Stereoselective allylation of 4-oxoazetidine-2-carbaldehydes. Application to the stereocontrolled synthesis of fused tricyclic β-lactams via intramolecular Diels-Alder reaction of 2-azetidinone-tethered trienes

Article abstract of DOI:10.1021/jo991641j

Allylation reactions of racemic and optically pure 4-oxoazetidine-2- carbaldehydes were investigated both under anhydrous conditions and in aqueous media. Different Lewis acid or metal mediators showed varied diastereoselectivities on product formation du

Full text of DOI:10.1021/jo991641j

3310
J . Org. Chem. 2000, 65, 3310-3321
Ster eoselective Allyla tion of 4-Oxoa zetid in e-2-ca r ba ld eh yd es.
Ap p lica tion to th e Ster eocon tr olled Syn th esis of F u sed Tr icyclic
â-La cta m s via In tr a m olecu la r Diels-Ald er Rea ction of
2-Azetid in on e-Teth er ed Tr ien es†
Benito Alcaide,* Pedro Almendros, and Nati R. Salgado
Departamento de Quı´mica Orga´nica I, Facultad de Quı´mica, Universidad Complutense,
28040-Madrid, Spain
Received October 20, 1999
Allylation reactions of racemic and optically pure 4-oxoazetidine-2-carbaldehydes were investigated
both under anhydrous conditions and in aqueous media. Different Lewis acid or metal mediators
showed varied diastereoselectivities on product formation during allylation reactions of the above
aldehydes with allyltrimethylsilane, allyltributylstannane, or allyl bromide. Under standard reaction
conditions, tin(IV) chloride-promoted addition of allyltrimethylsilane to 4-oxoazetidine-2-carbal-
dehydes provided the highest diastereoselectivity and the best yield. Boron trifluoride-diethyl ether-
promoted reaction of allyltributylstannane provided slightly lower diastereoselectivity with the
same facial preference. Indium-promoted allylation showed a reverse diastereofacial preference,
although the observed selectivity is not synthetically useful. The mesylates of these homoallylic
alcohols were used for the stereoselective preparation of cis-4-butadienyl-2-azetidinones. Interest-
ingly, mesylates having an extra alkene or alkyne tether at position 1 or 3 of the â-lactam ring, on
heating in a sealed tube with equimolecular amounts of DBU in toluene, yielded fused tricyclic
2-azetidinones through a tandem one-pot elimination-intramolecular Diels-Alder reaction.
In tr od u ction
for asymmetric synthesis. An attractive feature of this
reaction resides in the possibility, in principle, of gener-
ating up to four contiguous stereocenters in one step. The
intramolecular version (IMDA) is a powerful method for
the construction of bicyclic and polycyclic systems.4 At
the outset of the present study,5 it was known that
racemic trans-3-butadienyl-2-azetidinones react with
some dienophiles on heating,6 but there is no report
involving IMDA reaction of 2-azetidinone-tethered trienes.
The importance and structural diversity of biologically
active â-lactam antibiotics led to the development of
many novel methods for the construction of appropriately
substituted 2-azetidinones with attendant control of
functional groups and stereochemistry. In addition, the
increased resistance of bacteria to classical antibiotics has
The reactions of propenylmetal reagents with chiral
carbonyl compounds are of great interest in the context
of acyclic diastereoselective synthesis.1 Lewis acid-
promoted addition of allylsilanes and allylstannanes to
carbonyl compounds is now a well-established methodol-
ogy and an important synthetic tool.2 Although many
investigations have been made in this field into various
types of chiral R-substituted aldehydes, no information
is available regarding the stereochemistry of reactions
involving 4-oxoazetidine-2-carbaldehydes with allylmet-
als. There are a limited number of reports on the use of
â-lactams as chiral building blocks for the allylation
reaction, just Bose and Paquette having recently reported
the allylindation of 2,3-azetidinediones in aqueous tet-
rahydrofuran.3 On the other hand, the Diels-Alder
reaction has been developed to provide a valuable vehicle
(4) For reviews of the IMDA reaction, see for example: (a) Craig,
D. In Stereoselective Synthesis, Methods of Organic Chemistry; Helm-
chen, G., Hoffmann, R. W., Mulzer, J ., Schaumann, E., Eds.; Georg
Thieme Verlag: 1995; Vol. E 21c, p 2872. (b) Roush, W. R. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Paquette,
L. A., Eds.; Pergamon: Oxford, 1991; Vol. 5, Chapter 4.4, p 513. (c)
Carruthers, W. Cycloaddition Reactions in Organic Synthesis; Perga-
mon: Oxford, 1990. (d) Craig, D. Chem. Soc. Rev. 1987, 16, 187. (e)
Ciganek, E. Org. React. 1984, 32, 1. (f) Fallis, A. G. Can. J . Chem.
1984, 62, 183. For very recent, selected examples, see: (g) Batey, R.
A.; Thadani, A. N.; Lough, A. J . J . Am. Chem. Soc. 1999, 121, 450. (h)
Paulvannan, K. Tetrahedron Lett. 1999, 40, 1851. (i) Brosius, A. D.;
Overman, L. E.; Schwink, L. J . Am. Chem. Soc. 1999, 121, 700. (j)
Bull, J . R.; Gordon, R. S.; Hunter, R. J . Synlett. 1999, 599. (k) Frey,
B.; Schnaubelt, J .; Reissig, H. U. J . Eur. J . Org. Chem. 1999, 1377, 7.
(l) Chu, C. S.; Lee, T. H.; Rao, P. D.; Song, L. D.; Liao, C. C. J . Org.
Chem. 1999, 64, 4111. (m) Padwa, A.; Brodney, M. A.; Liu, B.; Satake,
K.; Wu, T. J . Org. Chem. 1999, 64, 3595. (n) Bushby, N.; Moody, C. J .;
Riddick, D. A.; Waldron, I. R. Chem. Commun. 1999, 793. (o) Grieco,
P. A.; Kaufman, M. D. J . Org. Chem. 1999, 64, 6041. (p) Andre´s, C.;
Garc´ıa-Valverde, M.; Nieto, J .; Pedrosa, R. J . Org. Chem. 1999, 64,
5230.
† Dedicated to Prof. J ose L. Soto on the occasion of his 70th birthday.
(1) (a) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207. (b) Roush,
W. R. In Comprehensive Organic Synthesis; Heathcock, C. H., Ed.;
Pergamon: Oxford, 1991; Vol. 2, p 1. (c) Fleming, I. In Comprehensive
Organic Synthesis; Heathcock, C. H., Ed.; Pergamon: Oxford, 1991;
Vol. 2, p 595.
(2) For reviews, see: (a) Thomas, E. J . Chem. Commun. 1997, 411.
(b) Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063. (c)
Marshall, J . A. Chem. Rev. 1996, 96 (6), 31. (d) Nishigaichi, Y.; Takuwa,
A.; Naruta, Y.; Maruyama, K. Tetrahedron 1993, 49, 7395. For very
recent examples, see: (e) Wang, Z.; Kisanga, P.; Verkade, J . G. J . Org.
Chem. 1999, 64, 5506. (f) Chan, T. H.; Yang, Y.; Li, C. J . J . Org. Chem.
1999, 64, 4452. (g) Wang, D. K.; Zhou, Y. G.; Tang, Y.; Hou, X. L.; Dai,
L. X. J . Org. Chem. 1999, 64, 4233. (h) Keck, G. E.; Yu, T. Org. Lett.
1999, 1, 289. (i) Masuyama, Y.; Ito, T.; Tachi, K.; Ito, A.; Kurusu, Y.
Chem. Commun. 1999, 1261. (j) Motoyama, Y.; Narusawa, H.; Nish-
iyama, Y. Chem. Commun. 1999, 131. (k) Chataigner, I.; Piarulli, U.;
Gennari, C. Tetrahedron Lett. 1999, 40, 3633. (l) Chataigner, I.; Loh,
T. P.; Xu, J . Tetrahedron Lett. 1999, 40, 2431.
(5) For a preliminary communication of a part of this work, see:
Alcaide, B.; Almendros, P. Tetrahedron Lett. 1999, 40, 1015.
(6) Sharma, A. K.; Mazumdar, S. N.; Mahajan, M. P. J . Org. Chem.
1996, 61, 5506.
(3) (a) J ayaraman, M.; Manhas, M. S.; Bose, A. K. Tetrahedron Lett.
1997, 38, 709. (b) Paquette, L. A.; Rothhaar, R. R.; Isaac, M.; Rogers,
L. M.; Rogers R. D. J . Org. Chem. 1998, 63, 5463.
10.1021/jo991641j CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/06/2000

