Asymmetric synthesis of 5-substituted γ-lactones and butenolides via nucleophilic additions to oxycarbenium ions derived from 5(R)-(menthyloxy)-4(R)-(phenylsulfanyl)-2(3H)-dihydrofuranone

Full text of DOI:10.1021/jo960078r

2920
J . Org. Chem. 1996, 61, 2920-2921
Asym m etr ic Syn th esis of 5-Su bstitu ted
γ-La cton es a n d Bu ten olid es via
Nu cleop h ilic Ad d ition s to Oxyca r ben iu m
Ion s Der ived fr om 5(R)-(Men th yloxy)-4(R)-
(p h en ylsu lfa n yl)-2(3H)-d ih yd r ofu r a n on e
Arjan van Oeveren and Ben L. Feringa*
Department of Organic and Molecular Inorganic Chemistry,
Groningen Center for Catalysis and Synthesis,
University of Groningen, Nijenborgh 4,
F igu r e 1.
Sch em e 1
9747 AG Groningen, The Netherlands
Received J anuary 12, 1996
Optically active 5-alkyl-substituted butenolides and
γ-lactones are attractive building blocks in natural
product synthesis1 and comprise structural moieties
frequently present in, e.g., insect pheromones,2 cardeno-
lides,3 lignans, and flavor components.4 Efficient and
stereoselective synthetic routes to these products in
enantiomerically pure form are highly desirable.5 As part
of our explorative studies toward the use of 5(R)-(men-
thyloxy)-2(5H)-furanone (1) as a chiral synthon,6,7 the
enantioselective synthesis of a number of naturally
occurring lignans has been reported.8
5(R)-(Menthyloxy)-2(5H)-furanone (1) reacts with thio-
phenol and a catalytic amount of triethylamine to give
stereospecifically and in excellent yield the trans addition
product 2 (Scheme 1), which features an attractive
functional group arrangement to generate R-sulfanyl
oxycarbenium ion 3. Here we report the fast and highly
stereoselective transformations of 2 to 5-alkyl-substituted
4-(phenylsulfanyl)-2(3H)-dihydrofuranones 4 or 4-(men-
thyloxy)-3-(phenylsulfanyl) carboxylic acids 5, which are
precursors for butenolides and γ-lactones.
and SN1-type processes. It has been shown that Lewis
acid-mediated additions of silylated nucleophiles to R-
and â-sulfanyl-substituted aldehydes proceed with excel-
lent diastereoselectivities.11 Furthermore, reactions of
R-sulfanyl acetals with carbon nucleophiles have been
studied by Saigo and co-workers.12 In furanone 2, an
R-sulfanyl-substituted, mixed acyloxy-alkoxy acetal moi-
ety is present, and upon treatment with a Lewis acid it
is observed that the acyloxy acetal bond is always
broken13 and this reaction path leaves only two likely
intermediates (Figure 1). The stereoselectivity of these
reactions can be rationalized by the Felkin-Ahn model,
and conformers A and B lead to anti and syn adducts,
respectively. Conformer A is preferred, and in most cases
the anti adduct is the only detectable diastereomer.
When 4(R)-(phenylsulfanyl)-substituted furanone 2 is
treated at -70 °C with 1-2 equiv of TiCl4 in the presence
of a variety of nucleophiles such as allylsilanes, silyl enol
ethers, or diorganozinc reagents a very fast reaction
occurs. After a reaction time of 5 min and subsequent
aqueous workup, â,γ-substituted acids 5 are isolated in
56-72% yield and in most cases with a diastereomeric
ratio >98:2 according to 1H and 13C NMR (Scheme 2, path
A, Table 1, entries 2, 4, 6, 8, and 12). In addition to the
acids 5 small amounts of lactones 4 (5-20%) are also
found in the crude product, but these could be easily
separated.
