One-pot diastereoselective preparation of α,β-unsaturated-γ-silylated-δ-lactones: Application towards natural compounds

Article abstract of DOI:10.1055/s-2001-9700

Rearrangement of silylated vinyloxiranes into highly functionalized α-silylated-β,γ-unsaturated aldehydes occurs with total chirality transfer and retention of double bond configuration under Pd(0) catalysis. We show that this reaction is a versatile tool in the field of total stereoselective synthesis: enantiomerically pure lactones are obtained. The pheromone 6-n-undecyltetrahydro-2-pyrone 2 and massoilactone, 5-hydroxy-2-decenoic acid lactone 3, are synthesized. We describe herein a novel highly diastereoselective route to α,β-unsaturated-γ-silylated-δ-substituted-δ-lact ones 1.

Full text of DOI:10.1055/s-2001-9700

1
38
LETTER
One-Pot Diastereoselective Preparation of a,b-Unsaturated-g-Silylated-d-
Lactones: Application towards Natural Compounds
Frédéric Marion, Rachel Le Fol, Christine Courillon, Max Malacria*
Université P. et M. Curie, Laboratoire de Chimie Organique de Synthèse, associé au CNRS, Tour 44-54, B. 229, 04 place Jussieu,
7
5252 Paris Cedex 05, France
Fax 33-1-44-27-73-60; E-mail: malacria@ccr.jussieu.fr
Received 22 September 2000
O
O
Abstract: Rearrangement of silylated vinyloxiranes into highly
functionalized a-silylated-b,g-unsaturated aldehydes occurs with
total chirality transfer and retention of double bond configuration
under Pd(0) catalysis. We show that this reaction is a versatile tool
in the field of total stereoselective synthesis : enantiomerically pure
lactones are obtained. The pheromone 6-n-undecyltetrahydro-2-py-
rone 2 and massoilactone, 5-hydroxy-2-decenoic acid lactone 3, are
synthesized. We describe herein a novel highly diastereoselective
route to a,b-unsaturated-g-silylated-d-substituted-d-lactones 1.
1
2
2
4
: R = C11H23 R = H
O
3
O
1
2
: R = CH3 R = OH
R1
H11C5
R2
Scheme 2
Key words: assymetric synthesis, lactones, natural products, palla-
dium
We present here a short stereoselective synthesis of com-
9
7a
10,11
pounds 2 and 3 . We recently reported
that the silyl-
ated vinyloxiranes 5 rearrange into the a-silylated-b,g-
unsaturated aldehydes 6 with a complete transfer10 of
chirality and retention of the double bond configuration.
Enantiomerically pure 6-substituted-5,6-dihydro-2H-pyr-
an-2-ones (a,b-unsaturated-d-lactones) I are key structur-
al subunits of widely occurring natural products.1 Their
saturated analogues II are important aroma compounds2
which are abundantly found in meat, dairy and fruit prod-
ucts. The 5-hydroxy derivatives III display diverse bio-
logical activities and appear as part of some antibiotic
11
This stereoselective palladium-catalyzed 1,2-silicon shift,
-4
12,13
combined with the high diastereoselective alkylation
of aldehydes 6 led us to propose a one-pot transformation
of the silylated vinylepoxides 5 into the d-lactones 1
(
Scheme 3).
5
structures (Scheme 1).
O
O
TBDMS
Pd(0)
H
O
O
O
CO2CH3
TBDMS
H3CO2C
O
O
O
5
6
I
III
II
R
R
O
O
R
O
OH
H3CO
O
R'M
Scheme 1
R'
-
78 °C
R'
TBDMS
TBDMS
or -100 °C
Herein, we describe an enantioselective method to synthe-
1
size d-lactones of type I, II and III, based on the utiliza-
Scheme 3
tion
of
a,b-unsaturated-g-silylated-d-substituted-d-
lactones 1 as key intermediates. Thus, we synthesized
type II 6-n-undecyltetrahydro-2-pyranone 2, the phero-
6
Enantiomerically pure silylated vinyloxiranes 5 were pre-
pared using our previously described conditions1 and
were submitted to a catalytic amount of zerovalent palla-
mone of the oriental hornet called Vespa orientalis and
0a
type I 6-n-pentyl-5,6-dihydro-2-pyrone 3, also known as
massoilactone which is the major constituent of the bark
7
a, b
dium generated in situ from Pd(OAc) and P(OPh) . After
2 3
oil of Cryptocaria massoia. Massoilactone 3
has also
checking the completion of the rearrangement by TLC,
the organometallic reagent was added dropwise. The tem-
perature was increased to reach room temperature in order
to achieve complete cyclization. Grignard derivatives
give the best chemical yields of lactones 1 (Table 1), with
a very high degree of diastereoselectivity for the anti dia-
stereomeric form of a,b-unsaturated-g-silylated-d-substi-
