Organocatalytic Asymmetric Wittig Reactions: Generation of Enantioenriched Axially Chiral Olefins Breaking a Symmetry Plane

Abstract

The first catalytic asymmetric Wittig reaction is presented. Hydrogen-bond donors catalyze the [2+2] cycloaddition reaction between stabilized phosphorus ylides and 4-substituted cyclohexanones, breaking their symmetry plane and furnishing axially chiral olefins with moderate stereoselectivities.

Key words

asymmetric catalysis - chirality - olefination - Wittig ­reaction - ylides

References and Notes

• Reviews:
• 1a Enantioselective Organocatalysis   Dalko PI. Wiley-VCH; Weinheim: 2007. 
• 1b Asymmetric Organocatalysis   List B. Springer; Berlin: 2009. 
• 1c Special issue on organocatalysis: List B. Chem. Rev.  2007,  107:  5413 
• 2 Eliel E. Stereochemistry of Organic Compounds   Wiley-Interscience; New York: 1994. 
• 3a Bringmann G. Gulder T. Gulder TAM. Breuning M. Chem. Rev.  2011,  111:  563 
• 3b Hoffmann-Röder A. Krause N. Angew. Chem. Int. Ed.  2004,  43:  1196 
• 4a Noyori R. Angew. Chem. Int. Ed.  2002,  41:  2008 
• 4b Brunel JM. Chem. Rev.  2005,  105:  857 
• 4c Akiyama T. Chem. Rev.  2007,  107:  5744 
• 4d Terada M. Synthesis  2010,  1929 
• 4e Fu GC. Acc. Chem. Res.  2004,  37:  542 
• 5a Curran DP. Qi H. Geib SJ. DeMello NC. J. Am. Chem. Soc.  1994,  116:  3131 
• 5b Ma S. Chem. Rev.  2005,  105:  2829 
• 6 Koumura N. Zijlstra LWJ. van Delden LA. Harada N. Feringa BL. Nature (London)  1999,  401:  152 
• For exceptions, see:
• 7a Brandes S. Bella M. Kjærsgaard A. Jørgensen KA. Angew. Chem. Int. Ed.  2006,  45:  1147 
• 7b Liu H. Leow D. Huang K.-W. Tan C.-H. J. Am. Chem. Soc.  2009,  131:  7212 
• 7c Gustafson JL. Lim D. Miller SJ. Science  2010,  328:  1251 
• 7d Cozzi PG. Emer E. Gualandi A. Angew. Chem. Int. Ed.  2011,  50:  3847 
• 8 Wittig G. Geissler G. Justus Liebigs Ann. Chem.  1953,  580:  44 
• 9 Horner L. Hoffmann H. Wippel HG. Chem. Ber.  1958,  91:  61 
• 10a Horner L. Hoffmann H. Wippel HG. Klahre G. Chem. Ber.  1959,  92:  2499 
• 10b Wadsworth WS. Emmons WD. J. Am. Chem. Soc.  1961,  83:  1733. 
• 11a Maryanoff BE. Reitz AB. Chem. Rev.  1989,  89:  863 
• Recent developments:
• 11b O’Brien CJ. Tellez JL. Nixon ZS. Kang LJ. Carter AL. Kunkel SR. Przeworski KC. Chass GA. Angew. Chem. Int. Ed.  2009,  48:  6836 
• 11c Dong D.-J. Li H.-H. Tian S.-K. J. Am. Chem. Soc.  2010,  132:  5018 
• Reviews:
• 12a Brummond KM. DeForrest JE. Synthesis  2007,  795 
• 12b Hoffmann-Röder A. Krause N. Angew. Chem. Int. Ed.  2002,  41:  2933 
• Reviews:
• 13a Rein T. Pedersen TM. Synthesis  2002,  579 
• 13b Li A.-H. Dai L.-X. Aggarwal VK. Chem. Rev.  1997,  97:  2341 
• Representative examples:
• 13c Bestmann HJ. Lienert J. Angew. Chem., Int. Ed. Engl.  1969,  8:  763 
• 13d Hanessian S. Delorme D. Beaudoin S. Leblanc Y.
  J. Am. Chem. Soc.  1984,  106:  5754 
• 13e Denmark SE. Chen C.-T. J. Am. Chem. Soc.  1992,  114:  10674 
• 13f Mizuno M. Fuji K. Tomioka K. Angew. Chem. Int. Ed.  1998,  37:  515 
• Other examples of asymmetric Wittig reactions:
• 13g Li C.-Y. Wang X.-B. Sun X.-L. Tang Y. Zheng J.-C. Xu Z.-H. Zhou Y.-G. Dai L.-X. J. Am. Chem. Soc.  2007,  129:  1494 
