Diastereoselective [4+3] cycloadditions of enantiopure nitrogen-stabilized oxyallyl cations

Article abstract of DOI:10.1002/ejoc.200600226

Diastereoselective trapping of chiral enantiopure oxyallyl cations by common dienes is reported. Excellent diastereoselectivities were obtained and depending on which auxiliary was used cycloadditions proceeded through a chelated or non-chelated pathway.

Full text of DOI:10.1002/ejoc.200600226

FULL PAPER
DOI: 10.1002/ejoc.200600226
Diastereoselective [4+3] Cycloadditions of Enantiopure Nitrogen-Stabilized
Oxyallyl Cations
David I. MaGee,*[a] Edouard Godineau,[a] Paul D. Thornton,[a] Michael A. Walters,[b][‡] and
Deborah J. Sponholtz[b][‡‡]
Keywords: Cycloaddition / Diastereoselectivity / Chiral auxiliaries / Oxyallyl cations
Diastereoselective trapping of chiral enantiopure oxyallyl
cations by common dienes is reported. Excellent diastereo-
selectivities were obtained and depending on which auxil-
iary was used cycloadditions proceeded through a chelated
or non-chelated pathway.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
crude mixtures of [4+3] cycloadditions.[1] A large variety of
methods have been developed in order to generate oxyallyl
Introduction
[4+3] Cycloadditions between oxyallyl cations and com- cation intermediates, including reductive, acido-solvolytic
mon cyclic 1,3-dienes[1] offer easy access to highly versatile or basic conditions.[1] However, it was not until this past
seven-membered rings. Not only are such rings found in a decade that the first asymmetric versions appeared in the
great number of natural products like tropane alkaloids,[2] literature.[4] Most notable are examples using chiral ace-
but also the resulting [3.2.1] bicyclic ketones formed tals[4] or via epoxidation of enantiopure allenamides,[4] as
through cycloaddition with cyclic dienes, due to their rigid well as a recent enantioselective variant.[4]
conformations, are amenable to further regio- and stere-
Our laboratories successfully demonstrated the viability
ospecific transformations.[3] Extensive studies over the past of nitrogen-substituted oxyallyl cations a few years ago.[5,6]
thirty years have provided a good understanding of the rela- One of the major advantages of this type of oxyallyl cation
tive stereochemical outcome (endo vs. exo) observed in was the possibility to include the nitrogen atom in an op-
Scheme 1. Postulated mechanism of [4+3] cycloadditions under Föhlisch conditions.
[a] Department of Chemistry, University of New Brunswick,
P. O. Box 45222 Fredericton, New Brunswick, E3B 6E2,
Canada
tically pure heterocycle and potentially induce asymmetry
into the reaction. Recently Hsung et al. elegantly showed
that heterocycles such as Evans-type oxazolidinones were
excellent candidates for this task and that good levels of
diastereoselectivity could be achieved.[7]
During this same time period we were working on ex-
tending our previous studies on nitrogen-substituted oxyal-
lyl cations to an asymmetric variant. However, unlike
Hsung, who generated his oxyallyl cations by low-tempera-
E-mail: dmagee@unb.ca
[b] Department of Chemistry, Dartmouth College,
6128 Burke Laboratory, Hanover, New Hampshire, NH 03755,
USA
[‡] New address: Pfizer Global Research and Development, Ann
Arbor Laboratories, Lead Discovery Group, 2800 Plymouth
Road, Ann Arbor, MI 48105, USA
[‡‡] New address: Chembiotek, 39 School Street, Ashburnham,
MA 01430, USA
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FULL PAPER
ture oxidation of allenamides with dimethyldioxirane
(DMDO), we were attracted to the more straightforward
Föhlisch conditions, α-substituted α-bromo ketones under
basic conditions (typically triethylamine or sodium 2,2,2-
trifluoroethoxide),[8] in a polar media (MeOH or 2,2,2-tri-
fluoroethanol) (Scheme 1). We wish herein to report our
contribution toward the diastereocontrol of [4+3] cycload-
ditions involving chiral enantiopure oxyallyl cations under
such basic conditions and therefore set an alternative entry
to Hsung’s oxidative procedure.[4]
tion, and could be readily stored for long periods of time
in a refrigerator.[9] Gas evolution was immediately observed
upon exposure of 48% aqueous HBr to ice-cold dichloro-
methane solutions of diazo ketones 1e, 2e and 3e, thus pro-
viding quick and easy access to the α-bromo ketone inter-
mediates 1–3.[9] The α-bromo ketones were quite sensitive
and readily decomposed on standing at room temperature
or attempted silica gel chromatography. Consequently once
the precursors were prepared they were immediately sub-
jected to the cycloaddition reaction. Although it took 5
steps to generate the requisite precursors, the sequence pro-
ceeded in good overall yields and was completely amenable
to larger scale preparation.
Results and Discussion
Upon subjection of bromo ketones 1–3 to the cycload-
dition conditions developed by Föhlisch (CF3CH2OH,
Et3N),[8] in the presence of a large excess of diene (10 to
20 equiv.), the expected [4+3] cycloadditions readily oc-
curred, in moderate to good chemical yields (Table 1). Cy-
cloadditions involving 1 and 2 afforded the corresponding
bicyclic ketones 6a–c, 7a–c, 9a–c and 10a–c with excellent
relative stereoselectivity (endo vs. exo, see structural assign-
ment, vide supra), but with very moderate facial diastereo-
selectivities (Table 1).
Diastereoselective [4+3] Cycloadditions with Furan and
Cyclopentadiene
In initial studies, we decided to focus on the common
chiral oxazolidinones of type 1a, 2a and 3a, derived respec-
tively from phenylglycine, phenylalanine and tert-leucine,
because they were shown to be excellent chiral auxiliaries
in a variety of other asymmetric processes.[7] The synthesis
of our precursors commenced, as depicted in Scheme 2, by
alkylation of enantiopure chiral oxazolidinones 1a, 2a and
3a, with ethyl bromoacetate (NaH, THF, 0 °C), affording
Surprisingly, a low endo/exo ratio, unusual under these
alkyl esters 1b, 2b and 3b in good yields.[9] Saponification conditions, was observed during the course of the cycload-
readily occurred upon subjection of these oxazolinyl acetate dition of 2 and cyclopentadiene (Entry 5). As expected, in-
esters to an alkaline media (NaOH, THF, 0 °C) providing creasing the steric hindrance lead to significant improve-
the corresponding acetic acids.[9a] The diazo ketones 1e, 2e ment concerning the facial selectivity and ratios up to 95:5
and 3e were generated by converting the carboxylic acids were observed when the oxyallyl cation derived from the 4-
1c, 2c and 3c to their acid chlorides (respectively 1d, 2d and tert-butyloxazolidinyl bromo ketone 3 was treated with fu-
3b) (oxalyl chloride, THF, reflux), followed by trapping ran (Entries 3 and 6). In each case, major endo-cycloadducts
with diazomethane (ethereal solution, 0 °C). These com- were isolated diastereomerically pure by standard chroma-
pounds were then easily purified by standard column tographic techniques or recrystallization in good chemical
chromatography on silica without any observed degrada- yields.
