Expeditious formation of γ-lactones upon palladium-catalyzed double nucleophilic addition of bis(TMS)ketene acetals to vicinal allylacetates

Article abstract of DOI:10.1016/j.tetlet.2008.07.111

Polysubstituted γ-lactones are easily obtained, in one step, upon the interaction of bis(TMS)ketene acetals with vicinal allylic acetates in the presence of catalytic amounts of Pd(PPh₃)₄.

Full text of DOI:10.1016/j.tetlet.2008.07.111

Tetrahedron Letters 49 (2008) 5843–5846
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Expeditious formation of
c-lactones upon palladium-catalyzed double
nucleophilic addition of bis(TMS)ketene acetals to vicinal allylacetates
a
b
Cesar Sandoval Chavez a, Henri Rudler a, , Andrée Parlier , Patrick Herson
*
a Laboratoire de Chimie Organique, Université Pierre et Marie Curie, UMR CNRS 7611, CC 47, 4 Place Jussieu, 75252 Paris cedex 5, France
b Laboratoire de Chimie Inorganique et Matériaux Moléculaires, Université Pierre et Marie Curie, UMR CNRS 7071, CC 42, 4 Place Jussieu, 75252 Paris cedex 5, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Polysubstituted
c-lactones are easily obtained, in one step, upon the interaction of bis(TMS)ketene
Received 1 July 2008
Revised 18 July 2008
Accepted 21 July 2008
Available online 24 July 2008
acetals with vicinal allylic acetates in the presence of catalytic amounts of Pd(PPh3)4.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Lactones
Palladium-catalysis
Allyl acetates
Ketene acetals
Double nucleophilic additions
Our approaches to the synthesis of polycyclic c-lactones of bio-
OMe
O
R1
logical relevance relied on the use of bis(TMS)ketene acetals 1 as
1,3-dinucleophiles in either transition metal or organic reagent-
promoted di-addition reactions.1
R2
O
N
N
R1
R2
OSiMe3
OSiMe3
MeOCOCl
O
N
N
Although we have disclosed a two-step overall catalytic synthe-
sis of such lactones,2 no catalytic transformation, using this meth-
odology and involving a single metal, has yet been achieved. The
purpose of this Letter is to present preliminary results which dem-
onstrate, on a few examples, that this is, however, feasable.
The double nucleophilic addition of both the carbon and the
oxygen termini of bis(TMS)ketene acetals to two close, similar
electrophilic iminium carbon centers seemed obvious in the case
1
2
O
OMe
3
Scheme 1.
Indeed, this last step, the formation of the five-membered ring
is reversible: the lactone in 5 (Scheme 2) in an allylic position
might be prone to react with palladium(0) to give back a
complex B. This property has been used in the synthesis of highly
substituted complex organic molecules: such lactones, which
could also be synthesized by classical methods, either in the form
of the methylchloroformate-induced formation of
c-lactones 3
p-allyl
from pyrazine 23a,b (Scheme 1). However, less obvious would be
the addition of the same dinucleophilic species to potential
dielectrophiles such as unsaturated diacetates 4, which might lead
successively upon their interaction with palladium(0) and nucleo-
philes, to disubstitution products via two
having in common a carbon–carbon double bond. Although the ini-
tial step, the addition of carbon–nucleophiles to the first -allylic
complex (4?A), is well known, both for classical carbon–nucleo-
philes4a–i and for carbon–nucleophiles arising from ketene
acetals,2,5a–c the second step (B?5), the formation of a carbon–
p-allylic complexes
p
R2
R2
R2
O
O
O
O
O
R1
R3
R1
R3
R1
R3
OAc
OSiMe3
R3
R4
Pd(0)
Pd(0)
1
Pd(0)
R4
R4
R4
oxygen bond from 1, leading to a
c-lactone, although likely to
Pd
occur, would be more tricky.6
OAc
4
OAc
A
5
B
SiMe3OAc
* Corresponding author. Tel.: +33 (0)144 275092; fax: +33 (0)144 273787.
E-mail address: henri.rudler@upmc.fr (H. Rudler).
Scheme 2.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.111

