Lewis acid-promoted intermolecular carbonyl-ene reaction of enantiopure 4-oxoazetidine-2-carbaldehydes. Rapid entry to novel fused polycyclic β-lactams

Article abstract of DOI:10.1021/jo0340509

Lewis acid-promoted carbonyl-ene reaction of enantiomerically pure 4-oxoazetidine-2-carbaldehydes with various activated alkenes gives 4-[(1′-hydroxy)homoallyl]-β-lactams with a very high level of syn diastereofacial selectivity. The above homoallylic alc

Full text of DOI:10.1021/jo0340509

Lew is Acid -P r om oted In ter m olecu la r Ca r bon yl-en e Rea ction of
En a n tiop u r e 4-Oxoa zetid in e-2-ca r ba ld eh yd es. Ra p id En tr y to
Novel F u sed P olycyclic â-La cta m s
Benito Alcaide,*,† Pedro Almendros,‡ Carmen Pardo,† Carolina Rodr´ıguez-Ranera,† and
Alberto Rodr´ıguez-Vicente†
Departamento de Quı´mica Orga´nica I, Facultad de Qu´ımica, Universidad Complutense de Madrid,
28040 Madrid, Spain, and Instituto de Qu´ımica Orga´nica General, CSIC, J uan de la Cierva 3,
28006-Madrid, Spain
alcaideb@quim.ucm.es
Received J anuary 16, 2003
Lewis acid-promoted carbonyl-ene reaction of enantiomerically pure 4-oxoazetidine-2-carbaldehydes
with various activated alkenes gives 4-[(1′-hydroxy)homoallyl]-â-lactams with a very high level of
syn diastereofacial selectivity. The above homoallylic alcohols are used for the diastereoselective
preparation of fused bicyclic, tricyclic, and tetracyclic â-lactams of nonconventional structure using
tandem one-pot radical addition/cyclization or elimination-intramolecular Diels-Alder sequences.
In addition, a novel domino process was discovered, the C4-N1 â-lactam bond breakage/
intramolecular Diels-Alder reaction.
In tr od u ction
hyde, chloral, etc. have been successfully used in carbonyl-
ene reactions. Among different reported examples, only
a very few papers refer to the asymmetric version of this
reaction using chiral aminoaldehydes.5
The development of new approaches to the stereocon-
trolled synthesis of â-lactam systems is a subject of great
interest in the context of their possible use as biologically
active compounds6 or as versatile chiral building blocks.7
On the other hand, the chiral â-amino alcohol moiety is
present in many biologically important molecules such
as dipeptide isosteres and statine and its analogues, and
therefore, its stereocontrolled synthesis remains an
intensive research area.8 Our interest in the use of
The Lewis acid-promoted ene reaction of a carbonyl
compound (enophile) with an alkene having an allylic
hydrogen (an “ene”) represents a powerful method for
selective carbon-carbon bond formation.1 Although syn-
thetically very useful, the carbonyl-ene reaction is se-
verely substrate limited and only intramolecular ene
reactions1,2 or intermolecular reactions with either elec-
tron-deficient carbonyl compounds3 or electron-rich ole-
fins4 have been reported. The use of Lewis acid is crucial
to activate the carbonyl group due to the inherent low
nucleophilicity of the olefin. Simple aliphatic or aromatic
aldehydes are usually unreactive. However, electron-
deficient aldehydes such as glyoxylate esters, formalde-
(4) (a) Milles, W. H.; Berreth, C. L.; Anderton, C. A. Tetrahedron
Lett. 1996, 37, 7893. (b) Snider, B. B. Acc. Chem. Res. 1980, 13, 426
and references therein. (c) Snider, B. B.; Rodini, D. J .; Kirk, T. C.;
Cordova, R. J . J . Am. Chem. Soc. 1982, 104, 555. (d) Mikami, K.; Loh,
T.-P.; Nakai, T. J . Am. Chem. Soc. 1990, 112, 6737. (e) Mikami, K.;
Ohmura, H. Chem. Commun. 2002, 2626.
(5) (a) Nayak, S. K.; Thijs, L.; Zwanenburg, B. Synlett 1998, 1187.
(b) Mikami, K.; Terada, M.; Nakai, T. J . Am. Chem. Soc. 1990, 112,
3949. (c) Mikami, K.; Loh, T.-P.; Nakai, T. Tetrahedron: Asymmetry
1990, 1, 13. (d) Mikami, K.; Knaeko, M.; Loh, T.-P.; Terada, M.; Nakai,
T. Tetrahedron Lett. 1990, 31, 3909.
(6) See, for example: (a) Niccolai, D.; Tarsi, L.; Thomas, R. J . Chem.
Commun. 1997, 2333. (b) Southgate, R. Contemp. Org. Synth. 1994,
1, 417. (c) Southgate, R.; Branch, C.; Coulton, S.; Hunt, E. In Recent
Progress in the Chemical Synthesis of Antibiotics and Related Microbial
Products; Lukacs, G., Ed.; Springer: Berlin, 1993; Vol. 2, p 621. (d)
The Chemistry of â-Lactams; Page, M. I., Ed.; Chapman and Hall:
London, 1992.
(7) See, for instance: (a) Palomo, C.; Aizpurua, J . M.; Ganboa, I.;
Oiarbide, M. Amino Acids 1999, 16, 321. (b) Ojima, I.; Delaloge, F.
Chem. Soc. Rev. 1997, 26, 377. (c) Manhas, M. S.; Wagle, D. R.; Chiang,
J .; Bose, A. K. Heterocycles 1988, 27, 1755.
† Universidad Complutense de Madrid.
‡ Instituto de Qu´ımica Orga´nica General.
(1) For reviews, see: (a) Mikami, K. Advances in Asymmetric
Synthesis; J AI Press: 1995, Vol. 1, pp 1-44. (b) Mikami, K.; Shimizu,
M. Chem. Rev. 1992, 92, 1021. (c) Mikami, K.; Terada, M.; Narisawa,
S.; Nakai, Synlett. 1992, 255. (d) Snider, B. B. Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991;
Vol. 2, p 527. (e) Snieckus, V.; Oppolzer, W. Angew. Chem., Int. Ed.
Engl. 1978, 17, 476.
(2) See, for instance: (a) Williams, J . T.; Bahia, P. S.; Snaith, J . S.
