Ferrier-petasis rearrangement of 4-(vinyloxy)azetidin-2-ones: An entry to carbapenams and carbacephams

Article abstract of DOI:10.1021/jo101463w

Trimethylsilyl triflate promotes Ferrier-Petasis rearrangement of 4-(vinyloxy)-, 4-(propenyloxy)-, and 4-(isopropenyloxy)azetidin-2-ones to corresponding 4-(carbonylmethyl)azetidin-2-ones. The latter compounds may serve as attractive intermediates in the synthesis of carbapenem antibiotics. To illustrate the potential of this reaction, selected rearrangement products have been transformed into carbapenams.

Full text of DOI:10.1021/jo101463w

pubs.acs.org/joc
the N-acyliminium cations can be generated in acidic media
Ferrier-Petasis Rearrangement of
4-(Vinyloxy)azetidin-2-ones: An Entry to
Carbapenams and Carbacephams
from lactams bearing a leaving group in a position R to the
nitrogen atom.2 Recently, we have shown that 4-(vinyloxy)-
azetidin-2-one (1) is an attractive starting material for the
synthesis of 5-oxa-3 and 5-carbacephams.4 In contrast to the
commercially available 4-acetoxyazetidin-2-one,5 1 allows
for the N-alkylation of the substrate prior to the nucleophilic
substitution at the C-4 carbon atom.3,4 Subsequently, the
readily available acyloxyl (formyloxyl, obtained by ozono-
lysis of the vinyl double bond, for example), in the presence
of a Lewis acid, may undergo an intramolecular displace-
ment leading to ring closure.3,4 We have shown that, in the
presence of acid catalysts, the vinyloxyl can also play a role of
a leaving group to make possible generation of N-acylimi-
nium cations and consequently to promote reactions similar
to those of its 4-acyl congener.3,4,6 It is worth noting that
nucleophilic substitution at C-4 can be done as an intermo-
lecular process.3,4,7
Anna Kozioz,† Barbara Grzeszczyk,† Andrzej Kozioz,‡
Olga Staszewska-Krajewska,† Bartzomiej Furman,† and
Marek Chmielewski*,†
†Institute of Organic Chemistry of the Polish Academy of
Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland, and
‡Warsaw University of Technology, Faculty of Chemistry,
Koszykowa 75, 00-662 Warsaw, Poland
chmiel@icho.edu.pl
Received July 26, 2010
Unlike other common Lewis acids, which when added to a
mixture of 4-(vinyloxy)- or 4-(acyloxy)azetidinones with
nucleophilic reagents promote substitution at the C-4 carbon
atom, Me3SiOTf behaves in a different manner. It promotes
a Ferrier-Petasis rearrangement8 leading to 4-(formylmethyl)-
azetidinone (Scheme 1). The mechanism of this reaction
involves attack of trimethylsilyl triflate at the vinyloxyl
oxygen atom to form a silyl enol ether and an accompanying
N-acyliminium cation. Subsequently, as in the case of the
Mukaiyama reaction,9 the enol silyl ether adds to the electro-
philic center, C-4 of the azetidinone, to produce the correspond-
ing aldehyde (Scheme 1). The formation of rearrangement
ꢀ
(4) (a) Zambron, B.; Masnyk, M.; Furman, B.; Chmielewski, M. Tetra-
Trimethylsilyl triflate promotes Ferrier-Petasis rearrange-
ment of 4-(vinyloxy)-, 4-(propenyloxy)-, and 4-(isopro-
penyloxy)azetidin-2-ones to corresponding 4-(carbony-
lmethyl)azetidin-2-ones. The latter compounds may serve
as attractive intermediates in the synthesis of carbapenem
antibiotics. To illustrate the potential of this reaction,
selected rearrangement products have been transformed
into carbapenams.
hedron 2009, 65, 4440. (b) Grzeszczyk, B.; Szechner, B.; Furman, B.;
Chmielewski, M. Tetrahedron 2010, 66, 3904.
