Diastereo- and enantioselective synthesis of bicyclic α-methylene- δ-valerolactones by asymmetric Michael reaction

Article abstract of DOI:10.1055/s-2004-830877

A synthesis of optically active α-methylene-δ-valerolactones 7 and 13 with 97% ee was achieved by employing a highly stereoselective Michael reaction between chiral imines 2, 9 and the acrylate 3. Reduction of the carbonyl group of the resulting adducts 4

Full text of DOI:10.1055/s-2004-830877

LETTER
1995
Diastereo- and Enantioselective Synthesis of Bicyclic a-Methylene-d-valero-
lactones by Asymmetric Michael Reaction
S
a
ynthesis of Bicyc
e
lic
a
-Methy
n
lene-
d
-valer
r
olactone
y
s
k Krawczyk,*a Marcin Śliwiński,a Wojciech M. Wolf,b Ryszard Bodalskia
Institute of Organic Chemistry, Technical University (Politechnika), 90–924 Łódź, Żeromskiego 116, Poland
b
Institute of General and Ecological Chemistry, Technical University (Politechnika), 90–924 Łódź, Żeromskiego 116, Poland
Fax +48(42)6365530; E-mail: henkrawc@p.lodz.pl
Received 4 May 2004
dehyde.11 Based on this methodology we now report on
the synthesis of highly enantioenriched a-methylene-d-
valerolactones.
Abstract: A synthesis of optically active a-methylene-d-valerolac-
tones 7 and 13 with 97% ee was achieved by employing a highly
stereoselective Michael reaction between chiral imines 2, 9 and the
acrylate 3. Reduction of the carbonyl group of the resulting adducts
4 and 10 with KBH4 followed by lactonization and HWE reaction
with formaldehyde yielded the lactones 7 and 13 as mixtures of
diastereoisomers. Diastereoselectivity in the reduction of chiral 5-
oxoalkanoic acids 4 and 10 was improved by combination of metal
salt and hydride reducing agent.
The synthetic strategy depicted on Scheme 1 and
Scheme 2 relies on a variant of the asymmetric Michael
reaction pioneered by Pfau and d’Angelo.12 It is widely
recognized that imines derived from 2-substituted cy-
cloalkanones and enantiomerically pure 1-phenyl-ethyl-
amines undergo Michael reactions with excellent levels
of diastereoselectivity. The use of acrylates as the accep-
tors leads to highly enantioenriched 3-(2-oxocycloalkyl)
propanoates. Despite the synthetic significance of these
5-oxoesters their application for asymmetric synthesis of
d-valerolactones is relatively undeveloped.13 We reasoned
that the use of acrylate 3 as the acceptor holds consider-
able potential for enantio- and diastereoselective synthe-
sis of a-methylene-d-valerolactones.
Key words: asymmetric synthesis, Michael reaction, 5-oxoalkano-
ic acids, a-methylene-d-valerolactones
Over the years a number of biologically active natural
products containing a-methylene-d-valerolactone unit
such as vernolepin,1 vernomenin,1 pentalenolactone E,2
teucriumlactone,3 artemisitene,4 crassin,5 and crassin
acetate5 have been isolated and characterized. On the oth-
er hand, the application of enantiomerically pure a-meth-
ylene-d-valerolactones as chiral building blocks have
been restricted by the limited availability of their synthe-
ses. Some use has been made of the methylenation of a-
unsubstituted6 and a-methyl-d-valerolactones.4,7 Another
strategy reported in the literature is based on a sequential
oxidation and methylenation of sugars starting materials.8
To the best of our knowledge, asymmetric synthesis of
enantioenriched a-methylene-d-valerolactones has not
been described yet.
