DMAP-Organocatalyzed O-Silyl-O-(or C-)-Benzoyl Interconversions by Means of Benzoyl Fluoride

Abstract

A mild and efficient transprotection of alcohols from silyl ethers 1a-f to benzoates 2a-f is reported in fair to good yields (50-98%). This silyl-acyl exchange reaction proceeds readily in ­acetonitrile at room temperature in the presence of benzoyl fluoride and DMAP as an acyl transfer catalyst. A two-step ‘one-pot’ DMAP-catalyzed silylcyanation-transprotection sequence which gives the corresponding O-benzoyl cyanohydrines 2g-l in high yields (72-98%) from various benzaldehyde and ketone derivatives is also reported. This original organocatalytic acyl transfer process was also found to be effective in the O-benzoylation of trimethysilyl enolates 1m-o, providing enol esters 2m-o. Lastly, the potential of this strategy is also illustrated by a DMAP-mediated Claisen condensation between ketene silyl acetals 1p-r and benzoyl fluoride.

Key words

organocatalysis - DMAP - transprotection - acid fluorides - silyl ethers - benzoylation - alcohols - cyanohydrins - Claisen condensation

References and Notes

• 1 Kociensky P. Protecting Groups   3rd ed.:  Georg Thieme Verlag; Stuttgart: 2004. 
• 2a Stork G. Zhao K. Tetrahedron Lett.  1989,  30:  287 
• 2b Nicolaou KC. Baran PS. Zhong Y.-L. Choi H.-S. Yoon WH. He Y. Fong KC. Angew. Chem. Int. Ed.  1999,  38:  1669 
• 2c Jones TK. Reamer RA. Desmond R. Mills SG. J. Am. Chem. Soc.  1990,  112:  2998 
• 2d Aoyagi S. Wang T.-C. Kibayashi C. J. Am. Chem. Soc.  1993,  115:  11393 
• 3 Rawal VH. Michoud C. Monestel RF. J. Am. Chem. Soc.  1993,  115:  3030 
• 4a Roos EC. Bernabé P. Hiemstra H. Speckamp WN. J. Org. Chem.  1995,  60:  1733 
• 4b Furlán RLE. Mata EG. ARKIVOC  2003,  (x):  32-40  
• 4c Furlan RLE. Mata EG. Tetrahedron Lett.  1998,  39:  6421 
• 5a Oriyama T. Oda M. Gono J. Koga G. Tetrahedron Lett.  1994,  35:  2027 
• 5b Chandra KL. Saravanan P. Singh VK. Tetrahedron Lett.  2001,  42:  5309 
• 5c Ganem B. Small VR. J. Org. Chem.  1974,  39:  3728 
• 5d Stamatov DS. Kullberg M. Stawinski J. Tetrahedron Lett.  2005,  46:  6855 
• 5e Norsikian S. Holmes I. Lagasse F. Kagan H. Tetrahedron Lett.  2002,  43:  5715 
• 5f Harjani JR. Nara SJ. Salunkhe MM. Nucleosides, Nucleotides Nucleic Acids  2005,  24:  819 
• 6a Höfle G. Steglich W. Vorbruggen H. Angew. Chem., Int. Ed. Engl.  1978,  17:  569 
• 6b Hassner A. Krepski LR. Alexanian V. Tetrahedron  1978,  34:  2069 
• 6c Murugan R. Scriven EFV. Aldrichimica Acta  2003,  36:  21 
• 6d Scriven EFV. Chem. Soc. Rev.  1983,  12:  129 
• 7a Spivey AC. Arseniyadis S. Angew. Chem. Int. Ed.  2004,  43:  5436 
• 7b Xu S. Held H. Kempf B. Mayr H. Steglich W. Zipse H. Chem. Eur. J.  2005,  11:  4751 
• 8a Chuit C. Corriu RJP. Reye C. Chem. Rev.  1993,  93:  1371 
• 8b Rendler S. Oestreich M. Synthesis  2005,  1727 
• 12 Denmark SE. Chung W.-J. J. Org. Chem.  2006,  71:  4002 
• 14a Ito H. Ishizuka T. Tateiwa J.-I. Hosomi A. Tetrahedron Lett.  1998,  39:  6295 
• 14b Limat D. Schlosser M. Tetrahedron  1995,  51:  5799 
• 15 In contrast to this result, acylation of ketone silyl enol ethers under similar conditions (acetyl fluoride/boron trifluoride in nitromethane at -35 °C) was reported to afford mainly the C-acylated product. See: Kopka I. Rathke MW. J. Org. Chem.  1981,  46:  3772 
• 16 Iida A. Takai K. Okabayashi T. Misaki T. Tanabe Y. Chem. Commun.  2005,  3173 
• 17a Mermerian AH. Fu GC. J. Am. Chem. Soc.  2003,  125:  4050 
• 17b For a recent contribution from our group in the chemistry of chiral DMAPs, see: Poisson T. Penhoat M. Papamicaël C. Dupas G. Dalla V. Marsais F. Levacher V. Synlett  2005,  2285 

9

General Procedure for the Preparation of Silyl Ethers 1a-f.
To a solution of 1-phenylethanol (122 mg, 1 mmol) and Et₃N (120 mg, 1.1 mmol) in CH₂Cl₂ (5 mL) was added TMSCl (115 mg, 1.05 mmol). The reaction was stirred at r.t. overnight. The solvent was removed under reduced pressure and the resultant residue was diluted with pentane (10 mL). Simple filtration through a short pad of Celite^® provided silyl ether 1a in 95% yield which could be used in the silyl ether exchange reaction without further purification.