(5) (a) Clauss, K.; Grimm, D.; Prossel, G. Liebigs Ann. Chem. 1974, 539.
(b) Hoppe, D.; Hilpert, T. Tetrahedron 1987, 43, 2467. (c) De Bernardo, S.;
Tengi, J. P.; Sasso, G. J.; Weigele, M. J. Org. Chem. 1985, 50, 3457. (d) Singh,
G. S. Tetrahedron 2003, 59, 7631. (e) Georg, G. I., Ed. The Organic Chemistry
of β-Lactams; VCH: Weinheim, Germany, 1993.
_
(6) Kazuza, Z.; Park, S.-H. Synlett 1996, 895.
(7) (a) Campbell, M. M.; Nelson, K. H.; Cameron, A. F. J. Chem. Soc.,
Chem. Commun. 1979, 532. (b) Arnoldi, A.; Merlini, L.; Scaglioni, L.
J. Heterocycl. Chem. 1987, 75. (c) Kozioz, A.; Furman, B.; Frelek, J.;
ꢀ
Woznica, M.; Altieri, E.; Chmielewski, M. J. Org. Chem. 2009, 74, 5687.
(8) (a) Ferrier, R. J. J. Chem. Soc., Perkin Trans. 1 1979, 1455. (b) Ferrier,
R. J.; Hoberg, J. O. Adv. Carbohydr. Chem. Biochem. 2003, 58, 55. (c) Ferrier,
R. J.; Middleton, S. Chem. Rev. 1993, 93, 2779. (d) Meek, S. J.; Harrity,
J. P. A. Tetrahedron 2007, 63, 3081. (e) Petasis, N. A.; Akritopoulou, I.
Tetrahedron Lett. 1993, 34, 586. (f) Petasis, N. A.; Lu, S.-P. J. Am. Chem. Soc.
1995, 117, 6394. (g) Petasis, N. A.; Lu, S.-P. Tetrahedron Lett. 1996, 37, 141.
(h) Frauenrath, H.; Arenz, T.; Raabe, G.; Zorn, M. Angew. Chem., Int. Ed.
Engl. 1993, 32, 83. (i) Kozikowski, A. P.; Park, P. J. Org. Chem. 1984, 49,
1674. (j) Kozikowski, A. P.; Park, P. J. Am. Chem. Soc. 1985, 107, 1763.
(k) Tayama, E.; Hashimoto, R. Tetrahedron Lett. 2007, 48, 7950. (l) Tayama,
E.; Isaka., W. Org. Lett. 2006, 8, 5437. (m) Tayama, E.; Otoyama, S.; Isaka,
W. Chem. Commun. 2008, 4216. (n) Terada, M.; Toda, Y. J. Am. Chem. Soc.
2009, 131, 6354.
(9) For reviews see: (a) Carreira, E. M. Mukaiyama aldol reaction. In
Comprehensive Asymmetric Catalysis I-III; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer-Verlag: Berlin, Germany, 1999; Vol. 3,
p 997. (b) Ishihara, K.; Yamamoto, H. Boron and Silicon Lewis Acids for
Mukaiyama Aldol Reactions. In Modern Aldol Reactions; Mahrwald, R.,
Ed.; Wiley-VCH: Weinheim, Germany, 2004; Vol. 2, p 25. (c) Hosokawa, S.;
Tatsuta, K. Asymmetric Vinylogous Mukaiyama Aldol Reactions Using
Vinylketene N,O-Acetals in Total Syntheses of Natural Products. In Mini-
Reviews in Organic Chemistry; Atta-ur-Rahman, Ed.; Bentham Science:
Bussum, Netherlands, 2008; Vol. 5, p 1.