Scheme 2. Synthesis of chiral nonracemic oxyallyl precursors 1–5.
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Cycloadditions of Enantiopure Nitrogen-Stabilized Oxyallyl Cations
FULL PAPER
Table 1. Diastereoselectivities obtained in [4+3] cycloadditions of 1, 2, and 3.
Entry
Bromo ketone[a]
Xn see Scheme 2
Diene
Products
endo/exo[c]
(a + b)/c
dr[c]
a/b
Yield[b]
[%]
1
2
3
4
5
6
1
2
3
1
2
3
furan
furan
furan
Cp
Cp
Cp
6a–c
7a–c
8a–c
9a–c
10a–c
11a–c
93:7
90:10
95:5
93:7
67:3
89:11
66:34
67:33
95:5
66:34
67:33
89:11
70
70
80
65
65
70
[a] Typical conditions: 1 equiv. of bromo ketone in diene (0.25 ), trifluoroethanol (0.5 ), followed by 1.5 equiv. of Et3N. [b] Combined
isolated yield. [c] Measured by GC.
X-ray crystallographic analyses of the resulting cycload- oxazolidinyl bromo ketone 1, with magnesium bromide
ducts allowed us to unambiguously assign the absolute proved encouraging as facial diastereoselectivities with both
stereochemistry of the three new stereogenic centers created furan and cyclopentadiene were significantly improved
during the cycloaddition. Similarly to Hsung’s observa- from a disappointing 2:1 ratio to a more acceptable 4:1 ratio
tions,[4] the stereochemical outcome of this type of [4+3] with the inclusion of MgBr2, (Table 2, Entries 2 and 4), al-
cycloaddition was consistent with a concerted transition beit with slightly reduced yields and/or relative stereoselecti-
state, where the diene approached from the least congested vities. Unfortunately, bromo ketones 2 and 3 did not offer
face of the most stable W-form of the oxyallyl cation (Fig- any benefit under such conditions as lower diastereoselec-
ure 1).[10] The acidity of 2,2,2-trifluoroethanol was presum- tivities were observed along with lower yields.
ably sufficient to render the alcoholic proton capable of che-
The decreased diastereoselections observed with 3 might
lating the two carbonyl units in a seven-membered ring be attributed to a lower propensity of lithium and magne-
transition state, as predicted by computational calculations sium oxyallyls to form seven-membered chelating rings or
previously carried out by our laboratories.[5]
might simply be a consequence of a larger excess of “avail-
It was felt at this stage that the diastereoselectivity might able chelating agent”, because, as in our first series of re-
be improved by the use of stronger chelating Lewis acids sults, 2,2,2-trifluoroethanol was used as the solvent.
such as lithium perchlorate or magnesium bromide, in an
Our efforts towards the organization of a structurally de-
aprotic media such as acetonitrile.[11,12] Initial results using fined transition state therefore lead us to investigate the
Figure 1. Chelated model proposed for [4+3] cycloaddition with 1, 2 and 3.
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D. I. MaGee, E. Godineau, P. D. Thornton, M. A. Walters, D. J. Sponholtz
Table 2. Diastereoselectivities obtained in the presence of Lewis acids.
FULL PAPER
Entry
Bromo ketone[a]
Xn see Scheme 2
Diene
Products
Lewis acid
endo/exo[c]
(a + b)/c
dr[c]
a/b
Yield[b]
[%]
1
2
3
4
5
6
7
8
1
1
1
1
2
2
2
2
3
3
3
3
furan
furan
Cp
6a–c
6a–c
7a–c
7a–c
8a–c
8a–c
9a–c
9a–c
10a–c
10a–c
11a–c
11a–c
LiClO4
MgBr2
LiClO4
MgBr2
LiClO4
MgBr2
LiClO4
MgBr2
LiClO4
MgBr2
LiClO4
MgBr2
85:15
98:2
67:33
98:2
22
40
45
50
35
40
60
50
25
20
25
20
71:29
86:14
88:12
89:11
88:12
77:23
89:11
77:23
83:17
83:17
71:29
86:14
88:12
89:11
88:12
77:23
89:11
77:23
83:17
83:17
Cp
furan
furan
Cp
Cp
9
furan
furan
Cp
10
11
12
Cp
[a] Typical conditions: 1 equiv. of bromo ketone in CH3CN (0.25 ), 4 equiv. of Lewis acid, 20 equiv. of diene followed by 1.7 equiv. of
Et3N. [b] Combined isolated yield. [c] Measured by GC.
closely related ephedrine-derived imidazolidinone 10,[13] in Diels–Alder reactions and organocuprate conjugate ad-
which the lone pairs on the carbonyl oxygen should be more dition.[15] Given these successes, it was felt that these types
basic and thus better adept at chelating with a Lewis acid. of auxiliaries should be investigated in our [4+3] cycload-
Unfortunately reacting this new oxyallyl precursor with fu- ditions.
ran or cyclopentadiene did not lead to any improvement
Syntheses of these auxiliaries were achieved according to
and only identical diastereomeric ratios as those observed methods described in the literature [except for the resolu-
with 1 were obtained. Given this lack of improvement, we tion of the tricyclic oxazolidinone 5a, which was conve-
abandoned this route, even though it has been shown that niently realized with the readily available (1S,4R)-cam-
replacing the methyl substituent on similar imidazolidinyl phanic acid chloride,[16] see experimental section for de-
auxiliaries have resulted in increased diastereoselection in tails].[15] Applying our five-step sequence to 4a and 5a
other processes (Scheme 3).[14]
yielded the expected α-bromo ketones 4 and 5, respectively,
Examination of Table 1 clearly indicates that increasing in good overall yields. To our delight, both auxiliary-bound
the steric bulk of the oxazolidinone five-membered ring re- oxyallyl precursors afforded [4+3] cycloadducts with excel-
sults in increased levels of stereoinduction. With this in lent diastereoselectivities, and chemical yields (Table 3). Op-
mind it was felt that if increased steric bulk could be incor- timal conditions for cycloaddition of the oxyallyl cation
porated in the oxazolidinone ring then there was a good arising from 5 required, however, the increase of the diene
chance of getting superior results. Kunieda et al. recently amount to 200 equiv. due to a significant amount of 2,2,2-
designed two new classes of chiral oxazolidinones, 4a and trifluoroethanol by-products. Presumably the amount of
5a, that are highly sterically congested and conformation- diene could be reduced if the solvent was changed to
ally rigid (Scheme 2). These auxiliaries were reported to in- 1,1,1,3,3,3-hexafluoropropanol. To the best of our knowl-
duce exceptional facial discrimination, particularly in edge, such facial diastereoselections using chiral nitrogen sub-
Scheme 3. Imidazolidinone-derived bromo ketone 12.
