
• 1c Tyrkov A. Urlyapova N. Daudova A. Pharm. Chem. J.  2006,  40:  377 
• 1d Kendall J. Rewcastle G. Frederick R. Mawson C. Denny W. Marshall E. Baguley B. Chaussade C. Jackson S. Shepherd P. Bioorg. Med. Chem.  2007,  15:  7677 
• 1e Lombart HG. Feyfant E. Joseph-McCarthy D. Huang A. Lovering F. Sun LH. Zhu Y. Zeng CM. Zhang Y. Levin J. Bioorg. Med. Chem. Lett.  2007,  17:  4333 
• 2a Wang X. Guo Z. Anti-Cancer Agents Med. Chem.  2007,  7:  19 
• 2b Jacob C. Nat. Prod. Rep.  2006,  23:  851 
• 2c Ariga T. Seki T. BioFactors  2006,  26:  93 
• 2d Motohashi N. Kawase M. Satoh K. Sakagami H. Curr. Drug Targets  2006,  7:  1055 
• 3a Liu Y. Zhang HY. Chen LX. He XW. Wada T. Inoue Y. J. Org. Chem.  2000,  65:  2870 
• 3b Yano T. Wasada-Tsutsui Y. Arii H. Yamaguchi S. Funahashi Y. Ozawa T. Masuda H. Inorg. Chem.  2007,  46:  10345 
• 3c Calatayud D. López-Torres E. Mendiola M. Inorg. Chem.  2007,  46:  10434 
• 3d Enders D. Klumpen T. J. Organomet. Chem.  2001,  637:  698 
• 4 van Zanten A. Oudijk M. Nohlmans-Paulssen M. van der Meer Y. Girbes A. Polderman K. Br. J. Clin. Pharmacol.  2007,  63:  100 
• 5a Brown HC. Midland MM. J. Am. Chem. Soc.  1971,  93:  3291 
• 5b Pelter A. Pardasani R. Pardasani P. Tetrahedron  2000,  56:  7339 
• 5c Kneisel F. Knochel P. Synlett  2002,  1799 
• 6a Munavalli S. Rossman DI. Rohrbaugh DK. Ferguson CP. J. Fluorine Chem.  1993,  61:  147 
• 6b Munavalli S. Rossman DI. Rohrbaugh DK. Ferguson CP. J. Fluorine Chem.  1993,  61:  155 
• 6c Negishi E. In Organometallics in Organic Synthesis   Wiley; New York: 1980.  p.243-247  
• 7a Menichetti S. Nativi C. In Targets in Heterocyclic Systems - Chemistry and Properties   Vol. 7:  Attanasi OA. Spinelli D. Società Chimica Italiana; Rome: 2003.  p.108-139  
• 7b Bartolozzi A. Capozzi G. Menichetti S. Nativi C. Org. Lett.  2000,  2:  251 
• 7c Bartolozzi A. Capozzi G. Menichetti S. Nativi C. Eur. J. Org. Chem.  2001,  2083 
• 7d Li GM. Niu S. Segi M. Tanaka K. Nakajima T. Zingaro RA. Reibenspies JH. Hall MB. J. Org. Chem.  2000,  65:  6601 
• 7e Osborn HMI. Coisson D. Mini-Rev. Org. Chem.  2004,  1:  41 
• 7f Ogurtsov V. Rakitin O. Rees C. Smolentsev A. Belyakov P. Golovanov D. Lyssenko K. Org. Lett.  2005,  7:  791 
• 8a Ueda M. Uchiyama K. Kano T. Synthesis  1984,  323 
• 8b Graybill BM. J. Org. Chem.  1967,  32:  2931 
• 9a Carlson R. Lundstedt T. Acta Chem. Scand., Ser. B  1987,  41:  164 
• 9b Lundstedt T. Carlson R. Shabana R. Acta Chem. Scand., Ser. B  1987,  41:  157 
• 9c Oae S. In The Organic Chemistry of Sulfur   Oae S. Plenum; New York: 1977.  p.58-63  
• 10a Ranu B. Dey S. Hajra A. Tetrahedron  2003,  59:  2417 
• 10b Merajuddin Baag M. Sahoo M. Puranik V. Argade N. Synthesis  2007,  457 
• 10c Hummel G. Jobron L. Hindsgaul O. J. Carbohydr. Chem.  2003,  22:  781 
• 10d Kawatsura M. Komatsu Y. Yamamoto M. Hayase S. Itoh T. Tetrahedron Lett.  2007,  48:  6480 
• 10e Zhao Y. Ge Z. Cheng T. Li R. Synlett  2007,  1529 
• 10f Hiemstra C. van der Aa L. Zhong Z. Dijkstra P. Feijen J. Biomacromolecules  2007,  8:  1548 
• 10g Nilsson K. Mellin L. Nederberg F. Bowden T. Macromolecules  2007,  40:  901 
• 10h Meciarova M. Toma S. Lett. Org. Chem.  2006,  3:  794 
• 10i Manickam G. Sundararajan G. Tetrahedron  1999,  55:  2721 
• 10j Mukherjee C. Misra AK. J. Carbohydr. Chem.  2007,  26:  213 
• 10k Movassagh B. Zakinezhad Y. Z. Naturforsch., B  2006,  61:  47 