Various methods for C-C bond formation via Lewis
acid-mediated reactions of acetals with nucleophiles have
been developed.9 As demonstrated by a number of
groups,10 there is a mechanistic divergence between SN2-
(1) (a) Hanessian S. In The total synthesis of natural products: The
chiron approach; Pergamon Press: New York, 1983; Chapter 9. (b)
Fernandez, A.-M.; J acob, M.; Gralak, J .; Al-Bayati, Y.; Ple´, G.;
Duhamel, L. Synlett 1995, 431. (c) Takahata, H.; Uchida, Y.; Momose,
T. J . Org. Chem. 1994, 59, 7201. (d) Canan Koch, S. S.; Chamberlin,
A. R. J . Org. Chem. 1993, 58, 2725.
(2) (a) Fukusaki, E.; Senda, S.; Nakazono, Y.; Omata, T. Tetrahedron
1991, 47, 6223. (b) Wheeler, J . W.; Happ, G. M.; Araujo, J .; Pasteels,
J . M. Tetrahedron Lett. 1972, 46, 4635. (c) Mori, K. Tetrahedron 1989,
45, 3233.
(3) Rao, Y. S. Chem. Rev. 1976, 78, 625.
(4) (a) Bloch, R.; Gilbert, L. J . Org. Chem. 1987, 52, 4603. (b) Thijs,
L.; Waanders, W. P.; Stokkingreef, E. H. M.; Zwanenburg, B. Recl.
Trav. Chim. Pays-Bas 1986, 105, 332.
(5) For recent examples, see: (a) Brown, H. C.; Kulkarni, S. V.;
Racherla, U. S. J . Org. Chem. 1994, 59, 365. (b) Miller, M.; Hegedus,
L. S. J . Org. Chem. 1993, 58, 6779. (c) Doyle, M. P.; Protopopova, M.
N.; Zhou, Q.-L.; Bode, J . W. J . Org. Chem. 1995, 60, 6654.
(6) For reviews see: (a) Feringa, B. L.; De J ong, J . C. Bull. Soc.
Chim. Belg. 1992, 101, 627. (b) Feringa, B. L.; De Lange, B.; De J ong,
J . C.; Lubben, M.; Faber, W.; Schudde, E. P. Pure Appl. Chem. 1992,
64, 1865. (c) De J ong, J . C.; Van Bolhuis, F.; Feringa, B. L. Tetrahe-
dron: Asymmetry 1991, 2, 1247.
(7) (a) Feringa, B. L.; De Lange, B.; De J ong, J . C. J . Org. Chem.
1989, 54, 2471. (b) Rispens, M. T.; Keller, E.; De Lange, B.; Zijlstra,
W. J .; Feringa, B. L. Tetrahedron: Asymmetry 1994, 5, 607. (c) Hulst,
R.; De Vries, N. K.; Feringa, B. L. J . Org. Chem. 1994, 59, 7453.
(8) (a) Van Oeveren, A.; J ansen, J . F. G. A.; Feringa, B. L. J . Org.
Chem. 1994, 59, 5999 and references cited. (b) Middel, O.; Woerdenbag,
H. J .; Van Uden, W.; Van Oeveren, A.; J ansen, J . F. G. A.; Feringa, B.
L.; Konings, A. T.; Pras, N.; Kellogg, R. M. J . Med. Chem. 1995, 38,
2112.
When the addition of nucleophiles 9-16 is performed
in the presence of 2 equiv of TiCl4 for 1 min at ambient
temperature, followed by aqueous workup, the lactones
4 are obtained. In a few cases small amounts of the acids
5 (e10%) are also formed. Apparently, the intermediate
6 is activated by the excess of Lewis acid present, and
upon addition of water hydrolysis to the hydroxy acid 8
(10) (a) Mori, I.; Ishihara, K.; Flippin, L. A.; Nozaki, K.; Yamamoto,
H.; Bartlett, P. A.; Heathcock, C. H. J . Org. Chem. 1990, 55, 6107. (b)
Denmark, S. E.; Almstead, N. G. J . Am. Chem. Soc. 1991, 113, 8089.
(c) Sammiaka, T.; Smith, R. S. J . Am. Chem. Soc. 1994, 116, 7915.
(11) Annunziata, R.; Cinquini, M.; Cozzi, F.; Cozzi, P. G.; Consolandi,
E. J . Org. Chem. 1992, 57, 456.
(12) Kudo, K.; Hashimoto, Y.; Sukegawa, M.; Hasegawa, M.; Saigo,
K. J . Org. Chem. 1993, 58, 579.
(13) Van Oeveren, A,; Feringa, B. L. Tetrahedron Lett. 1994, 35,
8437.
(9) For representative reviews, see: (a) Alexakis, A.; Mangeney, P.