10

One can notice that acylation of alcohols with DMAP/AC₂O is reported to be more effective in less polar solvents; see ref. 6. There is apparently no rational explanation for this opposite solvent effect.

11

General Procedure for the Transprotection of Silyl Ethers 1a-f, Silyl Enol Ethers 1m-o and Ketene Silyl Acetals 1p-r. To a solution of silylated alcohol 1f (268 mg, 1 mmol) and DMAP (12 mg, 0.1 mmol) in MeCN (2 mL) was added benzoyl fluoride (130 mg, 1.05 mmol). The resulting solution was stirred for 6 h at r.t., followed by addition of sat. aq NaHCO₃ (4 mL). After phase separation, the aqueous phase was extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with sat. aq NH₄Cl (10 mL) and brine (10 mL). After drying (MgSO₄) and evaporation of the organic solvents under vacuum, the resulting residue was chromatographed on silica gel (cyclohexane-EtOAc, 9:1) affording benzoate 2f in 62% yield.
Selected Data for Benzoate 2f.
¹H NMR (300 MHz, CDCl₃): δ = 8.01 (s, 1 H), 7.97 (d, 2 H, J = 8.3 Hz), 7.46 (t, 1 H, J = 5.4 Hz), 7.27 (m, 3 H), 7.16 (m, 1 H), 6.85 (m, 2 H), 5.27 (s, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 168.56, 155.39, 133.52, 131.89, 130.91, 129.86, 129.28, 128.40, 121.88, 120.55, 117.38, 63.53. IR (KBr): ν_max = 1693, 3317 cm^-1. Mp 64-66 °C.
Selected Data for 2q.
¹H NMR (300 MHz, CDCl₃): δ = 7.95 (d, 2 H, J = 7.9 Hz), 7.52 (m, 1 H), 7.44 (t, 2 H, J = 7.9 Hz), 4.40 (t, 2 H, J = 6.9 Hz), 3.05 (m, 1 H), 2.22 (m, 1 H), 1.67 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 196.65, 177.48, 134.88, 133.40, 129.50, 128.87, 66.39, 55.30, 35.70, 22.01. IR (KBr): ν_max = 1766, 1678 cm^-1.
Selected Data for 2r.
¹H NMR (300 MHz, CDCl₃): δ = 7.78 (d, 2 H, J = 7.3 Hz), 7.49 (m, 1 H), 7.38 (m, 2 H), 3.63 (s, 3 H), 2.09 (t, 4 H, J = 6.2 Hz), 1.53 (m, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 198.56, 174.71, 136.50, 132.67, 128.73, 128.62, 58.35, 52.72, 32.68, 25.71, 22.58. IR (KBr): 1735, 1682 cm^-1. All other synthesized compounds are in accordance with the literature data.

13

General ‘One-Pot’ Procedure for the Preparation of O -Benzoyl Cyanohydrins 2g-l.
To a solution of methyl 4-formylbenzoate (164 mg, 1 mmol) and DMAP (12 mg, 0.1 mmol) in MeCN (2 mL) was added TMSCN (241 mg, 1.05 mol). The resulting solution was stirred for 1 h at r.t., after which benzoyl fluoride (130 mg, 1.05 mmol) was added and the solution was stirred for a further 12 h. The solution was treated with sat. aq NaHCO₃ (4 mL). After dilution with H₂O, the aqueous phase was extracted with EtOAc (3 × 10 mL). The combined organic phases were washed with sat. aq NH₄Cl (10 mL), brine (10 mL) and dried (MgSO₄). The solvents were evaporated under vacuum and the residue was chromatographed on silica gel (cyclohexane-EtOAc, 9:1).
Selected Data for O -Benzoyl Cyanohydrine ( 2i).
¹H NMR (300 MHz, CDCl₃): δ = 8.05 (d, 2 H, J = 7.3 Hz), 7.56 (m, 3 H), 7.45 (m, 2 H), 6.97 (d, 2 H, J = 8.6 Hz), 6.62 (s, 1 H), 3.84 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 166.43, 164.85, 136.66, 134.70, 132.40, 130.89, 130.51, 129.14, 128.27, 128.15, 116.17, 63.19, 52.86. IR (KBr): 1732, 1729 cm^-1. All other synthesized O-benzoyl cyanohydrins are in accordance with the literature data.