N-acyliminium ions are important reactive intermediates
in organic synthesis that can act as electron-deficient carbo-
cations toward weak, soft nucleophiles, providing useful
methodologies for both inter- and intramolecular carbon-
carbon and carbon-heteroatom bond formation.1 In particular,
(1) Royer, J.; Bonin, M.; Micouin, L. Chem. Rev. 2004, 104, 231.
(2) Maryanoff, B. E.; Zhang, H. C.; Cohen, J. H.; Turchi, I. J.; Maryanoff,
C. A. Chem. Rev. 2004, 104, 1431.
_
(3) (a) Kazuza, Z.; Łysek, R. Tetrahedron: Asymmetry 1997, 8, 2553.
_
_
(b) Kazuza, Z. Tetrahedron Lett. 1998, 39, 8349. (c) Kazuza, Z. Tetrahedron
€
_
Lett. 1999, 40, 1025. (d) Furman, B.; Thurmer, R.; Kazuza, Z.; Łysek, R.;
Voelter, W.; Chmielewski, M. Angew. Chem, Int. Ed. 1999, 38, 1121.
_
(e) Kazuza, Z.; Furman, B.; Krajewski, P.; Chmielewski, M. Tetrahedron
_
ꢀ
2000, 56, 5553. (f) Kazuza, Z.; Kazimierski, A.; Lewandowski, K.; Suwinska,
K.; Szcze-sna, B.; Chmielewski, M. Tetrahedron 2003, 59, 5893. (g) Kozioz, A.;
ꢀ
Frelek, J.; Woznica, M.; Furman, B.; Chmielewski, M. Eur. J. Org. Chem.
2009, 338.
6990 J. Org. Chem. 2010, 75, 6990–6993
Published on Web 09/20/2010
DOI: 10.1021/jo101463w
r
2010 American Chemical Society

Kozioz et al.
JOCNote
SCHEME 1
SCHEME 3a
SCHEME 2a
aLegend: (i) 0.6 equiv of Zn(OAc)2 2H2O, 6 equiv of allyl alcohol,
3
PhMe, 80 °C, 24 h, 60%; (ii) 1.0 equiv of Bu4NBr, 5 equiv of PhCH2Br,
50% NaOH, PhMe, room temperature, 0.5 h, 90%; (iii) 1.0 equiv of
[Ni-H], THF, room temperature, 22-67%; (iv) 0.3 equiv of TMSOTf,
CH2Cl2, -30 °C.
aLegend: (i) 0.6 equiv of Zn(OAc)2 2H2O, 6 equiv of allyl alcohol,
3
PhMe, 80 °C, 12 h, 75%; (ii) 1.0 equiv of [Ni-H], THF, room tem-
perature, 56-68%; (iii) 1.0 equiv. of Bu4NBr, 5 equiv of PhCH2Cl, 50%
NaOH, PhMe, room temperature, 30 min, 90-92%; (iv) 0.3 equiv of
TMSOTf, CH2Cl2, -30 °C; (v) 1.1 equiv of TBSCl, 1.1 equiv of NEt3,
CH2Cl2, room temperature, 12 h, 96%; (vi) 1.0 equiv of Tebbe reagent,
PhMe, room temperature, 48 h; (vii) 1.1 equiv of Bu4NF, THF, 0 °C,
30 min, 95%; (viii) O3, CH2Cl2, -78 °C, than Me2S, 69%.
product 4was not observed for the N-unsubstituted 4-(vinyloxy)-
azetidinone (1). The mass spectrum of the crude postreaction
mixture showed the presence of the unstable dimeric struc-
tures 7 (MS: ESI, m/e 249, [M þ Na]þ), which was not iso-
lated and characterized, and the dioxacepham 8, which was
isolated in 20% yield. The NMR spectrum proved the struc-
ture and relative configuration of 8.