Org. Lett. 2002, 4, 3727. (b) Alcaide, B.; Pardo, C.; Rodr´ıguez-Ranera,
C.; Rodr´ıguez-Vicente, A. Org. Lett. 2001, 3, 4205. (c) Srikrishna, A.;
Dinesh, C.; Anebouselvy, K. Tetrahedron Lett. 1999, 40, 1031. (d)
Aggarwal, V. K.; Vennall, G. P.; Davey, P. N.; Newman, Ch. Tetrahe-
dron Lett. 1998, 39, 1997. (e) Mikami, K.; Sawa, E.; Terada, M.
Tetrahedron: Asymmetry 1991, 2, 1403.
(3) Glyoxylates: (a) Gathergood, N.; J orgensen, K. A. Chem. Com-
mun. 1999, 1869. (b) Nakai, T.; Mikami, K.; Terada, M. J . Am. Chem.
Soc. 1989, 111, 1940. (c) Mikami, K.; Terada, M.; Nakai, T. J . Am.
Chem. Soc. 1990, 112, 3949. Formaldehyde: (d) Okachi, T.; Fujimoto,
K.; Onaka, M. Org. Lett. 2002, 4, 1667. (e) Snider, B. B.; Phillips, G.
B. J . Org. Chem. 1983, 48, 464. Chloral: (f) Benner, J . P.; Gill, G. B.;
Parrot, S. J .; Wallace, B.; Begley, M. J . J . Chem. Soc., Perkin Trans.
(8) See, for example: (a) Enders, D.; Reinhold: U. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 1219. (b) Rich, D. H. Peptidase Inhibitors in
Comprehensive Medicinal Chemistry; Sammes, P. G., Ed; Pergamon
Press: Oxford, 1990; Vol. 2, p 391. (c) Huff, J . R. J . Med. Chem. 1991,
34, 2305. (d) Thaisrivongs, S.; Pals, D. T.; Kroll, L. T.; Turner, S. R.;
Han, F.-S. J . Med. Chem. 1987, 30, 976.
1
1984, 315. Fluoral: (g) Mikami, K.; Yajima, T.; Terada, M.;
Uchimaru, T. Tetrahedron Lett. 1993, 34, 7591. (h) Mikami, K.; Yajima,
T.; Takasaki, T.; Matsukawa, S.; Terada, M.; Uchimaru, T.; Maruta,
M. Tetrahedron 1996, 52, 85.
10.1021/jo0340509 CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/21/2003
3106
J . Org. Chem. 2003, 68, 3106-3111

Novel Fused Polycyclic â-Lactams
TABLE 1. Lew is Acid -P r om oted In ter m olecu la r Ca r bon yl-en e Rea ction of 4-Oxoa zetid in e-2-ca r ba ld eh yd es 1 w ith
Olefin sa
aldehyde
R1
R2
PMP
PMP
PMP
R3, R4
Lewis acid
t (h)
productb
yield (%)c
(+)-1a
(+)-1a
(+)-1b
(+)-1b
(+)-1c
(+)-1c
(+)-1d
(+)-1e
(+)-1e
(+)-1f
(+)-1g
(+)-1h
(-)-1i
(+)-1b
(+)-1b
(+)-1c
(+)-1c
(+)-1a
(+)-1d
(+)-1e
(+)-1f
(+)-1g
(+)-1h
(-)-1i
OMe
OMe
OPh
OPh
OBn
OBn
OBn
OMe
OMe
OMe
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)3-
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)4-
H, Ph
SnCl4
BF3‚Et2O
SnCl4
5
5
3
3
3
1
26
6
6
3
2
2
18
5
5
5
5
5
26
4
(+)-syn-2a
(+)-syn-2a
(+)-syn-2b
(+)-syn-2b
(+)-syn-2c
(+)-syn-2c
(+)-syn-2d
(+)-syn-2e
(+)-syn-2e
(+)-syn-2f
(+)-syn-2g
(+)-syn-2h
(-)-syn-2i
(+)-syn-3a
(+)-syn-3a
(+)-syn-3b
(+)-syn-3b
(+)-syn-4a
(+)-syn-4b
(+)-syn-4c
(+)-syn-4d
(+)-syn-4e
(+)-syn-4f
(-)-syn-4g
45
65
60
40
41
60
61
40
51
45
83d
85d
51f
70
33
37
15
66
60
64
52
42g
66g
46f
PMP
BF3‚Et2O
SnCl4
BF3‚Et2O
BF3‚Et2O
SnCl4
BF3‚Et2O
BF3‚Et2O
BF3‚Et2O
BF3‚Et2O
BF3‚Et2O
SnCl4
2-propenyl
2-propenyl
3-butenyl
2-propynyl
2-propynyl
3-butynyl
PMP
PMP
3-butenyl
PMP
O-allyl
O-propargyl
Phte
OPh
OPh
OBn
OBn
OMe
OBn
OMe
OMe
PMP
BF3‚Et2O
SnCl4
2-propenyl
2-propenyl
PMP
3-butenyl
2-propynyl
3-butynyl
PMP
BF3‚Et2O
BF3‚Et2O
BF3‚Et2O
BF3‚Et2O
BF3‚Et2O
BF3‚Et2O
BF3‚Et2O
BF3‚Et2O
H, Ph
H, Ph
H, Ph
H, Ph
H, Ph
H, Ph
17
5
4
O-allyl
O-propargyl
Phte
PMP
3-butenyl
26
a
All reactions were run at -78 °C in dichloromethane in a molar ratio of aldehyde/alkene/Lewis acid ) 1:2:1.2 unless otherwise noted.
PMP ) 4-methoxyphenyl. Isomer shown was the only product detected in the crude mixture by 300 MHz 1H NMR spectroscopy. c Yields
b
d
are for pure products purified by column chromatography with correct analytical and spectroscopic data. Reaction was run at -40 °C.
e Pht ) phthalimido. f Reaction was run at 0 °C. Reaction was run at -25 °C.
g
4-oxoazetidine-2-carbaldehydes 1 as substrates for ad-
SCHEME 1
dition reactions and cyclization processes9 prompted us
to evaluate their ene reactions with activated alkenes as
a route to unusual, functionalized monocyclic and poly-
cyclic 2-azetidinones.10 We wish to report here the use of
enantiomerically pure 4-oxoazetidine-2-carbaldehydes 1
as novel enophiles for Lewis acid-catalyzed carbonyl-ene
reactions, to give â-lactam homoallylic alcohols 2-4 with
extremely high syn diastereofacial selectivity (Scheme 1),
together with further interesting synthetic transforma-
tions to structurally novel fused bicyclic, tricyclic, and
tetracyclic â-lactams.