As model substrates for our studies we selected the readily
available (aR)-imine 2 and (S)-b-enaminoester 9. These
compounds were prepared by condensation of 2-methyl-
cyclohexanone (1) with (R)-1-phenylethylamine (97% ee)
and 2-ethoxycarbonylcyclohexanone (8) with (S)-1-phe-
nylethylamine (97% ee), respectively, according to the lit-
erature procedures.12a,14 Preliminary studies were focused
on the diastereo- and enantioselective synthesis of 2-(di-
ethoxy-phosphoryl)-5-oxoalkanoic acids 4 and 10. We
found that the addition of (aR)-imine 2 to acrylate 3 pro-
ceeded effectively in benzene at room temperature and it
was completed within two days. Acidic hydrolysis of the
crude adduct afforded exclusively the acid 4 in 83% yield
as a mixture of diastereoisomers in a 1:1 ratio. The same
procedure was next employed in the addition of (S)-enam-
inoester 9 to acrylate 3. It appeared that this reaction was
also completely regioselective giving after acidic work-up
a 1:1 mixture of the diastereoisomeric acids 10 in 93%
yield. All attempts to separate particular diastereoisomers
by column chromatography were in both cases unsuccess-
ful. One can assume that diastereoisomeric products 4 and
10 are mixtures of epimers, which possess the same abso-
lute stereochemistry at the quaternary carbon stereocenter
and differ in configuration at the stereogenic center bear-
ing diethoxyphosphoryl and carboxylic acid groups. Giv-
en the acidity of the hydrogen at this center it is likely that
diastereoisomeric products 4 and 10 undergo rapid
epimerization. In this context it is worth to note that a few
In 1998, we reported the synthesis of dicyclohexylammo-
nium 2-(diethoxyphosphoryl) acrylate (3) and demon-
strated that it undergoes Michael reaction with 1,3-
dicarbonyl and monocarbonyl compounds without partic-
ipation of any external catalyst.9 Since then, this type of
self-catalytic conjugate addition has been developed as an
efficient method for the synthesis of various 2-(diethoxy-
phosphoryl)alkanoic acids.10 We have recently demon-
strated that 2-(dietoxyphosphoryl)-5-oxoalkanoic acids
can be easily transformed into the corresponding a-meth-
ylene-d-valerolactones through the sequence of standard
reactions involving reduction of the carbonyl group, lac-
tonization of the resulting 5-hydroxyalkanoic acids and fi-
nally Horner–Wadsworth–Emmons (HWE) olefination of
the obtained a-phosphono-d-valerolactones with formal-
SYNLETT 2004, No. 11, pp 1995–1999
0
6
.0
9
.2
0
0
4
Advanced online publication: 06.08.2004
DOI: 10.1055/s-2004-830877; Art ID: G12804ST
© Georg Thieme Verlag Stuttgart · New York

1996
H. Krawczyk et al.
LETTER
O
Ph CH3
1)
2)
(EtO)2P
CO2 NH2(C6H11)2
O
O
H
N
O
P(OEt)2
CH3
CH3
a
CH3
3
CO2H
Dowex 50W/H2O
83%
1
2
4
O
b or c
OH
H
H
P(OEt)2
CH3
O
O
O
O
d (85%)
CO2H
(EtO)2P
O
(EtO)2P
O
CH3
CH3
6a
6b
5
e (90%)
H
H
O
O
O
O
7a:7b = 1:1 (method b)
7a:7b = 1:3 (method c)
ee = 97%
CH3
CH3
7a
7b
Scheme 1 Reagents and conditions: a. (R)-1-Phenylethylamine, pTSA (cat.), toluene, reflux, 12 h; b. EtOH, KOH (1 equiv), KBH4 (1 equiv),
r.t., 24 h; c. MeOH, BaCl2·2H2O (1 equiv), KBH4 (1 equiv), –70 °C, 1 h, r.t., 24 h; d. pTSA (cat.), benzene, reflux, 4 h; e. t-BuOK (1.1 equiv),
(HCHO)n (5 equiv), Et2O, r.t., 1 h.
O
H3C Ph
1)
2)
(EtO)2P
CO2 NH2(C6H11)2
O
H
NH
O
O
CO2Et
CO2Et
CO2Et
P(OEt)2
3
a
CO2H
Dowex 50W/H2O
90%
8
9
10
b or c
OH
O
H
O
H
CO2Et
P(OEt)2
O
O
O
d (86%)
CO2H
P(OEt)2
O
P(OEt)2
O
CO2Et
CO2Et
12a
12b
11
e (91%)
H
O
H
O
O
O
13a:13b = 2:1 (method b)
13a:13b = 95:5 (method c)
ee = 97%
CO2Et
CO2Et
13a
13b
Scheme 2 Reagents and conditions: a. (S)-1-Phenylethylamine, pTSA (cat.), toluene, reflux, 8 h; b. EtOH, KOH (1 equiv), KBH4 (1 equiv),
r.t., 24 h; c. MeOH, CeCl3·7H2O (1 equiv), KBH4 (1 equiv), –70 °C, 1 h, r.t., 24 h; d. pTSA (cat.), benzene, reflux, 4 h; e. t-BuOK (1.1 equiv),
(HCHO)n (5 equiv), Et2O, r.t., 1 h.