been isolated from cane molasses as a flavor product and
from two species of ants as a defense substance. Type III
d-lactones may be obtained after oxidation of the carbon-
silicon bond into a hydroxyl group to give the (+) Osmun-
8
dalactone 4 (R = CH ), (Scheme 2).
3
Synlett 2001, No. 1, 138–140 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
One-Pot Diastereoselective Preparation of a,b-Unsaturated-g-Silylated-d-Lactones
139
Table Preparation of d-Lactones 1a-g. Diastereomeric Ratio
O
KF
O
H2, Pd/C
d.e.[%]a
R'
Yield [%]
78
Product
1
d
2
CH3
i-Pr
1ab
DMSO
C11H23
54% overall
74
8
1bb,c
79
90
O
>
>
96
96
KF, DMSO
76%
1cd
t-Bu
1e
3
9
O
C11H23
73
70
1dd
>96
>96
R
C H
5
1eb
1fb
11
HC
C
70
Scheme 5
>
96
60
1ge
>
96
In summary, this paper shows a simple and efficient gen-
eral access to diastereomerically pure a,b-unsaturated-g-
silylated-d-lactones 1. The two natural lactones 2 and 3
could be synthesized in overall yields of 70-90%. These
results also suggest that the enantiopure a,b-unsaturated-
g-silylated-d-lactones are interesting building blocks for
further 1,4-addition reactions on the a,b-unsaturated ester
moiety and electrophilic additions on the allylsilane skel-
eton.
1
a) Measured by H NMR. b) Purified as a white solid by recrystalli-
sation. c) ee = 93-99%. The enantiomeric excesses were measured
by chiral GC. They were checked to be equal to the starting vinylo-
xiranes’ees, proving that chirality is totally transferred through this
one-pot procedure. d) Purified by flash chromatography on silica
gel. e) Synthesized in a racemic form.
1
4
tuted-d-lactones 1a-g. This selectivity can be explained
1
2,13
by a Felkin model.
References and Notes
Other alkylating agents have been added to aldehydes 6.
In the case of methyllithium and methylcerium dichloride
(1) Davies-Coleman, M.T.; Rivett D.E.A. Fortschr. Chem. Org.
Naturst. 1989, 55, 1-35.
(
(
2) Ohloff, G. Fortschr. Chem. Org. Naturst. 1978, 35, 431-527.
3) Takano, S.; Kamikubo, T.; Sugihara, T.; Ogasawara, K.
Tetrahedron : Asymmetry 1992, 3, 853-856.
(
7
Scheme 4), the d-lactone 1a and the homoallylic alcohol
are isolated. The intermediate aldehyde 6 is also recov-
ered. Alcohol 7 could be conveniently cyclized to lactone
(
(
4) Grove, J. F. J. Chem. Soc. Perkin Trans. I 1985, 865-869.
5) Ley, S.V.; Armstrong, A.; Diez-Martin, D.; Ford, M.J.; Grice,
P.; Knight, J.G.; Kolb, H.C.; Madin, A.; Marby, C.A.;
Mukherjee, S.; Shaw, A.N.; Slawin, A.M.Z.; Vile, S.; White,
A.D.; Williams, D.J.; Woods, M. J. Chem. Soc. Perkin Trans.
I 1991, 667-692.
1
5
1
a by Otera’s procedure in 85% yield. Grignard reagents
led to higher yields of lactones probably due to magne-
sium-catalyzed transesterification.
Desilylation (Scheme 5) of lactones 1d and 1e was con-
ducted in dimethyl sulfoxide at room temperature with a
large excess of potassium fluoride. Lactone 1d leads to the
desilylated product 8, which was directly hydrogenated to
the pheromone 2; whereas 1e was directly transformed
into the natural product 3. Partial racemization of 1d and
(
6) Ikan, R.; Gottlieb, R.; Bergmann, E. D.; Ishay, J. J. Insect.
Physiol. 1969, 15, 1709-1712.
(7) (a) Mori, K. Agric. Biol. Chem. 1976, 40, 1617-1619
(b) Cavill, G. W. K.; Clark, D. V.; Whitfield, F. B. Aust. J.
Chem. 1968, 21, 2819-2823.
(
8) Murayama, T.; Sugiyama, T.; Yamashita, K. Agric. Biol.
Chem. 1986, 50, 2347-2351.
1
e during the desilylation process, led to less optical activ-
2
0
20
ity for 2 (aD 9.47(c 0.95, THF)) and 3 (a -28.7 (c 1.02,
CHCl )) than reported in litterature for 2 and 3. Isola-
D
(
9) (a) Kuo, Y.-H.; Shih, K.-S. Heterocycles 1990, 31, 1941-1949
1
6
17
3
(
(
b) Bacardit, R.; Moreno-Manas, M. Chem. Lett. 1982, 5-6
c) Pirkle, W. H.; Adams, P.E. J. Org. Chem. 1980, 45, 4117-
tion of the acidic form of the intermediate conjugated car-
boxylate 9 gave an explanation for the loss of
enantiomeric purity observed during the desilylation reac-
tion which is currently under study in our group.
4121 (d) Pirkle, W. H.; Adams, P.E. J. Org. Chem. 1979, 44,
2169-2175.
OH
O
1
) Pd(0)
H3C
TBDMS
+
H
+
5
1a
2) CH3M
CO2CH3
(~ 25%)
TBDMS
2
CO CH3
7
6 (~ 10%)
(~ 35%)
(
85%) 15
Scheme 4
Synlett 2001, No. 1, 138–140 ISSN 0936-5214 © Thieme Stuttgart · New York