Allylation of 4-Oxoazetidine-2-carbaldehydes
J . Org. Chem., Vol. 65, No. 11, 2000 3311
Ch a r t 1
triggered a renewed interest in the building of new
polycyclic systems having the 2-azetidinone ring as a
common feature.7 Recently, trinem antibiotics have been
the subject of considerable study owing to their broad
spectrum of antibacterial activity, resistance to â-lacta-
mases, and stability to renal dehydropeptidases.8 As a
result of their impressive biological activity, polycyclic
â-lactams have become interesting targets for synthesis.9
Continuing with our work on the synthesis and synthetic
applications of chiral, functionalized 2-azetidinones,10 we
now report full details of a straightforward synthesis of
different types of fused tricyclic â-lactams which involves
the use of both stereoselective allylation of â-lactam
aldehydes and IMDA reaction. In addition, a study on
the stereoselectivity of reactions between 4-oxoazetidine-
2-carbaldehydes and allylic organometallics is also de-
scribed.
Resu lts a n d Discu ssion
The starting substrates, 4-oxoazetidine-2-carbalde-
hydes 1, were prepared both in racemic and in optically
pure forms using standard methodology. Racemic com-
pounds 1a -c were obtained as single cis-diastereoiso-
mers, following our one-pot method from N,N-di(p-
methoxyphenyl)glyoxal diimine.10d,11 Enantiomerically
pure 2-azetidinones (+)-2a -h were obtained from imines
of (R)-2,3-O-isopropylidenepropanal, through Staudinger
reaction with the corresponding acid chlorides in the
presence of Et3N as single cis-enantiomers (Chart 1).12
Transesterification of 3-acetoxy-2-azetidinone (+)-2a with
sodium methoxide in methanol gave alcohol (+)-3, which
by treatment either with allyl bromide or methyl propi-
olate, under different basic conditions, gave the 2-azeti-
dinones (+)-4 and (+)-5, respectively (Scheme 1). Stan-
dard acetonide hydrolysis to provide diols 6, followed by
oxidative cleavage (NaIO4/CH2Cl2/NaHCO3),13 smoothly
formed 4-oxoazetidine-2-carbaldehydes (+)-1d -j in excel-
lent yields (Scheme 2). Compound (+)-2d required further
manipulation to obtain the desired 4-oxoazetidine-2-
carbaldehydes (+)-1k and (+)-1l (see later; Schemes 4,
6).
(7) For excellent articles on the bacterial resistance to the commonly
used antibiotics, see: (a) Hook, V. Chem. Br. 1997, 33, 34. (b) Niccolai,
D.; Tarsi, L.; Thomas, R. J . Chem. Commun. 1997, 2333. (c) Spratt, B.
G. Science 1994, 264, 388.
(8) For recent examples on the application of cyclization reactions
to trinem and trinem derivatives synthesis, see: (a) Camerini, R.;
Donati, D.; Marchioro, C.; Mazzoni, A.; Pachera, R.; Panunzio, M.
Tetrahedron: Asymmetry 1997, 8, 15. (b) Di Fabio, R.; Rossi, T.;
Thomas, R. J . Tetrahedron Lett. 1997, 38, 3587. (c) Marchioro, C.;
Pentassuglia, G.; Perboni, A.; Donati, D. J . Chem. Soc., Perkin Trans.
1 1997, 463. (d) Rossi, T.; Marchioro, C.; Paio, A.; Thomas, R. J .;
Zarantonello, P. J . Org. Chem. 1997, 62, 1653. (e) Hanessian, S.;
Griffin, A. M.; Rozema, M. J . BioMed. Chem. Lett. 1997, 7, 1857. (f)
Guiron, C.; Rossi, T.; Thomas, R. J . Tetrahedron Lett. 1997, 20, 3569.
(g) Hanessian, S.; Rozema, M. J . J . Am. Chem. Soc. 1996, 118, 9884.
(h) Schmidt, G.; Schro¨ck, W.; Endermann, R.; BioMed. Chem. Lett.
1993, 3, 2193.
(9) See, for example: (a) Hanessian, S.; Reddy, B. G. Tetrahedron
1999, 55, 3427. (b) Alcaide, B.; Rodr´ıguez-Vicente, A. Tetrahedron Lett.
1998, 39, 6589. (c) Sakya, S. M.; Strohmeyer, T. W.; Lang, S. A.; Lin,
Y.-I. Tetrahedron Lett. 1997, 38, 5913. (d) Annibalc, A. D.; Pesce, A.;
Resta, S.; Irogolo, C. T.; Tetrahedron 1997, 53, 13129. (e) Banik, B.
K.; Gottumukkala, V.; Manhas, M. S.; Bose, A. K. Tetrahedron Lett.
1996, 37, 1363. (f) Chuansheng, N.; Pettersson, T.; Miller, M. J . J . Org.
Chem. 1996, 61, 1014. (g) Crocker, P. J .; Miller, M. J . J . Org. Chem.
1995, 60, 6176. (h) Alcaide, B.; Polanco, C.; Sa´ez, E.; Sierra, M. A. J .
Org. Chem. 1996, 61, 7125. (i) Alpegiani, M.; Bissolino, P.; Corigli, R.;
Rizzo, V.; Perrone, E. BioMed. Chem. Lett. 1995, 5, 687. (j) Gilchrist,
T. L.; Graham, K. Tetrahedron Lett. 1995, 47, 8693. (k) Hanessian, S.;
Reddy, B. G. BioMed. Chem. Lett. 1994, 4, 2285.
First, we studied the allylation reactions of 4-oxoaze-
tidine-2-carbaldehyde 1a with some propenylmetal re-
agents derived from a number of metallic elements (e.g.,
Bi, In, Mg, Si, Sn, and Zn). Chemical yields were
generally good in all cases, but the diastereoselectivity
of the process was a function of the nature of both the
allylmetal reagent and the Lewis acid (Table 1).
The results in Table 1 crearly show that tin(IV)
chloride-promoted reaction of allyltrimethylsilane (Table
1, entry 1) and boron trifluoride-diethyl ether-promoted
reaction of allyltributylstannane (Table 1, entry 3) are
the best methods for the stereoselective addition to
(12) The cis-selectivity observed for compounds 1a -c, and (+)-2a -h
was expected according to the current model for the Staudinger
reaction. (a) Arrieta, A.; Lecea, B.; Cossio, F. P. J . Org. Chem. 1998,
63, 5869. (b) Cossio, F. P.; Arrieta, A.; Lecea, B.; Ugalde, J . M. J . Am.
Chem. Soc. 1994, 116, 2085. (c) Hegedus, L. S.; Montgomery, J .;
Narukawa, Y.; Snustad, D. C. J . Am. Chem. Soc. 1991, 113, 5784. (d)
Palomo, C.; Aizpurua, J . M.; Mielgo, A.; Linden, A. J . Org. Chem. 1996,
61, 9186. This model accounts for
a 3R,4S stereochemistry for
(10) See, for instance: (a) Alcaide, B.; Almendros, P.; Aragoncillo,
C. Chem. Commun. 1999, 1913. (b) Alcaide, B.; Rodr´ıguez-Campos, I.
M.; Rodr´ıguez-Lo´pez, J .; Rodr´ıguez-Vicente, A. J . Org. Chem. 1999,
64, 5377. (c) Alcaide, B.; Alonso, J . M.; Aly, M. F.; Sa´ez, E.; Mart´ınez-
Alca´zar, M. P.; Herna´ndez-Cano, F. Tetrahedron Lett. 1999, 40, 5391.
(d) Alcaide, B.; Polanco, C.; Sierra, M. A. J . Org. Chem. 1998, 63, 6786.
(e) Alcaide, B.; Rodr´ıguez-Vicente, A.; Sierra, M. A. Tetrahedron Lett.
1998, 39, 163. (f) Alcaide, B.; Aly, M. F.; Sierra, M. A. J . Org. Chem.
1996, 61, 8819. (g) Alcaide, B.; Mart´ın-Cantalejo, Y.; Sierra, M. A. J .
Org. Chem. 1996, 61, 9156.
(11) (a) Alcaide, B.; Mart´ın-Cantalejo, Y.; Plumet, J .; Rodr´ıguez-
Lo´pez, J .; Sierra, M. A. Tetrahedron Lett. 1991, 32, 803. (b) Alcaide,
B.; Mart´ın-Cantalejo, Y.; Pe´rez-Castells, J .; Rodr´ıguez-Lo´pez, J .; Sierra,
M. A.; Monge, A.; Pe´rez-Garc´ıa, V. J . Org. Chem. 1992, 57, 5921.
D-glyceraldehyde-derived 2-azetidinones. For an experimental study
on the synthesis of 2-azetidinones derived from D- and L-glyceraldehyde
acetonide imines, see: (e) Niu, Ch.; Miller, M. J . Tetrahedron Lett.
1995, 36, 497. (f) Hubschwerelen, C.; Schmid, G. Helv. Chim. Acta
1983, 66, 2206. (g) Welch, J . T.; Araki, K.; Kawecki, R.; Wichtowski,
J . A. J . Org. Chem. 1993, 58, 2454. (h) Wagle, D. R.; Garai, C.; Chiang,
J .; Monteleone, M. G.; Kurys, B. E.; Strohmeyer, T. W.; Hedge, V. R.;
Manhas, M. S.; Bose, A. K. J . Org. Chem. 1988, 53, 4227, and
references therein.
(13) The system (NaIO4/CH2Cl2/NaHCO3) is more convenient that
our previously reported method involving the reagent (NaIO4/MeOH/
H2O), avoiding the formation of a diastereomeric mixture of methoxy
hemiacetals, which requires an azeotropic distillation using a Dean-
Stark apparatus to give the free aldehyde.

3312 J . Org. Chem., Vol. 65, No. 11, 2000
Alcaide et al.
Ta ble 1. Effect of Or ga n om eta llic Rea gen ts on th e
Sch em e 1
Ster eoselective Allyla tion of 4-Oxa zetid in e-2-
ca r ba ld eh yd e 1a a
Lewis acid
or metal T (°C)/t (h) solvent
syn:anti yield
ratiob (%)c
entry
M
1
2
3
4
5
6
7
SiMe3 SnCl4
SnCl3
-78/0.75
-78/1
CH2Cl2
CH2Cl2
CH2Cl2
THF/H2O 72:28
THF/H2O 46:54
92:8
75:25
91:9
79
80
75
50
75
73
51
SnBu3 BF3.Et2O -78/1
Br
Mg/BiCl3 20/18
Br
In
20/5
-78/3
ZnBr
Br
THF
DMF
62:38
61:39
NaI/SnCl2 20/20
a
All reactions were carried out on a 1 mmol scale. PMP )
4-MeOC6H4. The ratio based on 1H NMR. Yield of pure, isolated
b
c
product with correct analytical and spectral data.
than its counterpart, allyltributylstannane, for allylation
in our study with different substituted 4-oxoazetidine-
2-carbaldehydes 1. Reaction of 4-oxoazetidine-2-carbal-
dehydes 1 with allyltrimethylsilane in the presence of
tin(IV) chloride, at -78 °C for 45 min, gave homoallylic
alcohols 7 with good to excellent syn-stereoselectivities
(de 80-100%, by integration of well-resolved signals in
the 1H NMR spectra of the crude reaction mixtures before
purification) (Table 2). Additionally, ketones were found
to be completely unreactive under these conditions, and
it was possible to chemoselectively add allyltrimethylsi-
lane to 4-oxoazetidine-2-carbaldehyde (+)-1k bearing an
R,â-unsaturated ketone. None of the allylated ketone was
obtained, giving exclusively the product (+)-7k by ste-
reoselective addition to the aldehyde moiety (see Scheme
4). Configuration at the carbinolic chiral center of the
major isomers for products (+)-7d and (+)-7i was estab-
Sch em e 2
1
lished by comparison of the H NMR chemical shifts of
their acetylmandelates (+)-8d , (+)-9d and (+)-8i, (+)-
9i20 and was assumed to be the same for the rest of the
1
â-lactams 7. It should be noted that the relative H NMR
chemical shifts of the â-lactamic and alcoholic protons
were diagnostic for the 7-syn- and 7-anti-homoallylic
alcohols for the relative stereochemistry. For any pair of
syn- and anti-diastereomers, the â-lactamic (3-H) and
alcoholic hydrogens of the 7-syn-isomers were ca. 0.1 ppm
4-oxoazetidine-2-carbaldehyde 1a . Boron trifluoride-
diethyl ether-promoted reaction of allyltributylstannane
provided slightly lower diastereoselectivity with the same
facial preference. Reaction with allyltin trichloride14
(Table 1, entry 2) or allylzinc bromide15 (Table 1, entry
6) further lowered the diastereoselectivity. Allylation
with allyl bromide using the bimetal system magnesium/
bismuth trichloride16 (Table 1, entry 4) or tin(II) chloride17
(Table 1, entry 7) as the mediators provided a low
diastereoselectivity. With allylindium reagent in aqueous
medium,18 the diastereofacial preference is reversed,19
although the observed selectivity is not synthetically
useful (Table 1, entry 5). From these results, we chose
the inexpensive, nontoxic allyltrimethylsilane rather
(18) Reviews on organic reactions in aqueous media: (a) Pardo, R.;
Santelli, M. Bull. Chem. Soc. Fr. 1985, 99. (b) Einhorn, C.; Einhorn,
J .; Luche, J .-L. Synthesis 1989, 787. (c) Ressig, H.-U. In Organic
Synthesis Highlights; VCH: Weinheim, 1991; p 71. (d) Li, C. J . Chem.
Rev. 1993, 93, 2303. (e) Lubineau, A.; Auge´, J .; Queneau, Y. Synthesis
1994, 741. (f) Li, C. J . Tetrahedron 1996, 52, 5643. (g) Li, C. J .; Chan,
T. H. Organic Reactions in Aqueous Media; J ohn Wiley & Sons: New
York, 1997. (h) Lubineau, A.; Auge´, J .; Queneau, Y. In Organic
Synthesis in Water; Grieco, P. A., Ed.; Blackie Academic & Profes-
sional: London, 1998. (i) Paquette, L. A. In Green Chemistry: Frontiers
in Benign Chemical Synthesis and Processing; Anastas, P., Williamson,
T., Eds.; Oxford University Press: New York, 1998. (j) Li, C. J .; Chan,
T. H. Tetrahedron 1999, 55, 11149.
(19) For
a different facial preference, leading to syn-configured
(14) (a) McNeill, A. H.; Thomas, E. J . Synthesis 1994, 322. (b)
Almendros, P.; Thomas, E. J . J . Chem. Soc., Perkin Trans. 1 1997,
2561.
products, on the indium-mediated allyl adition of 2-(bromomethyl)-
acrylate to R-amino aldehydes, see: Steurer, S.; Podlech, J . Eur. J .
Org. Chem. 1999, 1551, 1.
(15) Gaudemar, M. Bull. Chem. Soc. Fr. 1962, 974.
(16) Wada, M.; Fukuma, T.; Morioka, M.; Takahashi, T.; Miyoshi,
N. Tetrahedron Lett. 1997, 38, 8045.
(17) Pereyre, M.; Quintard, J .-P.; Rahm, A. Tin in Organic Synthesis;
Butterworth: London, 1987.
(20) See, for example: (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.

Allylation of 4-Oxoazetidine-2-carbaldehydes
J . Org. Chem., Vol. 65, No. 11, 2000 3313
Ta ble 2. Tin (IV) Ch lor id e-Med ia ted Allyla tion of 4-Oxoa zetid in e-2-ca r ba ld eh yd es 1 w ith Allyltr im eth ylsila n e
entry
product
R1
R2
R3
syn:anti ratio
yield (%)a
1
2
3
4
5
6
7
8
(()-7a
(()-7b
(()-7c
(+)-7d
(+)-8d
(+)-9d
(+)-7e
(+)-7f
(+)-7g
(+)-7h
(+)-7i
(+)-8i
(+)-9i
(+)-7j
(+)-7k
(+)-7l
CH3
allyl
propargyl
OCH3
OCH3
OCH3
OPh
OBn
OCH3
OCH3
O-allyl
O-allyl
O-allyl
O-(â-acryloxymethyl)
OCH3
PMPb
PMP
PMP
PMP
PMP
PMP
allyl
homoallyl
homopropargyl
4-pentynyl
PMP
PMP
PMP
PMP
2-oxo-3-pentenyl
2,4-pentadienyl
H
H
H
H
92:8
100:0
95:5
79
60
66
85
88c
79c
57
54
83
71
71
77c
68c
55
50
74
90:10
(R)-PhCH(OAc)CO
(S)-PhCH(OAc)CO
H
H
H
H
H
(R)-PhCH(OAc)CO
(S)-PhCH(OAc)CO
H
H
H
90:10
100:0
95:5
95:5
95:5
9
10
11
12
13
14
15
16
93:7
100:0
100:0
OCH3
a
b
Yield of pure, isolated product with correct analytical and spectral data. PMP ) 4-MeOC6H4. c Yield refers to the O-acetylmandelate
(8 or 9) starting from the corresponding alcohol 7.
Sch em e 3
Sch em e 4
upfield of the analogous hydrogens of the 7-anti-isomers.
The stereochemical result can be tentatively interpreted
by the transition state model as proposed by Felkin et
al.21 and modified by Anh (see Figure 1).22 This model
neglects the coordinating action of M+ and stresses
nonbonding interactions of approaching atoms. In our
case it could explain that the stereochemical sense of the
process is not affected by the Lewis acid or by the
different coordinative abilities of the substituents at C3
in the â-lactam ring.
In contrast to the stereoselectivity observed in allyla-
tion with 4-oxoazetidine-2-carbaldehydes 1, aldehydes
(+)-10a and (+)-10b were found to react with propenyl-
metal reagents with useless stereoselectivity (Scheme 3).
(21) Cherest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968,
18, 2199.
(22) Anh, N. Top. Curr. Chem. 1980, 88, 114.