4-substituted carbapenems.12 We found that the ratio of Z and
E isomers depended on the type of catalyst (see the Support-
ing Information). Among the catalysts tested, NiCl2(PPh3)2
was found to be the most attractive, since within just 2 h it
provided exclusively the Z isomer in good yield. We have
found that both (Z)- and (E)-propenyl ethers 11, 17, and 30
furnished a similar ratio of the corresponding R-substituted
propyl aldehydes 12/13, 18/19, and 31/32. This observation
may suggest that under the reaction conditions (TMSOTf),
from both diastereomeric aldehydes 12/13, 18/19, and 31/32
the same corresponding TMS-enol ether is formed and
consequently the ratio of isomeric products does not depend
on an E,Z) configuration of the propenyl ethers11, 17, and 30.
Since the Z isomers 11a and 16a offered the most effective
rearrangement of allyl ethers into propenyl ones, they were
used for the next steps.
Since Me3SiOTf is the only currently known Lewis acid
that promotes the rearrangement, we were unable to test
whether the reaction can be carried out as an enantioselective
process. In the case of azetidinones 16, 17, 21, and 24 derived
from Kaneka’s compound 14, the absolute configuration at
C-4 of the azetidinone is well-defined since the nucleophile
approaches the four-membered ring exclusively anti to the
existing substituent at C-3.13
This Ferrier-Petasis rearrangement which offers an attrac-
tive entry to carbapenam and carbacepham antibiotics,10
prompted us to investigate its scope and limitation. In order
to avoid formation of compounds analogous to 7 and 8, a
comparison of the reactivity of different 4-vinyloxy-azetidi-
nones and their methyl substituted congeners (propenyloxy
and isopropenyloxy) was carried out with respective N-benzyl-
azetidinones. As model substrates compounds 2, 3, 11, 17, 21,
and 24, derived from 4-vinyloxy-azetidinone (1) and commer-
cially available Kaneka’s azetidinone 1411 were selected.
Compounds 2, 3, 11, 17, 21, and 24 were obtained by
standard reaction sequences which involved either nucleo-
philic substitution at C-4 of azetidinones with allyl alcohol
followed by a nickel-catalyzed migration of the double bond
and subsequent N-benzylation or treatment of the 4-acyloxy
group (formyloxyl or acetoxyl) with Tebbe’s methylation
reagent.12 The latter reaction can be performed only if the
β-lactam nitrogen atom is protected by a silyl or benzyl group.
4-(Propenyloxy)azetidinones can be N-benzylated as easily
as their 4-vinyloxy congeners (Schemes 2 and 3). All reac-
tions smoothly proceeded to provide the expected products
in good yields.
Special attention was directed at the rearrangement of allyl
ethers into the corresponding (Z)- and (E)-propenyl species,
since this reaction could offer an entry to biologically active
In order to demonstrate the usefulness of the reported
Ferrier-Petasis rearrangement in the synthesis of carbape-
nams, we carried out a reaction sequence following the pro-
tocol of Hanessian at al.14 (Schemes 4 and 5). Compound 6
was selected as the starting material. An analogous reaction
sequence was applied to the isomeric compounds 31 and 32,
readily available from 16 by the N-alkylation-rearrange-
ment sequence. In the latter case, we intended to examine
(10) Oida, S. Recent Advances in β-Lactam Antibiotics; Royal Society of
Chemistry: London, 1981; p 330.
(11) (a) Berks, A. H. Tetrahedron 1996, 52, 331. (b) Ohki, E.; Oida, S.;
Yoshida, A.; Hayashi, T.; Sugawara, S. U.S. Patent US 4395418, July 26,
1983 (Derwent WPI 81-95037D).
(12) Tebbe, F. N.; Parshall, G. W.; Reddy, G. S. J. Am. Chem. Soc. 1978,
100, 3611.
J. Org. Chem. Vol. 75, No. 20, 2010 6991

Kozioz et al.
