Synlett 2011(9): 1255-1258  
DOI: 10.1055/s-0030-1260545
© Georg Thieme Verlag Stuttgart ˙ New York

Metal-Free Chiral Phosphoric Acid or Chiral Metal Phosphate as Active Catalyst in the Activation of N-Acyl Aldimines

Masahiro Terada*, Kyohei Kanomata
Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan
Fax: +81(22)7956602; e-Mail:;
Further Information

Publication History

Received 21 February 2011
Publication Date:
29 April 2011 (online)


Whether metal-free chiral phosphoric acid or chiral metal phosphate functions as an active catalyst was confirmed in three reactions. In the aza-Friedel-Crafts and aza-ene-type reactions, a metal-free chiral phosphoric acid, namely, a chiral Brønsted acid, was verified to be the active catalyst. In contrast, the substitution ­reaction of α-diazoacetate with aldimine was accelerated by a salt-containing chiral phosphoric acid and hence chiral metal phosphate presumably functioned as an active catalyst.

    References and Notes

  • For reviews, see:
  • 1a Doyle AG. Jacobsen EN. Chem. Rev.  2007,  107:  5713 
  • 1b Akiyama T. Chem. Rev.  2007,  107:  5744 
  • 1c Yu X. Wang W. Chem. Asian J.  2008,  3:  516 
  • 1d Yamamoto H. Payette N. In Hydrogen Bonding in Organic Synthesis   Pihko PM. Wiley-VCH; Weinheim: 2009.  p.73-140  
  • 1e Kampen D. Reisinger CM. List B. Top. Curr. Chem.  2010,  291:  395 
  • For seminal studies, see:
  • 2a Akiyama T. Itoh J. Yokota K. Fuchibe K. Angew. Chem. Int. Ed.  2004,  43:  1566 
  • 2b Uraguchi D. Terada M. J. Am. Chem. Soc.  2004,  126:  5356 
  • 3a Nakashima D. Yamamoto H. J. Am. Chem. Soc.  2006,  128:  9626 
  • For a review, see:
  • 3b Cheon CH. Yamamoto H. Chem. Commun.  2011,  47:  3043 
  • For reviews, see:
  • 4a Connon SJ. Angew. Chem. Int. Ed.  2006,  45:  3909 
  • 4b Akiyama T. Itoh J. Fuchibe K. Adv. Synth. Catal.  2006,  348:  999 
  • 4c Adair G. Mukherjee S. List B. Aldrichimica Acta  2008,  41:  31 
  • 4d Terada M. Chem. Commun.  2008,  4097 
  • 4e Terada M. Bull. Chem. Soc. Jpn.  2010,  83:  101 
  • 4f Terada M. Synthesis  2010,  1929 
  • 4g Zamfir A. Schenker S. Freund M. Tsogoeva SB. Org. Biomol. Chem.  2010,  8:  5262 
  • 5 Xu S. Wang Z. Zhang X. Zhang X. Ding K. Angew. Chem. Int. Ed.  2008,  47:  2840 
  • 6a Rueping M. Theissmann T. Kuenkel A. Koenigs RM. Angew. Chem. Int. Ed.  2008,  47:  6798 
  • 6b Rueping M. Nachtsheim BJ. Koenigs RM. Ieawsuwan W. Chem. Eur. J.  2010,  16:  13116 
  • 7 Terada M. Sorimachi K. J. Am. Chem. Soc.  2007,  129:  292 
  • Ishihara and co-workers reported that the outcome of the Mannich reaction of N-Boc aldimine 6 with acetylacetone catalyzed by chiral calcium phosphate [G = 4-(β-naphthyl) phenyl] was comparable to our reported result (see ref. 2b) obtained using silica gel purified chiral phosphoric acid (G = same as above), see:
  • 9a Hatano M. Moriyama K. Maki T. Ishihara K. Angew. Chem. Int. Ed.  2010,  49:  3823 
  • Also see:
  • 9b Hatano M. Ishihara K. Synthesis  2010,  3785 
  • List and co-workers compared the catalytic activities of metal-free and silica gel purified, i.e., salt-containing phosphoric acids 1a in an asymmetric transfer hydro-genation of imine. They reported that both acids yielded the corresponding products with the same enantioselectivity. However, the metal-free acid displayed significantly higher catalytic activity than the salt-containing acid, see:
  • 10a Klussmann M. Ratjen L. Hoffmann S. Wakchaure V. Goddard R. List B. Synlett  2010,  2189 
  • Also see:
  • 10b Lu G. Birman VB. Org. Lett.  2011,  13:  356 
  • Selected examples of binaphthol-derived monophosphoric acids as the chiral ligand for enantioselective catalysis. For palladium catalysts, see:
  • 11a Alper H. Hamel N. J. Am. Chem. Soc.  1990,  112:  2803 
  • For rhodium catalysts, see:
  • 11b McCarthy N. McKervey MA. Ye T. McCann M. Murphy E. Doyle MP. Tetrahedron Lett.  1992,  33:  5983 
  • 11c Pirrung MC. Zhang J. Tetrahedron Lett.  1992,  33:  5987 
  • For gold catalysts, see:
  • 11d Hamilton GL. Kang EJ. Mba M. Toste FD. Science  2007,  317:  496 
  • 11e LaLonde RL. Wang ZJ. Mba M. Lackner AD. Toste FD. Angew. Chem. Int. Ed.  2010,  49:  598 
  • For copper catalysts, see:
  • 11f Zhao B. Du H. Shi Y. J. Org. Chem.  2009,  74:  8392 
  • For silver catalysts, see:
  • 11g Zhang Q.-W. Fan C.-A. Zhang H.-J. Tu Y.-Q. Zhao Y.-M. Gu P. Chen Z.-M. Angew. Chem. Int. Ed.  2009,  48:  8572 
  • For iron catalysts, see:
  • 11h Yang L. Zhu Q. Guo S. Qian B. Xia C. Huang H. Chem. Eur. J.  2010,  16:  1638 
  • For rare-earth metal catalysts, see:
  • 11i Inanaga J. Sugimoto Y. Hanamoto T. New J. Chem.  1995,  19:  707 
  • 11j Furuno H. Hanamoto T. Sugimoto Y. Inanaga J. Org. Lett.  2000,  2:  49 
  • 11k Sugihara H. Daikai K. Jin XL. Furuno H. Inanaga J. Tetrahedron Lett.  2002,  43:  2735 
  • 11l Jin XL. Sugihara H. Daikai K. Tateishi H. Jin YZ. Furuno H. Inanaga J. Tetrahedron  2002,  58:  8321 
  • 11m Furuno H. Kambara T. Tanaka Y. Hanamoto T. Kagawa T. Inanaga J. Tetrahedron Lett.  2003,  44:  6129 
  • 11n Furuno H. Hayano T. Kambara T. Sugimoto Y. Hanamoto T. Tanaka Y. Jin YZ. Kagawa T. Inanaga J. Tetrahedron  2003,  59:  10509 
  • 11o Suzuki S. Furuno H. Yokoyama Y. Inanaga J. Tetrahedron: Asymmetry  2006,  17:  504 
  • For aluminum catalysts, see:
  • 11p Yue T. Wang M.-X. Wang D.-X. Masson G. Zhu J. J. Org. Chem.  2009,  74:  8396 
  • For a combination of chiral phosphoric acid and magnesium salt as a binary catalytic system, see:
  • 11q Lv J. Li X. Zhong L. Luo S. Cheng J.-P. Org. Lett.  2010,  12:  1096 
  • After the report by Ishihara and co-workers, the enantioselective catalysis by chiral calcium phosphate was developed by three research groups, see:
  • 12a Drouet F. Lalli C. Liu H. Masson G. Zhu J. Org. Lett.  2011,  13:  94 
  • 12b Zhang Z. Zheng W. Antilla JC. Angew. Chem. Int. Ed.  2011,  50:  1135 
  • 12c Rueping M. Bootwicha T. Sugiono E. Synlett  2011,  323 
  • Also see chiral sodium phosphate:
  • 12d Hennecke U. Müller CH. Fröhlich R. Org. Lett.  2011,  13:  860 
  • In the reaction of trimethylsilyl cyanide, the formation of hypervalent silicate might be responsible for the acceleration of the reactions, see:
  • 13a Hatano M. Ikeno T. Matsumura T. Torii S. Ishihara K. Adv. Synth. Catal.  2008,  350:  1776 
  • 13b Shen K. Liu X. Cai Y. Lin L. Feng X. Chem. Eur. J.  2009,  15:  6008 
  • 15 Uraguchi D. Sorimachi K. Terada M. J. Am. Chem. Soc.  2004,  126:  11804 
  • 16 Uraguchi D. Sorimachi K. Terada M. J. Am. Chem. Soc.  2005,  127:  9360 
  • 17 Terada M. Machioka K. Sorimachi K. Angew. Chem. Int. Ed.  2006,  45:  2254 
  • For the enantioselective substitution reaction of α-diazo-acetates with aldimines catalyzed by chiral Brønsted acids, see:
  • 20a Hashimoto T. Maruoka K. J. Am. Chem. Soc.  2007,  129:  10054 
  • 20b Hashimoto T. Maruoka K. Synthesis  2008,  3703 
  • For the enantioselective aziridine formation (aza-Darzens) reaction of α-diazoacetates with aldimines catalyzed by chiral Brønsted acids, see:
  • 21a Hashimoto T. Uchiyama N. Maruoka K. J. Am. Chem. Soc.  2008,  130:  14380 
  • 21b Akiyama T. Suzuki T. Mori K. Org. Lett.  2009,  11:  2445 
  • 21c Zeng X. Zeng X. Xu Z. Lu M. Zhong G. Org. Lett.  2009,  11:  3036 

