Synthesis of (±)-10-epi-Elemol by a Highly Stereoselective Intramolecular Palladium-Catalyzed Coupling of an Allylstannane with an Allyl Acetate

Full text of DOI:10.1021/jo9714021

7540
J . Org. Chem. 1997, 62, 7540-7541
Sch em e 1a
Syn th esis of (()-10-epi-Elem ol by a High ly
Ster eoselective In tr a m olecu la r
P a lla d iu m -Ca ta lyzed Cou p lin g of a n
Allylsta n n a n e w ith a n Allyl Aceta te
J uan M. Cuerva, Enrique Go´mez-Bengoa,
Mar´ıa Me´ndez, and Antonio M. Echavarren*
Departamento de Qu´ımica Orga´nica, Universidad
Auto´noma de Madrid, Cantoblanco, 28049 Madrid, Spain
Received J uly 30, 1997 (Revised Manuscript Received
September 16, 1997)
The potential of nickel-promoted allyl/allyl coupling for
the construction of sesquiterpenes was early demon-
strated by Corey in the syntheses of (()-elemol.1,2 How-
ever, the regio- and stereoselectivity of this coupling is
rather low, and the reaction requires a stoichiometric
amount of the metal complex Ni(CO)4. The alternative
intramolecular insertion of (η3-allyl)palladium complexes
into alkenes allows for the efficient synthesis of five- or
six-membered ring carbocycles (Scheme 1).3,4 However,
increasing the steric hindrance by introduction of methyl
groups at C-3 of the allyl and the alkene termini in
substrates of type I leads to recovering of unchanged
starting materials under catalytic conditions. Thus,
substrates 1-3,5 which could give rise to (η3-allyl)palla-
dium complexes by oxidative addition to Pd(0),4 failed to
cyclize under all the conditions examined. This failure
a
Z ) -SO2Ph.
this facile â-elimination proceeds from intermediates of
type IV through a concerted pathway, probably via a six-
electron six-center transition state.11
Herein we wish to report that, despite the ample pre-
cedent for elimination in the reaction of allyl stannanes
with allylic electrophiles,6,11 the intramolecular coupling
outlined in Scheme 1 could be efficiently carried out. The
presence of water in the solvent was shown to be a key
parameter for the success of this transformation. Fur-
thermore, the stereoselectivity of this process was excep-
tionally high, allowing for the efficient preparation of epi-
elemol (17),12 a rare member of the elemane family of
sesquiterpenes bearing cis vinyl and isopropenyl groups.
The synthesis of the required precursor for the cycliza-
tion was completed by using organometallic transforma-
tions in all but one step (Scheme 2).5b Reaction of keto
disulfone 413 with vinylmagnesium bromide gave 5 (87%),
which was allowed to react with isoprene epoxide in the
presence of a palladium catalyst14 to give 6 as a 1:1
mixture of E/Z isomers (97%).15 Acetylation of 6 afforded
either 7 (pyridine catalyst, 79%) or 8 (DMAP catalyst,
80%). Stannane 9 was efficiently prepared in 79% yield
is most probably a consequence of the instability of
complex III due to the lower coordination ability of the
trisubstituted alkene to Pd(II) (Scheme 1). Therefore, we
decided to examine the prospect of effecting the cycliza-
tion of substrate II by an intramolecular palladium-
catalyzed cross-coupling of an allylstannane with an allyl
acetate.6 This coupling could proceed through complexs
IV or V,7,8 which would suffer reductively elimination to
give carbocycle VI.9 However, precedents for this second
approach were not particularly encouraging since this
type of Stille coupling reaction is limited to allyl sub-
strates that cannot eliminate to form a conjugated diene
such as VII.6,10 In fact, Keinan has recently shown that
(1) Corey, E. J .; Broger, E. A. Tetrahedron Lett. 1969, 1779.
(2) (a) Corey, E. J .; Hamanaka, E. J . Am. Chem. Soc. 1967, 89, 2758.
(b) Vig, O. P.; Ram, B.; Atwal, K. S.; Bari, S. S. Indian J . Chem. 1976,
14B, 855.
(3) Reviews: (a) Oppolzer, W. In Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 5,
Chapter 1.2. (b) Oppolzer, W. In Comprehensive Organometallic
Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.;
Pergamon: Oxford, 1995; Vol. 12, Chapter 8.3.