JOCNote
SCHEME 4a
H-2, H-3, and H-5 protons. The relative configuration in 28
was found to be the same as that of compound 29 obtained by
Hanessian’s group.14
The same reaction sequence was carried out with the
isomerically defined 16a (Scheme 5). 16a was alkylated with
benzyl bromoacetate to afford 30, which subsequently was
subjected to a Ferrier-Petasis rearrangement to afford an
inseparable mixture of 31 and 32 in a ratio of about 7:1. The
configuration of both products was established by analyzing
the results of the subsequent steps of the synthesis.
A mixture of 31 and 32 was subjected to the same sequence
of reactions as for compound 6 to afford a mixture of
carbapenams 35 and 36 in a ratio of about 7:1, respectively,
which was separated by HPLC into individual pure compo-
nents. The assignment of the absolute configuration of dia-
stereomers 35 and 36 was established as above by NOE’s.
The proportion of stereoisomers did not change during
transformation steps from 31/32 to 35/36; therefore, the ab-
solute configuration of the R-substituted propanal fragment
at C-4 of the azetidinone ring in 31 and 32 was assumed to be
the same. By analogy, the same structural assignment can be
made for the stereoisomeric pairs 12/13 and 18/19.
aLegend: (i) 2.0 equiv of DBU, CH3NO2, -20 °C, 1 h; (ii) 1.1 equiv of
MsCl, 2.2 equiv of Et3N, CH2Cl2, room temperature, 3 h; (iii) 1.1 equiv
of LiHMDS, THF, -78 °C, 1 h.
SCHEME 5a
It was demonstrated that the Ferrier-Petasis rearrange-
ment at the C-4 carbon atom of azetidin-2-ones can be
performed in good yield, and this reaction offers an attrac-
tive entry to carbapenem and carbacephem antibiotics.
So far, the enantioselective protocol was not achieved, owing
to the specific character of the activating reagent, which
enables silylation of the vinyloxyl oxygen atom. In the case of
a diastereoselective process, however, the Ferrier-Petasis
rearrangement offers an alternative entry to known antibio-
tics. It is also worth noting that Tebbe’s olefination reaction
can be used to effectively modify the 4-acyl group to give
simple vinyloxy or isopropenyloxy residues.
aLegend: (i) 0.3 equiv of TMSOTf, CH2Cl2, -30 °C, 1 h; (ii) 2.0 equiv
of DBU, CH3NO2, -20 °C, 1 h; (iii) 1.1 equiv of MsCl, 2.2 equiv of
Et3N, CH2Cl2, room temperature, 3 h; (iv) 1.1 equiv of LiHMDS, THF,
-78 °C, 1 h.
whether Hanessian’s reaction sequence,14 when applied to
the 4-propenyloxy compounds, would furnish the 4-methyl-
carbacephams. Moreover, the transformation of 16 into 35
and 36 should verify the configuration of both Ferrier-Peta-
sis rearrangement products 31 and 32 if the R-substituted
propanal fragment does not undergo epimerization under
the reaction conditions.