Resu lts a n d Discu ssion
romethane at -78 °C for 5 h gave homoallylic alcohol
(+)-2a in moderate yield and essentially complete syn
Starting substrates, enantiopure 4-oxoazetidine-2-carb-
aldehydes 1a -i, were obtained as single cis enantiomers
from imines of (R)-2,3-O-isopropylideneglyceraldehyde
through Staudinger reaction with the appropriate acid
chloride in the presence of Et3N, followed by sequential
acidic acetonide hydrolysis and oxidative cleavage.9
A model reaction of aldehyde (+)-1a with methylene-
cyclopentane in the presence of tin(IV) chloride in dichlo-
diastereoselectivity (>99%) (Table 1). This preliminary
result encouraged us to screen other Lewis acids for the
above reaction for better yield. We were pleased to find
that use of BF3‚Et2O under similar conditions also gave
(+)-2a but with much improved results in terms of yield.
The stereochemical outcome of the process is not affected
by the different coordinative abilities of the Lewis acid
(BF3‚Et2O has only one coordination site). In addition,
other tested Lewis acid such as Me2AlCl, Et2AlCl, TiCl4,
or Sc(OTf)3 were less effective for the ene process, even
after longer times.11 From the above results we focused
our attention on SnCl4 and BF3.Et2O as catalysts to
explore the scope of this process with different enan-
tiopure â-lactam aldehydes 1 and alkenes. All ene reac-
(9) See, for instance: (a) Alcaide, B.; Almendros, P. Chem. Soc. Rev.
2001, 30, 226. (b) Alcaide, B.; Almendros, P. Synlett 2002, 381. (c)
Alcaide, B.; Almendros, P.; Aragoncillo, C. Chem. Eur. J . 2002, 8, 1719.
(d) Alcaide, B.; Almendros, P.; Alonso, J . M.; Aly, M. F. Org. Lett. 2001,
3, 3781. (e) Alcaide, B.; Pardo, C.; Sa´ez, E. Synlett 2002, 85.
(10) For a recent review on the synthesis and biological properties
of polycyclic-â-lactams with nonclassical structures, see: Alcaide, B.;
Almendros, P. Curr. Org. Chem. 2002, 6, 245.
J . Org. Chem, Vol. 68, No. 8, 2003 3107

Alcaide et al.
SCHEME 2a
tions afforded syn products 2-4 exclusively in moderate
to good yields independently of the catalyst used (Table
1). Tin(IV) chloride gave a superior yield for the meth-
ylenecyclohexane carbonyl-ene reaction. Interestingly,
reactions of aldehydes 1 with R-methylstyrene only
occurred in the presence of BF3‚Et2O to furnish products
3 in reasonable yields. R-Methylstyrene was not so prone
to afford the carbonyl-ene product under tin(IV) chloride
catalysis because a competing event took place, namely,
the polymerization of the alkene.12 Probably, BF3‚Et2O
can activate the carbonyl group of 4-oxoazetidine-2-
carbaldehydes and effectively scavenge the acidic proton
of the ene adduct.
Configuration at the carbinolic chiral center of the
1
above alcohols was established by comparison of the H
NMR chemical shifts of the (R)- and (S)-acetylmandelates
of compound (+)-2b.13 It should be noted that the
observed syn selectivity is even higher than that obtained
by us in a related reaction of some compounds 1 with
different propenylmetal reagents under Lewis acid ca-
talysis.14 Moreover, in contrast to our previous report on
addition reactions,15 the stereoselectivity of the ene
reaction was not dependent on the bulkiness of substit-
uents on the â-lactam ring. As in previous Lewis acid-
promoted reactions with allylmetal reagents, the ob-
served syn diastereoselectivity can be explained by
invoking the Felkin-Anh model.14
Among different ene products 2-4, enyne derivatives
are of particular interest due to their propensity to
undergo different cyclization processes using various
methodologies involving both radicals and transition
metal-catalyzed reactions. Moreover, the presence of the
homoallylic alcohol moiety in all these compounds led us
to consider alternative cycloaddition methods mainly
based on the IMDA reaction. Thus, we turned our
attention to the synthesis of fused â-lactams, which may
have antibacterial potential because they are novel
polycyclic-2-azetidinones with nonclassical structures.10
Mesylates 5 possessing a pendant alkyne at position 1
or 3 of the â-lactam ring, on heating in a sealed tube with
1.0 equiv of DBU in benzene, afforded the corresponding
Diels-Alder cycloadducts 6 in a completely stereoselec-
tive fashion.16 1,4-Cyclohexadienes 6 are prone to undergo
aromatization as illustrated in Scheme 2. In fact, when
mesylates (+)-5b and (+)-5d were heated in the presence
a
°
Key: (i) MsCl, Et3N, rt. (ii) DBU, benzene, 190 C, 96 h. (iii)
CDCl3, rt, 24 h. (iv) DBU, benzene, 170 °C, 72 h. (v) DBU, benzene,
°
°
140 C, 44 h. (vi) Pd-C, benzene, 150 C, 24 h.
SCHEME 3a
(11) Recently, Sc(OTf)3 has been reported to be a highly efficient
catalyst for reaction of aromatic aldehydes and methylenecyclohexane.
See ref 2b.
(12) This is partly because the homoallylic alcohol product (ene
adduct) forms a complex with the Lewis acid promoter to generate a
strongly acidic proton. This acidic proton migrates intramolecularly
to a double bond of the ene adduct or intermolecularly to a starting
styrene derivative to produce a labile cationic intermediate, which
triggers various side reactions.
(13) (a) Trost, B. M.; Belletire, J . L.; Godleski, S.; McDougal, P. G.;
Balkovic, J . M.; Balwin, J . J .; Christy, M. E.; Ponticello, G. S.; Varga,
S. L.; Springer, J . P. J . Org. Chem. 1986, 51, 2370. (b) Latypov, Sh.
K.; Seco, J . M.; Quin˜oa´, E.; Riguera, R. J . Am. Chem. Soc. 1998, 120,
877. (c) Garc´ıa, R.; Seco, J . M.; Va´zquez, S. A.; Quin˜oa´, E.; Riguera, R.