5844
C. S. Chavez et al. / Tetrahedron Letters 49 (2008) 5843–5846
O
R1
R2
R1
R2
OAc
OSiMe3
AcO
OAc
Pd(0)
O
AcO
OAc
OSiMe3
AcO
1a R1= R2 = Me
8
9
6
7a,b
1b R1R2 = (CH2)5
Scheme 3.
O
O
2
COOH
Ph
Ph
Ph
OSiMe3
OSiMe3
Ph
Pd(0)
1O
O
3
AcO
AcO
OAc
Me
Me
4
Me
5
Me
6
7
6
1c
7c'
7c
10
Pd(0)
Scheme 4.
of racemates or in enantiomerically pure forms, were used as the
starting material for the stereocontrolled synthesis of acyclic scaf-
folds in the presence of Pd(0) and suitable nucleophiles.6,7a–d We
nevertheless attempted the reaction with the simplest potential
of the proton H-5 could be noticed. Finally, a much more polar
product was also isolated as a viscous liquid in 23% yield. The
NMR data agreed fully with a structure such as 10 and depicted
the presence, besides a disubstituted carbon–carbon double bond,
of a phenyl group and of a methyl group as a singlet, of an acid and
of a methylester. They gave signals, respectively, at d 181.50 ppm
and 170.95, the latter confirmed by the presence of a signal for a
methyl group at d 2.01 ppm and of a doublet J = 5.2 Hz at d 4.44.
Accordingly, 10 was therefore the monoaddition product of the ke-
tene acetal 1c to diacetate 6, having suffered hydrolysis of the TMS
ester function. Since carboxylic acids are also excellent nucleo-
di-p-allyl complex precursor, diacetate 6. In order to take the less
chances for this subsequent ring-reopening to occur (5?B), we
first used highly substituted bis(TMS)ketene acetals such as 1a
(R1 = R2 = Me), 1b (R1–R2 = (CH2)5), and 1c (R1 = Ph, R2 = Me), which
might act favorably in the second step on the grounds of the Thorp-
Ingold effect, and carried out the reactions at room temperature8a,b
(see Schemes 3 and 4).
Thus, when the ketene acetal 1a (1.1 equiv) was added drop-
wise to a solution of diacetate 6 (1 equiv) and Pd(PPh3)4 (5%) and
the mixture stirred at room temperature for two days, then,
according to TLC, the formation of a new, less polar product 7a
was observed. Silica gel column chromatography allowed to isolate
the new compound as a white solid, mp 30 °C, in 47% yield besides
some more polar isomerized starting diacetates 8 and 9. The 13C
NMR spectrum of 7a was in agreement with the presence of a
philes for p
-allyl complexes of palladium,9 we submitted com-
pound 10 to a catalytic amount of Pd(0): a fast reaction took
place leading after one night at room temperature to a mixture
of the expected lactones 7c and 7c0, in the same ratio as for the di-
rect double addition reaction. The observation of the monoadduct
10, which exists in the reaction mixture, before workup, as the TMS
ester, might be ascribed to its lower reactivity toward the catalyst.
The presence of bulky substituents and especially of the TMS group
would considerably slow down the second addition reaction, and
thus allow the isolation of the monoaddition product. The presence
of a phenyl group in lactones 7c and 7c0 gave us the opportunity to
convert the more polar liquid lactone 7c0 into an arenetricarbonyl-
chromium complex upon its heating for two days in the presence
of an excess of chromium hexacarbonyl in a refluxing mixture of
dibutylether/THF (Scheme 5). A silica gel column chromatography
allowed us to purify that complex and, after recrystallization from
dichloromethane/hexane solutions, to get yellow crystals of 11
(37% yield, mp 150 °C) suitable for an X-ray structure determina-
tion.10 The 1H NMR spectrum confirmed the coordination of the
arene group to the metal, all the signals for the aromatic protons
being shifted toward higher field. As shown (Fig. 1) the phenyl
group, coordinated to Cr(CO)3, is cis with respect to the vinyl
group. Therefore, in the less polar solid lactone 7c these two sub-
stituents are trans.
c-lactone, with a signal at d 181.68 ppm, of a monosubstituted car-
bon–carbon double bond according to a DEPT sequence, with sig-
nals at d 136.02 (CH) and 117.67 (CH2) ppm. The 1H NMR
spectrum confirmed these data and also depicted a deshielded sig-
nal for one proton at d 4.82 ppm as a quartet of triplets, J = 6.3 and
1.1 Hz. An HMQC sequence allowed to assign this signal to a proton
linked to a carbon at d 77.12 ppm. Moreover, signals as doublets of
doublets for two geminated protons were also apparent at d 2.21
and 1.84 ppm. Finally, the two methyl groups gave a singlet at d
1.24 ppm. It is therefore clear that the expected double nucleo-
philic addition took place leading to a c-lactone. The ketene acetal
1b behaved similarly and gave the same type of lactone 7b, again
as a solid (71% yield, mp 31 °C). However, confirmation of the
structure of these new lactones by an X-ray analysis could not be
achieved due to the poor quality and the low melting points of
crystals of 7a and 7b. In the case of the ketene acetal 1c, the same
procedure led however to a more complex mixture of three com-
pounds, two of them having almost the same polarity. Careful silica
gel column chromatography allowed the separation, besides the
starting isomerized diacetates, of three compounds. To the less po-
lar compound, isolated in 10% yield as a solid, mp 37 °C, was as-
signed structure 7c on the grounds of its NMR data, which were
very close to those of 7a (except for the presence of a phenyl
group). A slightly more polar product 7c0, obtained as a liquid, in
5% yield, showed almost the same 13C NMR spectrum as 7c, but
as far as the 1H NMR spectrum was concerned, differences in the
chemical shifts of the protons of both the methylene group and
Finally, we carried out the same reaction by using two mono-
substituted bis(TMS)ketene acetals, 1d (R1 = H, R2 = Me) and 1e
(R1 = H, R2 = iPr). The reason behind this choice was that lactone
O
O
Ph
Cr(CO)6
O
Cr(CO)3
O
Me
Me
11
n
Bu2O / THF / Δ
7c'
Scheme 5.