Synlett 2004, No. 11, 1995–1999 © Thieme Stuttgart · New York

LETTER
Synthesis of Bicyclic a-Methylene-d-valerolactones
1997
1
precedents of such isomerization involving different a- with ee of 97%.18 Additionally, H NMR shifts experi-
phosphonoalkanoic acids derivatives are known.15
ments using (R)-(–)-9-(anthryl)-2,2,2-trifluoroethanol as
the chiral solvating agent19 indicated an ee of ≥95%. A
slight divergence of the found ee values is in line with ac-
curacy of the latter measurements.
Transformation of the acids 4 and 10 into the correspond-
ing a-methylene-d-valerolactones enabled to determine
enantiomeric excesses at the quaternary stereogenic cen-
ters. The phosphonolactones 6 and 12 were obtained from The optical purity of the acid 4 was further enhanced by a
the oxoacids 4 and 10, respectively, by using the previous- single recrystallization of its dicyclohexylammonium salt
ly reported protocol.11 Reduction of the acids 4 and 10 14 from ethyl acetate20 (Scheme 3). The salt was convert-
with KBH4 followed by lactonization of the obtained hy- ed by standard means into the lactones 7a and 7b with an
droxyacids 5 and 11 provided the phosphonolactones 6 ee better then 99%. Assignment of the absolute configura-
and 12, each as a mixture of diastereoisomers. At this tion to the acids 4, 10, and the lactones 7a,b and 13a,b was
stage, we were not able to establish diastereoselectivity of based on X-ray crystallographic analysis. The X-ray anal-
the reduction. Finally, the HWE reaction of phosphono- ysis conducted on the salt 1421 (Figure 1) unequivocally
lactones 6 and 12 with an excess of paraformaldehyde confirmed that there are two independent molecules of
performed in diethyl ether in the presence of potassium t- epimers in the asymmetric unit of the crystal and both of
butoxide afforded the corresponding a-methylenelactones them have S absolute configuration at quaternary stereo-
7a,b and 13a,b in high yields. We found that this proce- genic centers. This result indicates that trans- and cis-lac-
dure gave better results in terms of yield and purity of the tones 7a,b must be 4a(S),8a(R)- and 4a(S),8a(S)-isomers,
products than the previously reported.11 The lactones 7a,b respectively. The absolute configuration of the cis-lactone
and 13a,b were formed as mixtures of trans- and cis-dias- 7b was confirmed by X-ray analysis.22 An attempt to de-
tereoisomers in a ratio 1:1 and 2:1, respectively. These ra- termine the absolute configuration of trans-lactone 13a
tios represent roughly the degree of diastereoselection that failed due to internal disorder of its ethoxycarbonyl
one can attain in the reduction of the oxoacids 4 and 10. substituent23 (Figure 2). One should note that absolute
Improvement of these stereoselectivities was attained as configuration induced at the quaternary stereocenter in the
the advantage of the reductions, which were performed in adduct 4 is in agreement with the transition state model
the presence of metal salts.16 Model studies revealed that proposed for this type Michael additions.24 According to
the treatment of the oxoacid 4 with KBH4 and barium this model absolute configuration at the quaternary stereo-
chloride (BaCl2·2H2O, 1 equiv) followed by the sequence center in the adduct 10 was assigned to be S. As a conse-
of standard reactions afforded the lactone 7 as mixture of quence the absolute configuration of the trans-lactone 13a
trans- (7a) and cis-isomers (7b) in a ratio 1:3. Similarly, must be 4a(S),8a(S) and therefore that of cis-13b which
the reduction of oxoacid 10 with KBH4 performed in the differs for the configuration around C-8a is 4a(S),8a(R).
presence of cerium chloride (CeCl3·7H2O, 1 equiv) led to
In summary, the asymmetric Michael addition of chiral
the formation of the lactone 13 as a mixture trans- (13a)
imines to the acrylate 3 opens a new, simple and efficient
and cis-isomers (13b) in a ratio 95:5. The mixtures of dia-
entry to essentially enantiomerically pure bicyclic a-
stereoisomeric lactones 7a,b and 13a,b were separated
methylene-d-valerolactones. Since the used chiral auxilia-
by column chromatography. Pure diastereoisomers 7b
ry is commercially available in both optically pure forms
and a variety of a-substituted cycloalkanones can be used
and 13a were isolated as crystalline solids.17 Gas chroma-
tography analysis in chiral stationary phase showed that
it is possible to synthesize both enantiomers of a range of
the corresponding lactones 7a,b and 13a,b were formed
a-methylene-d-valerolactones.