J . Org. Chem. 2002, 67, 4579.
a
Key: (i) DBU, benzene, 80 °C, 70 h.
of DBU for a prolonged time, the tetracyclic â-lactams
(-)-7b and (-)-7d containing a benzene ring were the
only isolated products in reasonable yields.
Interestingly, the treatment of enantiomerically pure
mesylates (+)-5b and (+)-5d with a slight excess of DBU
(1.5 equiv) in benzene at reflux temperature gave rise to
unexpected products, the racemic amides (()-8a and (()-
8b (Scheme 3). The formation of compounds 8 could be
rationalized in terms of an unprecedented domino C4-
N1 â-lactam bond breakage/intramolecular Diels-Alder
(14) Alcaide, B.; Almendros, P.; Salgado, N. R. J . Org. Chem. 2000,
65, 3310.
(15) (a) Alcaide, B.; Almendros, P.; Aragoncillo, C. J . Org. Chem.
2001, 66, 1612. (b) Alcaide, B.; Almendros, P.; Aragoncillo, C. Chem.
Commun. 1999, 1913.
(16) Alternatively, the transformation of ene adducts 2-4 into
polycyclic 2-azetidinones 6 can be achieved in one pot upon heating in
a sealed tube the homoallylic alcohols in the presence of mesyl chloride
and DBU.
3108 J . Org. Chem., Vol. 68, No. 8, 2003

Novel Fused Polycyclic â-Lactams
SCHEME 4
SCHEME 5
and it was transferred unaltered during the further
synthetic steps. The polycyclic structures (by DEPT,
HETCOR, and COSY) and the stereochemistry (by vicinal
proton couplings and qualitative homonuclear NOE dif-
ference spectra) of fused â-lactams 6, 7, 11, and 12 were
established by NMR one- and two-dimensional tech-
niques.20
Con clu sion s
In conclusion, the present study provides the first
insight into the manner in which 4-oxoazetidine-2-
carbaldehydes and activated alkenes undergo coupling
under Lewis acid catalysis. In addition, we have shown
that combination of carbonyl-ene reaction and IMDA or
radical cyclization is a useful methodology for the prepa-
ration of enantiopure fused bicyclic, tricyclic, and tetra-
cyclic â-lactams of nonconventional structure. In addition,
a novel domino process, the C4-N1 â-lactam bond
breakage/intramolecular Diels-Alder reaction, was dis-
covered.
reaction.9b,17 The driving force of the reaction may be the
formation of the highly conjugate trienes 9 under the
reaction conditions (excess of base). Amides 8 presumably
arise from the isomerization of the initially formed [4 +
2] cycloadducts 10 (Scheme 4). However, it is not clear
whether the first step of the domino reaction is the
cleavage of the â-lactam ring or the Diels-Alder cyclo-
addition.
Exp er im en ta l Section
Although construction of medium-sized rings18 using
free radical methodology is difficult to achieve and the
synthesis of eight- and nine-membered rings fused to
â-lactams has been virtually ignored,19 we planned to
investigate this strategy in ene adducts 4 bearing an
extra alkyne tether. The tin-promoted radical cyclization
proceeded elegantly in enynes (+)-4c and (+)-4d to
provide the desired nonconventional bicyclic â-lactams
11 as single isomers in moderate yields (Scheme 3).
Treatment of vinylic stannane (+)-11a with PTSA in CH2-
Cl2 yielded the destannylated eight-membered fused
adduct (+)-12.
Gen er a l. General experimental data and procedures have
been previously reported.9c,15 NMR spectra were recorded in
CDCl3 solutions, unless otherwise stated. Chemical shifts are
given in parts per million relative to TMS (1H, 0.0 ppm) or
CDCl3 (13C, 77.0 ppm). All commercially available compounds
were used without further purification.
Gen er a l P r oced u r e for th e Lew is Acid -P r om oted En e
Rea ction of 4-Oxoa zetid in e-2-ca r ba ld eh yd es 1. Syn th e-
sis of Hom oa llylic Alcoh ol Der iva tives 2-4. To a stirred
solution of the appropriate aldehyde 1 (1 mmol) and methyl-
enecyclopentane, methylenecyclohexane, or R-methylstyrene
(2 mmol) in dry dichloromethane (10 mL) at -78 °C was added
SnCl4 or BF3‚OEt2 (1.2 mmol) dropwise, and the mixture was
stirred at this temperature for the time indicated in Table 1.
Saturated aqueous sodium hydrogen carbonate (3 mL) was
added, and the mixture was allowed to warm to room tem-
perature before being partitioned between dichloromethane
and water. The organic extract was washed with brine and
dried (MgSO4). Removal of solvent under reduced pressure
followed by flash chromatography (SiO2; hexanes/ethyl acetate
mixtures) yielded the corresponding ene adducts 2-4 in
analytically pure form. Spectroscopic and analytical data for
some representative pure forms of 2-4 follow.21
The structure and stereochemistry of compounds 6, 7,
11, and 12 were assigned by NMR studies. The cis
stereochemistry of the four-membered ring was set
during the cyclization step to form the 2-azetidinone ring,
(17) There is in the literature a precedent, described some time ago
in our group, for opening â-lactams in the presence of base by a related
mechanism. See: Alcaide, B.; Dom´ınguez, G.; Mart´ın-Domenech, A.;
Plumet, J .; Monge, A.; Pe´rez-Garc´ıa, V. Heterocycles 1987, 26, 1461.
(18) Synthesis of medium-sized rings, notably eight- and nine-
membered ring systems, has usually been hampered by entropic/
enthalpic factors and transannular interactions between the methylene
groups. For reviews, see: (a) Galli, L.; Mandolini, L. Eur. J . Org. Chem.
2000, 3117. (b) Illuminati, G.; Mandolini, L. Acc. Chem. Res. 1981,
14, 95. In view of these difficulties, the synthesis of these structures
still remains a partially unsolved problem. For selected reviews on
medium-sized ring preparation, see: (c) Yet, L. Chem. Rev. 2000, 100,
2963. (d) Molander, G. Acc. Chem. Res. 1998, 31, 603. (e) Lautens, M.
Top. Curr. Chem. 1997, 190, 1.