(4) (a) Go´mez-Bengoa, E.; Cuerva, J . M.; Echavarren, A. M.; Mar-
torell, G. Angew. Chem., Int. Ed. Engl. 1997, 26, 7767. (b) Go´mez-
Bengoa, E.; Noheda, P.; Echavarren, A. M. Tetrahedron Lett. 1994,
35, 7097.
(5) (a) These substrates were readily prepared from known 5,5-
bis(phenylsulfonyl)-8-methyl-7-nonen-2-one.13 (b) See the Supporting
Information for experimental details and characterization data.
(6) (a) Trost, B. M.; Keinan, E. Tetrahedron Lett. 1980, 21, 2595.
(b) Godschalx, J .; Stille, J . K. Ibid. 1980, 21, 2599. (c) Keinan, E.;
Peretz, M. J . Org. Chem. 1983, 48, 5302. (d) Trost, B. M.; Pietrusiewicz,
K. M. Tetrahedron Lett. 1985, 26, 4039.
(7) J olly, P. W. Angew. Chem., Int. Ed. Engl. 1985, 24, 283.
(8) The cyclization could also proceed through a (η1-allyl)(η3-al-
lyl)palladium complex regioisomeric to IV or a bis(η1-allyl)palladium
complex in equilibrium with IV and V.
(9) (a) Goliaszewski, A.; Schwartz, J . Organometallics 1985, 4, 417.
(b) Goliaszewski, A.; Schwartz, J . Tetrahedron 1985, 41, 5779. (c)
Bertani, R.; Berton, A.; Carturan, G.; Campostrini, R. J . Organomet.
Chem. 1988, 349, 263. (d) Krause, J .; Bonrath, W.; Po¨rschke, K. R.
Organometallics 1992, 11, 1158.
(10) Coupling of allyl derivatives with stannanes (but not
allylstannanes): (a) Allyl acetates: Del Valle, L.; Stille, J . K.; Hegedus,
L. S. J . Org. Chem. 1990, 55, 3019. (b) Allyl carbonates: Castan˜o, A.
M.; Echavarren, A. M. Tetrahedron Lett. 1996, 36, 6587.
(11) (a) Keinan, E.; Kumar, S.; Dangur, V.; Vaya, J . J . Am. Chem.
Soc. 1994, 116, 11151. (b) For the mechanism of the base-promoted
elimination of (η3-allyl)palladium complexes to form 1,3-dienes, see:
Takacs, J . M.; Lawson, E. C.; Clement, F. J . Am. Chem. Soc. 1997,
119, 5956.
(12) Thomas, A. F.; Ozainne, M. Helv. Chim. Acta 1978, 61, 2875.
(13) Go´mez-Bengoa, E.; Cuerva, J . M.; Mateo, C.; Echavarren, A.
M. J . Am. Chem. Soc. 1996, 118, 8553.
(14) (a) Tsuji, J .; Kataoka, H.; Kobayashi, Y. Tetrahedron Lett. 1981,
22, 2575. (b) Trost, B. M.; Molander, G. A. J . Am. Chem. Soc. 1981,
103, 5969.
S0022-3263(97)01402-3 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 22, 1997 7541
Sch em e 2
Sch em e 3
Sch em e 4
a
Z ) -SO2Ph.
from diacetate 8 by a highly regioselective reaction with
a mixed cuprate.16 The desired carbocyclization was
effected in the presence of Pd(dba)2 catalyst (10 mol %),17
PPh3 (20 mol %), and excess LiCl in 0.5% aqueous DMF
at 80 °C for 20 h to give 10 as a single isomer in 91%
yield. The presence of water in the solvent10b and the
addition of LiCl18 were essential for the success of the
reaction. The reaction could also be performed in the
absence of PPh3, although a full equivalent of palladium
was required under these conditions.19
tuted silanes toward external attack to the (η3-allyl)pal-
ladium intermediate.
