Synlett 2008(10): 1565-1570  
DOI: 10.1055/s-2008-1077789
CLUSTER
© Georg Thieme Verlag Stuttgart · New York

The Effectiveness of Proteinogenic Amino Acids in the Asymmetric Aldol Reaction in DMSO and Aqueous DMSO

Yujiro Hayashi*, Takahiko Itoh, Norio Nagae, Masahiro Ohkubo, Hayato Ishikawa
Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Fax: +81(3)52614631; e-Mail: hayashi@ci.kagu.tus.ac.jp;
Further Information

Publication History

Received 2 February 2008
Publication Date:
16 May 2008 (online)

Abstract

The effects of twenty proteinogenic amino acids have been investigated in the aldol reaction of aldehyde and ketone in DMSO and aqueous DMSO (in the presence of three equivalents of water). Not only proline but also other amino acids promote the aldol reaction enantioselectively. The effect of water varies with amino acid, and water does not affect the enantioselectivity in most cases, the exceptions being Pro, Ser and His. In the case of Pro, large positive effects on diastereo- and enantioselectivities were observed in the reaction of α-substituted methyl ketone, while no effect was observed in that of methyl ketone.

    References and Notes

  • For reviews, see:
  • 1a Modern Aldol Reactions   Vol. 1:  Mahrwald R. Wiley-VCH; Weinheim: 2004. 
  • 1b Modern Aldol Reactions   Vol. 2:  Mahrwald R. Wiley-VCH; Weinheim: 2004. 
  • 2a Yamada YMA. Yoshikawa N. Sasai H. Shibasaki M. Angew. Chem. Int. Ed.  1997,  36:  1871 
  • 2b For a review, see: Shibasaki M. Matusnaga S. Kumagai N. In Modern Aldol Reaction   Vol. 2:  Mahrwald R. Wiley-VCH; Weinheim: 2004.  Chap. 6. p.197-227  
  • 3a List B. Lerner RA. Barbas CF. J. Am. Chem. Soc.  2000,  122:  2395 
  • 3b Sakthivel K. Notz W. Bui T. Barbas CF. J. Am. Chem. Soc.  2001,  123:  5260 
  • For reviews, see:
  • 4a List B. In Modern Aldol Reactions   Vol. 1:  Mahrwald R. Wiley-VCH; Weinheim: 2004.  Chap. 4. p.161-200  
  • 4b List B. Tetrahedron  2002,  58:  5573 
  • 4c List B. Acc. Chem. Res.  2004,  37:  548 
  • 4d Saito S. Yamamoto H. Acc. Chem. Res.  2004,  37:  570 
  • 4e Notz W. Tanaka F. Barbas CF. Acc. Chem. Res.  2004,  37:  580 
  • 4f Seayad J. List B. Org. Biomol. Chem.  2005,  3:  719 
  • 4g Mukherjee S. Yang JW. Hoffmann S. List B. Chem. Rev.  2007,  107:  5471 
  • For reviews of organocatalysis, see:
  • 5a Berkessel A. Groger H. Asymmetric Organocatalysis   Wiley-VCH; Weinheim: 2005. 
  • 5b Dalko PI. Moisan L. Angew. Chem. Int. Ed.  2004,  43:  5138 
  • 5c Hayashi Y. J. Synth. Org. Chem., Jpn.  2005,  63:  464 
  • 5d List B. Chem. Commun.  2006,  819 
  • 5e Marigo M. Jørgensen KA. Chem. Commun.  2006,  2001 
  • 5f Lelais G. MacMillan DWC. Aldrichimica Acta  2006,  39:  79 
  • 5g Gaunt MJ. Johnsson CCC. McNally A. Vo NT. Drug Discovery Today  2007,  12:  8 
  • 5h Enantioselective Organocatalysis   Dalko PI. Wiley-VCH; Weinheim: 2007. 
  • 6a Ribe S. Wipf P. Chem. Commun.  2001,  299 
  • 6b Lindstrom UM. Chem. Rev.  2002,  102:  2751 
  • 6c Kobayashi S. Manabe K. Acc. Chem. Res.  2002,  35:  209 
  • 6d Pirrung MC. Chem. Eur. J.  2006,  12:  1312 
  • 6e Organic Reactions in Water   Lindstrom UM. Blackwell Publishing; Oxford: 2007. 
  • 6f For the criticism toward the notion that water is an environmentally friendly solvent, see: Blackmond DG. Armstrong A. Coombe V. Wells A. Angew. Chem. Int. Ed.  2007,  46:  3798 
  • For organocatalysis-mediated asymmetric aldol reaction in aqueous solvent, see:
  • 7a Torii H. Nakadai M. Ishihara K. Saito S. Yamamoto H. Angew. Chem. Int. Ed.  2004,  43:  1983 
  • 7b Nyberg AI. Usano A. Pihko PM. Synlett  2004,  1891 
  • 7c Tang Z. Yang Z.-H. Cun L.-F. Gong LG. Mi L.-Q. Jiang YZ. Org. Lett.  2004,  6:  2285 
  • 7d Casas J. Sunden H. Cordova A. Tetrahedron Lett.  2004,  45:  6117 
  • 7e Ward DE. Jheengut V. Tetrahedron Lett.  2004,  45:  8347 
  • 7f Ibrahem I. Cordova A. Tetrahedron Lett.  2005,  46:  3363 
