The experimental procedure for these acetylations is re-
markably simple, requiring neither dry glassware nor inert
atmospheres: a catalytic quantity of lanthanide(iii) salt (5–10
mol%) was added to a stirred solution of the alcohol (1 mmol)
in acetic acid (2 ml). In the case of primary alcohols the
reactions can be run at room temperature: quantitative acetyla-
tion occurs over 24 h and a range of functional groups can be
tolerated (Table 1, entries 1–5). In the control experiments with
no lanthanide(iii) salts only small quantities of the alcohols
were converted to their acetates over the same reaction time.
Alternatively, the reaction can be carried out at higher
temperature and acetylation is essentially complete in the time
taken to bring the reaction mixture to reflux. For simple
secondary alcohols somewhat elevated temperatures are re-
quired for acceptable reaction times, and again quantitative
acetylation occurred (Table 1, entries 6–9). It is of interest to
note that no elimination adducts were observed. Cyclohex-
2-enol, an allylic alcohol, was acetylated remarkably quickly,
the reaction being complete within 1 h at room temperature,
while in the corresponding control experiment only traces of the
acetate were detected after 24 h (Table 1, entry 5). Acetylation
of adamantan-1-ol, an extremely bulky tertiary alcohol, was
somewhat less successful (Table 1, entries 10 and 11). However
a remarkable rate acceleration was observed and the equilibrium
position was obtained in less than 0.5 h in refluxing acetic acid
in the presence of a catalytic quantity of scandium(iii) triflate.
Partition work-up with CH2Cl2 and water leads to the
isolation of the acetylated alcohols which are essentially single
components by standard analytical techniques (1H and 13C
NMR) and require no further purification (primary and
secondary alcohols). The aqueous phase containing both the
catalyst and acetic acid can be evaporated under reduced
pressure to furnish the lanthanide(iii) salt as a white solid which
can be recycled and used repeatedly without loss of activity
(Table 2).‡
ciably more effective than lanthanum, praeseodymium or
europium triflates (Table 3).
In conclusion, we have demonstrated the use of scandium(iii)
or lanthanide(iii) triflates for the acetylation of alcohols using
acetic acid only as the acetyl source and where the catalyst is
readily recovered and re-used. This underscores the use of
lanthanide salts as environmentally acceptable catalysts for
atom economic transformations.
The Imperial College group thank Air Products and Chem-
icals, Inc. for support of our research under the auspices of the
Joint Strategic Alliance, Glaxo Group Research Ltd. for the
most generous endowment (to A. G. M. B), the EPSRC and the
Wolfson Foundation for establishing the Wolfson Centre for
Organic Chemistry in Medical Science at Imperial College.
Footnotes
† Scandium(iii) and lanthanide(iii) triflates are commercially available from
the Aldrich chemical company as their hydrated forms.
‡ The FT-IR spectrum of the recovered material was identical to that of the
commercially available salt.
References
1 M. A. Ogliaruso and J. F. Wolfe, in The Chemistry of Functional
Groups, ed. S. Patai, Wiley, Chichester, suppl. B, part 1, p. 411;
H. Pielartzik, B. Irmisch-Pielartzik and T. Eicher, in Methoden Org.
Chem. (Houben-Weyl), 1985, 5, (E), 659; I. O. Sutherland, in
Comprehensive Organic Chemistry, ed. D. H. R. Barton and W. D.
Ollis, Pergamon Press, Oxford, 1979, vol. 2, p. 869.
2 J. Mulzer, in Comprehensive Organic Synthesis, ed. B. M. Trost and I.
Fleming, Pergamon Press, Oxford, 1991, vol. 6, p. 323.
3 B. M. Trost, Angew. Chem., Int. Ed. Engl., 1995, 34, 259.
4 G. Ho¨fle, W. Steglich and H. Vorbru¨ggen, Angew. Chem., Int. Ed. Engl.,
1978, 17, 569. For the use of tributylphosphine as an acylation catalyst,
see E. Vedejs and S. T. Diver, J. Am. Chem. Soc., 1993, 115, 3358;
E. Vedejs, N. S. Bennet, L. M. Conn, S. T. Diver, M. Gingrass, S. Lin,
P. A. Oliver and M. J. Peterson, J. Org. Chem., 1993, 58, 7286.
5 J. Izumi, I. Shiina and T. Mukaiyama, Chem. Lett., 1995, 141; I. Shiina
and T. Mukaiyama, Chem. Lett., 1994, 677; A. K. Kumar and
T. K. Chattopadhyay, Tetrahedron Lett., 1987, 28, 3713.
6 R. H. Baker and F. G. Bordwell, Org. Synth., 1955, Coll. Vol III, 141;
E. Vedejs and O. Daugulis, J. Org. Chem., 1996, 61, 5702.
7 T. Imamaoto, in Lanthanides in Organic Synthesis, Academic Press,
London, 1994.