1
40
F. Marion et al.
LETTER
(
10) (a) Le Bideau, F.; Aubert, C.; Malacria, M. Tetrahedron :
Asymmetry 1995, 6, 697-700 (b) Gilloir, F.; Malacria, M.
Tetrahedron Lett. 1992, 33, 3859-3862.
11) Courillon, C.; Le Fol, R.; Vandendris, E.; Malacria, M.
Tetrahedron Lett. 1997, 38, 5493-5496.
12) Le Bideau, F.; Gilloir, F.; Nilsson, Y.; Aubert, C.; Malacria,
M. Tetrahedron Lett. 1995, 36, 1641-1644.
13) Le Bideau, F.; Gilloir, F.; Nilsson, Y.; Aubert, C.; Malacria,
M. Tetrahedron 1996, 52, 7487-7510.
mixture was quenched by a saturated solution of ammonium
chloride. The mixture was extracted with diethyl ether, the
organic layers were combined and dried over sodium sulfate.
After filtration the solvent was evaporated under reduced
pressure. The lactone was then purified by flash
chromatography with a petroleum ether / ethyl acetate (9/1)
eluent.
(
(
(
(
(15) Otera, J.; Dan-oh, N.; Nozaki, H. J. Org. Chem. 1991, 56,
5307-5311.
(16) (a) Paolucci, C.; Mazzini, C.; Fava, A. J. Org. Chem. 1995, 60,
169-175 (b) Mori, K. The Total Synthesis of Natural Products;
ApSimon, J., Ed.; J. Wiley & Sons : New York 1992, 9,
Chapter 15, 242-251.
14) General procedure for the preparation of compounds 1a-g :
Triphenyl phosphite (0.2 equiv, 0.4 mmol) was added via a
syringe to a stirred solution of palladium diacetate (0.05 equiv,
0.1mmol) in freshly distilled THF (3mL). A solution of
vinylepoxysilane 5a-g (1 equiv, 2 mmol) in THF (10mL) was
cannulated into the pale yellow reaction mixture. After
completion of the rearrangement (checked by TLC),
temperature was lowered to -78 °C and the Grignard reagent
(17) (a) Cavill, G.W.K.; Clark, D. V.; Whitfield, F.B. Aust. J.
Chem. 1968, 21, 2819-2823 (b) Pirkle, W. H.; Adams, P. E. J.
Org. Chem. 1980, 45, 4117-4121.
(1.1 equiv, 2.2 mmol) was added dropwise via a syringe to
minimize temperature fluctuations. The mixture was stirred an
additional hour at -78 °C. Then, under continuous stirring, the
temperature was raised toward room temperature and the
Article Identifier:
1437-2096,E;2001,0,01,0138,0140,ftx,en;G20500ST.pdf
Synlett 2001, No. 1, 138–140 ISSN 0936-5214 © Thieme Stuttgart · New York