(3R,4S)-4-[(R)-1-Hyd r oxy-2-(1-cyclop en ten yl)-eth yl]-3-
m eth oxy-1-(3-bu tyn yl)-2-a zetid in on e, (+)-2f. From 157 mg
(0.87 mmol) of aldehyde (+)-1f was obtained 100 mg (45%) of
compound (+)-2f as a colorless oil. [R]D ) +39.6 (c 1.6, CHCl3).
(20) Compounds 6, 7, 11, and 12 showed values of coupling constants
and NOE enhancements in good agreement with those reported for
analogous systems. See refs 14 and 15.
(21) Full spectroscopic and analytical data for compounds not
included in this Experimental Section are described in Supporting
Information.
(19) Only examples available have been recently reported by us. See
ref 15.
J . Org. Chem, Vol. 68, No. 8, 2003 3109

Alcaide et al.
1H NMR: δ 1.88 (m, 2H), 1.99 (t, 1H, J ) 2.7 Hz), 2.34 (m,
7H), 2.52 (m, 2H), 3.37 (m, 1H), 3.59 (s, 3H), 3.65 (m, 1H),
3.74 (t, 1H, J ) 4.8 Hz), 4.00 (m, 1H), 4.48 (d, 1H, J ) 4.8
Hz), 5.52 (br s, 1H). 13C NMR: δ 167.8, 140.0, 127.6, 83.0, 81.0,
70.1, 68.9, 61.0, 59.3, 40.3, 35.9, 35.0, 32.5, 23.3, 17.7. IR
(CHCl3, cm-1): ν 3420, 1747. MS (EI), m/z: 264 (M+ + 1, 7),
263 (M+, 100). Anal. Calcd for C15H21NO3: C, 68.42; H, 8.04;
N, 5.32. Found: C, 68.51; H, 8.08; N, 5.30.
5 mL), dried (MgSO4), and concentrated under reduced pres-
sure. Chromatography of the residue eluting with hexanes/
ethyl acetate mixtures gave analytically pure methane-
sulfonates 5. Spectroscopic and analytical data for some
representative pure forms of 5 follow.
Meth a n esu lfon a te of (3R,4S)-4-[(R)-1-Hyd r oxy-2-(1-cy-
clop en t en yl)-et h yl]-3-m et h oxy-1-(3-b u t yn yl)-2-a zet id i-
n on e, (+)-5a . From 37 mg (0.14 mmol) of alcohol (+)-2f was
obtained 33 mg (67%) of compound (+)-5a as a colorless oil.
(3R,4S)-3-P r op a r gyloxy-4-[(R)-1-h yd r oxy-2-(1-cyclo-
pen ten yl)-eth yl]-1-(p-m eth oxyp h en yl)-2-a zetid in on e, (+)-
2h . From 111 mg (0.43 mmol) of aldehyde (+)-1h was obtained
123 mg (85%) of compound (+)-2h as a yellow solid. Mp: 88-
1
[R]D ) +42.7 (c 1.0, CHCl3). H NMR: δ 1.90 (m, 2H), 1.99 (t,
1H, J ) 2.7 Hz), 2.37 (m, 8H), 3.00 (s, 3H), 3.38 (dt, 1H, J )
14.2, 6.2 Hz), 3.58 (s, 3H), 3.75 (m, 1H), 4.02 (dd, 1H, J ) 8.0,
5.1 Hz), 4.52 (d, 1H, J ) 5.1 Hz), 5.06 (ddd, 1H, J ) 8.0, 6.6,
4.3 Hz), 5.55 (br s, 1H). 13C NMR: δ 167.6, 138.5, 129.1, 82.7,
81.0, 80.7, 70.4, 59.2, 58.4, 39.7, 39.3, 35.2, 34.3, 32.4, 23.4,
17.2. IR (CHCl3, cm-1): ν 1749. MS (CI), m/z: 342 (M+ + 1,
100), 343 (M+, 11). Anal. Calcd for C16H23NO5S: C, 56.29; H,
6.79; N, 4.10. Found: C, 56.38; H, 6.76; N, 4.06.
1
89 °C (hexanes/ethyl acetate). [R]D ) +78.6 (c 1.0, CHCl3). H
NMR: δ 1.87 (m, 2H), 2.31 (m, 6H), 2.36 (d, 1H, J ) 3.4 Hz),
2.55 (t, 1H, J ) 2.4 Hz), 3.79 (s, 3H), 4.24 (m, 1H), 4.33 (t, 1H,
J ) 5.0 Hz), 4.52 (m, 2H), 4.96 (d, 1H, J ) 5.1 Hz), 5.50 (br s,
1H), 6.86 (m, 2H), 7.44 (m, 2H). 13C NMR: δ 164.7, 156.8,
140.3, 130.8, 127.2, 120.4, 114.1, 79.7, 78.4, 76.0, 69.2, 60.7,
59.0, 55.5, 35.7, 35.0, 32.5, 23.3. IR (KBr, cm-1): ν 3420, 1741.
MS (CI), m/z: 342 (M+ + 1, 100), 341 (M+, 19). Anal. Calcd for
Meth a n esu lfon a te of (3R,4S)-3-P r op a r gyloxy-4-[(R)-1-
h yd r oxy-3-p h en yl-3-bu ten yl]-1-(p-m eth oxyp h en yl)-2-a ze-
tid in on e, (+)-5d . From 116 mg (0.31 mmol) of aldehyde (+)-
4f was obtained 91 mg (65%) of compound (+)-5d as a colorless
C
20H23NO4: C, 70.36; H, 6.79; N, 4.10. Found: C, 70.28; H,
6.75; N, 4.12.
