Synlett 2009(3): 487-489  
DOI: 10.1055/s-0028-1087534
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Simple and Efficient Procedure for the Synthesis of Ketone Di-sec-alkyl ­Acetals

Fumiaki Ono, Hirotaka Takenaka, Yuko Eguchi, Masato Endo, Tsuneo Sato*
Department of Life Science, Kurashiki University of Science and the Arts, Kurashiki 712-8505, Japan
Fax: +81(86)4401062; e-Mail: sato@chem.kusa.ac.jp;
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Publikationsverlauf

Received 22 September 2008
Publikationsdatum:
21. Januar 2009 (online)

Abstract

Ketone di-sec-alkyl acetals are obtained in good to excellent yields by treatment of ketones with tri-sec-alkyl orthoformate and the corresponding alcohol in the presence of a catalytic amount of cerium(III) trifluoromethanesulfonate.

    References and Notes

  • 1a Kocienski PJ. Protecting Groups   3rd ed.:  Thieme; New York: 2004.  Chap. 2.
  • 1b Wuts PGM. Greene TW. Greene’s Protective Groups in Organic Synthesis   4th ed.:  Wiley; New York: 2007.  Chap. 4.
  • 2a Mukaiyama T. Murakami M. Synthesis  1987,  1043 
  • 2b Alexakis A. Mangeney P. Tetrahedron: Asymmetry  1990,  1:  477 
  • 3a Meskens FAJ. Synthesis  1981,  501 
  • 3b Sandler SR. Karo W. Organic Functional Group Preparations   2nd ed., Vol. III:  Academic; New York: 1989.  Chap. 1.
  • 3c Macpherson DT. Harshad KR. In Comprehensive Organic Functional Group Transformations   Vol. 4:  Kirby GW. Pergamon; Oxford: 1995.  p.159 
  • 4 Howard WL. Lorette NB. J. Org. Chem.  1960,  25:  525 
  • 5 Roelofsen DP. van Bekkum H. Synthesis  1972,  419 
  • 6 α-Hydroxy ketone di-sec-alkyl acetals were obtained by addition of secondary alcohols to sec-alkyl epoxy ethers: Stevens CL. McLean RL. Weinheimer AJ. J. Am. Chem. Soc.  1958,  80:  2276 
  • For the use of Ce(OTf)3 in other types of reactions, see:
  • 7a Dalpozzo R. De Nino A. Maiuolo L. Procopio A. Tagarelli A. Sindona G. Bartoli G. J. Org. Chem.  2002,  67:  9093 
  • 7b Keh CCK. Namboodiri VV. Varma RS. Li C.-J. Tetrahedron Lett.  2002,  43:  4993 
  • 7c Dalpozzo R. De Nino A. Maiuolo L. Procopio A. Nardi M. Bartoli G. Romeo R. Tetrahedron Lett.  2003,  44:  5621 
  • 7d Bartoli G. Dalpozzo R. De Nino A. Maiuolo L. Nardi M. Procopio A. Tagarelli A. Eur. J. Org. Chem.  2004,  2176 
  • 7e Bartoli G. Dalpozzo R. De Nino A. Maiuolo L. Nardi M. Procopio A. Tagarelli A. Green Chem.  2004,  6:  191 
  • 7f Bartoli G. De Nino A. Dalpozzo R. Maiuolo L. Nardi M. Procopio A. Tagarelli A. Lett. Org. Chem.  2005,  2:  51 
  • 8 MacKenzie et al. reported the reaction of acetone, tri-sec-butyl orthformate, S-BuOH, and PTSA did not occur and the orthoester was recovered unchanged: MacKenzie CA. Stocker JH. J. Org. Chem.  1955,  20:  1695 
9

When this reaction was attempted in the absence of i-PrOH or triisopropyl orthformate, diisopropyl acetalization did not proceed at all.

10

None (85%), CH2Cl2 (80%), Et2O (83%), THF (81%), MeCN (76%).

