A two-step, catalytic synthesis of δ-hydroxy-γ-lactones from allylic acetates and bis(trimethylsilyl)ketene acetals

Article abstract of DOI:10.1039/b001175o

Bis(trimethylsilyl) ketene acetals react successively with allylic acetates, in the presence of Pd(0) then with H₂O₂, in the presence of methyltrioxorhenium, to give δ-hydroxy-γ-lactones via γ-unsaturated carboxylic acids.

Full text of DOI:10.1039/b001175o

A two-step, catalytic synthesis of d-hydroxy-g-lactones from allylic acetates
and bis(trimethylsilyl)ketene acetals
Henri Rudler,*a Andrée Parlier,a Frederic Cantagrel,a Paul Harrisa and Moncef Bellassouedb
a Laboratoire de Synthèse Organique et Organométallique, UMR 7611, Université Pierre et Marie Curie, T 44-45, 4
place Jussieu, 75252 Paris Cedex 5, France. E-mail: rudler@ccr.jussieu.fr
b Laboratoire de Synthèse Organométallique associé au CNRS, Université de Cergy-Pontoise, 5 Mail Gay Lussac,
Neuville-sur-Oise, 95031 Cergy-Pontoise Cedex, France
Received (in Liverpool, UK) 11th February 2000, Accepted 21st March 2000
Bis(trimethylsilyl) ketene acetals react successively with
allylic acetates, in the presence of Pd(0) then with H2O2, in
the presence of methyltrioxorhenium, to give d-hydroxy-g-
lactones via g-unsaturated carboxylic acids.
3
h -allyl palladium complexes, formed upon oxidative addition
Scheme 2
of allylic compounds to Pd(0), have found wide applications, as
intermediates, in their reaction with nucleophiles.1 Much effort
parallel, on a formal point of view, the transformation of anisole
depicted in Scheme 1. And this indeed turned out to be the
case.
Depending on the nature of the starting ketene acetals,
cyclopropane carboxylic acids could be isolated as secondary
products, and epoxycarboxylic acids detected by NMR as
intermediates in the lactonization reactions.
has been devoted to the modification of the structure of the
allylic moiety, the ligands around the metal, and also of the
nucleophiles. It is this last point on which will focus our
attention. Indeed, we have shown recently that bis(trimethylsi-
lyl) acetals of ketenes could be used either as nucleophiles or
versatile precursors of nucleophiles, when suitably activated, in
reactions with a large variety of electrophiles such as carbonyl
compounds, organic and organometallic peroxo derivatives,2
and arene tricarbonyl chromium complexes.3 These acetals lead
directly, in contrast to other precursors, to functionalized
carboxylic acids in high yield. Moreover, for chromium
complexes, a direct double nucleophilic addition of potassium
enolates originating from these acetals on a carbon–carbon
double bond of anisole (and its derivatives) has been brought to
the fore. This one pot reaction leads to functionalized lactones
(Scheme 1).
Alkoxy monotrimethylsilyl ketene acetals have already been
used in palladium(0) catalyzed alkylations in conjunction with
allylic acetates for the preparation of unsaturated esters.4–6
Under the same conditions, bis(trimethylsilyl) ketene acetals
might thus lead to unsaturated carboxylic acids. Moreover, we
have shown7 that g-unsaturated hydroxyalkenes underwent a
high yield catalytic oxidative cyclization to lactols promoted by
the system H2O2/MTO (methyltrioxorhenium),8 a reaction
which has recently been applied to the transformation of g-
unsaturated carboxylic acids into hydroxylactone (Scheme
2).9
Thus, a mixture of allyl acetate (10 mmol) and bis-
(trimethylsilyl)ketene acetal 1a† (11 mmol) was heated in THF
(70 mL) for 24 h in the presence of Pd(PPh3)4 (0.2 mmol, 2%).
Evaporation of the volatiles, under vacuum, left a residue which
was diluted in dichloromethane and filtered through a pad of
silica gel. Extraction with aqueous sodium hydroxide followed
by acidification and extraction with dichloromethane gave a
mixture of acids. After cooling the solution to 0 °C, MTO (5%
with respect to the unsaturated acids) was added followed by a
30% solution of hydrogen peroxide (1.1 equiv. with respect to
the acids). The biphasic mixture was then stirred for three days
at room temperature, the excess oxidant destroyed with aqueous
sodium bisulfite, and the organic products extracted with
dichloromethane. Treatment of the organic layer with dilute
sodium hydroxide left an organic phase containing the hydroxy-
lactone (5 mmol). Acidification of the aqueous layer followed
by extraction with diethyl ether gave, after evaporation of the
solvents, the cyclopropyl acid (1.5 mmol).
The same reactions were carried out on a series of
bis(trimethylsilyl) ketene acetals and two allylic acetates.† They
led to hydroxylactones and, for the more substituted ketene
acetals, to mixtures of lactones and cyclopropyl acids (Table
1).‡
Taken together, the interaction of bis(trimethylsilyl) ketene
acetals first with allylic acetates to give unsaturated carboxylic
acids, then with MTO/H2O2 to give hydroxylactones (Scheme
3) would constitute a means for the catalytic addition of two
nucleophiles on a carbon–carbon double bond,10 and would thus
For cinnamyl acetate 2a (R3 = Ph) and the ketene acetal 1a
(R1 = R2 = Me), the two acids 3a and 4a resulting,
respectively, from SN2 and SN2A reactions, were separated by
crystallization and by silica gel chromatography. Their oxida-
tion led, respectively, to the lactones 6a and 7a (Scheme 4).
Whereas the transformation of 3a into 6a, obtained as a single
isomer was complete within 6 h, the conversion of 4a into 7a
took three days. This result is in agreement with the difference
of epoxidation rate observed for substituted and terminal olefins
with the system H2O2/MTO.8
Scheme 1
Scheme 3
DOI: 10.1039/b001175o
Chem. Commun., 2000, 771–772
This journal is © The Royal Society of Chemistry 2000
771