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Cycloadditions of Enantiopure Nitrogen-Stabilized Oxyallyl Cations
FULL PAPER
Table 3. Diastereoselectivities obtained with 4 and 5.
Entry
Bromo ketone[a]
Xn see Scheme 2
Diene
Products
endo/exo[c]
(a + b)/c
dr[c]
a/b
Yield[b]
[%]
1
2
3
4
4
5
4
5
furan
furan
Cp
15a–c
16a–c
17a–c
18a–c
93:7
92:8
95:5
83:17
96:4
97:3
Ͼ 98:2
Ͼ 98:2
89
90
94
90
Cp
[a] Typical conditions: 1 equiv. of bromo ketone in diene (0.25 ), trifluoroethanol (0.5 ), followed by 1.5 equiv. of Et3N. [b] Combined
isolated yield. [c] 1H NMR ratio and isolated yield.
stituted oxyallyl cations are unprecedented, and it is also that dienes such as 3-bromofuran and methyl 1H-pyrrole-
noteworthy that examples of [4+3] cycloadditions proceed- 1-carboxylate would be of importance because they would
ing in essentially quantitative yields are rare.
provide access to regioselective functionalization of the ole-
To our surprise, X-ray crystallographic analyses assigned fin in the cycloadducts, thus providing a simple “handle”
absolute stereochemistries to the cycloadducts 17a and 18a to further manipulate the products, and to the important
consistent with a nonchelated transition state (Figure 2). tropane alkaloid framework, respectively. Reaction of each
The reason for this complete reversal of stereochemistry re- of these dienes (200 equiv.) with 5 proceeded readily with
mains unclear. Intervention of some type of chelation by excellent facial stereoselectivity in favour of the endo dia-
the silicon atom in 5 cannot be ruled out, however, this stereomers, albeit in modest yields (Table 4).
should be largely unfavoured due to the bulky groups di-
rectly linked to this atom, and such a chelation is not pos-
sible in 4. Clearly another as yet unidentified factor must
be responsible for this intriguing stereochemical phenome-
Structure Determination of the Cycloadducts
non. We briefly investigated the possibility of reversing this
The [3.2.1] bicyclic ketones formed were easily deter-
stereochemical outcome, however, efforts at forcing the re- mined to be endo or exo isomers, e.g. 6a–b and 6c simply
1
action to proceed through a chelated pathway by the ad- by looking at the H NMR signal of H1. In endo cycload-
dition of Lewis acid (MgBr2, LiClO4) remained unsuccess- ducts, the dihedral angle between H1 and H2, is close to 0°,
ful, because only slight diminutions in diastereoselectivities so H1 appears as a singlet (axial–equatorial J couplings Ϸ
were obtained.
0–2 Hz), as opposed to exo isomers, in which H1 appears
Given the remarkable ability of the above auxiliaries to as a doublet (equatorial–equatorial J coupling Ϸ 4–5 Hz).
effect diastereoselective [4+3] cycloadditon, we were inter- It was also usually observed that, like in cyclohexanone
ested in extending this study to other dienes. It was thought compounds, axial α protons are very often found downfield
Table 4. [4+3] Cycloaddition with 3-bromofuran and methyl 1H-pyrrole-1-carboxylate.
Entry
Bromo ketone[a]
X5 see Scheme 2
Diene
Products
endo/exo[c]
(a + b)/c
dr[c]
a/b
Yield[b]
[%]
1
2
5
5
3-bromofuran
methyl 1H-pyrrole-1-carboxylate 22
20–21
Ͼ 98:2
90:10
Ͼ 98:2
Ͼ 98:2
21
53
[a] Typical conditions: 1 equiv. of bromo ketone in diene (0.25 ), trifluoroethanol (0.5 ), followed by 1.5 equiv. of Et3N. [b] Combined
isolated yield. [c] 1H NMR ratio and isolated yield.
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FULL PAPER
Table 5. Predicted anisotropic effect on H3 and H4 chemical shift
in cycloadducts 6a and 6b.
Cycloadduct 6a
Cycloadduct 6b
Proton
H3
H4
H3
H4
Calculated
Experimental 5.08 ppm
5.34 ppm
6.13 ppm
6.16 ppm
7.08 ppm
7.58 ppm
6.28 ppm
6.19 ppm
Conclusions
We have demonstrated that chiral enantiopure nitrogen-
stabilized oxyallyl cations can undergo highly diastereo-
selective [4+3] cycloadditions with common cyclic 1,3-
dienes such as furan and cyclopentadiene. Using the bromo
ketone 3, excellent yields of cycloadducts were obtained
along with diastereoselectivities as high as 95:5 with furan
as a trapping agent, similar to the results obtained by
Hsung.[7] The absolute stereochemistries of the resulting bi-
cyclic ketones were consistent with a chelated transition
state. Surprisingly, but nevertheless quite fortuitous, a com-
plete reversal of the stereochemical course of the cycload-
dition towards a nonchelated pathway was obtained with
the enantiopure bromo ketones 4 and 5. Selective cleavage
of oxazolidinone auxiliaries, extension of the scope of the
method to substituted oxyallyl precursors, as well as efforts
concerning the design of enantioselective processes are cur-
rently sustaining our ongoing endeavours.
Figure 2. Nonchelated transition state proposed for diastereoselec-
tive [4+3] cycloaddition of 4 and 5.
from equatorial α protons.[17] Assignments of the absolute
stereochemistry (unambiguously verified by X-ray crystal-
lography), e.g. 6a and 6b, proved to also be possible by com-
mon NMR techniques. Strong magnetic anisotropies ob-
served in cycloadducts arising from 1, have been explained
by strong interaction of H2 with the chiral auxiliary (Fig-
ure 3).
Experimental Section
General Methods: All reactions were carried out in flame-dried
round-bottomed flasks (RBF) or in oven-dried glassware (pyrex)
(180 °C, 1 h) unless stated otherwise. Temperatures indicated refer
to an external bath. All reaction mixtures were stirred unless stated
otherwise. Standard techniques were used for solvent purifications.