Figure 1 Both epimers of the salt 14 which are present in the asymmetric unit of the crystal. Dicyclohexylammonium cations have been omit-
ted for clarity. Displacement ellipsoids are drawn at the 50% probability level.
Synlett 2004, No. 11, 1995–1999 © Thieme Stuttgart · New York

1998
H. Krawczyk et al.
LETTER
(4) (a) Liao, X.-B.; Han, J.-Y.; Li, Y. Tetrahedron Lett. 2001,
42, 2843. (b) Ekthawatchai, S.; Kamchonwongpaisan, S.;
Kongsaeree, P.; Tarnchompoo, B.; Thebtaranonth, Y.;
Yuthavong, Y. J. Med. Chem. 2001, 44, 4688. (c) Avery,
M. A.; Alvim-Gaston, M.; Vroman, J. A.; Wu, B.; Ager, A.;
Peters, W.; Robinson, B. L.; Charman, W. J. Med. Chem.
2002, 45, 4321.
O
O
O
O
P(OEt)2
P(OEt)2
CH3
CH3
a
CO2H
CO2 NH2(C6H11)2
4
14
(5) (a) Weinheimer, A. J.; Chang, C. W. J.; Matson, J. A.
Fortschr. Chem. Org. Naturst. 1979, 36, 285. (b)McMurry,
J. E.; Dushin, R. G. J. Am. Chem. Soc. 1990, 112, 6942.
(6) Demuth, M.; Schaffner, K. Angew. Chem., Int. Ed. Engl.
1982, 21, 820.
b,c,d,e
H
H
O
O
O
O
(7) (a) Paitayatat, S.; Tarnchompoo, B.; Thebtaranonth, Y.;
Yuthavong, Y. J. Med. Chem. 1997, 40, 633.
CH3
7a
CH3
(b) Ekthawatchai, S.; Lertvorachon, J.; Meepowpan, P.;
Thongpanchang, T.; Thebtaranonth, Y.; Yuthavong, Y.
Synth. Commun. 2003, 33, 1855.
7b
7a:7b = 1:3
ee >99%
(8) (a) Giese, B.; Hoch, M.; Lamberth, C.; Schmidt, R. R.
Tetrahedron Lett. 1988, 29, 1375. (b) Kast, J.; Hoch, M.;
Schmidt, R. R. Liebigs Ann. Chem. 1991, 481. (c) Ramana,
C. V.; Nagarajan, M. Synlett 1997, 763. (d) Hamann, H. J.;
Höft, E.; Mostowicz, D.; Mishnev, A.; Urbańczyk-
Lipkowska, Z.; Chmielewski, M. Tetrahedron 1997, 53,
185. (e) Gupta, A.; Vankar, Y. D. Tetrahedron 2000, 56,
8525.
Scheme 3 Reagents and conditions: a. (C6H11)2NH (1 equiv), crys-
tallization from EtOAc; b. Dowex 50 W, H2O; c. MeOH, BaCl2·2H2O
(1 equiv), KBH4 (1 equiv), –70 °C, 1 h, r.t., 24 h; d. pTSA (cat.), ben-
zene, reflux, 4 h; e. t-BuOK (1.1 equiv), (HCHO)n (5 equiv), Et2O,
r.t., 1 h.
(9) Krawczyk, H. Synlett 1998, 1114.
(10) (a) Krawczyk, H. Synth. Commun. 2000, 30, 1787.
(b) Krawczyk, H.; Bodalski, R. J. Chem. Soc., Perkin Trans.
1 2001, 1559. (c) Krawczyk, H.; Śliwiński, M. Synthesis
2002, 1351. (d) Krawczyk, H.; Wolf, W. M.; Śliwiński, M.
J. Chem. Soc., Perkin Trans. 1 2002, 2794.
(11) Krawczyk, H.; Śliwiński, M. Tetrahedron 2003, 59, 9199.
(12) (a) Pfau, M.; Revial, G.; Guignant, A.; d’Angelo, J. J. Am.