C. S. Chavez et al. / Tetrahedron Letters 49 (2008) 5843–5846
5845
Figure 1. X-ray structure of compound 11.
7d which might be formed upon the interaction of 1d with diace-
tate 6 is known from the literature.11
reaction to structurally different diacetates able to give rise to
two successive -allyl complexes, and involving also different
p
However, to our surprise and in spite of many efforts to achieve
this goal, only trace amounts of the expected lactone 7d could be
detected by NMR: only isomerization of the starting diacetate to
the more stable trans diacetate 8 took place (Scheme 6).
achiral and chiral catalysts, which might improve the stereoselec-
tivity of these transformations, and introduce enantioselectivity
are in progress.
However, under the same conditions 1e led to a 2:1 mixture of
the expected isomeric lactones 7e and 7e0 in 42% yield (Scheme 7).
They could also be partially separated. Their NMR data agreed with
the suggested structures (see the Supplementary data). Indications
that indeed the catalyst reacted with, and was deactivated by the
ketene acetal 1e were obtained: a yellow precipitate, the nature
of which has not yet been established forms rapidly in the absence
of diacetate 6. No such a interaction took place with for example
1b: stirring a dichloromethane solution of 1b in the presence of
the catalyst for one day did not induce its deactivation since the
addition of diacetate 6 led to the expected lactone 7b.
Acknowledgment
Acknowledgements are made to CONACYT (México) for a Grant
to C. Sandoval-Chavez, on assignment from Instituto de Quimica,
Universidad Nacional Autonoma de México, México D.F., México.
Supplementary data
Experimental section and physical data for compounds 7a, 7b,
7c, 7c0, 10, 11, 7e, 7e0 are available. Supplementary data associated
with this article can be found, in the online version, at doi:10.1016/
j.tetlet.2008.07.111.
As a conclusion, the expected di-addition reactions leading to
satisfactory yields of c-lactones took place as expected, provided
that two rather bulky substituents were present on the bis(TMS)-
ketene acetals 2. In the case of monosubstituted acetals, and
depending on the size of the substituent either a partial or a com-
plete deactivation of the catalyst was observed. Extensions of the
References and notes
1. (a) Rudler, H.; Comte, V.; Garrier, E.; Bellassoued, M.; Chelain, E.; Vaissermann,
J. J. Organomet. Chem. 2001, 621, 284–298; (b) Rudler, H.; Denise, B.; Xu, Y.;
Parlier, A.; Vaissermann, J. Eur. J. Org. Chem. 2005, 3724–3744; (c) Aldeco-Perez,
E.; Xu, Y.; Rudler, H.; Parlier, A.; Alvarez, C. Tetrahedron Lett. 2006, 47, 4553–
4556.
2. Rudler, H.; Harris, P.; Parlier, A.; Cantagrel, F.; Denise, B.; Bellassoued, M.;
Vaissermann, J. J. Organomet. Chem. 2001, 624, 186–202.
3. (a) Xu, Y.; Rudler, H.; Denise, B.; Parlier, A.; Chaquin, P.; Herson, P. Tetrahedron
Lett. 2006, 47, 4541–4544; For related transformations see: (b) Langer, P. Eur. J.
Org. Chem. 2007, 2233–2238. and references cited therein.
4. For reviews, see for example: (a) Harrington, P. J. In Comprehensive
Organometallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.;
Elsevier: Oxford, 1995; Vol. 12, Chapter 8.2, pp 797–904 and references cited
therein (b) Nishibayashi, Y.; Uemura, S. In Comprehensive Organometallic
Chemistry III; Mingos, D. M. P., Crabtree, R. H., Eds.; Elsevier: Oxford, 2007;
Vol. 11, Chapter 11.03, pp 75–122 and references cited therein (c) Trost, B. M.;
Crawley, M. L. Chem. Rev. 2003, 103, 2921–2943; (d) Trost, B. M.; Van Vranken,
D. L. Chem. Rev. 1996, 96, 395–422; (e) Tsuji, J. Pure Appl. Chem. 1982, 54, 197–
206; (f) Transition Metal Organometallics for Organic Synthesis; McQuillin, F. J.,
Parker, D. G., Stephenson, G. R., Eds.; Cambridge University Press, 1991; pp
111–148; (g) Hegedus, L. S.; Lipshutz, B. H.; Marshall, J. A.; Nakamura, E.;
Negishi, E.; Reetz, M. T.; Semmelhack, M. F.; Smith, K.; Yamamoto, Y. In
Organometallics in Synthesis; Schlosser, M., Ed.; Wiley: J. England, 2002; pp
1178–1188; For selected close examples see, (h) Genêt, J. P.; Balabane, M.
O
OSiMe3
OSiMe3
Me
Me
O
6
H
1d
7d
Scheme 6.
O
O
Me
Me
Me
2
Me
OSiMe3
OSiMe3
Me
Me
1O
O
8
H
6
3
H
H
5
4
7
6
1e
7e
7e'
Scheme 7.

