A chemoselective and regioselective catalytic way to a novel nine-membered lactone

Article abstract of DOI:10.1016/S0040-4039(01)00548-2

Cyclocarbonylation of dihydromyrcenol into the corresponding lactone can be selectively performed in the presence of PdCl₂(PPh₃)₂)/SnCl₂·2H ₂O and 4 A? molecular sieves.

Full text of DOI:10.1016/S0040-4039(01)00548-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3697–3700
A chemoselective and regioselective catalytic way to a novel
nine-membered lactone
Ge´raldine Lenoble, Martine Urrutigo¨ıty and Philippe Kalck*
Laboratoire de Catalyse, Chimie Fine et Polyme`res, Ecole Nationale Supe´rieure de Chimie, 118 route de Narbonne,
31077 Toulouse Cedex 04, France
Received 2 April 2001
Abstract—Cyclocarbonylation of dihydromyrcenol into the corresponding lactone can be selectively performed in the presence of
,
PdCl2(PPh3)2)/SnCl2·2H2O and 4 A molecular sieves. © 2001 Elsevier Science Ltd. All rights reserved.
Lactones play an important role in organic synthesis
because they give an elegant access to other functional-
ities and have themselves a number of biological prop-
erties.1 They can be prepared by carbonylation of
unsaturated alcohols provided the carbon chain
between the alkene and OH function are not too short
(Scheme 1); most of the catalysts include palladium
complexes generally used under moderated to high CO
pressures.2
tative substrate for its selective carbonylation into the
corresponding nine-membered lactone. In addition to
this product we have summarized in Scheme 2 all the
products which can be expected from the reaction
either by isomerization or by carbonylation of dimethyl-
octadiene 3 which results from dehydration of 1.
In a typical run we have introduced [PdCl2(PPh3)2] as a
catalyst precursor, SnCl2·2H2O as a promoter, 2 equiv.
of extra triphenylphosphine in order to maintain a
[P]/[Pd] molar ratio of 4, 40 bar CO pressure, 75°C and
a duration of 16 h.3 Table 1 displays the main results
obtained during this study.4 In run 1, for a [substrate]/
[Pd] ratio of 50, a yield of 94% was observed.
We were interested in the preparation of large ring
lactones and we chose dihydromyrcenol 1 as a represen-
Traces of isomer 2 resulting from the migration of the
terminal carbonꢀcarbon double bond toward an inter-
Scheme 1.
Scheme 2.
Keywords: cyclocarbonylation; lactone; homogeneous catalysis; palladium.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00548-2