Diethyl ether, tetrahydrofuran, xylenes, benzene and toluene were
distilled over sodium, using benzophenone as an indicator prior to
use. Dichloromethane, triethylamine and acetonitrile were distilled
over calcium hydride. Tetrahydrofuran, diethyl ether, dichlorometh-
ane, methanol, xylene, hexane, benzene and toluene were also avail-
able via the use of Grubbs type columns. Air and moisture sensitive
reagents were handled via standard techniques. Reagents were pur-
chased from common suppliers and used as received unless stated
otherwise. LiClO4 was recrystallized from H2O, dried overnight at
170 °C in an oven and stored in a dessicator. Diazomethane was
prepared according to literature methods.[9b,9c,9d] Analytical thin
layer chromatography (TLC) was performed using Merck 60 F-254
silica gel precoated aluminum plates (0.25 mm). Visualization was
effected by short-wave UV irradiation, and/or by potassium per-
Figure 3. Anisotropic effects on H3 and H4.
We corroborated our assumption on the structure of 6a,
1
by calculation of the H chemical shift of H3 and H4 in manganate or phosphomolybdic acid dip followed by staining on a
hot plate. SiO2 flash chromatography was performed using Silicycle
silica gel (30–60 µm particle size) or EM Reagents silica gel 60
(230–400 mesh). Nuclear magnetic resonance (NMR) spectroscopy
was performed with a Varian INNOVA 300 MHz or with a Varian
UNITY 400 MHz (referred to proton resonance frequency). 1H
NMR spectroscopic data are presented in parts per million (ppm,
δ) relative to tetramethylsilane as an internal standard. All proton–
proton NMR coupling constants (J) are expressed in Hertz (Hz).
13C NMR spectroscopic data are presented in parts per million (δ)
relative to CDCl3 (δ = 77.16 ppm) as an internal standard unless
otherwise stated. Infrared spectra (IR) were recorded either with a
both 6a and 6b, using the GIAO (Gauge Independent
Atomic Orbital) method[18] implemented in GAUSSIAN
94.[19] The results (Table 5) were highly consistent with the
observed NMR spectrum (see experimental section for de-
tails). When the oxazolidinyl bromo ketone 1 was em-
1
ployed, the H NMR spectrum therefore was sufficient to
assign both relative and absolute stereochemistries. The ole-
finic regions of the cycloadducts 13a–b and 14a–b derived
from bromo ketone 12 possessed a similar spectroscopic be-
haviour.
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Cycloadditions of Enantiopure Nitrogen-Stabilized Oxyallyl Cations
FULL PAPER
Bruker IFS 25 FTIR or a NEXUS 470 FTIR. Main peaks are
reported as wavenumbers in cm–1. Mass spectra (MS) were re-
corded with a Hewlett–Packard 5971 instrument or a Kratos
MS50TC mass spectrometer at 70 eV unless otherwise stated, with
fragments reported as their m+/z ratio. Optical rotations were mea-
sured with a Perkin–Elmer 241 polarimeter with dichloromethane
as solvent unless otherwise stated. Gas chromatographic (GC)
analyses were recorded with a Hewlett–Packard 6890 series with a
flame ionization detector (FID). Melting points were measured
with a Gallenkamp melting-point apparatus and all melting points
are uncorrected. X-ray crystallography was performed with a
Bruker AXSP4/SMART 1000 diffractometer.
chilled to 0 °C, and lithium borohydride (4 equiv.) was added in
one portion. After 5 minutes, methanol (8 equiv.) was carefully
added and the resulting mixture was stirred at room temp. over-
night, after which time TLC indicated complete consumption of
the starting material. Citric acid (5.6 g) was carefully added in small
portions and stirring was continued for an additional 10 minutes.
The white solid was filtered and the filtrate was concentrated in
vacuo. Purification of the resulting crude solid via column
chromatography (CH2Cl2/EtOAc, 1:2) afforded the enantiomer-
ically pure oxazolidinones (–)-5a and (+)-5a as colourless solids in
84% and 82% yield, respectively.
(–)-(1R,2S,6R,7S)-3-Oxa-5-azatricyclo[5.2.1.02,6]dec-8-en-4-one and
(+)-(1S,2R,6S,7R)-3-Oxa-5-azatricyclo[5.2.1.02,6]dec-8-en-4-one.
(–)-5a: Rf = 0.27 (CH2Cl2/EtOAc, 1:2). [α]2D5 = –71.7 (c = 1.1,
CH2Cl2) (ref.[15b] [α]2D5 = –85.5, c = 1.0, MeOH). M.p. 181–183 °C
Resolution of ( )-3-Oxa-5-azatricyclo[5.2.1.02,6]dec-8-en-4-one with
(+)-(1S,4R)-Camphanoyl Chloride. Preparation of Enantiopure (–)-
(1R,2S,6R,7S)-3-Oxa-5-azatricyclo[5.2.1.02,6]dec-8-en-4-one (–)-5a
(ref.[15b] 189–190 °C). IR (CDCl ): ν = 3271 (br. s), 2986, 1711,
(+)-(1S,2R,6S,7R)-3-Oxa-5-azatricyclo[5.2.1.02,6]dec-8-en-4-
˜
and
3
1392, 1333, 1300, 1239, 1044, 951, 934 cm–1. H NMR (300 MHz,
1
one (+)-5a. Step 1: In a 500-mL RBF fitted with a dropping funnel
was placed ( )-3-oxa-5-azatricyclo[5.2.1.02,6]dec-8-en-4-one[15b]
(7.80 g, 51.6 mmol, 1 equiv.) and THF (65 mL). The slurry was co-
oled to 0 °C and sodium hydride (60% dispersion in mineral oil,
4.128 g, 103.2 mmol, 2 equiv.) was added in small portions at a
rate such that the vigorous foaming was controlled. Stirring was
continued for 1 hour at room temp., then the dropping funnel was
charged with a solution of (–)-(1S,4R)-camphanoyl chloride[16]
(12.28 g, 56.7 mmol, 1.1 equiv.) in THF (60 mL), which was slowly
added dropwise over 30 minutes, producing noticeable heat evol-
ution which was controlled with the aid of a water bath. The reac-
tion mixture was stirred overnight at room temp. and then
quenched with MeOH, followed by NH4Cl. The organic layer was
washed with NH4Cl (1×), brine (1×), dried with Na2SO4, and con-
centrated in vacuo. The resulting crude oil was subjected to SiO2
chromatography (EtOAc/hexanes, 1:2) to afford 4.485 g (29% yield)
and 7.23 g (45% yield) of the two diastereoisomers, both as colour-
less solids (74% total yield). Data for the least polar diastereo-
CDCl3): δ = 6.14 (t, J = 1.77 Hz, 2 H), 5.54–5.86 (br. s, 1 H), 4.96
(dd, J = 4.2, 8.4 Hz, 1 H), 4.04 (dd, J = 3.7, 8.5 Hz, 1 H), 3.21–
3.26 (m, 1 H), 2.97–3.02 (m, 1 H), 1.61 (td, J = 1.9, 9.8 Hz, 1 H),
1.23 (dquint, J = 0.6, 9.9 Hz, 1 H) ppm. 13C NMR (300 MHz,
CDCl3): δ = 106.9, 135.2, 133.9, 80.1, 56.4, 46.3, 46.2, 43.8 ppm.