• 13h Li C.-Y. Sun X.-L. Jing Q. Tang Y. Chem. Commun.  2006,  2980 
• 13i Pinho e Melo TMVD. Cardoso AL. Rocha Gonsalves AM. d’A. Pessoa JC. Paixão JA. Beja AM. Eur. J. Org. Chem.  2004,  4830 
• Optically active alkenes of type 3 can be converted to synthetically useful acyclic compounds:
• 14a Hanessian S. Beaudoin S. Tetrahedron Lett.  1992,  33:  7659 
• Related alkenes from cyclopentanones have been studied as chirooptical triggers for a nematic liquid crystal:
• 14b Suarez M. Schuster GB. J. Am. Chem. Soc.  1995,  117:  6732 
• 15 Arai S. Hamaguchi S. Shioiri T. Tetrahedron Lett.  1998,  39:  2997 
• Organocatalytic desymmetrization of cyclohexanones via enanine catalysis, giving nonaxially chiral compounds:
• 16a Ramachary DB. Barbas CF. Org. Lett.  2005,  7:  1577 
• 16b Li L. Seidel D. Org. Lett.  2010,  12:  5064 ; and references therein
• See also:
• 16c Jiang H. Halskov KS. Johansen TK. Jørgensen KA. Chem. Eur. J.  2011,  17:  3842 
• 17a Vedejs E. Peterson MJ. Top. Stereochem.  1994,  21:  1 
• 17b Robiette R. Richardson J. Aggarwal VK. Harvey JN. J. Am. Chem. Soc.  2006,  128:  2394 ; and references cited therein
• Reviews on hydrogen-bond organocatalysis:
• 18a Taylor M. Jacobsen EN. Angew. Chem. Int. Ed.  2006,  45:  1520 
• 18b Zhang Z. Schreiner P. Chem. Soc. Rev.  2009,  38:  1187 
• 19 Gung BW. Chem. Rev.  1999,  99:  1377 
• 20 Acceleration of the Wittig reaction in alcoholic solvents has been reported. See for example: Rüchardt C. Panse P. Eichler S. Chem. Ber.  1967,  100:  1144 
• For a review on organophosphorus compounds in organocatalysis, see:
• 21a Albrecht Ł. Albrecht A. Krawczyk H. Jørgensen KA. Chem. Eur. J.  2010,  16:  28 
• Representative examples:
• 21b Zhang Y. Liu Y.-K. Kang T.-R. Hu Z.-K. Chen Y.-C. J. Am. Chem. Soc.  2008,  130:  2456 
• 21c Hong B.-C. Jan R.-H. Tsai C.-W. Nimje RY. Liao J.-H. Lee G.-H. Org. Lett.  2009,  11:  5246 
• 21d Mazzotta S. Gramigna L. Bernardi L. Ricci A. Org. Process Res. Dev.  2010,  14:  687 
• 22 Sohtome Y. Tanatani A. Hashimoto Y. Nagasawa K. Tetrahedron Lett.  2004,  45:  5589 
• 23a Seebach D. Beck AK. Heckel A. Angew. Chem. Int. Ed.  2001,  40:  92 
• 23b Huang Y. Unni AK. Thadani AN. Rawal VH. Nature (London)  2003,  424:  146 
• An asymmetric Wittig reaction in an inclusion complex of TADDOL has been reported, proceeding with moderate enantioselectivity (<57% ee). See:
• 23c Toda F. Akai H.
  J. Org. Chem.  1990,  55:  3446 
• 24 Cid MB. Duce S. Morales S. Rodrigo E. García Ruano JL. Org. Lett.  2010,  12:  3586 
• 25 Giese B. Schoch J. Rüchardt C. Chem. Ber.  1978,  111:  1395 

26

We tested 3-phenylcyclobutanone and a 3,4-cis-disubstituted cyclopentanone, using both catalyst 4a and 4g under different reaction conditions. Whereas the cyclopentanone was found to be much less reactive than
4-substituted cyclohexanones, giving the corresponding olefins only in low yields (<20%), the cyclobutanone showed good reactivity, but the alkene was obtained with rather poor enantioselectivity (<36% ee). See the Supporting Information for details.