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G. Lenoble et al. / Tetrahedron Letters 42 (2001) 3697–3700
Table 1. Reactions of carbonylation of dihydromyrcenol
Run
S/C
P (bar)
Time (h)
Conversion (%)
Yield (%)
2
3
4
5
1
2
3
4
5
6
7
50
100
50
100
50
40
40
40
16
16
40
40
16
16
16
94
43
n.d.
n.d.
–
–
n.d.
–
33 (35)a
60 (64)a
–
5 (12)a
25 (59)a
80
12 (28)a
100
100
100
100
100
20
20
9
8
6
–
2
–
–
5
40
78
90
92
89
100
100
100
100
150
–
Conditions: catalytic precursor=1 mmol, excess of diphosphine=1 mmol, SnCl2·2H2O=2.5 mmol, toluene=25 mL, T=75°C, n.d.=not
determined.
a Selectivity (%).
run 1 shows clearly that during the first 3 h 3, 4 and 5
are coproduced in parallel ways, after which time the
quantities of lactone begin to decrease.
nal position (only one isomer has been represented in
Scheme 4) were detected. Dehydration of 1 occurred to
produce 3 containing two carbonꢀcarbon double bonds
lying in various positions. The main product is the
terminal carboxylic acid 4 which corresponds exclu-
sively to the hydroxycarbonylation of the less hindered
carbonꢀcarbon bond. As abundant quantities of 3 are
obtained we suspect that 4 results directly from 3 and
not from the dehydration of the carbonylated product
of 1 which has been detected.
We have explored various operating conditions to drive
the selectivity toward the formation of lactone 5
(Scheme 4).
Addition of trimethylorthoformate to the medium in
order to remove water induced 10% selectivity in 5, but
When twice the quantity of dihydromyrcenol was intro-
duced (run 2) to reach a molar substrate/catalyst ratio,
the reaction proceeded faster at the beginning so that
12% of lactone 5 was obtained, thus with a selectivity of
28%, beside 3 and 4 (12 and 59% selectivity, respec-
tively). Increasing the duration of the experiments to 40
h, as in runs 3 and 4, shows that compound 4 is
significantly more abundant, and should also be per-
haps formed from the lactone 5.
Scheme 3 shows that opening the lactone provides
directly the unsaturated carboxylic acid 4 and can, by
decarboxylation, restore the dehydrated product 3.
These observations were confirmed by working at 100
bar (runs 5–7), where the reaction proceeds faster since
the substrate is fully transformed in 16 h; for a ratio
[S]/[C]=150 a low yield of lactone was obtained,
whereas in a lower lactone 5/acid 4 ratio. Thus, we
consider that lactone 5 is formed by carbonylation of
dihydromyrcenol in the early stages of the reaction, and
that in a competitive way dehydration occurs directly
from the substrate and can be hydroxycarbonylated
(3+CO/H2O“4). A kinetic study in the conditions of
Scheme 3.
Scheme 4.