Tetrahedron: Asymmetry 1990, 1, 477. (b) Mukaiyama, T.; Murakami,
M. Synthesis 1987, 1043.
S0022-3263(96)00078-3 CCC: $12.00 © 1996 American Chemical Society

Communications
J . Org. Chem., Vol. 61, No. 9, 1996 2921
Sch em e 2
Sch em e 3
Sch em e 4
Ta ble 1. Ad d ition s of Nu cleop h iles to Oxyca r ben iu m
Ion s Der ived fr om 2
of synthetically useful transformations. Reductive des-
ulfurization of 4 could best be performed with Bu3SnH/
AIBN and provided enantiomerically pure 5(S)-alkyl-
2(3H)-dihydrofuranones 17 (Scheme 3). The flavor
components and insect pheromones4 5(S)-ethyl-2(3H)-
dihydrofuranone (17g) [85% yield, [R]D ) -50 (c 1,
MeOH) (lit.17 [R]D ) -53.2 (c 1, MeOH))] and 5(S)-octyl-
2(3H)-dihydrofuranone (17h ) [66% yield, [R]D ) -35 (c
0.48, MeOH) (lit.17 [R]D ) -36.8 (c 0.3, MeOH))] were
obtained using this procedure.
Alternatively, 5(S)-alkyl-2(5H)-furanones 19 are ac-
cessible via the sulfones 18 (Scheme 4). Oxidation of 4
with Oxone18 and subsequent elimination with basic
alumina in CH2Cl2 gave the corresponding 5(S)-alkyl-
2(5H)-furanones 19 in good yields.19 For example, 5(S)-
ethyl-2(5H)-furanone (19g) [95% overall yield, [R]D
)
+105 (c 4.1,CH2Cl2) (lit.20 for 5(R)-19g [R]D ) -97.6 (c
2.08, CH2Cl2))] and 5(S)-(1-prop-2-enyl)-2(5H)-furanone
(19a ) (72% overall yield, [R]D ) +105 (c 1.08, MeOH) were
obtained using this procedure.
In conclusion, we have demonstrated that 2 is a
valuable synthon for the synthesis of 3,4-disubstituted
carboxylic acids, 5-substituted butenolides, and γ-lactones
in enantiomerically pure form.
followed by lactonization takes place (Scheme 2, path B).
A key feature of the second Lewis acid-mediated step is
the stereoselective cleavage of the auxiliary group as-
sisted by the R-sulfanyl functionality. Except for 4f,
trans lactones 4 are formed as the major, or in most cases
only detectable, diastereomer. Even in the few cases
(entries 1 and 11, Table 1) where small amounts of cis
lactones 4 were obtained, these could be separated by
simple column chromatography using silica gel.
Ack n ow led gm en t. Financial support was provided
by the Netherlands Organization for Scientific Research
(NWO/SON).
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for the Lewis acid mediated additions and spectro-
scopic data for compounds 4a -h and 5a ,b,c,d ,g. (5 pages).
Single crystal X-ray analysis of 4b confirmed the trans
relationship of the substituents at C4 and C5.21 The trans
configuration for the products 4a -e,g,h has been as-
J O960078R
1
signed by comparison on the basis of H NMR coupling
(16) Carretero, J . C.; De Lombaert, S.; Ghosez, L. Tetrahedron Lett.
1987, 28, 2135.
constants and on the expected mechanistic similarity in
this reaction for all nucleophiles used.14
(17) Roder, H.; Helmchen, G.; Peters, E.-M.; Peters, K.; Von Schner-
ing, H.-G. Angew. Chem., Int. Ed. Engl. 1984, 23, 898.
(18) Trost, B. M.; Curran, D. P. Tetrahedron Lett. 1981, 22, 1287.
(19) Vidal, J .; Huet, F. Tetrahedron Lett. 1986, 27, 3733.
(20) Cardellach, J .; Font, J .; Ortunˇo, R. M. J . Heterocyclic Chem.
1984, 21, 327.
(21) The author has deposited atomic coordinates for 4b with the
Cambridge Crystallographic Data Centre. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
The enantiomerically pure 5(S)-alkyl-4(R)-(phenylsul-
fanyl)-2(3H)-dihydrofuranones 4 are excellent precursors
for 5-alkyl-substituted butenolides or butanolides,15,16
whereas the phenylsulfanyl substituent allows a number
(14) See the supporting information.
(15) Lo´pez, C.; Go´mez, A. M.; Valverde, S. Synlett 1991, 825.