Chem. Soc. 1985, 107, 273. (b) d’Angelo, J.; Desmaële, D.;
Dumas, F.; Guignant, A. Tetrahedron: Asymmetry 1992, 3,
459.
(13) Mastuyama, H.; Fujii, S.; Nakamura, Y.; Kikuchi, K.;
Ikemoto, J.; Kamigata, N. Bull. Chem. Soc. Jpn. 1993, 66,
1743.
(14) Guignant, A.; Hammani, H. Tetrahedron: Asymmetry 1991,
2, 411.
Figure 2 The crystal structure of lactone 13a. The exocyclic O3 and
C12 atoms are disordered. Each of both atoms was refined in two par-
tially occupied positions. The picture shows sites for which the oc-
cupation factor was 0.62(1). For clarity, the less occupied positions
are not shown. Displacement ellipsoids are drawn at the 50% proba-
bility level.
(15) (a) Du, Y.; Wiemer, D. F. J. Org. Chem. 2002, 67, 5701.
(b) Chen, X.; Wiemer, D. F. J. Org. Chem. 2003, 68, 6597.
(16) (a) Taniguchi, M.; Fujii, H.; Oshima, K.; Utimoto, K.
Tetrahedron 1993, 48, 11169. (b) Bartoli, G.; Bosco, M.;
Dalpozzo, R.; Marcantoni, E.; Sambri, L. Chem.–Eur. J.
1997, 3, 1941.
(17) Analytical data for 7a: colorless oil. 1H NMR (250 MHz,
CDCl3): d = 0.88 (3 H, s, CH3), 1.07–1.31 (2 H, m, CH2),
1.36–1.61 (4 H, m, 2 × CH2), 1.75–1.86 (2 H, m, CH2), 2.28
(1 H, dt, 4J = 2.5 Hz, 2J = 14.0 Hz, CH), 2.36 (1 H, dt,
4J = 1.5 Hz, 2J = 14.0 Hz, CH), 3.98 (1 H, dd, 3J = 5.0 Hz,
3J = 16.5 Hz, CHO), 5.49 (1 H, dt, 4J = 2J = 1.5 Hz, 4J = 2.5
Hz, CH), 6.42 (1 H, dt, 4J = 2J = 1.5 Hz, 4J = 2.5 Hz, CH).
13C NMR (62 MH z, CDCl3): d = 15.3 (CH2), 20.8 (CH2),
24.2 (CH3), 27.1 (CH2), 34.0 (C), 37.5 (CH2), 44.2 (CH2),
84.2 (CHO), 129.3 (CH2), 133.8 (C), 165.9 (COO).
Compound 7b: white solid; mp 71–73 °C; [a]D –18.00 (c
0.5, MeOH). IR (KBr): 3079, 1748, 1625, 1234 cm–1. 1H
NMR (250 MHz, CDCl3): d = 1.07 (3 H, s, CH3), 1.15–1.30
(2 H, m, CH2), 1.38–1.67 (4 H, m, 2 × CH2), 1.70–1.90 (m,
2 H, CH2), 2.33 (1 H, dt, 4J = 1.5 Hz, 2J = 16.0 Hz, CH), 2.58
(1 H, dt, 4J = 2.0 Hz, 2J = 16.0 Hz, CH), 4.20 (1 H, dd,
3J = 3.0 Hz, 3J = 6.0 Hz, CHO), 5.53 (1 H, dt, 4J = 2J = 1.5
Hz, 4J = 2.0 Hz, CH), 6.45 (1 H, dt, 4J = 2J = 1.5 Hz, 4J = 2.0
Hz, CH). 13C NMR (62 MHz, CDCl3): d = 20.7 (CH2), 20.8
(CH2), 24.6 (CH3), 28.1 (CH2), 32.3 (CH2), 32.5 (C), 39.9
Acknowledgment
This work has been supported by the Polish State Committee for
Scientific Research (KBN, Project No T09B 054 24) and Institute
of General and Ecological Chemistry (WMW).
References
(1) Kupchan, S. M.; Hemingway, R. J.; Werner, D.; Karim, A.;
McPhail, A. T.; Sim, G. A. J. Am. Chem. Soc. 1968, 90,
3596.
(2) Cane, D. E.; Rossi, T. Tetrahedron Lett. 1979, 2973.