5846
C. S. Chavez et al. / Tetrahedron Letters 49 (2008) 5843–5846
Tetrahedron Lett. 1982, 23, 331–334; (i) Genêt, J. P.; Piau, F.; Ficini, J. Tetrahedron
Lett. 1980, 21, 3183–3186.
Chupak, L. S.; Lübbers, T. J. Am. Chem. Soc. 1998, 120, 1732–1740; (d) Trost, B.
M.; Tanimori, S.; Dunn, P. T. J. Am. Chem. Soc. 1997, 119, 2735–2736.
8. (a) Bruice, T. C.; Lightstone, F. C. Acc. Chem. Res. 1999, 32, 127–136; (b) Jung, M.
E.; Piizi, G. Chem. Rev. 2005, 105, 1735–1766.
5. (a) Carfagna, C.; Galarini, R.; Musco, A. J. Mol. Catal. 1992, 72, 19–27; (b)
Carfagna, C.; Galarini, R.; Musco, A.; Santi, R. Organometallics 1991, 10, 3956–
3958; (c) Satake, A.; Nakata, T. J. Am. Chem. Soc. 1998, 120, 10391–10396.
6. For a close, yet different approach to five-membered disubstitution products
using such diacetates and dimethyl 3-ketoglutarate, see: (a) Yoshizaki, H.;
Satoh, H.; Sato, Y.; Nukui, S.; Shibasaki, M.; Mori, M. J. Org. Chem. 1995, 60,
2016–2021; (b) Fillion, E.; Carret, S.; Mercier, L. G.; Trépanier, V. E. Org. Lett.
2008, 10, 437–440.
9. (a) Tsuji, J.; Sakai, K.; Nagashima, H.; Shimizu, I. Tetrahedron Lett. 1981, 22, 131–
134; (b) Bäckvall, J. E.; Nordberg, R. E. J. Am. Chem. Soc. 1981, 103, 4959–4960;
(c) Larock, R. C.; Harrison, L. W.; Hsu, M. H. J. Org. Chem. 1984, 49, 3662–3666.
10. Crystal data for 11: C16H14CrO5, M = 338, monoclinic, space group P21/n,
a = 10.3919(6) Å, b = 13.7841(8) Å, c = 11.4571(8) Å, V = 1516.65(17) Å3, Z = 4,
Dc = 1.48 g cmꢀ3
wR2 [I > 3
11. Gierasch, T. M.; Shi, Z.; Verdine, G. L. Org. Lett. 2003, 5, 621–624.
,
l
= 0.774 mmꢀ1 (Mo K
a, k = 0.71073) T = 250 K, R1 (0.034),
7. (a) Trost, B. M.; Klun, T. P. J. Am. Chem. Soc. 1979, 101, 6756–6758; (b) Trost, B.
M.; Li, L.; Guile, S. D. J. Am. Chem. Soc. 1992, 114, 8745–8747; (c) Trost, B. M.;
r(I)] = 0.037; R1 (0.0538), wR2 (all data) = 0.0491, CCDC-687772.