  • 7g Amedjkouh M. Tetrahedron: Asymmetry  2005,  16:  1411 
  • 7h Cordova A. Zou W. Ibrahem I. Reyes E. Engqvist M. Liao W.-W. Chem. Commun.  2005,  3586 
  • 7i Wu Y.-S. Chen Y. Deng D.-S. Cai J. Synlett  2005,  1627 
  • 7j Dziedzic P. Zou W. Hafren J. Cordova A. Org. Biomol. Chem.  2006,  4:  38 
  • 7k Pihko PM. Laurikainen KM. Usano A. Nyberg AI. Kaavi JA. Tetrahedron  2006,  62:  317 
  • 7l Cordova A. Zou W. Dziedzic P. Ibrahem I. Reyes E. Xu Y. Chem. Eur. J.  2006,  12:  5383 
  • 7m Guillena G. Hita MC. Najera C. Tetrahedron: Asymmetry  2006,  17:  729 
  • 7n Recently, Blackmond and co-workers reported the role of water in aldol reaction. See: Zotova N. Franzke A. Armstrong A. Blackmond DG. J. Am. Chem. Soc.  2007,  129:  15100 
  • For the reaction in the presence of water, see:
  • 8a Jiang Z. Liang Z. Wu X. Lu Y. Chem. Commun.  2006,  2801 
  • 8b Wu Y. Zhang Y. Yu M. Zhao G. Wang S. Org. Lett.  2006,  8:  4417 
  • 8c Font D. Jimeno C. Pericas MA. Org. Lett.  2006,  8:  4653 
  • 8d Guillena G. Hita MC. Najera C. Tetrahedron: Asymmetry  2006,  17:  1493 
  • 8e Wu X. Jiang Z. Shen H.-M. Lu Y. Adv. Synth. Catal.  2007,  349:  812 
  • 8f Maya V. Raj M. Singh VK. Org. Lett.  2007,  9:  2593 
  • For the terms about ‘in the presence of water’ and ‘water’, see:
  • 9a Hayashi Y. Angew. Chem. Int. Ed.  2006,  45:  8103 
  • 9b Brogan AP. Dickerson TJ. Janda KD. Angew. Chem. Int. Ed.  2006,  45:  8100 
  • 10a Hayashi Y. Sumiya T. Takahashi J. Gotoh H. Urushima T. Shoji M. Angew. Chem. Int. Ed.  2006,  45:  958 
  • 10b Aratake S. Itoh T. Okano T. Nagae N. Sumiya T. Shoji M. Hayashi Y. Chem. Eur. J.  2007,  13:  10246 
  • 11 Mase N. Nakai Y. Ohara N. Yoda H. Takabe K. Tanaka F. Barbas CF. J. Am. Chem. Soc.  2006,  128:  734 
  • 12 Hayashi Y. Aratake S. Itoh T. Okano T. Sumiya T. Shoji M. Chem. Commun.  2007,  957 
  • 13 Mangion IK. Northrup AB. MacMillan DWC. Angew. Chem. Int. Ed.  2004,  43:  6722 
  • 14a Kano T. Takai J. Tokuda O. Maruoka K. Angew. Chem. Int. Ed.  2005,  44:  3055 
  • 14b Kano T. Tokuda O. Takai J. Maruoka K. Chem. Asian J.  2006,  1:  210 
  • 15 DMSO was purified by the distillation over CaH2 under reduced pressure after standing over CaH2 overnight: Armarego WLF. Chai CLL. Purification of Laboratory Chemicals   5th ed.:  Elsevier; Burlington: 2003. 
  • All compounds are known:
  • 17a 2-(Hydroxy-4-nitrophenyl-methyl)cyclohexanone: Cobb AJA. Shaw DM. Longbottom DA. Gold JB. Ley SV. Org. Biomol. Chem.  2005,  3:  84 
  • 17b 2-(2-Chlorophenylhydroxy-methyl)cyclohexanone: Chen J. Lu H. Li X. Cheng L. Wan J. Xiao W. Org. Lett.  2003,  5:  4369 
  • 17c 4-Hydroxy-4-(4-nitrophenyl)-2-butanone: Rodriguez B. Bruckmann A. Bolm C. Chem. Eur. J.  2007,  13:  4710 
  • 17d 4-(2-Chlorophenyl)-4-hydroxy-2-butanone: Maya V. Raj M. Singh VK. Org. Lett.  2007,  9:  2593 
  • 17e 1-(2-Chloro-phenyl)-1-hydroxy-3-pentanone and 4-(2-chlorophenyl)-4-hydroxy-3-methyl-2-butanone: Luo S. Xu H. Li J. Zhang L. Cheng J.-P. J. Am. Chem. Soc.  2007,  129:  3074 
16

Typical Experimental Procedure (Table 1): To a DMSO solution (0.40 mL [] ) or aq DMSO solution (DMSO: 0.40 mL; H2O: 22 µL [] ) of amino acid (0.12 mmol) were added p-nitrobenzaldehyde (60.5 mg, 0.4 mmol) and cyclohexanone (207 µL, 2.0 mmol) under an argon atmosphere at r.t. When the reaction was complete, it was quenched with pH 7.0 phosphate buffer solution. The organic materials were extracted with EtOAc (3 ×) and the combined organic extracts were dried over anhyd Na2SO4, and concentrated in vacuo after filtration. The residue was purified by flash chromatography to give an aldol product. Diastereoselectivity was determined by 1H NMR (400 MHz). Enantiomeric excess was determined by HPLC analysis with a Chiralpak AS-H column (hexane-2-pro-
panol = 10:1, λ = 231 nm), 1.0 mL/min; major enantiomer t R = 11.5 min, minor enantiomer t R = 18.7 min.