HRMS (EI) calcd. for C8H9NO2: 151.06332, found: 151.06308.
(+)-5a: [α]2D5 = +73.4 (c = 0.75, CH2Cl2) (ref.[15b] [α]2D5 = +85.3, c =
1.0, MeOH).
General Procedure for Formation of the Oxazolidinyl Acetates 1b–
5b: A solution of the corresponding substituted 2-oxazolidinone
(6.00 mmol) in THF (15 mL) was added to a suspension of NaH
(60% dispersion in mineral oil) (320 mg, 13 mmol) in THF (10 mL)
at 0 °C. After stirring the mixture at 0 °C for 1 h, ethyl bromoace-
tate (0.7 mL, 6.3 mmol) was added. The resulting mixture was
warmed to room temp. and stirred overnight. The mixture was co-
oled to 0 °C, quenched with ethanol (1 mL), followed by H2O
(3 mL) and THF was removed in vacuo. The crude mixture was
diluted with CH2Cl2, washed with brine, dried with MgSO4 and
concentrated in vacuo.
isomer
(1R,2S,6R,7S)-5-[(1S,4R)-7,7-Dimethyl-3-oxo-2-oxabicy-
clo[2.2.1]hept-1-ylcarbonyl]-3-oxa-5-azatricyclo[5.2.1.02,6]dec-8-en-
4-one: Rf = 0.32 (EtOAc/hexanes, 1:2). [α]2D5 = –20.4 (c = 5.95,
Ethyl (S)-2-(2-Oxo-4-phenyl-1,3-oxazolidin-3-yl)acetate (1b): Purifi-
cation by flash chromatography (50% EtOAc/hexanes) yielded ester
1b (1.19 g, 80%) as a tan liquid. Rf = 0.6 (50% EtOAc/hexanes).
CH Cl ). M.p. 224–226 °C. IR (CDCl ): ν = 2970, 1782, 1693,
˜
2
2
3
1372, 1353, 1283, 1213, 1075, 1020, 929 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 6.20 (dd, J = 3.1, 5.7 Hz, 1 H), 6.13 (dd, J = 3.0,
5.6 Hz, 1 H), 4.97 (dd, J = 4.2, 8.1 Hz, 1 H), 4.38 (dd, J = 3.7,
8.1 Hz, 1 H), 3.52–3.56 (m, 1 H), 3.42–3.46 (m, 1 H), 2.91 (hept, J
= 4.7 Hz, 1 H), 2.14 (ddt, J = 1.8, 4.6, 10.8 Hz, 1 H), 1.89 (ddt, J
= 2.3, 4.6, 10.7 Hz, 1 H), 1.72–1.82 (m, 2 H), 1.33 (d, J = 10.1 Hz,
1 H), 1.20 (s, 3 H), 1.09 (s, 3 H), 1.00 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 178.0, 168.4, 151.5, 135.3, 134.6, 91.8, 77.0,
59.7, 56.0, 54.0, 46.6, 44.1, 29.3, 17.6, 16.9, 9.8 ppm. LRMS (EI)
calcd. for C19H22NO5 (M+): 331.15, found 331.7. Data for the most
polar diastereoisomer (1S,2R,6S,7R)-5-[(1S,4R)-7,7-Dimethyl-3-
oxo-2-oxabicyclo[2.2.1]hept-1-ylcarbonyl]-3-oxa-5-azatricyclo[5.2.1.
02,6]dec-8-en-4-one: Rf = 0.26 (EtOAc/hexanes, 1:2). [α]2D5 = +63.8
IR (CDCl ): ν = 3476, 2989, 2970, 2244, 1770, 1716, 1420, 1010
˜
3
cm–1. H NMR (300 MHz, CDCl3): δ = 7.42 (m, 3 H), 7.29 (m, 2
1
H), 5.07 (dd, J = 8.4, 8.4 Hz, 1 H), 4.71 (dd, J = 8.7, 8.7 Hz, 1 H),
4.27 (ABq, J = 18.0 Hz, 1 H), 4.14 (m, 3 H), 3.37 (ABq, J = 18 Hz,
1 H), 1.24 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 168.6, 158.7, 137.0, 129.7, 129.6, 127.5, 70.5, 61.7, 60.3, 43.4,
14.4 ppm. HRMS (EI) calcd. for C12H13NO4 [M+] 235.2395, found
235.2395.
Ethyl (S)-2-(4-Benzyl-2-oxo-1,3-oxazolidin-3-yl)acetate (2b): Purifi-
cation by flash chromatography (50% EtOAc/hexanes) yielded the
ester 2b (1.26 g, 80%) as a colourless liquid. Rf = 0.6 (50% EtOAc/
(c = 1.94, CH Cl ). M.p. 232–234 °C. IR (CDCl ): ν = 2979, 1782,
˜
hexanes). IR (CDCl ): ν = 2981, 2912, 2257, 1743, 1709, 1427,
˜
2
2
3
3
1698, 1366, 1351, 1323, 1284, 1213, 1074, 929 cm–1 1H NMR
.
1358, 1215, 1094, 1019 cm–1. 1H NMR (300 MHz, CDCl3): δ =
7.32 (m, 3 H), 7.18 (m, 2 H), 4.30 (m, 5 H), 4.08 (m, 1 H), 3.71 (d,
J = 18.0 Hz, 1 H), 3.08 (dd, J = 5.4, 13.6 Hz, 1 H), 2.80 (dd, J =
7.8, 13.6 Hz, 1 H), 1.29 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 168.8, 158.8, 135.7, 129.3, 129.2, 127.5, 67.8,
61.8, 56.6, 44.1, 39.0, 14.4 ppm. HRMS (EI) calcd. for C13H15NO4
[M+] 249.2664, found 249.2668.