3314 J . Org. Chem., Vol. 65, No. 11, 2000
Alcaide et al.
Ta ble 3. Ster eoselective P r ep a r a tion of Mesyla tes 17
a n d Con ju ga ted Dien es 20
entry product
R1
(()-17a CH3
(()-17b allyl
R2
ratio E:Z yield (%)a
F igu r e 1.
1
2
PMPb
PMP
97
82
83
92
79
89
88
83
The diastereomeric alcohols (+)-11a and (+)-11b could
be separated by bench chromatography. The absolute
configuration of the minor alkenol (+)-11b was assigned
3
4
5
6
7
8
9
10
11
12
13
14
15
16
(()-17c propargyl PMP
(+)-17d O-allyl
(+)-17e OPh
(+)-17f OBn
(+)-17g OCH3
(+)-17h OCH3
(()-20a CH3
(()-20b allyl
PMP
allyl
1
homoallyl
homopropargyl
4-pentynyl
PMP
by comparison of the H NMR chemical shifts of its (R)-
and (S)-acetylmandelates (-)-12a and (+)-12b. Products
(+)-13a and (+)-13b could not be separated and were
characterized as mixture (Scheme 3). Swern oxidation of
homoallylic alcohol (+)-11a or (+)-11b, generated from
aldehyde (+)-10a and allyltrimethylsilane, gave an
equimolecular mixture of R,â- and â,γ-unsaturated ke-
tones (+)-E-14 and (+)-15. Exposure of â,γ-unsaturated
ketone (+)-15 to an excess of triethylamine was not
efficient to promote isomerization to (+)-E-14.23 However,
treatment of ketone (+)-15 with a catalytic DBU in
toluene at reflux temperature resulted in complete
conversion to the R,â-unsaturated ketone 14, but as a
mixture of E/ Z isomers (60:40). To our delight, Swern
oxidation of homoallylic alcohols (+)-11a and (+)-11b,
generated from the aldehyde (+)-10a and allyltin trichlo-
ride, provided the R,â-unsaturated ketone (+)-E-14 as the
only product. This difference in behavior to Swern
conditions of alcohols (+)-11, generated from either
allyltrimethylsilane or allyltributylstannane, may be due
to the very small amount of tin compounds that may still
remain after chromatographic purification on homoallylic
alcohols (+)-11, working as a catalyst for the isomeriza-
tion.24 Product (+)-E-14 after acidic treatment gave
dihydroxyketone (+)-16, which was cleaved using sodium
periodate to give keto aldehyde (+)-1k . This aldehyde was
chemo- and stereoselectively allylated, yielding the ho-
moallylic alcohol (+)-7k (Scheme 4).
100:0
75:25
100:0
100:0
90:10
95:5
75
74
58
89
66
66
71
92
PMP
(()-20c propargyl PMP
(+)-20d O-allyl
(+)-20e OPh
(+)-20f OBn
(+)-20g OCH3
(+)-20h OCH3
PMP
allyl
homoallyl
homopropargyl
4-pentynyl
95:5
95:5
a
Yield of pure, isolated product with correct analytical and
b
spectral data. PMP ) 4-MeOC6H4.
Sch em e 5
Next, we investigated the dehydration of hydroxy-â-
lactams 7, 11, and 13 to give 4-butadienyl, 1-pentadienyl,
and 1-hexadienyl derivatives 20, 21, and 22, respectively
(Table 3 and Scheme 5). Compounds 7, 11, and 13 were
transformed, in very good yields, into mesylates 17, 18,
and 19 by treatment with mesyl chloride and Et3N.
Finally, mesylates 17, 18, and 19 stereoselectively gave
the novel conjugated dienes 20, 21, and 22 by gentle
heating in benzene or toluene in the presence of DBU.
The trans-geometry of the internal double bond in these
compounds was consistent with vinylic coupling con-
This methodology for the preparation of chiral dienes
is superior in yield and stereoselectivity to Wittig reaction
between the semistabilized allylidenetriphenylphospho-
rane and chiral aldehydes.25 In fact, when allylidene-
triphenylphosphorane, generated from allyltriphenylphos-
phonium bromide and BuLi in THF, was allowed to react
with 4-oxoazetidine-2-carbaldehyde 1a , the diene 20a
was obtained in a 10% overall yield and low E/ Z
selectivity (isomeric ratio 60:40). Reaction between sta-
bilized carboxymethylentriphenylphosphorane and 4-oxo-
azetidine-2-carbaldehyde (+)-1l gave two major products,
which were separated and identified as the isomeric
products (+)-25 and (+)-26. A similar result was obtained
when the aldehyde (+)-24 was used instead of (+)-1l,
giving olefins (+)-27 and (+)-28. Trienes (+)-25 and (+)-
27 showed a trans-geometry on the new double bonds
1
stants of ca. 16.5 Hz in their H NMR spectra.
Elimination of mesylate (+)-18 gave the 1,3-diene (-)-
21 as a major product, which was easily separated by
flash chromatography from a minor 1,4-diene (+)-23.
Conjugation of the new double bond with the lone pair
of the nitrogen atom is believed to promote the formation
of (+)-23. However, in the case of (+)-19, 1,3-diene (+)-
22 was the only product from the elimination (Scheme
5).
(23) For a similar transformation, see: Folmer, J . J .; Acero, C.; Thai,
D. L.; Rapoport, H. J . Org. Chem. 1998, 63, 8170.
(24) This experiment was carried out several times on a 1 mmol
scale, reproducing the same result every single attempt.
(25) (a) Lubineau, A.; Auge´, J .; Lubin, N. J . Chem. Soc., Perkin
Trans. 1 1990, 3011. (b) Maryanoff, B. E.; Reitz B. A. Chem. Rev. 1989,
89, 863.

Allylation of 4-Oxoazetidine-2-carbaldehydes
J . Org. Chem., Vol. 65, No. 11, 2000 3315
Sch em e 6
Sch em e 8
Sch em e 9
Sch em e 7
failed to give the corresponding IMDA compounds, un-
reacted starting material being recovered in all cases.
Triene (+)-27 was heated in a sealed tube in toluene
at 190 °C to give a mixture of cycloadducts (+)-31a and
(+)-31b in good yield (73%) with modest stereoselectivity
(65:35) in favor of the epimer (+)-31a . Both isomers (+)-
31a and (+)-31b could be separated by flash chromatog-
raphy (Scheme 9). Exposure of trienes (+)-20e and (+)-
25 to standard Diels-Alder conditions afforded none of
the desired adducts. The results above show that the
IMDA reaction is a simple and, most of the time, an
efficient entry to different tricyclic 2-azetidinones with
a five- or six-membered ring fused to the â-lactam
nucleus. Exceptions are those monocyclic 2-azetidinone-
tethered trienes having an N-allyl moiety. The sharp
contrast in reactivity between (+)-20e and (+)-20f or (+)-
25 and (+)-27 may have its origin in the instability of
the 2-azetidinone ring with a pyramidalized lactam
nitrogen.26 Transition states leading to fused tricyclic
â-lactams from 2-azetidinone-tethered trienes are ex-
pected to have highly pyramidalized â-lactam nitrogens.
To confirm that this effect was responsible for the failure
of compounds (+)-20e and (+)-25 to form cyclized deriva-
tives, azetidine (+)-32 was prepared. The planarity of the
1
(vinylic coupling constants of ca. 16.0 Hz in their H NMR
spectra) (Scheme 6).
Interestingly, mesylates 17 having an extra alkene or
alkyne tether at position 1 or 3 of the â-lactam ring, on
heating in a sealed tube with 1 equiv of DBU in toluene,
yielded the corresponding Diels-Alder cycloadducts 29.
These adducts were obtained in good yields (50-88%)
with reasonable levels of stereoselectivity (Schemes 7 and
8; only major isomers for adducts 29 are represented).
Thus, for example, adduct 29e was obtained as a single
diastereomer, and the tricycle 29a accounted for an
excellent (95%) yield of the products formed. This ste-
reoselectivity is not affected significantly by the nature
of the substituents on the â-lactam ring. When mesylate
17c was heated in the presence of DBU, product 30 was
obtained as a major component, along with a minor
Diels-Alder cycloadduct 29d (dr ) 85:15) (Scheme 8).
Tricycle 30 presumably arises from the aromatization of
the initially formed adduct 29d . Cycloadducts were
characterized as mixtures of diastereomers, except for
29e (obtained as a single diastereomer) and 29a , which
could be separated by flash chromatography. By contrast,
treatment of some dienes 20 with Lewis acids (Et2AlCl,
SnCl4, and ZnI2) under different experimental conditions
(26) For some selected examples reporting the bizarre effects caused
by the inhibition of the NCdO resonance in amides, especially in the
so-called anti-Bredt amides, see: (a) Alcaide, B.; Casarrubios, L.;
Dom´ınguez, G.; Sierra, M. A.; Monge, A. J . Am. Chem. Soc. 1995, 117,
5604. (b) Brouillette, W. J .; Einspahr, H. M. J . Org. Chem. 1984, 49,
5113. (c) Collins, T. J .; Coots, R. J .; Furutani, T. T.; Keech; J . T.; Peake,
G. T.; Santarsiero, B. D. J . Am. Chem. Soc. 1986, 108, 5333. (d)
Somayaji, V.; Brown, R. S. J . Am. Chem. Soc. 1987, 109, 4738. (e)
Somayaji, V.; Skorey, K. I.; Brown, R. S. J . Org. Chem. 1986, 51, 4866.
Slebocka-Tilk, H.; Brown, R. S. J . Org. Chem. 1987, 52, 805. (f)
Williams, R. M.; Lee, B. H.; Miller, M. M.; Anderson, O. P. J . Am.
Chem. Soc. 1989, 111, 1073.

3316 J . Org. Chem., Vol. 65, No. 11, 2000
Alcaide et al.
Sch em e 10
Sch em e 11
amide nitrogen, imposed by the amide resonance, is
excluded in azetidines.27 Azetidine (+)-32 was smoothly
obtained by reduction of â-lactam (+)-20e with monochlo-
roalane (AlH2Cl), generated in situ from LiAlH4/AlCl3,
following the procedure reported by Ojima.28 The reaction
was instantaneous at room temperature, and the stere-
ochemistry of the starting monolactam remained unal-
tered during the process. Azetidine (+)-32 was further
heated in a sealed tube in toluene at 190 °C for 21 h to
give a mixture of tricyclic azetidines 33, analyzed by the
1H NMR spectrum of the crude reaction mixture. Unfor-
tunately these cycloadducts could not be fully character-
ized because of their instability to chromatographic
conditions applied (Scheme 10).
The stereochemical outcome of the IMDA reactions in
2-azetidinone-tethered trienes producing compounds 29-
31 may be explained through the transition states
depicted in Scheme 11. In all cases the sense of diaste-
reoselectivity seems to be controlled by the C4 stereogenic
center in the â-lactam ring.
Con figu r a tion a l Assign m en t for Tr icyclic Sys-
tem s. The structure and stereochemistry of compounds
29 and 31 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,
and it was transferred unaltered during the further
synthetic steps. Compounds 29a and 29d showed values
of coupling constant J 2,3 in good agreement with those
reported for analogous systems.29,30 Thus, an anti-relative
disposition between H2 and H3 was assigned for com-
pounds 29a and 29d with a J 2,3 ) 0 Hz. Furthermore,
NOE irradiation of H2 on compound 29a resulted in 2%
enhancement of the signal corresponding to H3, which
is in agreement with the proposed anti-stereochemistry
(27) Reviews on the synthesis and chemistry of azetidines: (a) De
Kimpe, N. In Comprehensive Heterocyclic Chemistry II, Padwa, A.,
Eds.; Elsevier: Oxford, U.K., 1996; Vol 1B, Chapter 1.18, p 507. (b)
Moore, J . A.; Ayers, R. S. In Chemistry of Heterocyclic Compounds-
Small Ring Heterocycles; Hassner, A., Ed.; Wiley: New York, 1983;
Part 3, p 1. (c) Cromwell, N. H.; Phillips, B. Chem. Rev. 1979, 79, 331.
(28) Ojima, I.; Zhao, M.; Yamato, T.; Nakahashi, K.; Yamashita, M.;
Abe, R. J . Org. Chem. 1991, 56, 5263.
(29) For clarity through this work, tricyclic systems have been
numbered according to the numeration used for trinems. Thus, the
four-membered ring nitrogen has been assigned the locator 1, and the
remaining positions have been numbered to place the higher number
on the carbonyl group (for 2-azetidinones).
F igu r e 2. Selected NOE effects and stereochemistry of fused
tricyclic â-lactams 29a , (+)-29b, 29d , (+)-31a , and (+)-31b.
(Figure 2), while irradiation of H3 resulted in an 8%
enhancement of the signal corresponding to H8. Thus, a
syn-stereochemistry was established for this moiety.
Irradiation of H2 on compound 29d gave an NOE
(30) (a) Galluci, J . C.; Ha, D.-C. Hart; D. J . Tetrahedron 1989 45,
1283. (b) Alcaide, B.; Esteban, G.; Mart´ın-Cantalejo, Y.; Plumet, J .;
Rodr´ıguez-Lo´pez, J . J . Org. Chem. 1994, 59, 7994.

