8144
S. K. De, R. A. Gibbs / Tetrahedron Letters 45 (2004) 8141–8144
17. General acetalization procedure: A mixture of aldehyde
(1mmol) and RuCl3 (5mol%, anhydrous available from
Aldrich) in dry alcohol (10mL) was refluxed for the
specified time (Table 1). After completion of reaction
(TLC monitoring), the reaction mixture was concentrated
in vacuo. The residue was chromatographed over silica gel
(10% ethyl acetate in hexane) to afford the pure product in
good to excellent yields.
complex B probably converts to acetal via prior forma-
tion of an oxocarbenium ion26 and subsequent addition
of methanol.
In conclusion, a very simple, efficient, and eco-friendly
method has been developed for the protection of alde-
hydes as acetals in the presence of a number of protect-
ing groups using
a catalytic amount of RuCl3.
18. Experimental procedure: A mixture of benzaldehyde
(1mmol), acetophenone (1mmol), and RuCl3 (5mol%)
in methanol (10mL) was refluxed for 5h. After usual
work-up, the crude mixture showed primarily the acetal of
benzaldehyde. In the same reaction after 12h, the ratio of
Moreover, the high chemoselectivity, good to high
yields, and non-aqueous work-up are the main advan-
tages of this new method and will make a useful and
important addition to the present methodologies.
1
2 and 3 was 91:13, was determined by H NMR of crude
mixture.
Acknowledgements
19. Reaction condition: A mixture of hexaldehyde (1mmol),
2-hexanone (1mmol), and RuCl3 (5mol%) in methanol
was refluxed for 8h. The ratio of 4 and 5 after 12h was 82:
8.
We thank the reviewers for their valuable suggestions
and comments.
20. Experimental condition: A mixture of 4-acetylbenzalde-
hyde (1mmol) and RuCl3 (5mol%) in methanol (10mL)
was refluxed. After 12h, the ratio of 6 and 7 was 78: 9.
21. Reaction condition: A mixture of keto-aldehyde (1mol)
and RuCl3 (5mol%) in methanol (10mL) was refluxed for
2h.
References and notes
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; John Wiley and Sons: New
York, 1999; (b) Kocienski, P. J. Protecting Groups, 1st ed.;
Thieme: New York, 1994.
22. All yields for the competition study were determined by
1H NMR analysis of crude mixture.
2. Cameron, A. F. B.; Hunt, J. S.; Oughton, J. F.; Wilkinson,
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27. Selected spectral data: 4-Nitrobenzaldehyde dimethyl acetal
(entry 4) 1H NMR (300MHz, CDCl3) d 3.35 (s, 6H),
5.46 (s, 1H), 7.64 (d, J = 8.2Hz, 2H), 8.21 (d, J = 8.2Hz, 2H);
13
C NMR (75MHz, CDCl3) d 52.8, 101.7, 123.4, 127.8,
145.1, 148.1; MS m/z 197 (M+); 2-Thiophenecarboxalde-
hyde dimethyl acetal (entry 9) 1H NMR (300MHz. CDCl3)
d 3.35 (s, 6H), 5.64 (s, 1H), 7.01 (dd, J = 3.9, 4.9Hz, 1H),
7.09 (d, J = 3.9Hz, 1H), 7.32 (d, J = 4.9Hz, 1H); 13C
NMR (75MHz, CDCl3) d 52.5, 100.1, 125.5, 125.7, 126.8,
141.6; 1-[4-(Dimethoxymethyl)phenyl]ethanone (com-
1
pound 6, Scheme 4) H NMR (300MHz, CDCl3) d 2.62
(s, 3H), 3.34 (s, 6H), 5.45 (s, 1H), 7.55 (d, J = 8.2Hz, 2H),
7.98 (d, J = 8.2Hz, 2H); 13C NMR (75MHz, CDCl3) d
26.8, 52.7, 102.4, 127.1, 128.4, 137.1, 143.2, 197.8; MS m/z
194 (M+), 163, 75, 43; 3,3-Dimethoxy-1-phenylpropan-1-
one (compound 9, Scheme 5) 1H NMR (300MHz, CDCl3)
d 3.31 (d, J = 5.2Hz, 2H), 3.46 (s, 6H), 5.03 (t, J = 5.2Hz,
1H), 7.40–7.62 (m, 3H), 7.92–8.01 (m, 2H); MS m/z 194
(M+), 163, 136, 105, 85, 77, 51.
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