11

Typical Procedure (Table 1, Entry 1)
To a mixture of cyclopentanone (84 mg, 1.0 mmol), Ce(OTf)3 (Alfa Aesar, 5.9 mg, 0.01 mmol), i-PrOH (1 mL), and toluene (1 mL) triisopropyl orthoformate (247 mg, 1.3 mmol)was added at 0 ˚C. After the mixture was kept stirring at the same temperature for 6 h, it was quenched by adding Et3N (101 mg, 1.0 mmol). The resulting mixture was passed through a short plug of neutral Al2O3 (activity III), which was then washed with Et2O (30 mL), and the solvent was removed under reduced pressure. The ¹H NMR (500 MHz) analysis of the crude product showed the absence of
1-cyclopentenyl isopropyl ether. The residue was chroma-tographed on neutral Al2O3 (activity III, hexane) to afford cyclopentanone diisopropyl acetal (168 mg, 90%). ¹H NMR (500 MHz, CDCl3): δ = 1.17 (d, J = 6.1 Hz, 12 H), 1.65-1.70 (m, 4 H), 1.75-1.81 (m, 4 H), 4.01-4.09 (m, 2 H). ¹³C NMR (125 MHz, CDCl3): δ = 21.7, 24.4, 35.6, 63.8, 111.6. 2-Octanone Diisopropyl Acetal
¹H NMR (500 MHz, CDCl3): δ = 0.88 (t, J = 7.1 Hz, 3 H), 1.14 (d, J = 6.4 Hz, 12 H), 1.24-1.37 (m, 8 H), 1.27 (s, 3 H), 1.54-1.59 (m, 2 H), 3.99-4.08 (m 2 H). ¹³C NMR (125 MHz, CDCl3): δ = 14.1, 22.6, 23.7, 24.5, 24.6, 24.8, 29.7, 31.9, 39.8, 62.1, 102.6.
1-Cyclohexyl-1-ethanone Diisopropyl Acetal
¹H NMR (500 MHz, C6D6): δ = 0.92-2.10 (m, 11 H), 1.10 (d, J = 6.0 Hz, 6 H), 1.13 (d, J = 6.0 Hz, 6 H), 1.15 (s, 3 H), 3.97-4.05 (m, 2 H). ¹³C NMR (125 MHz, C6D6): δ = 19.7, 24.6, 25.0, 27.1, 27.2, 29.0, 45.9, 62.0, 104.5.
Acetophenone Diisopropyl Acetal
¹H NMR (500 MHz, C6D6): δ = 0.98 (d, J = 6.5 Hz, 6 H), 1.12 (d, J = 6.0 Hz, 6 H), 1.61 (s, 3 H), 3.96-4.04 (m, 2 H), 7.08-7.76 (m, 5 H). ¹³C NMR (125 MHz, C6D6): δ = 24.2, 24.9, 28.3, 63.7, 101.3, 127.3, 127.6, 145.0.
Cyclohexanone Di- sec -butyl Acetal
¹H NMR (500 MHz, C6D6): δ = 0.87 (t, J = 7.7 Hz, 3 H), 0.88 (t, J = 7.7 Hz, 3 H), 1.14 (d, J = 6.4 Hz, 3 H), 1.16 (d, J = 6.1 Hz, 3 H), 1.26-1.35 (m, 2 H), 1.43-1.74 (m, 12 H), 3.82-3.93 (m, 2 H). ¹³C NMR (125 MHz, C6D6): δ = 9.5, 9.6, 21.3, 21.5, 23.8, 26.1, 31.3, 36.1, 36.2, 36.5, 66.8, 67.0, 101.3.
Cyclohexanone Dicyclohexyl Acetal ¹H NMR (500 MHz, C6D6): δ = 1.10-1.87 (m, 30 H), 3.82-3.89 (m, 2 H). ¹³C NMR (125 MHz, C6D6): δ = 23.8, 24.8, 26.2, 35.2, 36.7, 67.9, 101.5.

12

Other Brønsted and Lewis acids are less effective than Ce(OTf)3 in our reaction system. The reaction of 2-octanone under identical conditions are as follows: TfOH (23%), BF3˙OEt2 (0%), AlCl3 (15%), Mg(OTf)2 (0%), TMSOTf (58%), Sc(OTf)3 (62%), Cu(OTf)2 (63%), Zn(OTf)2 (35%), La(OTf)3 (36%), Gd(OTf)3 (63%), Bi(OTf)3˙4H2O (51%).

13

Reaction of benzophenone (r.t., 24 h) followed by the standard workup gave benzophenone diisopropyl acetal (5%) and the starting ketone (90%).

14

Di-sec-butyl acetalization of cyclohexanone by the Roelofsen method [5] afforded cyclohexanone di-sec-butyl acetal (80%) and sec-butyl 1-cyclohexenyl ether (15%).