Meerwein-Ponndorf-Verley-type reductive acetylation of carbonyl compounds to acetates by lanthanide complexes in the presence of isopropenyl acetate

Article abstract of DOI:10.1016/S0040-4039(00)00012-5

Meerwein-Ponndorf-Verley-type reductive acetylation of carbonyl compounds to acetates was successfully carried out in the presence of isopropenyl acetate under the influence of a catalytic amount of Ln(O(i)Pr)₃ at room temperature. Various carbonyl compounds were converted into the corresponding acetates in fair to good yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00012-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 1565–1569
Meerwein–Ponndorf–Verley-type reductive acetylation of
carbonyl compounds to acetates by lanthanide complexes in the
presence of isopropenyl acetate
Yasushi Nakano, Satoshi Sakaguchi and Yasutaka Ishii ∗
Department of Applied Chemistry, Faculty of Engineering & High Tecnology Research Center, Kansai University, Suita,
Osaka 564-8680, Japan
Received 7 October 1999; revised 29 November 1999; accepted 17 December 1999
Abstract
Meerwein–Ponndorf–Verley-type reductive acetylation of carbonyl compounds to acetates was successfully
carried out in the presence of isopropenyl acetate under the influence of a catalytic amount of Ln(OiPr)3 at room
temperature. Various carbonyl compounds were converted into the corresponding acetates in fair to good yields.
© 2000 Elsevier Science Ltd. All rights reserved.
Keywords: lanthanide; carbonyl compound; isopropenyl acetate; acetylation; Meerwein–Ponndorf–Verley reduction.
The Meerwein–Ponndorf–Verley (MPV) reduction of carbonyl compounds to alcohols by the use of
a stoichiometric amount of Al(OiPr)3 in 2-propanol is a well-established method.1 This is a mild and
relatively inexpensive route for reduction of aldehydes and ketones to alcohols. Recently, the MPV
reduction was reported to be efficiently promoted by lanthanide isopropoxides, Ln(OiPr)3, under mild
conditions.2 In a previous paper, we showed that the acetylation of a wide variety of alcohols with
isopropenyl acetate can be achieved by samarium compounds such as Cp*2Sm(thf)2 and Sm(OiPr)3
under neutral conditions.3 Thus, tertiary alcohols which are labile under acidic and basic conditions
are successfully acetylated by this method in good yields. During this study, we found that ketones are
reacted in the presence of Ln(OiPr)3, in particular Gd(OiPr)3 and Sm(OiPr)3, and isopropenyl acetate
at room temperature, giving acetates in fair to good yields. This reaction is referred to as MPV-type
reductive acetylation of ketones to acetates, since our reaction is analogous to the MPV reduction of
ketone which is prompted by Sm(OiPr)3 in the presence of an alcohol such as 2-propanol in place of
isopropenyl acetate (Eq. (1)).
∗
Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00012-5
tetl 16292

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(1)
For instance, the reaction of cyclohexanone (1a) (1 mmol) with Sm(OiPr)3 (0.67 mmol) in the presence
of isopropenyl acetate (2) (4 mmol) in THF (6 mL) at room temperature for 3 h afforded cyclohexyl
acetate (3a) in 83% selectivity at 88% conversion along with cyclohexylideneacetone (4a) (15%) which
is derived from an aldol reaction of 1a with acetone liberated from Sm(OiPr)3 and/or 2. This shows that
the hydrogen transfer from the isopropoxy moiety of Sm(OiPr)3 to 1a followed by acetylation with 2
easily takes place under mild conditions.
To know the effectiveness of lanthanide alkoxides in the present reaction, several lanthanide
isopropoxides5 were allowed to react with 1a in the presence of 2 (Table 1). Gd(OiPr)3 also promoted
the MPV-type reductive acetylation of 1a to 3a in good selectivity (Run 2). The same reaction using
Yb(OiPr)3 gave 3a in a similar selectivity as that using the Sm(OiPr)3, although the conversion was low
(43%) (Run 3). La(OiPr)3 resulted in 3a together with a substantial quantity of an aldol condensation
product 4a (Run 4).
Table 1
MPV-type reductive acetylation of cyclohexane (1a) to cyclohexyl acetate (3a) by several metal
isopropoxides in the presence of isopropenyl acetate (2)a
It is interesting to note that Al(OiPr)3, which is employed for the MPV reduction of ketones, was
completely inert for the present MPV-type reductive acetylation (Run 5). Similarly, the MPV type