Allylation of 4-Oxoazetidine-2-carbaldehydes
J . Org. Chem., Vol. 65, No. 11, 2000 3317
propylidene)-D-glyceraldehyde.34 4-Pentynamine was prepared
following the procedure of Taylor for 3-butynamine.32
enhancement of 1% on H3, being assigned an anti-
relative disposition between H2 and H3.
Tin (IV) Ch lor id e-P r om oted Rea ction s betw een Allyl-
t r im et h ylsila n e a n d 4-Oxoa zet id in e-2-ca r b a ld eh yd es.
Gen er a l P r oced u r e for th e Syn th esis of Hom oa llylics
Alcoh ols 7a -l, 11a ,b, a n d 13a ,b. A solution of the corre-
sponding aldehyde (1.0 mmol) in dichloromethane (3.5 mL) was
added dropwise to a stirred solution of tin(IV) chloride (1.0
mmol) in dichloromethane (5 mL) at -78 °C. After 5 min,
allyltrimethylsilane (1.5 mmol) was added, and the mixture
was stirred for 45 min at -78 °C. Saturated aqueous sodium
hydrogen carbonate (10 mL) was added, and the mixture was
allowed to warm to room temperature, before being partitioned
between dichloromethane and water. The organic extract was
washed with brine, dried (MgSO4), and concentrated under
reduced pressure. Chromatography of the residue using dichlo-
romethane/ethyl acetate (9:1) as an eluent gave analytically
pure compounds. Spectroscopic and analytical data for some
representative pure forms of 7 follow.35
(3SR,4SR)-4-[(RS)-1-Hyd r oxy-3-bu ten yl]-3-m eth yl-1-(p-
m eth oxyp h en yl)-2-a zetid in on e, 7a . From 219 mg (1 mmol)
of aldehyde 1a , 206 mg (79%) of compound 7a was obtained
as a white solid. Mp: 107-108 °C (hexanes/ethyl acetate). 1H
NMR: δ 1.28 (dd, 3H, J ) 7.5, 2.0 Hz), 1.92 (d, 1H, J ) 4.5
Hz), 2.17 and 2.31 (m, each 1H), 3.33 (m, 1H), 3.70 (s, 3H),
3.89 (m, 1H), 4.08 (qd, 1H, J ) 7.7, 5.8 Hz), 5.09 (dd, 1H, J )
8.8, 1.5 Hz), 5.13 (s, 1H), 5.79 (m, 1H), 6.77 and 7.37 (dt, each
2H, J ) 8.8, 2.5 Hz). 13C NMR: δ 169.0, 156.3, 133.5, 131.4,
120.5, 118.9, 114.0, 71.3, 58.6, 55.5, 45.6, 39.5, 9.5. IR (KBr,
cm-1): ν 3330, 1718. MS (EI), m/z: 262 (M+ + 1, 21), 261 (M+,
100), 163 (78). Anal. Calcd for C15H19NO3: C, 68.94; H, 7.33;
N, 5.36. Found: C, 68.97; H, 7.30; N, 5.37.
Azetidinones 29b,c,e and 31a ,b have a six-membered
ring fused to the â-lactam. The absence of NOE enhance-
ment was observed on H2 and H8 for compound 29b upon
irradiation of H3. NOE enhancement lower than 1% was
observed on H3 when H2 was irradiated, which is
consistent with an anti H2-H3/anti H3-H8 stereochem-
istry. NOE irradiation on H9 of compound 29c resulted
in values lower than 1% enhancements on the signals
corresponding to H4 and H10. The value of J 9,10 ) 10.3
Hz, typical for trans-diaxial disposition, and the absence
of NOE enhancement on H9 upon irradiation of H10
ensure an anti H4-H9/anti H9-H10 stereochemistry.
The anti H9-H10 stereochemistry for compound 29e was
obvious on the basis of the value of J 9,10 ) 9.8 Hz and
the absence of NOE enhancement on H9 upon irradiation
of H10. The assignment of the stereochemistry for
compounds 31a ,b was deduced by comparison with the
above results. Thus, values of J 9,10 ) 9.6 and 10.2 Hz for
compounds 31a and 31b, respectively, ensure an anti
H9-H10 stereochemistry. The absence of NOE enhance-
ments on H8 for compound 31a upon irradiation of H9
and on H9 for compound 31b on irradiating the signal
corresponding to H8 is in good agreement with an anti-
relative disposition between H8 and H9. The absence of
NOE enhancement on H9 upon irradiation of H4 for
compound 31b and a NOE enhancement of 6% on H4
upon irradiation of H9 for compound 31a showed that
compounds 31a and 31b are epimers at C4 (Figure 2).
(3SR,4SR)-4-[(RS)-1-Hyd r oxy-3-bu ten yl]-1-(p-m eth oxy-
p h en yl)-3-(2-p r op en yl)-2-a zetid in on e, 7b. From 245 mg (1
mmol) of aldehyde 1b, 172 mg (60%) of compound 7b was
obtained as a white solid. Mp: 85-86 °C (hexanes/ethyl
Con clu sion s
1
acetate). H NMR: δ 1.87 (d, 1H, J ) 5.4 Hz), 2.25 and 2.42
The present study provides the first insight into the
manner in which 4-oxoazetidine-2-carbaldehydes and a
variety of allylmetal reagents undergo coupling in both
anhydrous and aqueous environments. Tin(IV) chloride-
promoted reaction of allyltrimethylsilane and boron
trifluoride-diethyl ether-promoted addition of allyltribu-
tylstannane, both in anhydrous conditions, are the best
methods for the stereoselective addition to 4-oxoazetidine-
2-carbaldehydes. These results show that both the allyl-
ation of â-lactam aldehydes and tandem elimination/
intramolecular Diels-Alder reaction are highly diaste-
reoselective processes which can be used for the func-
tionalization of monocyclic 2-azetidinones and for the
preparation of fused tricyclic 2-azetidinones from simple
monocyclic precursors. Furthermore, as far as we know,
these are the first examples of stereoselective allylation
of 4-oxoazetidine-2-carbaldehydes, as well as the first
intramolecular Diels-Alder reaction of 2-azetidinone-
tethered trienes. Other aspects of this chemistry are
under investigation.
(m, each 1H), 2.65 (m, 2H), 3.46 (m, 1H), 3.79 (s, 3H), 4.00 (m,
1H), 4.23 (t, 1H, J ) 5.5 Hz), 5.14 (dq, 2H, J ) 17.0, 1.5 Hz),
5.15 and 5.20 (d, each 1H, J ) 1.5 Hz), 5.82 (m, 1H), 5.97 (m,
1H), 6.87 and 7.40 (dd, each 2H, J ) 9.0, 2.5 Hz). 13C NMR:
δ 168.0, 156.5, 135.6, 133.7, 131.2, 120.7, 118.8, 116.5, 114.1,
70.3, 58.5, 55.5, 50.3, 40.1, 29.1. IR (KBr, cm-1): ν 3335, 1707.
MS (EI), m/z: 288 (M+ + 1, 22), 287 (M+, 100), 189 (44). Anal.
Calcd for C17H21NO3: C, 71.06; H, 7.37; N, 4.87. Found: C,
71.07; H, 7.35; N, 4.87.
(3SR,4SR)-4-[(RS)-1-Hyd r oxy-3-bu ten yl]-1-(p-m eth oxy-
p h en yl)-3-(2-p r op yn yl)-2-a zetid in on e, 7c. From 243 mg (1
mmol) of aldehyde 1c, 199 mg (66%) of compound 7c was
obtained as a pale green solid. Mp: 83-84 °C (hexanes/ethyl
acetate). 1H NMR: δ 1.95 (d, 1H, J ) 4.1 Hz), 2.14 (t, 1H, J )
2.6 Hz), 2.35 and 2.56 (m, each 1H), 2.81 (dd, 1H, J ) 4.7, 2.6
Hz), 2.86 (dd, 1H, J ) 9.9, 2.6 Hz), 3.62 (q, 1H, J ) 5.1 Hz),
3.85 (s, 3H), 4.28 (m, 1H), 4.36 (dd, 1H, J ) 5.5, 4.2 Hz), 5.22
(m, 2H), 5.89 (m, 1H), 6.93 and 7.44 (dd, each 2H, J ) 7.0, 2.2
Hz). 13C NMR: δ 166.3, 156.7, 133.7, 130.9, 121.0, 118.9, 114.2,
81.4, 70.3, 69.6, 58.3, 55.5, 50.0, 40.5, 14.6. IR (KBr, cm-1): ν
3300, 1741. MS (EI), m/z: 286 (M+ + 1, 24), 285 (M+, 100).
Anal. Calcd for C17H19NO3: C, 71.56; H, 6.71; N, 4.91. Found:
C, 71.55; H, 6.70; N, 4.95.
(3R,4S)-4-[(R)-1-H yd r oxy-3-b u t en yl]-3-m et h oxy-1-(p -
m eth oxyp h en yl)-2-a zetid in on e, (+)-7d . From 236 mg (1
mmol) of aldehyde (+)-1d , 236 mg (85%) of compound (+)-7d
was obtained as a colorless oil. [R]D ) +150.4 (c 1.0, CH2Cl2).
1H NMR: δ 2.40 (m, 2H), 2.66 (d, 1H, J ) 3.9 Hz), 3.76 (s,
Exp er im en ta l Section
Gen er a l P r oced u r es. General experimental data and
procedures have been previously reported.10b NMR spectra
were recorded in CDCl3 solutions, except as otherwise stated.
Chemical shifts are given in ppm relative to TMS (1H, 0.0 ppm)
or CDCl3 (13C, 77.0 ppm). Specific rotation [R]D is given in deg
per dm at 20 °C, and the concentration (c) is expressed in g
per 100 mL. All commercially available compounds were used
without further purification. The following chemicals were
prepared according to literature procedures: 3-butenamine,31
3-butynamine,32 N,N-di(p-methoxyphenyl)diimine,33 2,3-O-(iso-
(32) Taylor, E. C.; Macor, J . E.; Pont, J . L. Tetrahedron 1987, 21,
5145.
(33) (a) Kliegman, J . M.; Barnes, R. K. J . Org. Chem. 1970, 35, 3140.
(b) Barnes, R. K.; Kliegman, J . M. Tetrahedron 1970, 26, 2555.
(34) Schmid, C.; Bryant, J . D.; Dowlatzedah, M.; Phillips, J .; Prather,
D. E.; Schantz, R. D.; Sear, N. L.; Vianco, C. S. J . Org. Chem. 1991,
56, 4056.
(35) Full spectroscopic and analytical data for compounds not
included in this Experimental Section are described in the Supporting
Information.
(31) Sato, T.; Nakamura, N.; Ikeda, K.; Okada, M.; Ishibashi, H.;
Ikeda, M. J . Chem. Soc., Perkin Trans. 1 1992, 2399.