Of the metal triflates examined in this study, scandium(iii)
triflate was found to be the most effective. The lanthanide(iii)
Table 2 Recycling ytterbium(iii) triflate for the acetylation of phenethyl
alcohol with acetic acid
cat. Yb(OTf)3
AcOH
8 R. W. Marshmann, Aldrichim. Acta, 1995, 28, 77.
OH
OAc
9 S. Kobayshi, H. Ishitani, I. Hachiya and M. Araki, Tetrahedron, 1994,
50, 11623; S. Kobayshi, M. Araki and I. Hachiya, J. Org. Chem., 1994,
59, 3758; L. B. Yu, D. P. Chen and P. G. Wang, Tetrahedron Lett., 1996,
37, 2169.
10 V. K. Aggarwal and G. P. Vennall, Tetrahedron Lett., 1996, 37, 3745;
C. Belluci, P. G. Cozzi and A. Umanironchi, Tetrahedron Lett., 1995,
36, 7289; H. C. Aspinall, A. F. Browning, N. Greeves and P.
Ravenscroft, Tetrahedron Lett., 1994, 35, 4639; I. Hachiya and
S. Kobayshi, J. Org. Chem., 1993, 58, 6958.
11 T. Tsuchimoto, K. Tobita, T. Hiyama and S. I. Fukuzawa, Synlett, 1996,
557; I. Hachiya, M. Moriwaki and S. Kobayashi, Bull. Chem. Soc. Jpn.,
1995, 68, 2053; A. Kawada, S. Mitamura and S. Kobayashi, Chem.
Commun., 1996, 183.
12 S. Kobayashi, I. Hachiya and M. Yasuda, Tetrahedron Lett., 1996, 37,
5569.
Runa
Isolated yield (%)
Recovery Yb(OTf)3 (%)
1
2
3
4
95
99
97
98
98
> 99
> 99
> 99
a Phenethyl alcohol (3 mmol) in refluxing acetic acid (5 ml) for 0.5 h with
ytterbium(iii) triflate (10 mol% for run 1).
Table 3 The effect of various lanthanide(iii) triflates for the acetylation of
phenethyl alcohol with acetic acida
cat. M(OTf)3
AcOH
13 S. Kobayashi and I. Hachiya, J. Org. Chem., 1994, 59, 3590 and
references cited therein.
OH
OAc
14 D. P. Chen, L. B. Wu and P. G. Wang, Tetrahedron Lett., 1996, 37,
4467; S. Kobayashi and I. Hachiya, J. Synth. Org. Chem. Jpn., 1995, 53,
370; S. Kobayashi, Synlett, 1994, 689 and references cited therein.
15 K. Ishihara, M. Kubota, H. Kurihara and H. Yamamoto, J. Org. Chem.,
1996, 61, 4560; K. Ishihara, M. Kubota, H. Kurihara and H. Yamamoto,
J. Am. Chem. Soc., 1995, 117, 4413, 6639 (corrections).
16 For an active scandium acylation catalyst derived from trifluoro-
methanesulfonimide see: K. Ishihara, M. Kubota and H. Yamamoto,
Synlett, 1996, 265.
Conversion (%)c
b
M(OTf)3
After 3 h
After 21 h
Sc
La
Pr
Eu
Yb
79
22
28
23
41
100
63
77
70
92
17 T. Hanamoto, Y. Sugimoto, Y. Yokoyama and J. Inanaga, J. Org.
Chem., 1996, 61, 4491.
a
All reactions run with alcohol (1 mmol) in acetic acid (2 ml) at room
temp. b 10 mol%. c GC–MS determination.
Received, 20th September 1996; Com. 6/06484A
352
Chem. Commun., 1997