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reductive acetylation was not induced by Zr(OiPr)4 (Run 6), although Zr(OtBu)4 promoted the MPV
reduction.4 These results show that the reactivity of Ln(OiPr)3 is quite different from that of Al(OiPr)3
or Zr(OtBu)4 in these reactions.
If the present MPV-type reductive acetylation can be carried out by a catalytic amount of Ln(OiPr)3,
this method provides a new route to acetates from ketones. To achieve the MPV-type reductive acetylation
via the catalytic process, it is important that Ln(OiPr)3 is regenerated in the course of the reaction. Thus,
the MPV-type reductive acetylation was examined by adding 2-propanol to the above reaction system
(Table 2).
Table 2
MPV-type reductive acetylation of various carbonyl compounds catalyzed by Ln(OiPr)3 in the pre-
sence of isopropenyl acetate 2 and 2-propanola
As expected, the MPV type reductive acetylation of 1a was promoted by a catalytic amount of
Ln(OiPr)3 in the presence of 2 and 2-propanol (Runs 1–4). In particular, Sm(OiPr)3 and Gd(OiPr)3
showed high catalytic activity to give 3a in good yields. The formation of aldol product 4a by Sm(OiPr)3
and Gd(OiPr)3 was negligibly small when 2-propanol was added to the reaction system. Unlike Gd(OiPr)3

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and Sm(OiPr)3, the reaction by Yb(OiPr)3 gave cyclohexanol rather than 3a as a major product (Run 3).
The catalytic activity of La(OiPr)3 was lower than that of Gd(OiPr)3 and Sm(OiPr)3 to result in 3a and a
considerable quantity of 4a (Run 4).
On the basis of these results, the MPV-type reductive acetylation of a variety of carbonyl compounds
by Gd(OiPr)3 and Sm(OiPr)3 under these conditions was examined (Table 2, Runs 5–17). Substituted
cyclohexanones, such as 4- methyl, 4-tert-butyl and 3-methylcyclohexanones 1b, 1c and 1d, respec-
tively, were acetylated to form the corresponding acetates in high yields (Runs 5–8). However, 2-
methylcyclohexanone (1e) and 2-adamantanone (1f) were converted into the corresponding acetates
3e and 3f in moderate selectivities (Runs 9 and 10). 1,4-Cyclohexanedione (1g) was acetylated to
diacetate, 1,4-diacetoxycyclohexanone (3g) (Run 11). The reaction of cycloheptanone (1h) led to the
corresponding acetate 3h in low conversion (25%), but the selectivity was high (96%) (Run 12).
Treatment of cyclopentanone (1i) under these conditions produced cyclopentylidene-cyclopentanone (5)
and cyclopentylideneacetone (4i), which are derived from homo- and cross-aldol reactions of 1i and of
1i with acetone, respectively, in preference to the acetate 3i expected (Run 13). The MPV reduction of
1i by Al(OiPr)3 is reported to lead to the aldol condensation product 5 rather than cyclopentanol as a
major product.6 2-Octanone (1j) was acetylated to 3j in high selectivity (97%), although the conversion
of 1j was 33% (Run 14). Benzaldehyde (1k) and cinnamaldehyde (1l) gave acetates 3k and 3l, and the
corresponding aldol products (Runs 15–17).
The present MPV-type reductive acetylation of carbonyl compounds by Gd(OiPr)3 is outlined as
Scheme 1. The reaction may be initiated by hydride transfer from the isopropoxy moiety of Gd(OiPr)3
to ketone to form a gadrinium alkoxide (A) as an intermediate. The resulting alkoxide A is subjected to
the acetylation by isopropenyl acetate to form acetate 3 and the resulting gadrinium enolate (B) readily
reacts with 2-propanol to regenerate Gd(OiPr)3. In the case of the Yb(OiPr)3-catalyzed reaction, the A
reacts easily with 2-propanol in preference to 2 to form alcohols as major products (Table 2, Run 3).
Scheme 1. A possible reaction path for MPV-type reductive acetylation of carbonyl compounds to acetates

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Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Research (No. 11119268) on Priority Areas
from the Ministry of Education, Science and Culture, Japan.
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