Table 1 Lactones and cyclopropyl carboxylic acids from allylic acetates and
bis(trimethylsilyl) ketene acetals. The ratios were obtained from H NMR
(400 MHz) data, after oxidation. The ratios of 8 vs. 6 and 7 was also
determined upon isolation of 8
acetals are thus nucleophilic enough to interact as such with the
p-allyl complexes of palladium.6,10
1
In addition, these transformations are interesting from a
double point of view. First, highly substituted, unsaturated
carboxylic acids can be obtained directly in the first step of the
process. Second, for the disubstituted ketene acetals, cyclopro-
pyl acids are formed, yet, up to now, in rather low yield. Their
purification, without the need of chromatography, can easily be
achieved by the use of the second step of the process; indeed, the
separation of the lactones from the cyclopropyl acids, whenever
formed, is possible by a simple extraction process.
The interaction of mono(trialkylsily) ketene acetals with
allylic acetates in the presence of complexes of palladium had
already been shown to give, besides unsaturated esters,
cyclopropyl esters in variable amounts.5 The reasons behind
this dual reactivity of the intermediate p-allyl complexes with
the nucleophiles (central vs. terminal addition) have not been
clearly established since contrasting results have be found in the
literature.12–15 Up to now, no attempts have been made in order
to optimize the yields of the reactions described above by
modifying the nature of the catalyst and the experimental
conditions, or to drive them in one or the other direction. It
seems nevertheless likely that steric factors are important both
as far as the ligands around the metal and the substituents on the
ketene acetals are concerned.
Notes and references
† Selected data for 6 [R1R2 = (CH2)5, R3 = H], colorless oil; IR(Nujol),
1750 cm21; dH(CDCl3, 400 MHz) 4.52 (m,1H, CHO), 3.89 (dd, J 12, 2.5
Hz, 1H, CHOH), 3.61 (dd, J 12, 5.1 Hz, 1 H, CHOH), 2.77 (1H, OH), 2.24
(dd, J 13 and 6.6 Hz, 1H, CHH), 1.88 (dd, 1H, J 13 and 8 Hz, 1H, CHH),
1.81–1.52 (m, 10H, 5 CH2); dC(CDCl3, 100 MHz) 182.0, 77.84, 63.9, 44.9,
34.1, 34.0, 32.1, 25.26, 22.2, 22.1; HRMS: 185.1178 (M+). For 8 [R1R2
=
(CH2)5, R3 = H]: colorless oil; dH(CDCl3) 2.1–1.07 (m, 10H), 0.87 (m, 1H),
0.18 (m, 4H); dC(CDCl3) 183.2, 45.14, 32.18, 25.8, 23.5, 20.9, 0.85; HRMS:
169.122 (M+). For 3a: white crystals, mp 38 °C, dH(CDCl3) 7.11–7.31 (m,
5H, ArH); 6.16 (d, J 16 Hz, 1H, PhCHN), 6.11 (dt, J 16, 7.5 Hz, 1H,
NCHCH2), 2.39 (d, J 7.5 Hz, 2H), 1.17 (s, 6H, 2 Me), dC(CDCl3) 184.3,
137.7, 133.7, 128.9, 127.6, 126.5, 126.0, 43.9, 43.0, 25.1. Anal. Calc. For
C13H14O3: C, 70.91; H, 7.27. Found: C, 70.71; H, 7.31%.
‡ Satisfactory elemental analyses or HRMS were obtained for the various
carboxylic acids and hydroxylactones.
1 B. M. Trost and T. R. Verhoeven, Organometallic Compounds in
Organic Synthesis and in Catalysis, in Comprehensive Organometallic
Chemistry, ed. G. Wilkinson, F. G. A. Stone and E. W. Abel, Pergamon
Press, New York, 1982, vol. 8, ch. 57; J. Tsuji, Organic Synthesis with
Palladium Compounds, Springer, Berlin, 1980, pp. 45–51.
2 Unpublished results from this Laboratory, manuscript in preparation.
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10 For consecutive nucleophilic additions on olefins, see: Y.-S. Lin, S.
Takeda and K. Matsumoto, Organometallics, 1999, 18, 4897 and
references therein.
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Scheme 4
That indeed epoxides were formed as intermediates in these
oxidation reactions as for g-hydroxyalkenes7 was demonstrated
as follows: when the acid 3a was subjected to the oxidation
reaction, a labile precursor could be detected by 1H NMR
spectroscopy after 2 h giving a doublet and a multiplet at d 4.92
and 3.95, respectively attributable to the two hydrogens of the
epoxide 5a (Scheme 4). These signals disappeared pro-
gressively in favour of those due to the hydroxylactone 6a at d
5.04 (doublet), and d 4.52 (multiplet). Attempts to isolate the
epoxide 5a by silica gel chromatography failed however, a
result which is reminiscent of previous observations.7
The results described herein allow the following comments to
be made.
13 L. S. Hegedus, W. H. Darlington and C. E. Russell, J. Org. Chem., 1980,
45, 5193.
14 C. Carfagna, L. Mariani, A. Musco, G. Sallese and R. Santi, J. Org.
Chem., 1991, 56, 3925.
As for mono(trialkylsilyl) ketene acetals, no base was
required for the interaction with the allylic acetates: the ketene
15 E. B. Tjaden and J. M. Stricker, Organometallics, 1992, 11, 16.
772
Chem. Commun., 2000, 771–772