Compound 6 was subjected to a nitro aldol reaction with
nitromethane followed by a two-step sequence (elimination of
water and intramolecular conjugated addition to the double
bond) that led to the racemic compound 28 as the sole product
(Scheme 4). The relative configuration at the three stereogenic
centers in 28 was established with the help of NOE experi-
ments, which showed spin-spin interactions between the
Experimental Section
Typical Procedure for Rearrangement of Allyl Ethers. To a
solution of NiCl2(PPh3)2 (0.196 g, 0.3 mmol, 1.0 equiv) in THF
(5 mL) at room temperature was added LiBHEt3 in THF (0.3 mL,
1.0 M, 1.0 equiv) under an argon atmosphere. After 15 min allyl
ether 10 (65 mg, 0.3 mmol, 1.0 equiv) was added. The reaction
mixture was stirred for 2 h until disappearance of the starting
material (TLC) and diluted with 5% HCl (5 mL). The aqueous
phase was extracted with ether (3 ꢀ 10 mL). The organic extracts
were combined and dried over Na2SO4. The solution was filtered
and the filtrate evaporated. The crude product was purified by
column chromatography (silica gel, 2:3 hexane-diethyl ether) to
give 44 mg (0.20 mmol) of 11a as a yellow species: yield 67%. IR
(film): ν 1764 cm-1. 1H NMR (500 MHz, CDCl3): δ 1.57 (dd, J =
6.9, 1.8 Hz, 3H, CH3CHd), 2.96 (dd, J = 14.9, 1.2 Hz, 1H, CH2),
3.12 (dd, J = 14.9, 3.9 Hz, 1H, CH2), 4.11 (d, J = 15.2 Hz, 1H,
CH2N), 4.57 (dq, J = 6.2, 6.9 Hz, 1H, dCHCH3), 4.66 (d, J =
15.2 Hz, 1H, CH2N), 5.08 (dd, J = 3.9, 1.2 Hz, 1H, CHO), 5.94
(dq, J = 6.2, 1.8 Hz, 1H, CHd), 7.28 (m, 2H, Ph), 7.34 (m, 3H,
Ph). 13C NMR (125 MHz, CDCl3): δ 9.4, 44.5, 80.9, 105.1, 127.8,
128.4, 128.8, 135.4, 140.5, 165.5. HR MS (ESI): m/z calcd for
[M þ Na]þ C13H15NO2Na 240.0995, found 240.0993.
(13) (a) Neu, H. C.; Novelli, A.; Chin, N.-X. Antimicrob. Agents Che-
€
mother. 1989, 33, 1009. (b) Schmidt, G.; Schrock, W.; Endermann, R. Bioorg.
Med. Chem. Lett. 1993, 3, 2193. (c) Imuta, M.; Itani, H.; Ona, H.; Konoike,
T.; Uyeo, S.; Kimura, Y.; Miwa, H.; Matsuura, S.; Yoshida, T. Chem.
Pharm. Bull. 1991, 39, 672. (d) Shih, D. H.; Baker, F.; Cama, L.; Christensen,
B. G. Heterocycles 1984, 21, 29. (e) Nagao, Y.; Kumagai, T.; Nagase, Y.;
Tamai, S.; Inoue, Y.; Shiro, M. J. Org. Chem. 1992, 57, 4232. (f) Shibuya, M.;
Kubota, S. Tetrahedron Lett. 1980, 21, 4009. (g) Sunagawa, M.; Matsumura,
H.; Inoue, T.; Fukasawa, M.; Kato, M. J. Antibiot. 1990, 43, 519. (h) Kant, J.;
Walker, D. G. In The Organic Chemistry of β-Lactams; Georg, G. I., Ed.;
VCH: Weinheim, Germany, 1993; p 121. (i) Alcaide, B.; Almendros, P. Curr.
Org. Chem. 2002, 6, 245. (j) Alcaide, B.; Almendros, P. Top. Heterocycl.
Chem. 2010, 22, 1. (k) Troisi, L.; Granito, C.; Pindinelli, E. Top. Heterocycl.
Chem. 2010, 22, 101.
Typical Procedure for Ferrier-Petasis Rearrangement. To a
solution of β-lactam 2 (102 mg, 0.5 mmol, 1.0 equiv) in CH2Cl2
(10 mL) was added TMSOTf (27 μL, 0.15 mmol, 0.3 equiv) at
-30 °C under an argon atmosphere. The reaction mixture was
stirred at 0 °C until disappearance of the starting material (TLC)
and diluted with saturated NaHCO3 (10 mL). The aqueous
phase was extracted with CH2Cl2 (3 ꢀ 15 mL). The organic
(14) Hanessian, S.; Desilets, D.; Bennani, Y. J. Org. Chem. 1990, 55, 3098.
6992 J. Org. Chem. Vol. 75, No. 20, 2010

Kozioz et al.