3318 J . Org. Chem., Vol. 65, No. 11, 2000
Alcaide et al.
3H), 3.87 (s, 3H), 4.16 (m, 1H), 4.38 (t, 1H, J ) 4.8 Hz), 4.71
(d, 1H, J ) 5.1 Hz), 5.18 (dd, 1H, J ) 8.5, 1.5 Hz), 5.23 (s,
1H), 5.94 (m, 1H), 6.95 and 7.49 (dd, each 2H, J ) 7.0, 2.2
Hz). 13C NMR: δ 165.1, 156.8, 134.4, 130.7, 120.5, 118.0, 114.2,
82.7, 70.4, 60.1, 59.7, 55.5, 38.3. IR (KBr, cm-1): ν 3489, 1736.
MS (EI), m/z: 278 (M+ + 1, 11), 277 (M+, 58), 149 (100). Anal.
Calcd for C15H19NO4: C, 64.97; H, 6.91; N, 5.05. Found: C,
65.02; H, 6.90; N, 5.03.
and water. The organic extract was washed with brine, dried
(MgSO4), and concentrated under reduced pressure. Chroma-
tography of the residue using dichloromethane/ethyl acetate
(9:1 containing 1% of triethylamine) as an eluent gave 209 mg
(80%) of compound syn-7a , containing ca. 25% of its anti-7a
epimer. Anal. Calcd for C15H19NO3: C, 68.94; H, 7.33; N, 5.36.
Found: C, 68.99; H, 7.27; N, 5.32.
Bor on Tr iflu or id e Dieth yl Eth er a te-P r om oted Rea c-
tion betw een Allyltr ibu tyltin a n d 4-Oxoa zetid in e-2-ca r -
ba ld eh yd e 1a . A solution of the aldehyde 1a (219 mg, 1.0
mmol) in dichloromethane (1 mL) was added dropwise to a
stirred solution of boron trifluoride diethyl etherate (213 mg,
1.5 mmol) in dichloromethane (4 mL) at -78 °C. After 5 min,
allyltributyltin (397 mg, 1.2 mmol) was added, and the mixture
was stirred for 1 h at -78 °C. Saturated aqueous sodium
hydrogen carbonate (10 mL) was added, and the mixture was
allowed to warm to room temperature, before being partitioned
between dichloromethane and water. The organic extract was
washed with brine, dried (MgSO4), and concentrated under
reduced pressure. Chromatography of the residue using dichlo-
romethane/ethyl acetate (9:1 containing 1% of triethylamine)
as an eluent gave 196 mg (75%) of compound syn-7a , contain-
ing ca. 9% of its anti-7a epimer. Anal. Calcd for C15H19NO3:
C, 68.94; H, 7.33; N, 5.36. Found: C, 68.87; H, 7.25; N, 5.30.
Ma gn esiu m /Bism u t h (III) Ch lor id e-P r om ot ed R ea c-
tion betw een Allylbr om id e a n d 4-Oxoa zetid in e-2-ca r -
ba ld eh yd e 1a . Allyl bromide (187 mg, 1.54 mmol) was added
to a well-stirred suspension of bismuth(III) chloride (501 mg,
1.59 mmol) and metallic magnesium (57 mg, 2.36 mmol) in
THF/water (4:1, 4 mL) at room temperature. After 20 min, a
solution of the aldehyde 1a (219 mg, 1.0 mmol) in tetrahydro-
furan (1 mL) was added dropwise, and the mixture was stirred
for 18 h at room temperature. Hydrochloric acid (1 M, 10 mL)
was added at 0 °C, and the mixture was allowed to warm to
room temperature, before being extracted with dichloromethane
(3 × 5 mL). The organic extract was washed with brine, dried
(MgSO4), and concentrated under reduced pressure. Chroma-
tography of the residue using dichloromethane/ethyl acetate
(9:1) as an eluent gave 131 mg (50%) of compound syn-7a ,
(3R,4S)-3-Ben zyloxy-1-(3-bu ten yl)-4-[(R)-1-h yd r oxy-3-
bu ten yl]-2-a zetid in on e, (+)-7f. From 259 mg (1 mmol) of
aldehyde (+)-1f, 163 mg (54%) of compound (+)-7f was
obtained as a colorless oil. [R]D ) +57.1 (c 1.5, CH2Cl2). 1H
NMR: δ 2.33 (m, 4H), 2.48 (d, 1H, J ) 3.0 Hz), 3.22 and 3.63
(dd, each 1H, J ) 14.0, 7.0 Hz), 3.67 (dd, 1H, J ) 8.0, 5.1 Hz),
3.90 (m, 1H), 4.61 (d, 1H, J ) 5.1 Hz), 4.68 and 4.95 (d, each
1H, J ) 11.7 Hz), 5.10 (m, 4H), 5.77 (m, 2H), 7.33 (m, 5H). 13
C
NMR: δ 167.8, 136.8, 134.9, 134.0, 128.6, 128.2, 127.9, 118.5,
117.1, 80.6, 73.2, 70.1, 60.0, 40.9, 38.8, 31.8. IR (CHCl3, cm-1):
ν 3480, 1735. MS (EI), m/z: 302 (M+ + 1, 3), 301 (M+, 7), 91
(100). Anal. Calcd for C18H23NO3: C, 71.73; H, 7.69; N, 4.65.
Found: C, 71.70; H, 7.71; N, 4.70.
(3R,4S)-1-(3-Bu t yn yl)-4-[(R)-1-h yd r oxy-3-b u t en yl]-3-
m eth oxy-2-a zetid in on e, (+)-7g. From 181 mg (1 mmol) of
aldehyde (+)-1 g, 185 mg (83%) of compound (+)-7 g was
obtained as a colorless oil. [R]D ) +62.3 (c 2.5, CH2Cl2). 1H
NMR: δ 1.98 (t, 1H, J ) 2.7 Hz), 2.49 (d, 1H, J ) 3.2 Hz),
2.50 (dt, 2H, J ) 7.0, 2.7 Hz), 3.33 (ddd, 1H, J ) 13.7, 13.0,
6.6 Hz), 3.57 (s, 3H), 3.66 (td, 1H, J ) 13.7, 13.0, 7.0 Hz), 3.76
(dd, 1H, J ) 5.6, 4.9 Hz), 3.88 (m, 1H), 4.46 (d, 1H, J ) 4.9
Hz), 5.15 (m, 2H), 5.81 (m, 1H). 13C NMR: δ 167.7, 133.8,
118.4, 82.9, 80.9, 70.1, 70.0, 60.6, 59.2, 40.2, 38.5, 17.7. IR
(CHCl3, cm-1): ν 3430, 3290, 1740. MS (EI), m/z: 224 (M+
+
1, 20), 223 (M+, 100). Anal. Calcd for C12H17NO3: C, 64.55; H,
7.67; N, 6.27. Found: C, 64.43; H, 7.77; N, 6.17.
(3R,4S)-4-[(R)-1-Hydr oxy-3-bu ten yl]-1-(p-m eth oxyph en -
yl)-3-(2-p r op en yloxy)-2-a zetid in on e, (+)-7i. From 261 mg
(1 mmol) of aldehyde (+)-1i, 215 mg (71%) of compound (+)-
7i was obtained as a pale green solid. Mp: 76-77 °C (hexanes/
ethyl acetate). [R]D ) +135.0 (c 1.0, CH2Cl2). 1H NMR: δ 2.27
(m, 2H), 2.54 (d, 1H, J ) 3.8 Hz), 3.72 (s, 3H), 4.05 (m, 1H),
4.18 (dd, 1H, J ) 5.1, 4.4 Hz), 4.19 (ddt, 1H, J ) 12.9, 6.6, 1.5
Hz), 4.39 (ddt, 1H, J ) 12.9, 5.1, 1.5 Hz), 4.71 (d, 1H, J ) 5.3
Hz), 5.03 (dd, 1H, J ) 8.5, 1.5 Hz), 5.08 (d, 1H, J ) 0.8 Hz),
5.22 (dq, 1H, J ) 9.0, 1.5 Hz), 5.29 (dq, 1H, J ) 17.2, 1.5 Hz),
5.83 (m, 2H), 6.80 and 7.33 (dd, each 2H, J ) 8.8, 2.5 Hz). 13C
NMR: δ 165.2, 156.8, 134.4, 133.1, 130.7, 120.5, 118.5, 118.0,
114.2, 80.5, 72.7, 70.5, 60.2, 55.5, 38.3. IR (KBr, cm-1): ν 3300,
1716. MS (EI), m/z: 304 (M+ + 1, 14), 303 (M+, 64), 149 (100).
Anal. Calcd for C17H21NO4: C, 67.31; H, 6.98; N, 4.62. Found:
C, 67.32; H, 7.00; N, 4.61.
containing ca. 28% of its anti-7a epimer. Anal. Calcd for C15H19
-
NO3: C, 68.94; H, 7.33; N, 5.36. Found: C, 68.81; H, 7.20; N,
5.26.
In d iu m -P r om oted Rea ction betw een Allylbr om id e
a n d 4-Oxoa zetid in e-2-ca r ba ld eh yd e 1a . Allyl bromide (242
mg, 2.0 mmol) was added to a well-stirred solution of the
aldehyde 1a (219 mg, 1.0 mmol) and indium powder (229 mg,
1.99 mmol) in THF/water (1:1, 5 mL) at room temperature.
After 5 h, saturated aqueous sodium hydrogen carbonate (10
mL) was added at 0 °C, and the mixture was allowed to warm
to room temperature, before being extracted with dichlo-
romethane (3 × 5 mL). The organic extract was washed with
brine, dried (MgSO4), and concentrated under reduced pres-
sure. Chromatography of the residue using dichloromethane/
ethyl acetate (9:1) as an eluent gave 196 mg (75%) of compound
syn-7a , containing ca. 54% of its anti-7a epimer. Anal. Calcd
for C15H19NO3: C, 68.94; H, 7.33; N, 5.36. Found: C, 68.79;
H, 7.22; N, 5.26.
Zin c-P r om oted Rea ction betw een Allylbr om id e a n d
4-Oxoa zetid in e-2-ca r ba ld eh yd e 1a . Allyl bromide (76 mg,
0.584 mmol) was added dropwise to a stirred solution of zinc
dust in tetrahydrofuran (730 µL) at room temperature. The
reaction was activated by a gentle heating, for a few seconds.
When the ebullition calmed down, the mixture was cooled at
5 °C, allyl bromide (303 mg, 2.50 mmol) was added dropwise,
and the mixture was stirred at 5 °C for 30 min. The resulting
allylzinc bromide was recooled to -78 °C, and a solution of
the aldehyde 1a (219 mg, 1.0 mmol) in tetrahydrofuran (1 mL)
was added. After 3 h at -78 °C, saturated aqueous sodium
hydrogen carbonate (10 mL) was added, and the mixture was
allowed to warm to room temperature, before being extracted
with dichloromethane (3 × 5 mL). The organic extract was
washed with brine, dried (MgSO4), and concentrated under
reduced pressure. Chromatography of the residue using dichlo-
romethane/ethyl acetate (9:1) as an eluent gave 191 mg (73%)
of compound syn-7a , containing ca. 38% of its anti-7a epimer.
(3R,4S)-4-[(R)-1-H yd r oxy-3-b u t en yl]-3-m et h oxy-1-(2-
oxo-3-p en ten yl)-2-a zetid in on e, (+)-7k . From 211 mg (1
mmol) of compound (+)-1k , 127 mg (50%) of compound (+)-
7k was obtained as a colorless oil. [R]D ) +75.0 (c 3.8, CH2-
1
Cl2). H NMR: δ 1.92 (dd, 3H, J ) 6.9, 1.5 Hz), 2.14 and 2.30
(m, each 1H), 2.73 (d, 1H, J ) 3.0 Hz), 3.60 (s, 3H), 3.91 (m,
2H), 4.26 and 4.47 (d, each 1H, J ) 18.5 Hz), 4.59 (d, 1H, J )
4.9 Hz), 5.07 (m, 1H), 5.15 (s, 1H), 5.82 (m, 1H), 6.13 (dq, 1H,
J ) 15.9, 1.7 Hz), 6.95 (qd, 1H, J ) 15.9, 6.9 Hz). 13C NMR:
δ 193.6, 168.5, 145.2, 133.9, 129.0, 118.4, 83.6, 70.2, 61.7, 59.5,
48.6, 38.6, 18.6. IR (CHCl3, cm-1): ν 3447, 1753, 1701. MS (EI),
m/z: 254 (M+ + 1, 25), 253 (M+, 100). Anal. Calcd for C13H19
-
NO4: C, 61.64; H, 7.56; N, 5.53. Found: C, 61.60; H, 7.59; N,
5.57.
Tin (IV) Ch lor id e-P r om oted Rea ction betw een Allyl-
tr ibu tyltin a n d 4-Oxoa zetid in e-2-ca r ba ld eh yd e 1a . A
cooled solution of tin(IV) chloride (313 mg, 1.2 mmol) in
dichloromethane (1.2 mL) was added dropwise to a stirred
solution of allyltributyltin (397 mg, 1.2 mmol) in dichlo-
romethane (4.5 mL) at -78 °C. After 5 min, a solution of the
aldehyde 1a (219 mg, 1.0 mmol) in dichloromethane (1 mL)
was added dropwise, and the mixture was stirred for 1 h at
-78 °C. Saturated aqueous sodium hydrogen carbonate (10
mL) was added, and the mixture was allowed to warm to room
temperature, before being partitioned between dichloromethane