(3) Nangia, A.; Prasuna, G.; Rao, P. B. Tetrahedron 1997, 53,
14507.
Synlett 2004, No. 11, 1995–1999 © Thieme Stuttgart · New York

LETTER
(CH2), 84.4 (CHO), 128.6 (CH2), 133.0 (C), 165.6 (COO).
Analytical data for racemic 13a and 13b have been
previously reported (ref.11). Compound 13a [a]D –99.09 (c
1.0, MeOH). Compound 13b [a]D –6.00 (c 1.20, MeOH).
(18) The ee values were determined by GC analysis by
comparison with racemates using a Lipodex E
Synthesis of Bicyclic a-Methylene-d-valerolactones
1999
(CH2, diaA), 20.9 (CH2, diaB), 21.3 (CH3, diaA), 22.3 (CH3,
diaB), 24.7 (4 × CH2), 25.0 (2 × CH2), 27.3 (CH2, diaA), 27.5
(CH2, diaB), 28.7 (2 × CH2), 28.8 (2 × CH2), 34.3 (CH2,
diaA), 34.4 (CH2, diaB), 34.5 (CH2, diaA), 34.6 (CH2, diaB),
38.5 (d, 2J = 13.1 Hz, CH2CHP, diaA), 39.5 (d, 2J = 28.6 Hz,
CH2CHP, diaB), 43.8 (d, 1J = 123.8 Hz, CHP, diaA), 44.1 (d,
1J = 123.6 Hz, CHP, diaB), 48.5 (d, 3J = 14.5 Hz, C, diaA),
49.2 (d, 3J = 14.0 Hz, C, diaB), 52.1 (2 × CHN), 61.5 (d,
2J = 5.8 Hz, CH2OP), 61.7 (d, 2J = 5.8 Hz, CH2OP), 171.7
(d, 2J = 4.4 Hz, COO, diaA), 172.3 (d, 2J = 4.4 Hz, COO,
diaB), 214.8 (CO, diaA), 215.7 (CO, diaB).
(50m × 0.25mm i.d.) column for 7a,b and a Gamma-dex
(30m × 0.25mm i.d.) column for 13a,b after purification by
column chromatography.
(19) Pirkle, W. H.; Sikkenga, D. L. J. Org. Chem. 1977, 42, 1370.
(20) Analytical data for 14: white solid, mp 149–151 °C. IR
(KBr): 2965, 1721, 1633, 1242 cm-1. 31P NMR (101 MHz,
CDCl3): d = 29.1, 29.00. 1H NMR (250 MHz, CDCl3): d =
1.06 (3 H, s, CH3), 1.02–1.27 (6 H, m, 3 × CH2), 1.22 (3 H,
t, 3J = 6.5 Hz, CH3CH2OP), 1.23 (3 H, t, 3J = 6.5 Hz,
CH3CH2OP), 1.40–1.65 (8 H, m, 4 × CH2), 1.70–2.10 (12 H,
m, 6 × CH2), 2.15–2.40 (2 H, m, CH2), 2.45–2.62 (2 H, m,
CH2), 2.61 (1 H, ddd, 3J = 3.7 Hz, 3J = 6.9 Hz, 2JHP = 25.7
Hz, CHP, diaA), 2.64 (1 H, ddd, 3J = 1.0 Hz, 3J = 10.3 Hz,
2JHP = 25.7 Hz, CHP, diaB), 2.91–2.99 (2 H, m, 2 × CHN),
3.95–4.11 (4 H, m, 2 × CH2OP). 13C NMR (62 MHz,
CDCl3): d = 16.2 (CH3CH2OP), 16.3 (CH3CH2OP), 20.7
(21) Absolute configuration was determined by refinement of
Flack parameter. Final value was 0.02 (4). Crystallographic
data for the salt 14 have been deposited at the Cambridge
Crystallographic Data Centre under number CCDC 241581.
(22) Krawczyk, H.; Śliwiński, M.; Wolf, W. M. Acta Cryst. Sect.
C 2004, submitted.
(23) Crystallographic data for the lactone 13a have been
deposited at the Cambridge Crystallographic Data Centre
under number CCDC 241582.
(24) Cavé, C.; Desmaële, D.; d’Angelo, J.; Riche, C.; Chiaroni,
A. J. Org. Chem. 1996, 61, 4361.
Synlett 2004, No. 11, 1995–1999 © Thieme Stuttgart · New York