The stereochemistry of 10 was demonstrated by its
transformation into naturally occurring 10-epi-elemol
(17)12 (Scheme 4).5b Thus, reductive desulfonation of 10
afforded 15 (74%),24 whose anion was acetylated to give,
after reductive desulfonation, 16 (95%)24 as a 9:1 mixture
of R-ketone epimers. Final reaction of 16 with methyl-
magnesium bromide afforded racemic 17 (82%).12,25
In summary, this work shows that, contrary to that
observed in the intermolecular coupling of allylstannanes
with allyl acetates,6,11a the intramolecular reaction leads
to the clean formation of a carbon-carbon bond. The
stereoselective cyclization of bis(η3-allyl)palladium com-
plex V was unexpected and suggests that the synthesis
of carbocycles bearing 1,2-cis dialkenyl substituents could
be general by this method. Further work on this issue
is in progress.
Carbocycle 10 probably arises by cyclization of bis(η3-
allyl)palladium complex syn-V in preference to anti-V,
which would yield stereoisomer 11 (Scheme 3). The
stereoselectivity of this reaction cannot be easily ex-
plained by steric hindrance arguments,20 and it may be
the result of an electronic preference for an endo cycliza-
tion pathway. The participation of bis(η3-allyl)palladium
complexes is strongly supported by the fact that 12,5b,21
a regioisomer of 9, also afforded 10 in the palladium-
catalyzed coupling process. In contrast, allysilanes 13
and 145b,22 failed to yield any cyclization derivative under
all the conditions examined.23 This failure is probably
due to the reduced nucleophilicity of these 3,3-disubsti-
Ack n ow led gm en t. This work was supported by the
DGICYT (Project PB-94-0163). We also thank J ohnson
Matthey PLC for a generous loan of palladium dichlo-
ride. J .M.C and M.M. acknowledge the receipt of
fellowships by the Comunidad Auto´noma de Madrid and
the Ministerio de Educacio´n y Cultura, respectively.
(15) Alternatively, 6 was obtained in five steps as follows: (i)
palladium-catalyzed reaction of bis(phenylsulfonyl)methane and iso-
prene epoxide (98%); (ii) protection of the alcohol as THP derivative
(89%); (iii) ruthenium-catalyzed Michael addition to methyl vinyl
ketone (100%);13 (iv) addition of vinylmagnesium bromide (74%); (v)
acid-catalyzed methanolysis of the THP protecting group (76%).5b
(16) Lipshutz, B. H.; Ellsworth, E. L.; Dimock, S. H.; Reuter, D. C.
Tetrahedron Lett. 1989, 30, 2065.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails and characterization data for new compounds (16 pages).
J O9714021
(17) The actual complex has the formula [Pd2(dba)3‚dba] (dba )
dibenzylideneacetone): Ukai, T.; Kawazura, H.; Ishii, Y.; Bonnett, J .
J .; Ibers, J . A. J . Organomet. Chem. 1974, 65, 253.
(18) (a) The use of LiI, CuI, or K2CO3 as the additives gave negative
results. (b) For the role of halide ions on the oxidative addition of Pd(0)
complexes, see: Amatore, C.; Azzabi, M.; J utand, A. J . Am. Chem. Soc.
1991, 113, 8375.
(19) Similar results were obtained by using NMP as the solvent.
Pd(PPh3)4 and Pd(dba)2/PCy3 were also active catalysts.
(20) The monosulfone derived from 9 by reductive elimination and
acetylation affords 15 after palladium-catalyzed cyclization a mixture
of C-1 epimers identical with that obtained by desulfonation of 10
(Scheme 4).
(21) This substrate was prepared via the Michael reaction of [5,5-
bis(phenylsulfonyl)-2-methyl-2-pentenyl](tri-n-butyl)stannane with meth-
yl vinyl ketone.13,5b
(22) These silanes were prepared by silylation of the corresponding
trifluoroacetates with (Me3Si)2: Tsuji, Y.; Funato, M.; Ozawa, M.;
Ogiyama, H.; Kajita, S.; Kawamura, T. J . Org. Chem. 1996, 61, 5579.
(23) It has been demonstrated that the cyclization of (η3-allyl)pal-
ladium complexes with allylsilanes does not proceed through a bis(η3-
allyl)palladium complex: Terakado, M.; Miyazawa, M.; Yamamoto, K.
Synlett 1994, 134.
(24) Based on unrecovered starting material.
(25) For previous syntheses of 17, see: Taber, D. F.; Wang, Y.
Tetrahedron Lett. 1995, 35, 6639 and references therein.