Allylation of 4-Oxoazetidine-2-carbaldehydes
J . Org. Chem., Vol. 65, No. 11, 2000 3319
Anal. Calcd for C15H19NO3: C, 68.94; H, 7.33; N, 5.36. Found:
C, 69.04; H, 7.39; N, 5.28.
ethyl acetate/hexane (2:1 containing 1% of triethylamine) gave
60 mg (60%) of R,â-unsaturated ketone (+)-E-14 as a pale
yellow oil.
Tin (II) Ch lor id e-P r om oted Rea ction betw een Allyl-
br om id e a n d 4-Oxoa zetid in e-2-ca r ba ld eh yd e 1a . Tin(II)
chloride monohydrate (462 mg, 2.05 mmol) and sodium iodide
(307 mg, 2.05 mmol) were sequentially added to a stirred
solution of the aldehyde 1a (219 mg, 1.0 mmol) and allyl
bromide (182 mg, 1.5 mmol) in DMF (2 mL) at room temper-
ature. After 20 h, saturated aqueous sodium hydrogen carbon-
ate (10 mL) was added at 0 °C, and the mixture was allowed
to warm to room temperature, before being extracted with
dichloromethane (3 × 5 mL). The organic extract was washed
with brine, dried (MgSO4), and concentrated under reduced
pressure. Chromatography of the residue using dichlo-
romethane/ethyl acetate (9:1) as an eluent gave 133 mg (51%)
of compound syn-7a , containing ca. 39% of its anti-7a epimer.
Anal. Calcd for C15H19NO3: C, 68.94; H, 7.33; N, 5.36. Found:
C, 68.78; H, 7.42; N, 5.18.
Gen er a l P r oced u r e for th e P r ep a r a tion of O-Acetyl-
m a n d ela tes 8d ,i, 9d ,i, a n d 12a ,b. (R)-O-Acetylmandelic acid
(20 mg, 0.10 mmol) and 4-(dimethylamino)pyridine (DMAP)
(cat.) were added to a solution of the corresponding homoallylic
alcohol (0.09 mmol) in dichloromethane (1.0 mL) followed by
a solution of dicyclohexylcarbodiimide (DCC) (37 mg, 0.18
mmol) in dichloromethane (500 µL) at 0 °C. The reaction
mixture was allowed to warm to room temperature and stirred
for 16 h. The solvent was removed under reduced pressure,
and diethyl ether was added. The mixture was then filtered,
and the filtrate was concentrated under reduced pressure.
Chromatography of the residue eluting with dichloromethane/
ethyl acetate mixtures gave analytically pure O-acetylman-
delates 8, 9, and 12. Spectroscopic and analytical data for some
representative pure forms of 8 follow.
(3R,4S)-4-[(S)-2,2-Dim eth yl-1,3-d ioxola n -4-yl]-1-[2-oxo-
3-p en ten yl]-3-m eth oxy-2-a zetid in on e, (+)-E-14. Pale yel-
low oil: [R]D ) +69.1 (c 2.0, CH2Cl2). 1H NMR: δ 1.29 and
1.32 (s, each 3H), 1.87 (dd, 3H, J ) 6.9, 1.7 Hz), 3.38 (m, 1H),
3.48 (s, 3H), 3.57 (dd, 1H, J ) 8.8, 5.4 Hz), 3.83 (dd, 1H, J )
9.2, 5.1 Hz), 4.02 (dd, 1H, J ) 8.8, 6.3 Hz), 4.09 (d, 1H, J )
18.0 Hz), 4.22 (m, 1H), 4.45 (d, 1H, J ) 18.0 Hz), 4.53 (d, 1H,
J ) 5.1 Hz), 6.06 (dq, 1H, J ) 15.9, 1.5 Hz), 6.86 (qd, 1H, J )
15.9, 6.9 Hz). 13C NMR: δ 192.6, 168.2, 144.4, 129.0, 109.5,
83.3, 76.9, 66.7, 60.6, 59.2, 48.0, 26.8, 25.2, 18.5. IR (CHCl3,
cm-1): ν 1755, 1705. MS (EI), m/z: 284 (M+ + 1, 20), 283 (M+,
100). Anal. Calcd for C14H21NO5: C, 59.35; H, 7.47; N, 4.94.
Found: C, 59.29; H, 7.35; N, 4.91.
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 17a -h , 18, a n d 19. Methanesulfonyl chloride (138
mg, 1.20 mmol) and triethylamine (243 mg, 2.40 mmol) were
sequentially added dropwise to a stirred solution of the
corresponding homoallylic alcohol (1.0 mmol), in dichlo-
romethane (10 mL) at 0 °C, and the mixture was stirred for 2
h at room temperature. The organic phase was washed with
water (2 × 5 mL), dried (MgSO4), and concentrated under
reduced pressure. Chromatography of the residue eluting with
dichloromethane/ethyl acetate or hexanes/ethyl acetate mix-
tures gave analytically pure methanesulfonates 17, 18, or 19.
Spectroscopic and analytical data for some representative pure
forms of 17 follow.
Meth a n esu lfon a te of (3SR,4SR)-4-[(RS)-1-Hyd r oxy-3-
bu ten yl]-1-(p-m eth oxyp h en yl)-3-(2-p r op en yl)-2-a zetid i-
n on e, 17b. From 100 mg (0.348 mmol) of homoallylic alcohol
7b, 103 mg (82%) of compound 17b was obtained as a colorless
solid after purification by flash chromatography (dichlo-
romethane/ethyl acetate, 9.5/0.5): colorless solid. Mp: 99-101
(R)-O-Acetylm a n d ela te of (3R,4S)-4-[(R)-1-Hyd r oxy-3-
b u t en yl]-3-m et h oxy-1-(p -m et h oxyp h en yl)-2-a zet id in o-
n e, (+)-8d . From 25 mg (0.09 mmol) of compound (+)-7d , 36
mg (88%) of compound (+)-8d was obtained as a colorless oil.
1
°C (hexanes/ethyl acetate). H NMR: δ 2.33 (s, 3H), 2.46 (m,
2H), 2.64 (m, 2H), 3.47 (dt, 1H, J ) 7.7, 5.9 Hz), 3.71 (s, 3H),
4.38 (dd, 1H, J ) 9.2, 5.9 Hz), 4.97 (m, 1H), 5.13 (dq, 2H, J )
8.8, 1.8 Hz), 5.21 (d, 2H, J ) 8.8 Hz), 5.89 (m, 2H), 6.81 and
7.24 (dd, each 2H, J ) 7.0, 2.2 Hz). 13C NMR: δ 166.8, 156.6,
134.5, 130.9, 130.6, 120.3, 117.6, 114.1, 80.8, 55.5, 55.0, 50.4,
38.0, 37.3, 31.5, 29.3. IR (KBr, cm-1): ν 1753, 1348, 1169. MS
(EI), m/z: 366 (M+ + 1, 23), 365 (M+, 100). Anal. Calcd for
1
[R]D ) +50.4 (c 1.0, CH2Cl2). H NMR: δ 2.09 (s, 3H), 2.46 (t,
2H, J ) 6.6 Hz), 3.29 (s, 3H), 3.72 (s, 3H), 4.27 (t, 1H, J ) 5.5
Hz), 4.38 (d, 1H, J ) 5.2 Hz), 5.03 (dd, 1H, J ) 6.6, 1.1 Hz),
5.07 (s, 1H), 5.28 (q, 1H, J ) 5.9 Hz), 5.70 (m, 1H), 5.71 (s,
1H), 6.71 and 7.18 (dd, each 2H, J ) 7.0, 2.2 Hz), 7.22 (m,
5H). 13C NMR: δ 170.3, 168.1, 164.8, 156.7, 133.0, 132.4, 130.2,
129.2, 128.7, 127.7, 119.7, 118.8, 114.2, 82.6, 74.6, 72.7, 59.2,
57.0, 55.4, 35.4, 20.7. IR (CHCl3, cm-1): ν 1747, 1647. MS (EI),
m/z: 454 (M+ + 1, 9), 453 (M+, 29), 149 (100). Anal. Calcd for
C
18H23NSO5: C, 59.16; H, 6.34; N, 3.83. Found: C, 59.10; H,
6.36; N, 3.85.
Meth a n esu lfon a te of (3SR,4SR)-4-[(RS)-1-Hyd r oxy-3-
bu ten yl]-1-(p-m eth oxyp h en yl)-3-(2-p r op yn yl)-2-a zetid i-
n on e, 17c. From 342 mg (1.13 mmol) of homoallylic alcohol
7c, 358 mg (83%) of compound 17c was obtained as a green
pale oil after purification by flash chromatography (dichlo-
C
25H27NO7: C, 66.21; H, 6.00; N, 3.09. Found: C, 66.25; H,
5.97; N, 3.04.
(S)-O-Acetylm a n d ela te of (3R,4S)-4-[(R)-1-Hyd r oxy-3-
b u t en yl]-3-m et h oxy-1-(p -m et h oxyp h en yl)-2-a zet id in o-
n e, 9d . From 25 mg (0.09 mmol) of compound (+)-7d , 32 mg
(79%) of compound (+)-9d was obtained as a colorless oil. [R]D
) +133.0 (c 1.0, CH2Cl2). 1H NMR: δ 2.03 (s, 3H), 2.27 (m,
2H), 3.53 (s, 3H), 3.73 (s, 3H), 4.30 (dd, 1H, J ) 7.0, 5.1 Hz),
4.54 (d, 1H, J ) 5.1 Hz), 4.69 (dd, 1H, J ) 17.0, 1.5 Hz), 4.77
(dd, 1H, J ) 10.3, 1.5 Hz), 5.33 (m, 2H), 5.59 (s, 1H), 6.82 (dd,
2H, J ) 7.0, 2.2 Hz), 7.27 (m, 7H). 13C NMR: δ 169.7, 167.8,
164.8, 156.8, 133.8, 131.9, 130.1, 129.1, 128.6, 127.8, 120.2,
118.6, 114.3, 82.6, 74.0, 73.3, 59.4, 57.5, 55.5, 35.3, 20.7. IR
(CHCl3, cm-1): ν 1751, 1645. MS (EI), m/z: 454 (M+ + 1, 8),
453 (M+, 28), 149 (100). Anal. Calcd for C25H27NO7: C, 66.21;
H, 6.00; N, 3.09. Found: C, 66.29; H, 6.06; N, 3.15.
Sw er n Oxid a tion of Hom oa llylic Alcoh ols 11a ,b. A
solution of dimethyl sulfoxide (67 mg, 0.856 mmol) in dichlo-
romethane (280 µL) was added dropwise to a stirred solution
of oxalyl chloride (54 mg, 0.423 mmol) in dichloromethane (468
µL) at -78 °C. After 20 min, a solution of the alcohol (+)-11
(from allyltributyltin) (100 mg, 0.351 mmol) in dichlo-
romethane (300 µL) was added, and the mixture was stirred
for 1 h at -78 °C. Triethylamine (270 µL) was added at -78
°C, and the mixture was allowed to warm to room temperature.
Water (1 mL) was added, and the mixture was partitioned
between dichloromethane and water. The organic extract was
washed with brine, dried (MgSO4), and concentrated under
reduced pressure. Chromatography of the residue eluting with
1
romethane/ethyl acetate, 9.5/0.5): pale green oil. H NMR: δ
2.20 (t, 1H, J ) 2.5 Hz), 2.39 (s, 3H), 2.74 (m, 4H), 3.61 (td,
1H, J ) 8.8, 5.5 Hz), 3.78 (s, 3H), 4.50 (dd, 1H, J ) 9.2, 5.5
Hz), 5.28 (m, 3H), 5.98 (m, 1H), 6.87 and 7.29 (dd, each 2H, J
) 6.9, 2.2 Hz). 13C NMR: δ 165.1, 156.8, 130.8, 130.3, 120.5,
120.4, 114.1, 80.3, 71.9, 55.5, 55.2, 49.8, 37.9, 37.6, 31.5, 14.7.
IR (CHCl3, cm-1): ν 3310, 1753, 1360, 1175. MS (EI), m/z: 364
(M+ + 1, 24), 363 (M+, 100). Anal. Calcd for C18H21NSO5: C,
59.49; H, 5.82; N, 3.85. Found: C, 59.40; H, 5.84; N, 3.87.
Meth an esu lfon ate of (3R,4S)-4-[(R)-1-Hydr oxy-3-bu ten -
yl]-1-(p-m eth oxyph en yl)-3-(2-pr open yloxy)-2-azetidin on e,
(+)-17d . From 277 mg (0.913 mmol) of homoallylic alcohol (+)-
7i, 319 mg (92%) of compound (+)-17d was obtained as a pale
green solid after purification by flash chromatography (dichlo-
romethane/ethyl acetate, 9.5/0.5): pale green solid. Mp: 64-
66 °C (hexanes/ethyl acetate). [R]D ) +79.9 (c 0.9, CH2Cl2).
1H NMR: δ 2.53 (s, 3H), 2.65 (m, 2H), 3.79 (s, 3H), 4.27 and
4.42 (ddt, each 1H, J ) 12.9, 5.5, 1.5 Hz), 4.51 (dd, 1H, J )
8.5, 5.2 Hz), 4.80 (d, 1H, J ) 5.2 Hz), 5.10 (m, 1H), 5.23 (dq,
1H, J ) 17.0, 1.5 Hz), 5.28 (2H, m), 5.38 (dq, 1H, J ) 17.0, 1.5
Hz), 5.94 (m, 2H), 6.88 and 7.37 (dd, each 2H, J ) 8.8, 2.2
Hz). 13C NMR: δ 164.9, 156.8, 133.0, 131.5, 130.2, 119.9, 119.7,
118.6, 114.3, 81.3, 80.1, 72.6, 57.3, 55.5, 38.0, 36.8, 31.5. IR
(KBr, cm-1): ν 1749, 1362, 1177. MS (EI), m/z: 382 (M+ + 1,
14), 381 (M+, 63), 149 (100). Anal. Calcd