(300 MHz, CDCl3): δ = 6.25 (dd, J = 3.0, 5.8 Hz, 1 H), 6.07 (dd,
J = 3.0, 5.8 Hz, 1 H), 4.95 (dd, J = 4.0, 8.7 Hz, 1 H), 4.77 (dd, J
= 3.7, 8.7 Hz, 1 H), 3.67 (m, 1 H), 3.30 (m, 1 H), 2.75 (hept, J =
4.7 Hz, 1 H), 2.20 (ddt, J = 1.8, 4.5, 10.9 Hz, 1 H), 1.90 (ddt, J =
2.2, 4.5, 10.8 Hz, 1 H), 1.70–1.79 (m, 2 H), 1.38 (d, J = 10.1 Hz, 1
H), 1.19 (s, 3 H), 1.10 (s, 3 H), 1.01 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 178.1, 167.9, 152.1, 134.8, 134.6, 91.8, 77.0,
59.3, 56.1, 54.0, 46.1, 45.3, 44.5, 29.4, 29.2, 17.4, 16.7, 9.7 ppm.
Ethyl (S)-2-(4-tert-Butyl-2-oxo-1,3-oxazolidin-3-yl)acetate (3b): Pu-
rification by flash chromatography yielded the ester 3b (1.16 g,
85%) as a colourless solid. Rf = 0.6 (50% EtOAc/hexanes). M.p.
Step 2: To a 25-mL RBF was added the enantiopure diastereomer
from above and THF (135 mL). The clear colourless solution was
72–74 °C. IR (CDCl ): ν = 3674, 3472, 3408, 2967, 2874, 2254,
˜
3
Eur. J. Org. Chem. 2006, 3667–3680
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3673

D. I. MaGee, E. Godineau, P. D. Thornton, M. A. Walters, D. J. Sponholtz
FULL PAPER
1763, 1699, 1482, 1427, 1371, 1026 cm–1. 1H NMR (300 MHz, 129.3, 129.2, 127.6, 68.1, 56.8, 43.9, 39.9 ppm. HRMS (EI) calcd.
CDCl3): δ = 4.41 (ABq, J = 18.0 Hz, 1 H), 4.35 (dd, J = 8.7, 8.7 Hz,
1 H), 4.20 (m, 2 H), 3.84 (ABq, J = 18.0 Hz, 1 H), 3.57 (dd, J =
4.8, 8.7 Hz, 1 H), 1.26 (t, J = 7.3 Hz, 3 H), 0.98 (s, 9 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 169.0, 160.4, 65.5, 64.3, 61.8, 47.3,
34.8, 25.7, 14.4 ppm. HRMS (EI) calcd. for C10H17NO4 [M+]
215.2493, found 215.2491.
for C12H13NO4 [M+] 235.2395, found 235.2399.
(S)-2-(4-tert-Butyl-2-oxo-1,3-oxazolidin-3-yl)acetic Acid (3c): Car-
boxylic acid 3c (724 mg, 80%) was isolated as a colourless solid.
R = 0.3 (75% EtOAc/hexanes). M.p. 166–168 °C. IR (CDCl ): ν
˜
f
3
= 3110, 2967, 2874, 2647, 1756, 1691, 1483, 1428, 1400, 1242, 1187
1
cm–1. H NMR (300 MHz, CDCl3): δ = 9.01 (br. s, 1 H), 4.48 (d,
(+)-Methyl (4R,5S)-2-(2-Oxo-4,5-[9,10]dimethylanthraceno-1,3-ox-
azolidin-3-yl)acetate (4b): Purification by SiO2 column chromatog-
raphy gave 4b (1.457 g, 93%) as a colourless solid. Rf = 0.5 (EtOAc/
hexanes, 1:2). [α]2D5 = +69 (c = 1.1, CH2Cl2). M.p. 197–199 °C. IR
J = 18.3 Hz, 1 H), 4.39 (dd, J = 9.0, 9.0 Hz, 1 H), 4.19 (dd, J =
9.0, 4.9 Hz, 1 H), 3.93 (d, J = 18.3 Hz, 1 H), 3.62 (dd, J = 9.0, 4.9
Hz, 1 H), 1.01 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
173.2, 160.9, 65.9, 64.6, 47.2, 34.8, 25.8 ppm. HRMS (EI) calcd.
for C9H15NO4 [M+] 201.2224, found 201.2221.
(neat): ν = 3020, 1744, 1524, 1420, 1228, 1200, 924 cm–1. 1H NMR
˜
(300 MHz, CDCl3): δ = 7.39 (m, 2 H), 7.24 (m, 6 H), 4.55 (d, J =
10.1 Hz, 1 H), 4.32 (d, J = 18.9, 1 Hz, 1 H), 3.88 (d, J = 10.2 Hz,
1 H), 3.84 (d, J = 19.0 Hz, 1 H), 3.71 (s, 3 H), 2.08 (s, 3 H), 2.03
(s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 168.9, 159.3, 142.8,
141.5, 140.5, 139.9, 126.9, 126.8, 126.6, 123.9, 122.8, 122.6, 122.1,
81.2, 64.5, 52.5, 46.5, 46.2, 45.6, 15.9, 14.8 ppm. LRMS-FAB: [M+]
363.4.
(+)-(4R,5S)-2-(2-Oxo-4,5-[9,10]dimethylanthraceno-1,3-oxazolidin-
3-yl)acetic Acid (4c): Carboxylic acid 4c (1.22 g, 97%) was isolated
as a white solid which was of sufficient purity for use in subsequent
steps. [α]2D5 = +67.1 (c = 1.5, CH2Cl2). M.p. 226–229 °C (dec). IR
1
(neat): ν = 3018, 2970, 1746, 1526, 1416, 1206, 1042, 932 cm–1. H
˜
NMR (CDCl3, 300 MHz): δ = 7.36 (m, 2 H), 7.23 (m, 6 H), 4.55
(d, J = 9.1 Hz, 1 H), 4.28 (d, J = 18.3 Hz, 1 H), 3.90 (d, J = 18.4,
1 H), 3.86 (d, J = 9.1 Hz, 1 H), 2.06 (s, 3 H), 2.03 (s, 3 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 173.2, 159.9, 143.0, 141.7, 140.7,
140.2, 127.4, 127.3, 127.2, 127.0, 124.2, 123.2, 123.0, 122.5, 81.8,
65.1, 46.8, 46.5, 45.9, 16.2, 15.1 ppm. LRMS-FAB: [M+] 348.5.