G. Lenoble et al. / Tetrahedron Letters 42 (2001) 3697–3700
Table 2. Reactions of cyclocarbonylation of dihydromyrcenol
3699
Run
Additive
Time (h)
Conversion (%)
Yield (selectivity)
2
3
4
5
1
2
3
H2Oa
40
40
23
40
16
48
21
56
60
42
–
n.d.
–
2
n.d.
n.d.
42 (90)
–
n.d.
–
2
5 (10)
2 (10)
53 (95)
59 (98)
39 (93)
HC(OMe)3
Zeolites
Zeolites
Zeolites
19 (90)
–
–
–
4
5b
,
Conditions: catalytic precursor=1 mmol, excess of diphosphine=1 mmol, SnCl2·2H2O=2.5 mmol, toluene=25 mL, 4 A molecular sieves=3 g,
T=75°C.
a H2O=50 mmol.
b P=100 bar, S/C=100.
with a low conversion (21%) and 90% of isomerisation
(2). In contrast, addition of water in order to shift the
equilibrium of dehydration of 1 to give 3 still provided
10% of 5 besides 90% of the expected acid 4 (48% of
conversion). In addition, to improve the selectivity into
5639; (b) Alper, H.; Leonard, D. J. Chem. Soc., Chem.
Commun. 1985, 511; (c) Tamaru, Y.; Mojo, M.; Yoshida,
Z. I. Tetrahedron Lett. 1987, 28, 325; (d) Alper, H.; Hamel,
N. J. Chem. Soc., Chem. Commun. 1990, 135; (e) El Ali,
B.; Alper, H. J. Org. Chem. 1991, 56, 5357; (f) Grigg, R.;
Sridharan, V. Tetrahedron Lett. 1993, 34, 7471; (g) Aggar-
wal, V. K.; Monteiro, N.; Tarver, G. J.; McCague, R. J.
Org. Chem. 1997, 62, 4665; (h) Ro¨nn, M.; Andersson, P.
G.; Ba¨ckwall, J. E. Acta Chem. Scand. 1998, 52, 524; (i)
Cao, P.; Zhang, X. J. Am. Chem. Soc. 1999, 121, 7708; (j)
El Ali, B.; Alper, H. Synlett 2000, 2, 161.
,
lactone 5, we introduced 4 A molecular sieves. Anhy-
drous zeolites added in an excess with regard to the
quantities of water which could result from the full
dehydration of 1, led to a moderate conversion of the
substrate, but to a quite complete selectivity in lactone
(Table 2). For shorter reactions times or at higher
pressure (runs 3 and 5, respectively) this selectivity is
maintained and only traces of the other products are
detected. We interpret these high yields in lactone as
being due mainly to the trapping of HCl generated
from PdCl2L2/SnCl2 when the active hydride species is
formed. Simultaneously, the system is completely anhy-
drous so that in the absence of wet HCl, no dehydra-
tion of the tertiary alcohol occurs.5
3. General procedure: a mixture of 0.702 g (1 mmol) of
dichlorobis(triphenylphosphine) palladium(II), 0.474 g (2.5
mmol) of hydrated tin(II) chloride and 0.524 g (2 mmol) of
triphenylphosphine was introduced into a 250 mL stainless
steel autoclave with mechanical stirring. A dinitrogen-satu-
rated mixture of 15.627 g of dihydromyrcenol (100 mmol)
in 25 mL toluene was introduced into the evacuated
autoclave by aspiration. It was heated to 70°C under 40
bar of carbon monoxide at constant pressure. After 16 h,
the autoclave was cooled and then slowly depressurized.
The yellow–orange reaction mixture was analyzed by gas
chromatography.
4. GC analyses, performed on a Carlo Erba MFC 500
apparatus equipped with a Econo-Cap FFAP (30 m; 0.53
mm; 1.2 mm) capillary column and a flame ionization
detector. Products were identified by GC/MS on a Perkin
Elmer QMass 910, with a Crompack CP WAX 52 CB (50
m; 0.32 mm; 0.2 mm) polar column. After the catalytic
reaction, organometallic compounds and phosphine excess
were separated from the crude solution by adding CCl4.
The deeply colored oily layer was decanted. After concen-
tration by rotary evaporation, the oily residue was purified
by column chromatography on silica gel (n-hep-
tane:dichloromethane:ethyl acetate, 75:15:10 for 5 and n-
heptane:dichloromethane:ethyl acetate, 90:5:5 for 4).
Spectral data for 4: IR (KBr): w=1709 cm−1 (CꢁO). 1H
NMR (250 MHz, CDCl3): l=10.79 (m, 1H, OH), 5.05 (t,
J=6 Hz, 1H), 2.31 (m, 2H), 1.95 (m, 1H), 1.64 (s, 3H),
1.57 (s, 3H), 1.5 and 1.1 (m, 6H), 0.86 (d, J=6.1 Hz, 3H).
13C{1H} NMR (250 MHz, CDCl3): l=180.8, 131.1, 124.4,
36.5, 31.7, 31.2, 25.5, 25.2, 19.0, 14.5. MS (CI) m/z (rel.
int.): 69 ((CH3)2CꢁC-CH2+, 1000), 41 (C3H5+, 998), 124
(MacLafferty, 29), 185 (M+1, 14). Microanalyses (exp. %;
cald %): C (71.9; 71.7), H (11.4; 10.9), O (16.6; 17.4).
Spectral data for 5: IR (KBr): w=1729 cm−1 (CꢁO). 1H
NMR (250 MHz, CDCl3): l=2.16 (m, 2H), 1.91 (m, 1H),
It should be underlined that this carbonylation reaction
presents a high level of chemoselectivity to introduce a
CO building block in the carbon framework. From a
structural point of view, the CO insertion occurs exclu-
sively on the terminal carbon atom of the starting
material 1 to give 4 and the lactone 5. In addition, the
presence of a molecular sieve permits an almost full
selectivity in the expected lactone.
Acknowledgements
We thank the Ministe`re de l’Education Nationale de la
Recherche et de la Technologie for a Research Grant
(L.G.). Acknowledgements are also due to Engelhard-
CLAL for a generous loan of palladium, and DRT SA
for the gift of dihydromyrcenol.
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G. Lenoble et al. / Tetrahedron Letters 42 (2001) 3697–3700
1.63–1.49 (m, 6H), 1.35 (s, 6H), 1.16 (m, 2H), 0.80 (d, J=5.8
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.