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Synlett 2003(4): 0558-0560
DOI: 10.1055/s-2003-37534
LETTER
© Georg Thieme Verlag Stuttgart · New York

Highly Efficient Silylcyanation of Ketones by a Catalytic Double Activation Method Using Lewis Acid and N-Oxide Catalysts

Fuxue Chenb, Xiaoming Feng*a, Bo Qina, Guolin Zhangc, Yaozhong Jiangb
a Sichuan Key Laboratory of Green Chemistry and Technology, College of Chemistry, Sichuan University, Chengdu 610064, China
Fax: +86(28)85418249; e-Mail: xmfeng@pridns.scu.edu.cn;
b Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China
c Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China
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Publication History

Received 29 December 2002
Publication Date:
26 February 2003 (online)

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Abstract

An efficient protocol for addition of TMSCN to ketones by employing 3 mol% achiral Schiff base-Ti(IV) complex as the Lewis acid and 3 mol% N-oxide as the Lewis base in a manner of double activation was described. Aromatic, aliphatic, cyclic and heterocyclic ketones all gave the racemic O-TMS cyanohydrins in good to excellent yields (up to 99%) under mild conditions.

Key words

cyanohydrins - double activation catalysis - ketones - N-oxides - Schiff bases

    References

  • 1 Gregory RJH. Chem. Rev.  1999,  99:  3649 
    CrossrefPubMedGoogle Scholar
  • For recent example, see:
  • 2a Singh VK. Saravanan P. Vijaya Anand R. Tetrahedron Lett.  1998,  39:  3823 
    CrossrefGoogle Scholar
  • 2b Wilkinson HS. Grover PT. Vandenbossche CP. Bakale RP. Bhongle NN. Wald SA. Senanayake CH. Org. Lett.  2001,  3:  553 
    CrossrefGoogle Scholar
  • 2c Bandini M. Cozzi PG. Melchiorre P. Umani-Ronchi A. Tetrahedron Lett.  2001,  42:  3041 ; and references cited therein
    CrossrefGoogle Scholar
  • 3a Shen YC. Feng XM. Li Y. Zhang GL. Jiang YZ. Synlett  2002,  793 
    CrossrefGoogle Scholar
  • 3b For representative bifunctional catalysis, see: Shibasaki M. Yoshikawa N. Chem. Rev.  2002,  102:  2187 
    CrossrefGoogle Scholar
  • 3c Yabu K. Masumoto S. Yamasaki S. Hamashima Y. Kanai M. Du W. Curran DP. Shibasaki M. J. Am. Chem. Soc.  2001,  123:  9908 
    CrossrefGoogle Scholar
  • 3d Hamashima Y. Kanai M. Shibasaki M. J. Am. Chem. Soc.  2000,  122:  7412 
    CrossrefGoogle Scholar
  • 3e DiMauro EF. Kozlowski MC. J. Am. Chem. Soc.  2002,  124:  12668 
    CrossrefGoogle Scholar
  • 4 For the first example of catalytic double activation method (CDAM), see: Itoh K. Kanemasa S. J. Am. Chem. Soc.  2002,  124:  13394 
    CrossrefPubMedGoogle Scholar
  • The ligand was prepared as described in:
  • 5a Jiang YZ. Gong LZ. Feng XM. Hu WH. Pan WD. Li Z. Mi AQ. Tetrahedron  1997,  53:  14327 
    CrossrefGoogle Scholar
  • 5b For other examples of achiral salen-Mn/Cr complexes, see: Srinivasan K. Michaud P. Kochi JK. J. Am. Chem. Soc.  1986,  108:  2309 
    CrossrefGoogle Scholar
  • 5c See also: Samel EG. Srinivasan K. Kochi JK. J. Am. Chem. Soc.  1985,  107:  7606 
    CrossrefGoogle Scholar
  • 6 The N-oxide 2 was prepared by oxidation of the N,N-dimethylaniline with H2O2 according to literature: Kruger TL. White WN. White H. Hartzell SL. Kress JW. Walter N. J. Org. Chem.  1975,  40:  77 
    CrossrefGoogle Scholar
  • Our related research on hydrocyanation of aldehydes, see:
  • 7a Pan WD. Feng XM. Gong LZ. Hu WH. Li Z. Mi AQ. Jiang YZ. Synlett  1996,  337 
    Article in Thieme ConnectGoogle Scholar
  • 7b Feng XM. Gong LZ. Hu WH. Li Z. Pan WD. Mi AQ. Jiang YZ. Chem. J. Chin. Univ.  1998,  19:  1416 
    Article in Thieme ConnectGoogle Scholar
  • 7c On Strecker reaction, see: Liu B. Feng XM. Chen FX. Zhang GL. Jiang YZ. Synlett  2001,  1551 
    Article in Thieme ConnectGoogle Scholar
  • 10 For review on ligand-accelerated catalysis, see: Berrisford DJ. Bolm C. Sharpless KB. Angew. Chem., Int. Ed. Engl.  1995,  34:  1059 
    CrossrefGoogle Scholar
  • 11a For review on N-oxide metals complexes, see: Karayannis NM. Pytlewski LL. Mikulski CM. Coord. Chem. Rev.  1973,  11:  93 
    Google Scholar
  • 11b For recent examples, see: Dyker G. Hölzer B. Henkel G. Tetrahedron:Asymmetry  1999,  10:  3297 
    Google Scholar
  • 12a Shen YC. Feng XM. Zhang GL. Jiang YZ. Synlett  2002,  1353 
    Article in Thieme ConnectGoogle Scholar
  • 12b

    When the reaction was catalyzed by (1R,2R)-N,N′-bis(3,5-di-tert-butyl-salicylidene)-1,2-diphenyl-1,2-diamine-Ti(O-i-Pr)4 complex (20 mol%) and achiral N-oxide 2 (20 mol%), the product was obtained in 95% yield with 67% ee at 0 °C for 84 h {GC [Varian, Chirasil DEX CB, column temperature = 100 °C (isothermal), injector temperature = 200 °C, detector temperature = 250 °C]: t r(major) = 24.5 min, t r(minor) = 25.4 min}.
    Article in Thieme Connect
8

When NMO (N-methylmorpholine N-oxide) and PyNO (pyridine N-oxide) were used as the Lewis bases under the optimized conditions, the yield was reduced to 42% and 52%, respectively.

9

The standard procedure is given: Ti(i-PrO)4 (96 µL, 1 M in toluene) was stirred with ligand 1 (47.4 mg, 0.096 mmol) in anhyd CH2Cl2 (1 mL) at 35 °C for 1 h under N2 atmosphere. The solvents were removed in vacuo. After redissolved in CH2Cl2 (0.5 mL), the mixture was added, in sequence, acetophenone (3.2 mmol) and a solution of N-oxide 2 (13.2 mg, 0.096 mmol) and TMSCN (2 equiv) in CH2Cl2 (1.0 mL), which was also stirred at 35 °C for 1 h. The reaction was performed at 23 °C. At completion, the reaction mixture was concentrated and put on a silica gel column to give the O-TMS cyanohydrin as clear colorless oil (680 mg, 97%).