August 1998
SYNLETT
849
Sc(OTf) , an Efficient Catalyst for Formation and Deprotection of Geminal Diacetates
3
(Acylals); Chemoselective Protection of Aldehydes in Presence of Ketones
Varinder K. Aggarwal* Silvia Fonquerna and Graham P. Vennall
Department of Chemistry, University of Sheffield, Brook Hill, Sheffield S3 7HF, UK
Received 9 April 1998
Abstract: Scandium triflate (2 mol%) has been found to be an
extremely efficient catalyst for the addition of acetic anhydride to both
aromatic and aliphatic aldehydes. Deprotection of the resulting geminal
diacetates (acylals) was achieved using the same catalyst in the presence
of water.
1
Acylals have been reported as efficient protecting groups for aldehydes
2
as they are stable in neutral and basic media. Typically, they are
synthesised from acetic anhydride and aldehydes using strong Brönsted
1
3
acids as catalysts (typically sulfuric acid or Nafion-H ) or Lewis acids
2
4
5
(e.g. FeCl , ZnCl or PCl ) but these methods are often accompanied
by long reaction times or low yields. More recently, zeolites and
iodine have also been shown to be efficient catalysts for this reaction.
3
2
3
6
Additionally, treatment of the acylals derived from benzaldehyde and
cyclohexanecarboxaldehyde with water in the presence of scandium
triflate gave a high yield of deprotected aldehyde.
7
During the course of investigations into Lewis acid catalysed additions
to benzaldehyde with a range of nucleophiles, we found that scandium
8
triflate catalysed the formation of the corresponding acylal, both cleanly
9
and efficiently. To probe the generality of this process, a range of both
aromatic, unsaturated and aliphatic aldehydes were screened in this
reaction (Table).
Typical Experimental Procedure for the Formation of Acylals: To a
stirred solution of scandium triflate (9.8 mg, 0.02 mmol) and
benzaldehyde (102 µL, 1.0 mmol) in nitromethane (10 mL) at room
temperature was added dropwise acetic anhydride (142 µL, 1.5 mmol).
The mixture was stirred at room temperature until complete
consumption of the aldehyde was achieved (as monitored by tlc).
Concentration in vacuo and chromatography (10% EtOAc/Petrol; silica
gel) gave the product as a white solid (206 mg, 0.99 mmol, 99%), R
f
5
0.26 (10% EtOAc/Petrol); mp 43-45°C [Lit., mp 44-46 °C]; δ (250
H
MHz; CDCl ) 2.12 (6 H, s, CH ), 7.39-7.43 (3 H, m, ArH), 7.50-7.54 (2
3
3
H, m, ArH) and 7.68 (1 H, s, CH).
Experimental Procedure for the Deprotection of Acetic Acid
Acetoxy Phenyl Methyl Ester: To a stirred solution of acetic acid
acetoxy phenyl methyl ester (104 mg, 0.5 mmol) in nitromethane (0.5
mL) was added scandium triflate (4.9 mg, 0.01 mmol) and water (9 µL,
0.5 mmol). The mixture was stirred at room temperature for 10 mins.
Concentration in vacuo and chromatography (10% EtOAc/Petrol; silica
gel) gave benzaldehyde (50 mg, 0.47 mmol, 94%).
We were pleased to find that both activated and weakly deactivated
aromatic aldehydes (entries 1-4) gave the corresponding acylals in near
quantitative yield after chromatographic purification. Aliphatic
aldehydes also reacted efficiently (entry 7). Highly deactivated aromatic
aldehyde (entry 5) gave a lower yield of the protected aldehyde, with the
remainder of the material recovered as unreacted aldehyde.
Acknowledgment: We wish to thank Quest International and Sheffield
University for support of this work and Pfizer for additional support.
References
(1) Gregory, M. J. J. Chem. Soc. (B) 1970, 1201.
Ketones (cyclohexanone, acetophenone) did not give any acylals under
the same reaction conditions and this suggested that chemoselective
protection of an aldehyde in the presence of a ketone could be achieved.
This was shown to be the case in the examples given.
(2) Pinnick, H. W.; Kochhar, K. S.; Bal, B. S.; Deshpande, R. P.;
Rajadhyaksha, S. N. J. Org. Chem. 1983, 48, 1765.
(3) Olah, G. A.; Mehrotra, A. K. Synthesis 1982, 962.
(4) Scriabine, I. Bull. Chem. Soc. Fr. 1961, 1194.
(5) Michie, J. K.; Miller, J. A. Synthesis 1981, 824.
(6) Gigante, B.; Pereira, C.; Marcelo-Curto, M. J.; Carreyre, H.;
Perot, G.; Guisnet, M. Synthesis 1995, 1077.
Aggarwal, Varinder K.