Sorimachi, K.; Terada, M. unpublished results.


List and co-workers reported that silica gel purified chiral phosphoric acid 1a contained substantial amounts of alkali and alkaline-earth metals along with several metal impurities as ascertained by ICP-OES elemental analysis. See ref. 10a.


For the Preparation of Acid-Washed 1b (Method A)
Silica gel purified 1b was dissolved in Et2O. The resultant solution was washed with HCl aq solution (2 M) in a separatory funnel. The resultant ether layer was dried over Na2SO4 and evaporated to remove organic solvents. The resultant residue was dried under reduced pressure for more than 12 h to eliminate organic solvents completely.
For the Preparation of Acid-Washed 1c (Method A)
Silica gel purified 1c was dissolved in MeOH. Then HCl aq solution (2 M) was added to the resultant MeOH solution to give a white suspension. The resultant suspension was extracted with CH2Cl2 (twice or more), and the combined organic layer was dried over Na2SO4. This was followed by the procedure as shown in the preparation of acid-washed 1b (method A).


Extra pure silica gel (Silica gel 60 extra pure for column chromatography: Catalogue No. 1.07754) was purchased from Merck KgaA. Short-path column chromatography was performed using CH2Cl2-MeOH (10:1) mixtures as eluent.


A silica gel purified chiral phosphoric acid contains considerable amounts of alkali and alkaline-earth metals with other metal impurities. Therefore it should be considered that a problem of reproducibility in yield and selectivity would happen, because the composition of metals is dependent on the conditions of silica gel column chromatography conducted.