1
oil. [R]D ) +49.1 (c 1.0, CHCl3). H NMR: δ 2.48 (t, 1H, J )
(3R,4S)-4-[(R)-1-H yd r oxy-2-(1-cycloh exen yl)-et h yl]-1-
(p-m eth oxyph en yl)-3-ph en oxy-2-azetidin on e, (+)-3a. From
100 mg (0.34 mmol) of aldehyde (+)-1b was obtained 93 mg
(70%) of compound (+)-3a as a colorless solid. Mp: 150-151
°C (hexanes/ethyl acetate). [R]D ) +178.6 (c 1.0, CHCl3). 1H
NMR: δ 1.60 (m, 4H), 2.14 (m, 5H), 2.43 (m, 1H), 3.80 (s, 3H),
4.27 (m, 1H), 4.40 (dd, 1H, J ) 7.0, 5.3 Hz), 5.38 (d, 1H, J )
5.4 Hz), 5.57 (br s, 1H), 6.88 (m, 2H), 7.11 (m, 3H), 7.35 (m,
2H), 7.56 (m, 2H). 13C NMR: δ 163.7, 157.4, 156.7, 133.5,
130.8, 129.6, 125.6, 122.5, 120.3, 115.8, 113.9, 79.3, 69.2, 61.2,
55.3, 42.6, 28.0, 25.2, 22.7, 22.1. IR (KBr, cm-1): ν 3489, 1757.
MS (EI), m/z: 394 (M+ + 1, 14), 393 (M+, 100). Anal. Calcd for
2.4 Hz), 2.57 (s, 3H), 3.10 (ddd, 1H, J ) 15.1, 4.6, 1.0 Hz),
3.22 (dd, 1H, J ) 15.1, 6.9 Hz), 3.80 (s, 3H), 4.46 (m, 3H), 4.90
(d, 1H, J ) 5.4 Hz), 5.15 (dt, 2H, J ) 6.9, 4.6 Hz), 5.27 (d, 1H,
J ) 1.0 Hz), 5.51 (d, 1H, J ) 1.2 Hz), 6.87 (m, 2H), 7.33 (m,
7H). 13C NMR: δ 164.0, 157.0, 142.4, 139.5, 129.9, 128.6, 127.9,
126.3, 119.8, 117.8, 114.4, 79.9, 79.6, 78.1, 76.2, 58.8, 57.7, 55.5,
38.0, 37.1. IR (CHCl3, cm-1): ν 1748. MS (EI), m/z: 456 (M+
+
1, 15), 455 (M+, 100). Anal. Calcd for C24H25NSO6: C, 63.28;
H, 5.53; N, 3.07. Found: C, 63.36; H, 5.56; N, 3.05.
Gen er a l P r oced u r e for th e P r ep a r a tion of Diels-
Ald er Cycloa d d u cts 6 or Tr ycycles 7. DBU (1.50 mmol)
was added dropwise to a solution of the corresponding meth-
anesulfonate 5 (1.0 mmol) and hydroquinone (cat.) in benzene
(10 mL). The resulting solution was heated in a sealed tube
at the appropriate temperature (140-190 °C). The reaction
mixture was allowed to cool to room temperature, and the
solvent was removed under reduced pressure. Chromatography
of the residue eluting with dichloromethane/ethyl acetate/
hexanes mixtures gave analytically pure adducts 6 or 7.
Cycloa d d u ct (+)-6a . From 31 mg (0.09 mmol) of meth-
anesulfonate (+)-5a and after heating at 190 °C for 96 h was
obtained 15 mg (68%) of compound (+)-6a as a colorless oil.
[R]D ) +44.2 (c 0.5, CHCl3). 1H NMR: δ 1.71 (m, 2H), 2.18 (m,
5H), 2.85 (m, 5H), 3.14 (dd, 1H, J ) 9.5, 3.9 Hz), 3.61 (s, 3H),
3.88 (m, 1H), 4.58 (dd, 1H, J ) 3.9, 1.2 Hz), 5.19 (br s, 1H),
5.76 (br s, 1H). 13C NMR: δ 166.8, 143.6, 132.0, 125.0, 114.6,
85.1, 59.4, 59.2, 40.8, 39.0, 36.9, 33.6, 32.5, 29.0, 21.9. IR
(CHCl3, cm-1): ν 1751. MS (ES), m/z: 269 (M+ + 23, 22), 246
(M+ + 1, 100), 245 (M+, 11). Anal. Calcd for C15H19NO2: C,
73.44; H, 7.81; N, 5.71. Found: C, 73.53; H, 7.78; N, 5.69.
Tr icyclic â-La cta m (-)-7b. From 52 mg (0.12 mmol) of
methanesulfonate (+)-5b and after heating at 170 °C for 22 h
was obtained 26 mg (65%) of compound (-)-7b as a colorless
oil. [R]D ) -174.9 (c 1.0, CHCl3). 1H NMR: δ 2.09 (m, 2H),
2.92 (m, 4H), 3.76 (s, 3H), 4.71 and 4.87 (d, each 1H, J ) 14.2
Hz), 5.13 (d, 1H, J ) 4.9 Hz), 5.32 (d, 1H, J ) 4.9 Hz), 6.85
(m, 2H), 7.07 (s, 1H), 7.41 (s, 1H), 7.49 (m, 2H). 13C NMR: δ
164.6, 156.6, 145.4, 144.0, 134.0, 130.7, 127.6, 127.0, 122.5,
119.1, 114.3, 80.4, 66.2, 55.5, 54.6, 32.7, 32.6, 25.3. IR (CHCl3,
cm-1): ν 1748. MS (CI), m/z: 322 (M+ + 1, 100), 321 (M+, 11).
Anal. Calcd for C20H19NO3: C, 74.75; H, 5.96; N, 4.36. Found:
C, 74.63; H, 6.00; N, 4.33.
C
24H27NO4: C, 73.26; H, 6.92; N, 3.56. Found: C, 73.37; H,
6.89; N, 3.54.
(3R,4S)-4-[(R)-1-Hyd r oxy-3-p h en yl-3-bu ten yl]-3-m eth -
oxy-1-(3-bu tyn yl)-2-a zetid in on e, (+)-4d . From 100 mg (0.55
mmol) of aldehyde (+)-1f was obtained 87 mg (52%) of
compound (+)-4d as a colorless solid. Mp: 91-92 °C (hexanes/
1
ethyl acetate). [R]D ) +2.3 (c 1.0, CHCl3). H NMR: δ 1.97 (t,
1H, J ) 2.7 Hz), 2.24 (d, 1H, J ) 2.9 Hz), 2.52 (m, 3H), 3.03
(ddd, 1H, J ) 13.9, 3.4, 1.2 Hz), 3.38 (m, 1H), 3.62 (s, 3H),
3.63 (m, 1H), 3.76 (dd, 1H, J ) 6.8, 5.1 Hz), 3.94 (ddd, 1H, J
) 12.7, 6.6, 3.2 Hz), 4.47 (d, 1H, J ) 4.9 Hz), 5.21 (br s, 1H),
5.52 (d, 1H, J ) 1.2 Hz), 7.40 (m, 5H). 13C NMR: δ 167.8, 144.0,
139.5, 128.5, 128.0, 126.0, 115.8, 82.8, 81.1, 70.0, 69.6, 61.0,
59.2, 40.3, 40.0, 17.8. IR (KBr, cm-1): ν 3402, 1743. MS (CI),
m/z: 300 (M+ + 1, 100), 299 (M+, 16). Anal. Calcd for C18H21
-
NO3: C, 72.22; H, 7.07; N, 4.68. Found: C, 72.32; H, 7.04; N,
4.65.