3320 J . Org. Chem., Vol. 65, No. 11, 2000
Alcaide et al.
for C18H23NSO6: C, 56.68; H, 6.08; N, 3.67. Found: C, 56.70;
H, 6.11; N, 3.66.
(0.252 mmol) of methanesulfonate (+)-17d , 64 mg (89%) of
compound (+)-20d was obtained as a colorless oil after
purification by flash chromatography (dichloromethane/ethyl
acetate, 9.8/0.2): colorless oil. [R]D ) +47.4 (c 1.0, CH2Cl2).
1H NMR: δ 3.78 (s, 3H), 4.17 (m, 2H), 4.64 (dd, 1H, J ) 9.0,
4.8 Hz), 4.83 (d, 1H, J ) 4.8 Hz), 5.27 (m, 4H), 5.83 (dd, 1H,
J ) 14.7, 8.8 Hz), 5.94 (m, 1H), 6.41 (td, 1H, J ) 16.5, 10.3
Hz), 6.51 (dd, 1H, J ) 14.5, 10.3 Hz), 6.85 and 7.37 (dd, each
2H, J ) 7.0, 2.2 Hz). 13C NMR: δ 163.7, 156.3, 137.2, 135.7,
133.5, 131.1, 127.6, 119.1, 118.6, 118.3, 114.3, 82.6, 72,0, 60.5,
55.5. IR (CHCl3, cm-1): ν 1746. MS (EI), m/z: 286 (M+ + 1, 5),
285 (M+, 23), 67 (100). Anal. Calcd for C17H19NO3: C, 71.56;
H, 6.71; N, 4.91. Found: C, 71.55; H, 6.75; N, 4.91.
Meth a n esu lfon a te of (3R,4S)-3-Ben zyloxy-1-(3-bu ten -
yl)-4-[(R)-1-h ydr oxy-3-bu ten yl]-2-azetidin on e, (+)-17f. From
192 mg (0.638 mmol) of homoallylic alcohol (+)-7f, 216 mg
(89%) of compound (+)-17f was obtained as a pale green oil
after purification by flash chromatography (dichloromethane/
ethyl acetate, 9.5/0.5): pale green oil. [R]D ) +46.2 (c 0.9, CH2-
Cl2). 1H NMR: δ 2.33 (m, 2H), 2.54 and 2.67 (m, each 1H),
3.02 (s, 3H), 3.20 and 3.68 (dd, each 1H, J ) 14.0, 7.0 Hz),
3.88 (dd, 1H, J ) 8.0, 5.1 Hz), 4.62 (d, 1H, J ) 5.1 Hz), 4.69
and 4.92 (d, each 1H, J ) 11.7 Hz), 5.11 (m, 5H), 5.76 (m, 2H),
7.35 (m, 5H). 13C NMR: δ 167.6, 136.5, 134.7, 131.7, 128.6,
128.2, 128.1, 119.9, 117.4, 81.5, 80.1, 73.1, 57.5, 40.3, 39.4, 36.9,
31.4. IR (CHCl3, cm-1): ν 1745, 1365, 1175. MS (EI), m/z: 380
(3R,4S)-3-Ben zyloxy-4-[(1E)-1,3-bu ta d ien yl]-1-(3-bu ten -
yl)-2-a zetid in on e, (+)-20f. From 120 mg (0.316 mmol) of
methanesulfonate (+)-17f, 51 mg (66%) of compound (+)-20f
was obtained as a colorless oil after purification by flash
chromatography (dichloromethane/ethyl acetate, 9.8/0.2): col-
(M+ + 1, 2), 379 (M+, 6), 91 (100). Anal. Calcd for C19H25
-
NSO5: C, 60.14; H, 6.64; N, 3.69. Found: C, 60.10; H, 6.65;
N, 3.66.
1
Meth a n esu lfon a te of (3R,4S)-1-(3-Bu tyn yl)-4-[(R)-1-h y-
d r oxy-3-bu ten yl]-3-m eth oxy-2-a zetid in on e, (+)-17g. From
550 mg (2.47 mmol) of homoallylic alcohol (+)-7g, 650 mg
(88%) of compound (+)-17g was obtained as a colorless oil after
purification by flash chromatography (ethyl acetate/hexane,
4/6): colorless oil. [R]D ) +36.3 (c 3.0, CH2Cl2). 1H NMR: δ
1.98 (t, 1H, J ) 2.7 Hz), 2.53 (m, 4H), 3.04 (s, 3H), 3.27 (td,
1H, J ) 14.0, 6.1 Hz), 3.56 (s, 3H), 3.73 (ddd, 1H, J ) 14.1,
7.5, 6.6 Hz), 4.02 (dd, 1H, J ) 8.3, 5.1 Hz), 4.51 (d, 1H, J )
5.1 Hz), 4.99 (m, 1H), 5.16 (dq, 1H, J ) 5.1, 1.2 Hz), 5.23 (q,
1H, J ) 1.2 Hz), 5.84 (m, 1H). 13C NMR: δ 167.6, 131.8, 119.8,
82.7, 81.5, 80.7, 70.5, 59.2, 58.0, 39.7, 39.4, 36.8, 17.3. IR
(CHCl3, cm-1): ν 3308, 1755, 1360, 1175. MS (EI), m/z: 302
orless oil. [R]D ) +64.4 (c 1.8, CH2Cl2). H NMR: δ 2.25 (m,
2H), 3.07 and 3.41 (ddd, each 1H, J ) 14.0, 7.0, 2.0 Hz), 4.15
(dd, 1H, J ) 9.2, 4.4 Hz), 4.58 and 4.61 (d, each 1H, J ) 11.4
Hz), 4.72 (d, 1H, J ) 4.4 Hz), 5.07 and 5.25 (m, each 2H), 5.72
(m, 2H), 6.32 (dd, 1H, J ) 14.7, 10.7 Hz), 6.38 (td, 1H, J )
16.5, 9.9 Hz), 7.32 (m, 5H). 13C NMR: δ 166.8, 136.9, 135.8,
134.8, 128.4, 128.2, 128.0, 127.7, 127.6, 119.0, 117.2, 83.1, 72.6,
60.6, 39.4, 32.0. IR (CHCl3, cm-1): ν 1745. MS (EI), m/z: 284
(M+ + 1, 3), 283 (M+, 10), 91 (100). Anal. Calcd for C18H21
-
NO2: C, 76.3; H, 7.47; N, 4.94. Found: C, 76.23; H, 7.49; N,
4.90.
(3R,4S)-4-[(1E)-1,3-Bu tadien yl]-1-(3-bu tyn yl)-3-m eth oxy-
2-a zetid in on e, (+)-20g. From 100 mg (0.332 mmol) of meth-
anesulfonate (+)-17g, 48 mg (71%) of compound (+)-20g was
obtained as a colorless oil after purification by flash chroma-
tography (ethyl acetate/hexane, 4/6): colorless oil. [R]D ) +44.0
(M+ + 1, 10), 301 (M+, 65), 149 (100). Anal. Calcd for C13H19
-
NSO5: C, 51.81; H, 6.35; N, 4.65. Found: C, 51.87; H, 6.25;
N, 4.53.
1
Gen er a l P r oced u r e for th e P r ep a r a tion of Dien es 20a ,
21-23, Tr ien es 20b,d -f, a n d Dien yn es 20c,g,h . DBU (1.10
mmol) was added dropwise to a solution of the corresponding
methanesulfonate (1.0 mmol) in benzene or toluene (10 mL).
The resulting solution was heated under reflux for 16 h. The
reaction mixture was allowed to cool to room temperature, and
the solvent was removed under reduced pressure. Chroma-
tography of the residue eluting with dichloromethane/ethyl
acetate or hexanes/ethyl acetate mixtures gave analytically
pure polyenes 20-23.
(c 2.1, CH2Cl2). H NMR: δ 1.95 (t, 1H, J ) 2.7 Hz), 2.35 (dt,
2H, J ) 7.0, 2.7 Hz), 3.11 (td, 1H, J ) 14.0, 6.9 Hz), 3.38 (s,
3H), 3.46 (dd, 1H, J ) 14.0, 7.0 Hz), 4.25 (dd, 1H, J ) 9.3, 4.8
Hz), 4.52 (d, 1H, J ) 4.8 Hz), 5.19 (m, 2H), 5.66 (m, 1H), 6.31
(dd, 1H, J ) 14.5, 10.0 Hz), 6.35 (td, 1H, J ) 16.5, 10.0 Hz).
13C NMR: δ 167.7, 137.4, 135.7, 126.9, 119.1, 85.3, 80.8, 70.2,
60.7, 58.6, 38.7, 18.1. IR (CHCl3, cm-1) ν: 3310, 1750. MS (EI),
m/z: 206 (M + + 1, 15), 205 (M+, 100). Anal. Calcd for C12H15
-
NO2: C, 70.22; H, 7.37; N, 6.82. Found: C, 70.30; H, 7.27; N,
6.74.
(3SR,4SR)-4-[(1E)-1,3-Bu tadien yl]-1-(p-m eth oxyph en yl)-
3-(2-p r op en yl)-2-a zetid in on e, 20b. From 100 mg (0.274
mmol) of methanesulfonate 17b, 40 mg (74%) of compound 20b
was obtained as a colorless oil after purification by flash
chromatography (dichloromethane/ethyl acetate, 9.8/0.2): col-
orless oil. 1H NMR: δ 2.29 and 2.45 (m, each 1H), 3.44 (td,
1H, J ) 9.2, 5.9 Hz), 3.70 (s, 3H), 4.55 (dd, 1H, J ) 7.5, 5.9
Hz), 5.11 (m, 4H), 5.73 (m, 2H), 6.29 (m, 2H), 6.77 and 7.27
(dd, each 2H, J ) 7.0, 2.2 Hz). 13C NMR: δ 166.5, 155.9, 136.0,
135.5, 134.9, 131.6, 128.1, 118.9, 118.2, 116.7, 114.3, 56.5, 55.5,
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 29a -e a n d Tr icycle 30. DBU (1.10
mmol) was added dropwise to a solution of the corresponding
methanesulfonate 17b-e,g (1.0 mmol) and hydroquinone (cat.)
in toluene (10 mL). The resulting solution was heated in a
sealed tube at 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 or hexanes/ethyl acetate mix-
tures gave analytically pure adducts 29 and 30.
Tr icyclic 2-Azetid in on e 29a . From 70 mg (0.192 mmol)
of methanesulfonate 17b and after heating at 110 °C for 24 h,
30 mg (57%) of compound 29a was obtained as a white solid
after purification by flash chromatography (dichloromethane/
ethyl acetate, 9.8/0.2): white solid. Mp: 131-132 °C (hexanes/
ethyl acetate). 1H NMR: δ 1.57 (1H, m), 1.66 (2H, m), 1.86
(dd, 1H, J ) 13.0, 7.0 Hz), 1.96 (m, 2H), 2.39 (1H, m), 2.77
(td, 1H, J ) 6.3, 3.0 Hz), 3.52 (dd, 1H, J ) 8.5, 3.8 Hz), 3.72
(s, 3H), 4.07 (d, 1H, J ) 3.8 Hz), 5.36 (dt, 1H, J ) 10.3, 3.0
Hz), 5.73 (m, 1H), 6.81 and 7.28 (dd, each 2H, J ) 7.0, 2.2
Hz). 13C NMR: δ 166.8, 155.9, 131.0, 129.4, 125.3, 118.0, 114.4,
61.6, 55.5, 53.9, 38.6, 34.1, 25.5, 21.2, 20.6. IR (KBr, cm-1): ν
1740. MS (EI), m/z: 270 (M+ + 1, 10), 269 (M+, 51), 149 (100).
Anal. Calcd for C17H19NO2: C, 75.81; H, 7.11; N, 5.20. Found:
C, 75.82; H, 7.12; N, 5.15.
53.4, 29.4. IR (CHCl3, cm-1): ν 1734. MS (EI), m/z: 270 (M+
+
1, 2), 269 (M+, 8), 149 (100). Anal. Calcd for C17H19NO2: C,
75.81; H, 7.11; N, 5.20. Found: C, 75.86; H, 7.11; N, 5.17.
(3SR,4SR)-4-[(1E)-1,3-Bu tadien yl]-1-(p-m eth oxyph en yl)-
3-(2-p r op yn yl)-2-a zet id in on e, 20c. From 120 mg (0.33
mmol) of methanesulfonate 17c, 54 mg (58%) of compound 20c
was obtained as a colorless oil after purification by flash
chromatography (dichloromethane/ethyl acetate, 9.8/0.2): col-
1
orless oil. H NMR: δ 1.96 (t, 1H, J ) 3.0 Hz), 2.63 (m, 2H),
3.10 (dt, 1H, J ) 5.1, 3.0 Hz), 3.71 (s, 3H), 4.34 (dd, 1H, J )
8.1, 2.2 Hz), 5.12 (dd, 1H, J ) 9.2, 1.8 Hz), 5.22 (dd, 1H, J )
15.0, 1.8 Hz), 5.73 (dd, 1H, J ) 15.0, 8.5 Hz), 6.29 (td, 1H, J
) 16.5, 10.5 Hz), 6.40 (dd, 1H, J ) 14.5, 10.5 Hz), 6.78 and
7.28 (dd, each 2H, J ) 7.0, 2.2 Hz). 13C NMR: δ 164.4, 156.1,
135.5, 135.0, 131.4, 130.4, 119.2, 118.3, 114.3, 79.4, 70.7, 58.6,
55.5, 55.0, 17.3. IR (CHCl3, cm-1): ν 3308, 1747. MS (EI), m/z:
Tr icyclic 2-Azetid in on e (+)-29b. From 100 mg (0.262
mmol) of methanesulfonate (+)-17d and after heating at 190
°C for 24 h, 66 mg (88%) of compound (+)-29b was obtained
as a white solid after purification by flash chromatography
(dichloromethane/ethyl acetate, 9.8/0.2): white solid. Mp:
102-103 °C (hexanes/ethyl acetate). [R]D ) +54.9 (c 1.0, CH2-
268 (M+ + 1, 5), 267 (M+, 23), 149 (100). Anal. Calcd for C17H17
-
NO2: C, 76.38; H, 6.41; N, 5.24. Found: C, 76.30; H, 6.40; N,
5.25.
(3R,4S)-4-[(1E)-1,3-Bu t a d ien yl]-1-(p-m et h oxyp h en yl)-
3-(2-p r op en yloxy)-2-a zet id in on e, (+)-20d . From 96 mg