JOCNote
extracts were combined and dried over MgSO4. The solution
was filtered and the filtrate evaporated. The crude product was
purified by column chromatography (silica gel, 95:5 dichloro-
methane-diethyl ether) to give 49 mg (0.24 mmol) of 5 as a
colorless oil: yield 48%. IR (film): ν1732 cm-1.1HNMR(500MHz,
CDCl3): δ 2.63 (ddd, J = 18.1, 6.6, 1.0 Hz, 1H, CH2CO), 2.66 (dd,
J = 14.8, 2.2 Hz, 1H, CH2), 2.73 (ddd, J = 18.1, 6.1, 1.0 Hz, 1H,
CH2CO), 3.21 (dd, J = 14.8, 5.1 Hz, 1H, CH2), 3.95 (m, 1H, CH),
4.36 (d, J = 15.2 Hz, 2H, CH2N), 7.25-7.36 (m, 5H, Ar), 9.62
(t, J = 1.0 Hz, 1H, CHO). 13C NMR (125 MHz, CDCl3): δ 43.1,
45.3, 46.1, 47.6, 127.9, 128.4, 128.6, 136.0, 166.5, 198.81. HR MS
(ESI): m/z calcd for [M þ MeOH þ Na]þ C13H17NO3Na
258.1101, found 258.1094.
Typical Procedure for Reaction with Tebbe’s Reagent. To a
solution of β-lactam 23 (78 mg, 0.3 mmol, 1.0 equiv) in toluene
(5 mL) at room temperature was added Tebbe’s reagent in
toluene (0.6 mL, 0.5 M, 1.0 equiv) under an argon atmosphere.
The reaction mixture was stirred for 48 h until disappearance of
starting material (TLC) and diluted with 5% HCl (5 mL). The
aqueous phase was extracted with ethyl acetate (3 ꢀ 10 mL). The
organic extracts were combined and dried over MgSO4. The solu-
tion was filtered and the filtrate evaporated. The crude product
was purified by column chromatography (silica gel, 4:1 hexane-
ethyl acetate) to give 65 mg (0.18 mmol) of 24 as a yellow wax:
yield 60%. [R]D =þ8.05° (c=0.8, CHCl3).IR(film):ν1771 cm-1
.
1H NMR (500 MHz, CDCl3): δ 0.03, 0.06 (2 s, 6H, (CH3)2Si),
0.83 (s, 9H, (CH3)3CSi), 1.23 (d, 3H, J = 6.1 Hz, CH3CH), 3.11
(d, J = 3.6 Hz, 1H, CH), 4.11 (dd, J = 6.3, 1.5 Hz, 1H, CH2d),
4.21-4.14 (m, 2H, CH-OTBS, CH2N), 4.39 (d, J = 15.2 Hz, 1H,
CH2N), 4,45 (dd, J = 13.9, 1.5 Hz, 1H, CH2d); 5.19 (s, 1H,
CHO), 6.21 (dd, J = 13.9, 6.3 Hz, 1H, CHd), 7.36-7.24 (m, 5H,
Ph). 13C NMR (125 MHz, CDCl3): δ -4.7, -4.6, 17.9, 22.6,
25.7, 44.3, 64.1, 65.0, 82.8, 92.1, 127.7, 128.4, 128.7, 128.8,
135.2, 148.1, 166.3. HR MS (ESI): m/z calcd for [M þ Na]þ
C20H31NO3NaSi 384.1965, found 384.1950.
Acknowledgment. This work was partially supported by
the Ministry of Education and Science, Grant No. N204
192738. A.K. thanks the President of the Polish Academy of
Sciences for a doctoral fellowship.
Supporting Information Available: Text, figures, and tables
giving general experimental procedures, characterization data,
and 1H NMR and 13C NMR spectra of all new compounds and
additional information on the rearrangement of allyl ethers.
This material is available free of charge via the Internet at http://
pubs.acs.org.
J. Org. Chem. Vol. 75, No. 20, 2010 6993