(3R,4S)-3-P r op a r gyloxy-4-[(R)-1-h yd r oxy-3-p h en yl-3-
bu ten yl]-1-(p-m eth oxyph en yl)-2-azetidin on e, (+)-4f. From
120 mg (0.46 mmol) of aldehyde (+)-1h was obtained 116 mg
(66%) of compound (+)-4f as a colorless oil. [R]D ) +77.6 (c
1
1.8, CHCl3). H NMR: δ 2.25 (d, 1H, J ) 3.7 Hz), 2.45 (t, 1H,
J ) 2.3 Hz), 2.62 (dd, 1H, J ) 14.2, 9.3 Hz), 3.04 (dd, 1H, J )
14.2, 3.2 Hz), 3.79 (s, 3H), 4.14 (m, 1H), 4.32 (t, 1H, J ) 5.7
Hz), 4.52 (dd, 2H, J ) 15.6, 2.4 Hz), 4.92 (d, 1H, J ) 5.4 Hz),
5.17 (br s, 1H), 5.45 (d, 1H, J ) 1.0 Hz), 6.85 (m, 2H), 7.37 (m,
7H). 13C NMR: δ 164.6, 156.8, 144.4, 139.8, 130.7, 128.4, 127.8,
126.3, 120.6, 115.8, 114.1, 79.8, 78.4, 76.0, 69.5, 60.9, 58.9, 55.4,
39.6. IR (CHCl3, cm-1): ν 3306, 1747. MS (CI), m/z: 378 (M+
+ 1, 100), 377 (M+, 9). Anal. Calcd for C23H23NO4: C, 73.19;
H, 6.14; N, 3.71. Found: C, 73.30; H, 6.11; N, 3.74.
Gen er a l P r oced u r e for th e P r ep a r a tion of Meth a n e-
su lfon a tes (+)-5a -d . Methanesulfonyl chloride (138 mg, 1.20
mmol) and triethylamine (243 mg, 2.40 mmol) were sequen-
tially added dropwise to a stirred solution of the corresponding
homoallylic alcohol (1.0 mmol), in dichloromethane (10 mL)
at 0 °C, and the mixture was stirred for 2 h at room
temperature. The organic phase was washed with water (2 ×
Tr icyclic â-La cta m (-)-7d . From 52 mg (0.11 mmol) of
methanesulfonate (+)-5d and after heating at 170 °C for 22 h
was obtained 22 mg (54%) of compound (-)-7d as a colorless
oil. [R]D ) -267.7 (c 0.5, CHCl3). 1H NMR: δ 3.76 (s, 3H), 4.82
and 4.95 (d, each 1H, J ) 14.2 Hz), 5.23 (d, 1H, J ) 4.9 Hz),
5.41 (d, 1H, J ) 5.1 Hz), 6.85 (m, 2H), 7.30 (d, 1H, J ) 8.1
Hz), 7.52 (m, 8H), 7.75 (d, 1H, J ) 1.9 Hz). 13C NMR: δ 164.4,
3110 J . Org. Chem., Vol. 68, No. 8, 2003

Novel Fused Polycyclic â-Lactams
157.0, 142.1, 141.6, 141.1, 135.1, 130.6, 129.8, 129.0, 127.7,
127.2, 127.0, 119.1, 114.5, 80.6, 65.7, 55.5, 54.3. IR (CHCl3,
cm-1): ν 1743. MS (CI), m/z: 358 (M+ + 1, 100), 357 (M+, 9).
Anal. Calcd for C23H19NO3: C, 77.29; H, 5.36; N, 3.92. Found:
C, 77.40; H, 5.33; N, 3.90.
P r ep a r a tion of Tr icyclic â-La cta m (+)-7c. Pd-C (cat.)
was added to a solution of the Diels-Alder cycloadduct (+)-
6c (20 mg, 0.08 mmol) in benzene (6 mL). The resulting
suspension was heated in a sealed tube at 150 °C for 24 h.
The reaction mixture was allowed to cool to room temperature,
and the solvent was removed under reduced pressure. Chro-
matography of the residue eluting with 7/0.5/7 hexane/ethyl
acetate/dichloromethane gave 8 mg (40%) of analytically pure
adduct (+)-7c.
Bicyclic â-La cta m (+)-11a . From 50 mg (0.17 mmol) of
ene adduct (+)-4c was obtained 50 mg (46%) of compound (+)-
11a as a colorless oil. [R]D ) +69.5 (c 2.0, CHCl3). 1H NMR: δ
1.84 (dd, 1H, J ) 14.4, 7.2 Hz), 2.28 (dd, 1H, J ) 14.4, 6.6
Hz), 2.65 (t, 1H, J ) 13.2 Hz), 2.85 (d, 1H, J ) 13.5 Hz), 2.91
(d, 1H, J ) 5.0 Hz), 3.17 (s, 1H), 3.25 (d, 1H, J ) 5.0 Hz), 3.37
(s, 3H), 3.51 (m, 1H), 3.91 (d, 1H, J ) 5.7 Hz), 3.97 (d, 1H, J
) 12.9 Hz), 4.03 (d, 1H, J ) 12.9 Hz), 6.50 (br s, 1H), 7.28 (m,
5H), 7.45 (m, 15H). 13C NMR: δ 166.7, 153.0, 148.5, 137.4,
136.7, 131.1, 129.1, 128.8, 128.4, 126.8, 125.7, 81.7, 66.5, 60.3,
59.2, 51.0, 47.8, 39.4, 34.5. IR (CHCl3, cm-1): ν 1749. MS (EI),
m/z: 636 (M+, 7), 560 (M+ - 76, 100). Anal. Calcd for C35H35
-
NO3Sn: C, 66.06; H, 5.54; N, 2.20. Found: C, 66.76; H, 5.58;
N, 2.18.