Allylation of 4-Oxoazetidine-2-carbaldehydes
J . Org. Chem., Vol. 65, No. 11, 2000 3321
Cl2). 1H NMR: δ 1.29 (1H, m), 1.65 (1H, m), 1.72 (1H, m), 2.14
(2H, m), 2.36 (dd, 1H, J ) 11.0, 7.1 Hz), 3.53 (t, 1H, J ) 11.0
Hz), 3.81 (s, 3H), 3.87 (dd, 1H, J ) 11.0, 4.5 Hz), 3.96 (dd, 1H,
J ) 7.1, 5.3 Hz), 4.94 (d, 1H, J ) 5.3 Hz), 5.77 (m, 1H), 5.89
(dd, 1H, J ) 10.3, 1.9 Hz), 6.90 and 7.40 (dd, each 2H, J )
7.0, 2.2 Hz). 13C NMR: δ 165.0, 156.5, 130.5, 129.0, 128.3,
119.8, 119.4, 114.5, 113.9, 69.7, 56.6, 55.4, 42.3, 34.4, 24.8. IR
(KBr, cm-1): ν 1736. MS (EI), m/z: 286 (M+ + 1, 10), 285 (M+,
100). Anal. Calcd for C17H19NO3: C, 71.56; H, 6.71; N, 4.91.
Found: C, 71.57; H, 6.65; N, 4.92.
(d, 2H, J ) 8.8 Hz), 7.13 and 7.20 (m, each 2H), 7.53 (d, 2H,
J ) 8.8 Hz). 13C NMR (DMSO-d6): δ 172.6, 155.1, 141.9, 132.5,
126.4, 124.2, 120.7, 113.8, 55.1 (2C), 44.9, 36.4. IR (CHCl3,
cm-1): ν 1742. MS (EI), m/z: 267 (M+ + 2, 77), 265 (M+, 3),
123 (100). Anal. Calcd for C17H15NO2: C, 76.96; H, 5.70; N,
5.28. Found: C, 76.91; H, 5.75; N, 5.30.
P r ep a r a tion of Diels-Ald er Cycloa d d u cts 31a ,b. A
solution of the triene (+)-27 (48 mg, 0.181 mmol) and hydro-
quinone (cat.) in toluene (5 mL) was heated in a sealed tube
at 190 °C for 96 h. The reaction mixture was allowed to cool
to room temperature, the solvent was removed under reduced
pressure, and after flash chromatography eluting with hex-
anes/ethyl acetate (1:1), 23 mg (41%) of the less polar com-
pound (+)-31a and 12 mg (32%) of the more polar compound
(+)-31b were obtained.
Tr icyclic 2-Azetid in on e (+)-29c. From 120 mg (0.316
mmol) of methanesulfonate (+)-17f and after heating at 190
°C for 72 h, 44 mg (50%) of compound (+)-29c was obtained
as a colorless oil after purification by flash chromatography
(dichloromethane/ethyl acetate, 9.8/0.2): colorless oil. [R]D
)
1
+83.4 (c 1.7, CHCl3). H NMR: δ 1.32 (3H, m), 1.50 (dd, 1H,
J ) 10.0, 4.0 Hz), 1.64 (1H, m), 2.16 (3H, m), 2.79 (1H, m),
3.21 (dd, 1H, J ) 10.3, 5.1 Hz), 3.91 (dd, 1H, J ) 14.0, 5.5
Hz), 4.73 (d, 1H, J ) 11.8 Hz), 4.74 (d, 1H, J ) 5.1 Hz), 4.92
(d, 1H, J ) 11.8 Hz), 5.50 (d, 1H, J ) 9.6 Hz), 5.77 (dd, 1H, J
) 9.5, 3.0 Hz), 7.35 (m, 5H). 13C NMR: δ 167.7, 137.4, 128.8,
128.4, 127.7, 127.6, 125.9, 82.5, 72.7, 57.6, 40.1, 38.4, 35.7, 31.5,
28.9, 25.4. IR (CHCl3, cm-1) ν: 1741. MS (EI), m/z: 283 (M+,
8), 91 (100). Anal. Calcd for C18H21NO2: C, 76.30; H, 7.47; N,
4.94. Found: C, 76.28; H, 7.51; N, 4.95.
Tr icyclic 2-Azetid in on e (+)-31a : colorless oil. [R]D )
+59.7 (c 1.9, CH2Cl2). 1H NMR (C6D6): δ 0.92 (dd, 1H, J )
13.4, 1.9 Hz), 1.25 (1H, m), 1.74 (ddd, 1H, J ) 18.5, 7.3, 4.4
Hz), 2.20 (td, 1H, J ) 12.2, 3.4 Hz), 2.37 (1H, brs), 2.42 (1H,
m), 2.51 (1H, brs), 2.70 (1H, m), 2.90 (dd, 1H, J ) 10.3, 4.9
Hz), 3.27 (s, 3H), 3.34 (dd, 1H, J ) 5.9, 3.9 Hz), 3.40 (s, 3H),
4.10 (dd, 1H, J ) 4.9, 1.5 Hz), 5.14 (d, 1H, J ) 9.8 Hz), 5.52
(dd, 1H, J ) 9.8, 2.5 Hz). 13C NMR: δ 174.4, 167.2, 128.3,
126.9, 85.0, 59.3, 52.0, 51.6, 39.4, 34.3, 31.9, 29.2, 29.1, 23.5.
IR (CHCl3, cm-1): ν 1745, 1740. MS (EI), m/z: 266 (M+, 30),
265 (M+, 100). Anal. Calcd for C14H19NO4: C, 63.38; H, 7.22;
N, 5.28. Found: C, 63.31; H, 7.25; N, 5.24.
Tr icyclic 2-Azetid in on e (+)-29e. From 125 mg (0.415
mmol) of methanesulfonate (+)-17g and after heating at 190
°C for 68 h, 43 mg (51%) of compound (+)-29e was obtained
as a colorless oil after purification by flash chromatography
(dichloromethane/ethyl acetate, 9.6/0.4): pale brown oil. [R]D
Tr icyclic 2-Azetid in on e (+)-31b: white solid. Mp: 103-
104 °C (hexanes/ethyl acetate). [R]D ) +250.2 (c 1.4, CH2Cl2).
1H NMR: δ 1.26 (dq, 1H, J ) 13.0, 5.7 Hz), 1.67 (2H, m), 2.09
(2H, m), 2.38 (dt, 1H, J ) 10.5, 4.5 Hz), 2.50 (1H, m), 2.71
(ddt, 1H, J ) 14.0, 4.5, 1.5 Hz), 3.48 (s, 3H), 3.58 (s, 3H), 3.62
(dd, 1H, J ) 10.2, 4.8 Hz), 3.81 (dd, 1H, J ) 14.0, 5.5 Hz),
4.32 (d, 1H, J ) 4.8 Hz), 5.36 (dd, 1H, J ) 10.0, 2.2 Hz), 5.64
(m, 1H). 13C NMR: δ 173.6, 167.1, 129.2, 125.9, 84.7, 58.6,
57.0, 51.5, 42.5, 39.9, 38.3, 38.0, 31.3, 27.3. IR (KBr, cm-1): ν
1745, 1741. MS (EI), m/z: 266 (M+, 41), 265 (M+, 100). Anal.
Calcd for C14H19NO4: C, 63.38; H, 7.22; N, 5.28. Found: C,
63.32; H, 7.20; N, 5.31.
1
) +122.7 (c 3.0, CH2Cl2). H NMR: δ 2.10 (2H, m), 2.66 (3H,
m), 2.87 (1H, m), 3.19 (dd, 1H, J ) 9.8, 4.2 Hz), 3.54 (s, 3H),
3.84 (ddd, 1H, J ) 13.0, 5.5, 2.0 Hz), 4.48 (dd, 1H, J ) 4.2, 1.5
Hz), 5.51 (m, 2H), 5.72 (m, 1H). 13C NMR: δ 167.3, 132.1,
125.7, 124.2, 121.4, 85.3, 59.5, 59.4, 39.9, 36.7, 34.1, 26.8. IR
(CHCl3, cm-1): ν 1745. MS (EI), m/z: 206 (M+ + 1, 92), 205
(M+, 33), 91 (100). Anal. Calcd for C12H15NO2: C, 70.22; H,
7.37; N, 6.82. Found: C, 70.32; H, 7.31; N, 6.74.
Th er m a l Tr ea tm en t of Com p ou n d 17c. From 110 mg
(0.302 mmol) of methanesulfonate 17c, after heating at 190
°C for 72 h, and after flash chromatography eluting with
dichloromethane/ethyl acetate (9.8:0.2), 8 mg (9%) of the less
polar compound 29d and 30 mg (37%) of the more polar
compound 30 were obtained.
Ack n ow led gm en t. Support for this work by the
DGES-MEC (Project PB96-0565) is gratefully acknowl-
edged. P. Almendros thanks the DGES (MEC, Spain)
for a “Contrato de Incorporacio´n”.
Tr icyclic 2-Azetid in on e 29d : colorless oil. 1H NMR: δ 2.16
(2H, s), 2.43 (dd, 1H, J ) 18.8, 10.3 Hz), 2.75 (dd, 1H, J )
18.8, 8.2 Hz), 3.23 (m, 1H), 3.67 (dd, 1H, J ) 4.4, 1.8 Hz), 3.72
(s, 3H), 3.81 (ddd, 1H, J ) 10.3, 4.8, 2.2 Hz), 4.79 (m, 1H),
5.64 (m, 1H), 6.06 (d, 1H, J ) 9.6 Hz), 6.79 and 7.29 (dd, each
2H, J ) 7.0, 2.2 Hz). IR (CHCl3, cm-1): ν 1740. MS (EI), m/z:
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic and
analytical data as well as experimental procedures for com-
pounds (+)-1d -l, (+)-2a -h , (+)-3, (+)-4, (+)-5, (+)-6a , (+)-
6c, (+)-6e, (+)-6g, 7a , (+)-7f, (+)-7h , (+)-7j, (+)-7l, (+)-8i, (+)-
9i, (+)-10a ,b, (+)-11a ,b, (-)-12a , (+)-12b, (+)-13a ,b, (+)-16,
17a , (+)-17f, (+)-17h , 18, 19, 20a , (+)-20f, (+)-20h , (-)-21,
(+)-22-28, and (+)-32. This material is available free of charge
via the Internet at http://pubs.acs.org.
268 (M++ 1, 11), 267 (M+, 53), 118 (100). Anal. Calcd for C17H17
-
NO2: C, 76.38; H, 6.41; N, 5.24. Found: C, 76.42; H, 6.41; N,
5.32.
Tr icyclic 2-Azetid in on e 30: colorless oil. 1H NMR (DMSO-
d6): δ 3.12 (s, 1H), 3.15 (s, 2H), 3.35 (s, 1H), 3.70 (s, 3H), 6.87
J O991641J