(–)-Methyl (1R,2S,6R,7R,8R)-2-[8-tert-Butyl(diphenyl)silanyloxy-4-
oxo-3-oxa-5-azatricyclo[5.2.1.02,6]dec-5-yl]acetate (5b): Purification
by column chromatography afforded the ester 5b (412 mg, 79%) as
a colourless solid. Rf = 0.42 (CH2Cl2/EtOAc, 20:1). [α]2D5 = –29.6
(c = 1.01, CH Cl ). M.p. 115–118 °C. IR (CDCl ): ν = 2957, 1749,
˜
2
2
3
(–)-(1R,2S,6R,7R,8R)-2-[8-tert-Butyl(diphenyl)silanyloxy-4-oxo-3-
oxa-5-azatricyclo[5.2.1.02,6]dec-5-yl]acetic Acid (5c): Carboxylic
acid 5c (363 mg, 95%) was isolated as a colourless solid which was
of sufficient purity for use in the next step. [α]2D5 = –43.0 (c = 0.59,
1429, 1212, 1133, 1109, 1072, 1033, 1012 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 7.61–7.67 (m, 4 H), 7.33–7.46 (m, 6 H),
4.76–4.83 (ddd, J = 1.4, 4.8, 10.5 Hz, 1 H), 4.49–4.57 (ABq, J =
18.1 Hz, 1 H), 4.24–4.32 (m, 1 H), 4.15–4.22 (ddd, J = 1.6, 4.3,
10.5 Hz, 1 H), 3.73–3.80 (ABq, J = 17.1 Hz, 1 H), 3.73 (s, 3 H),
2.46–2.52 (m, 2 H), 1.33–1.51 (m, 3 H), 1.17–1.24 (m, 1 H) 1.08 (s,
9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.9, 168.5, 136.1,
135.7, 133.8, 133.5, 130.1, 129.9, 127.9, 127.9, 76.6, 75.0, 58.2, 52.3,
45.4, 43.8, 40.8, 33.2, 28.9, 27.3 (3 C), 19.1 ppm. HRMS (EI) calcd.
for C23H24NO5Si [M+ –C4H9] 422.1433, found 422.1433.
CH Cl ). M.p. 218–219 °C. IR (CDCl ): ν = 3071, 2961, 2857,
˜
2
2
3
1751, 1462, 1427, 1264, 1184, 1129, 1141, 1112, 1071, 1036, 1017
1
cm–1. H NMR (300 MHz, CDCl3): δ = 7.60–7.67 (m, 4 H), 7.37–
7.49 (m, 6 H), 4.77–4.85 (dd, J = 4.7, 10.5 Hz, 1 H), 4.50–4.59 (d,
J = 18.4 Hz, 1 H), 4.25–4.34 (m, 1 H), 4.14–4.22 (dd, J = 3.8,
10.9 Hz, 1 H), 3.75–3.85 (d, J = 18.6 Hz, 1 H), 2.46–2.54 (m, 2 H),
1.34–1.52 (m, 3 H), 1.19–1.28 (m, 1 H) 1.08 (s, 9 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 173.2, 158.8, 136.1, 135.7, 133.7,
133.5, 130.1, 130.0, 128.0, 127.9, 77.4, 77.9, 74.9, 58.4, 45.5, 43.8,
40.7, 33.2, 28.9, 27.3 (3 C), 19.1 ppm. HRMS (EI) calcd. for
C22H22NO5Si [M+ –C4H9] 408.1267, found: 408.1272.
General Procedure for Formation of the Oxazolidinyl Acetic Acids
1c–5c: Sodium hydroxide (360 mg, 9.00 mmol) was dissolved in
H2O (2.2 mL) and added to a solution of the corresponding ester
(4.50 mmol) in THF (9.0 mL). The mixture was stirred at room
temperature overnight and THF was removed in vacuo. The aque-
ous layer was washed with CH2Cl2 (10 mL) and then acidified with
6  HCl. The aqueous phase was extracted with CH2Cl2
(2×10 mL) with vigorous stirring for 30 min prior to each extrac-
tion. The combined organic layers was washed with brine, dried
with MgSO4 and concentrated in vacuo.
General Procedure for the Formation of the Oxazolidinyl Diazo
Ketones 1e–5e: Oxalyl chloride (0.31 mL, 3.5 mmol) was added to
a solution of the corresponding oxazolidinyl acetic acid (2.3 mmol)
in THF (9 mL). The mixture was heated at reflux for 1 h, and then
all volatile materials were removed in vacuo. The acid chloride was
immediately re-dissolved in THF (9 mL) and added dropwise to a
solution of diazomethane in ether cooled to 0 °C. The reaction was
warmed to room temperature and stirred overnight to allow for
evaporation of excess CH2N2. The solvent was removed in vacuo.
(S)-2-(2-Oxo-4-phenyl-1,3-oxazolidin-3-yl)acetic Acid (1c): Carbox-
ylic acid 1c (796 mg, 80%) was isolated as a colourless solid. Rf =
0.2 (75% EtOAc/hexanes). M.p. 106–108 °C. IR (CDCl ): ν = 3036,
˜
3
2254, 1710, 1747, 1417, 1200, 1096, 1029 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 7.42 (m, 3 H), 7.32 (m, 2 H), 5.75 (s, 1 H),
5.06 (dd, J = 8.3, 8.3 Hz, 1 H), 4.71 (dd, J = 8.5, 8.5 Hz, 1 H), 4.34
(d, J = 18.0 Hz, 1 H), 4.18 (dd, J = 8.3, 8.3 Hz, 1 H), 3.44 (d, J =
18.0 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 172.6, 159.4,
136.6, 129.8, 127.6, 70.9, 60.4, 43.2 ppm. HRMS (EI) calcd. for
C11H11NO4 [M+] 221.2126, found 221.2120.
(S)-2-(2-Oxo-4-phenyl-1,3-oxazolidin-3-yl)acetyl Chloride (1d): An
aliquot was removed from the crude reaction mixture for 1H NMR
analysis. 1H NMR (300 MHz, CDCl3): δ = 7.42 (m, 3 H), 7.32 (m,
2 H), 5.02 (dd, J = 8.3, 8.3 Hz, 1 H), 4.75 (dd, J = 8.8, 8.8 Hz, 1
H), 4.70 (ABq, J = 19.0 Hz, 1 H), 4.23 (dd, J = 8.8, 8.8 Hz, 1 H),
3.81 (ABq, J = 19.0 Hz, 1 H) ppm.