Tr icyclic â-La cta m (+)-7c. [R]D ) +63.0 (c 0.4, CHCl3).
1H NMR: δ 2.76 (m, 1H), 3.11 (m, 2H), 3.51 (s, 3H), 4.12 (m,
1H), 4.83 (d, 1H, J ) 4.2 Hz), 4.86 (d, 1H, J ) 4.4 Hz) 7.42 (m,
8H). 13C NMR: δ 169.1, 149.9, 140.7, 133.5, 131.1, 130.2, 128.8,
127.3, 127.0, 126.2, 126.1, 85.3, 58.9, 54.2, 37.0, 29.7. IR
(CHCl3, cm-1): ν 1745. MS (CI), m/z: 358 (M+ + 1, 100), 357
(M+, 9). Anal. Calcd for C18H17NO2: C, 77.40; H, 6.13; N, 5.01.
Found: C, 77.50; H, 6.16; N, 4.99.
P r ep a r a tion of Bicyclic â-La cta m (+)-12. To a solution
of adduct (+)-11a (37 mg, 0.06 mmol) in dichloromethane (5
mL) was added solid p-TsOH‚H2O (14 mg, 0.07 mmol) in a
single portion. The resulting clear solution was stirred at room
temperature for 3 h and then neutralized with solid NaHCO3.
The mixture was washed with water (2 × 3 mL). The organic
layer was dried (MgSO4), and the solvent was removed under
reduced pressure. Chromatography of the residue eluting with
hexane/ethyl acetate (2:1) gave 16 mg (100%) of analytically
pure bicycle (+)-12.
Gen er a l P r oced u r e for t h e Syn t h esis of Bicyclic
Am id es 8. DBU (1.50 mmol) was added dropwise to a solution
of the corresponding methanesulfonate (1.0 mmol) in benzene
(10 mL). The resulting solution was heated under reflux for
70 h. The reaction mixture was allowed to cool to room
temperature, and the solvent was removed under reduced
pressure. Chromatography of the residue eluting with hexane/
ethyl acetate mixtures gave analytically pure amides 8.
Bicyclic Am id e (()-8a . From 50 mg (0.11 mmol) of
methanesulfonate (+)-5b was obtained 24 mg (61%) of bicycle
(()-8a as a colorless solid. Mp: 180-181 °C (hexane/ethyl
acetate). 1H NMR: δ 2.08 (m, 2H), 2.89 (m, 4H), 2.98 (dd, 1H,
J ) 16.3, 11.2 Hz), 3.26 (dd, 1H, J ) 16.3, 3.9 Hz), 3.81 (s,
3H), 4.29 (dd, 1H, J ) 11.2, 3.9 Hz), 4.90 (d, 1H, J ) 15.4 Hz),
5.00 (d, 1H, J ) 14.7 Hz), 6.89 (m, 3H), 7.07 (s, 1H), 7.54 (m,
2H), 8.38 (br s, 1H). 13C NMR: δ 169.2, 156.6, 143.4, 142.8,
131.2, 130.6, 130.1, 124.9, 121.5, 120.0, 114.3, 74.8, 68.7, 55.6,
32.6, 31.4, 25.7. IR (KBr, cm-1): ν 3320, 1665. MS (CI), m/z:
324 (M+ + 1, 100), 323 (M+, 10). Anal. Calcd for C20H21NO3:
C, 74.28; H, 6.55; N, 4.33. Found: C, 74.38; H, 6.58; N, 4.31.
Gen er a l P r oced u r e for th e Syn th esis of Vin ylic Sta n -
n a n es 11. A solution of the appropriate enyne 4 (0.40 mmol),
triphenyltin hydride (0.60 mmol), and AIBN (cat.) in benzene
(35 mL) was heated at reflux temperature until complete
disappearance (typically 1 h) of starting material (TLC). The
reaction mixture was allowed to cool to room temperature; the
solvent was removed under reduced pressure, and vinylstan-
nanes 11 were obtained after purification by flash chroma-
tography on silica gel using hexane/ethyl acetate/triethylamine
mixtures.
Bicyclic â-La cta m (+)-12. [R]D ) +72.5 (c 1.0, CHCl3). 1H
NMR: δ 1.83 (dd, 1H, J ) 14.7, 7.8 Hz), 2.32 (dd, 1H, J )
14.7, 6.9 Hz), 2.50 (m, 2H), 3.26 (s, 1H), 3.49 (m, 1H), 3.65 (s,
3H), 3.77 (dd, 1H, J ) 5.1, 1.3 Hz), 3.87 (d, 1H, J ) 12.7 Hz),
4.01 (d, 1H, J ) 12.7 Hz), 4.12 (d, 1H, J ) 5.5 Hz), 4.52 (d,
1H, J ) 5.5 Hz), 5.08 (br s, 1H), 5.24 (br s, 1H), 7.27 (m, 5H).
13C NMR: δ 167.0, 148.7, 140.6, 128.5, 126.8, 125.9, 119.7,
83.1, 66.6, 59.9, 59.5, 45.8, 45.5, 40.0, 34.9. IR (CHCl3, cm-1):
ν 1748. MS (EI), m/z: 287 (M+, 1), 87 (100). Anal. Calcd for
C
17H21NO3: C, 71.06; H, 7.37; N, 4.87. Found: C, 71.16; H,
7.31; N, 4.85.
Ack n ow led gm en t. We would like to thank the DGI-
MCYT (Project BQU2000-0645) for financial support.
C.R.R. and A.R.V. thank the DGI (CEC-Comunidad de
Madrid-Spain) for a predoctoral and postdoctoral grant,
respectively.
Su p p or tin g In for m a tion Ava ila ble: Compound charac-
terization data for isomerically pure compounds (+)-2a -e, (+)-
2g, (-)-2i, (+)-3b, (+)-4a -c, (+)-4e, (-)-4g, (+)-5b, (+)-5c, (+)-
6c, (+)-7a , (()-8b, (+)-11b, and (R)- and (S)-acetylmandelates
of compound (+)-2b, as well as experimental procedures for
(R)- and (S)-acetylmandelates of compound (+)-2b . This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O0340509
J . Org. Chem, Vol. 68, No. 8, 2003 3111