• 11a Prabhu K. Sivanand P. Chandrasekaran S. Angew. Chem. Int. Ed.  2000,  39:  4316 
• 11b Ranu B. Synth. Commun.  2007,  37:  1517 
• 11c Ranu B. Mandal T. Can. J. Chem.  2006,  84:  762 
• 11d Ranu B. Mandal T. Synlett  2004,  1239 
• 11e Friend C. Simpkins N. Anson M. Polywka M. Tetrahedron  1998,  54:  2801 
• 11f Taniguchi Y. Maruo M. Takaki K. Fujiwara Y. Tetrahedron Lett.  1994,  35:  7789 
• 11g Zheng X. Xu X. Zhang Y. Synlett  2003,  2062 
• 12a Ogawa A. Nishiyama Y. Kambe N. Murai S. Sonoda N. Tetrahedron Lett.  1987,  28:  3271 
• 12b Katritzky AR. Rogovoy BV. Chassaing C. Vvedensky V. Forood B. Flatt B. Nakai H. J. Heterocycl. Chem.  2000,  37:  1655 
• 13a Danehy JP. Hunter WE. J. Org. Chem.  1967,  32:  2047 
• 13b Maiti SN. Spevak P. Singh MP. Micetich RG. Reddy AVN. Synth. Commun.  1988,  18:  575 
• 13c Brown HC. Nazer B. Cha JS. Synthesis  1984,  498 
• 13d Gladysz JA. Wong VK. Jick BS. Tetrahedron  1979,  35:  2329 
• 13e Zhong W. Zhang Y. Tetrahedron Lett.  2001,  42:  3125 
• 13f Reddy GVS. Rao GV. Iyengar DS. Synth. Commun.  2000,  30:  859 
• 13g Singh R. Lamoureux GV. Lees WJ. Whitesides GM. Methods Enzymol.  1995,  251:  167 
• 14 Overman LE. Smoot J. Overman JD. Synthesis  1974,  59 
• 16a Krapcho J. Turk CF. Piala JJ. J. Med. Chem.  1968,  11:  361 
• 16b Ohno S. Izumi K. Mizukoshi K. Kato K. Hori M. Chem. Pharm. Bull.  1983,  31:  1780 
• 16c Kugita H. Inoue H. Ikezaki M. Konda M. Takeo S. Chem. Pharm. Bull.  1971,  19:  595 
• 16d Tseng TC. Wu MJ. Tetrahedron: Asymmetry  1995,  6:  1633 
• 17a Hansson L. Hedner T. Lund-Johansen P. Kjeldsen S. Lindholm L. Syvertsen J. Lanke J. de Faire U. Dahlöf B. Karlberg B. Lancet  2000,  356:  359 
• 17b Khatik GL. Kumar R. Chakraborti AK. Synthesis  2007,  541 
• 17c Kodomari M. Noguchi T. Aoyama T. Synth. Commun.  2004,  34:  1783 
• 17d Bertozzi F. Gundersen BV. Gustafsson M. Olsson R. Org. Lett.  2003,  5:  1551 
• 17e Cavalli A. Poluzzi E. De Ponti F. Recanatini M. J. Med. Chem.  2002,  45:  3844 
• 18a Solinas A. Taddei M. Synthesis  2007,  2409 
• 18b Kirschning A. Monenschein H. Wittenberg R. Angew. Chem. Int. Ed.  2001,  40:  650 
• 19 Nakahashi A. Fujita M. Miyoshi E. Umeyama T. Naka K. Chujo Y. J. Polym. Sci., Part A: Polym. Chem.  2007,  45:  3580 
• 20 Saloutina LV. Zapevalov AYa. Saloutin VI. Kodess MI. Kirichenko VE. Pervova MG. Chupakhin ON. Russ. J. Org. Chem. (Engl. Transl.)  2006,  42:  1307 

15

The ¹H NMR spectra of the isolated products confirmed the presence of a free hydroxy group as we would expect for compounds derived by thiol addition. The thiol moiety of 4-sulfanylphenol is the strongest and the most-reactive nucleophile in the compound as it has a pK _a of 6.8 compared with the hydroxy group pK _a of 12.4. However, the phenol is still a reactive species that could possibly undergo Michael addition under basic conditions if the disulfide reduction was too slow and the more-reactive thiol was not formed quickly enough. To confirm that the disulfide reduction occurred first in our protocol and that side products derived from a phenol addition were not formed, we repeated the experiment reported in entry 1 of Table [1] without adding triphenylphosphine. In this case, phenol addition was not observed, even after heating the reaction overnight.

21

¹H NMR spectra in accordance with data reported in the Wiley Subscription Services Inc., USA.