(S)-2-(4-Benzyl-2-oxo-1,3-oxazolidin-3-yl)acetic Acid (2c): Carbox-
ylic acid 2c (847 mg, 75%) was isolated as a colourless solid. Rf =
(S)-3-(3-Diazo-2-oxopropyl)-4-phenyl-1,3-oxazolidin-2-one (1e): Pu-
rification by flash chromatography (75% EtOAc/hexanes) gave the
diazo ketone 1e (446 mg, 79 %) as a yellow oil. Rf = 0.4 (50 %
0.2 (75% EtOAc/hexanes). M.p. 134–136 °C. IR (CDCl ): ν = 2996,
˜
3
2257, 1737, 1748, 1426, 1362, 1220 cm–1. 1H NMR (300 MHz, EtOAc/hexanes). IR (CDCl ): ν = 3482, 3102, 2911, 2246, 2109,
˜
3
CDCl3): δ = 10.06 (br. s, 1 H) 7.38 (m, 3 H), 7.18 (m, 2 H), 4.33
(m, 3 H), 4.11 (dd, J = 6.8, 6.8 Hz, 1 H), 3.78 (d, J = 18.3 Hz, 1
H), 3.10 (dd, J = 13.5, 5.3 Hz, 1 H), 2.81 (dd, J = 13.5, 7.9 Hz, 1
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 173.1, 159.3, 135.3,
1737, 1648, 1415, 1362 cm–1. 1H NMR (300 MHz, CDCl3): δ =
7.42 (m, 3 H), 7.32 (m, 2 H), 5.29 (br. s, 1 H), 5.05 (dd, J = 8.3,
8.3 Hz, 1 H), 4.73 (dd, J = 8.8, 8.8 Hz, 1 H), 4.25 (ABq, J =
17.0 Hz, 1 H), 4.19 (dd, J = 8.3, 8.3 Hz, 1 H), 3.36 (ABq, J =
3674
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3667–3680

Cycloadditions of Enantiopure Nitrogen-Stabilized Oxyallyl Cations
FULL PAPER
17.0 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 189.0, 158.8,
137.1, 129.7, 129.6, 127.5, 70.5, 60.7, 54.1, 48.6 ppm. HRMS calcd.
for C12H11N3O3 [M+] 245.0800, found 245.0878.
(300 MHz, CDCl3): δ = 7.59–7.67 (m, 4 H), 7.35–7.49 (m, 6 H),
4.85–4.93 (ABq, J = 19.2 Hz, 1 H), 4.78–4.86 (dd, J = 4.4, 10.2 Hz,
1 H), 4.28–4.37 (m, 1 H), 4.07–4.16 (m, 1 H), 4.07–4.16 (ABq, J =
19.1 Hz, 1 H), 2.45–2.56 (m, 2 H), 1.19–1.59 (m, 4 H), 1.10 (s, 9
H) ppm.
(S)-2-(4-Benzyl-2-oxo-1,3-oxazolidin-3-yl)acetyl Chloride (2d): An
aliquot was removed from the crude reaction mixture for 1H NMR
analysis. 1H NMR (300 MHz, CDCl3): δ = 7.39 (m, 3 H), 7.18 (m,
2 H), 4.58 (ABq, J = 19.0 Hz, 1 H), 4.42 (dd, J = 8.3, 8.3 Hz, 1
H), 4.29 (m, 1 H), 4.14 (dd, J = 6.4, 8.3 Hz, 1 H), 4.05 (ABq, J =
19.0 Hz, 1 H), 3.04 (dd, J = 6.6, 13.7 Hz, 1 H), 2.87 (dd, J = 7.3,
13.7 Hz, 1 H) ppm.
(–)-(1R,2S,6R,7R,8R)-8-tert-Butyl(diphenyl)silanyloxy-5-(3-diazo-2-
oxopropyl)-3-oxa-5-azatricyclo[5.2.1.02,6]decan-4-one (5e): Purifica-
tion by flash chromatography of the resulting crude oil (CH2Cl2/
EtOAc, 4:1) afforded the diazo ketone 5e (333 mg, 88% yield over
2 steps) as a colourless amorphous solid. Rf = 0.28 (CH2Cl2/
EtOAc, 5:1). [α]2D5 = –12.0 (c = 0.71, CH2Cl2). M.p. 104–105 °C
(S)-4-Benzyl-3-(3-diazo-2-oxopropyl)-1,3-oxazolidin-2-one (2e): Pu-
rification by flash chromatography (75% EtOAc/hexanes) gave the
diazo ketone 2e (447 mg, 75%) as a yellow solid. Rf = 0.4 (50%
(dec.). IR (CDCl ): ν = 3480, 3071, 2959, 2858, 2108, 1750, 1651,
˜
3
1471, 1428, 1373, 1106, 1072, 1032, 884 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 7.60–7.66 (m, 4 H), 7.34–7.47 (m, 6 H), 5.21–5.29 (br.
s, 1 H), 4.75–4.83 (dd, J = 0.8, 4.1, 10.3 Hz, 1 H), 4.36–4.38 (ABq,
J = 16.7 Hz, 1 H), 4.26–4.35 (m, 1 H), 4.12–4.20 (ddd, J = 1.0, 3.8,
10.1 Hz, 1 H), 3.58–3.69 (ABq, J = 17.5 Hz, 1 H), 2.47–2.55 (m, 2
H), 1.17–1.55 (m, 4 H), 1.08 (s, 9 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 190.1, 158.3, 136.1 (2 C), 135.7 (2 C), 133.9, 133.4,
131.0, 130.0, 128.9, 127.9 (2 C), 76.7, 74.9, 58.6, 53.8, 51.2, 43.8,
40.8, 33.2, 29.0, 27.3 (3 C), 19.2 ppm. HRMS (EI) calcd. for
C23H22NO4Si [M+ –C4H9 –N2] 404.1318, found: 404.1301.
EtOAc/hexanes). M.p. 101–102.5 °C. IR (CDCl ): ν = 3112, 2920,
˜
3
2254, 2113, 1750, 1653, 1430, 1377, 1324, 1144, 1102 cm–1 1H
.
NMR (300 MHz, CDCl3): δ = 7.38 (m, 3 H), 7.08 (m, 2 H), 5.34
(br. s, 1 H), 4.36 (dd, J = 8.3, 8.3 Hz, 1 H), 4.27 (m, 1 H), 4.20
(ABq, J = 17.1 Hz, 1 H), 4.11 (dd, J = 5.8, 8.3 Hz, 1 H), 3.71
(ABq, J = 17.1 Hz, 1 H), 3.08 (dd, J = 4.9, 13.4 Hz, 1 H), 2.73 (dd,
J = 8.4, 13.4 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
189.2, 158.8, 135.5, 129.2(7), 129.2(6), 127.5, 67.8, 57.1, 54.1, 49.6,
39.0 ppm. C13H13N3O3: calcd. C 60.21, H 5.06, N 16.21; found C
60.08, H 5.05, N 15.96.
General Procedure for Formation of the Oxazolidinyl Bromo
Ketones: HBr (48% aq.) (0.29 mL, 5.40 mmol) was added dropwise
to a solution of the corresponding diazo ketone (0.90 mmol) in
CH2Cl2 (3.6 mL) cooled to 0 °C (vigorous nitrogen evolution). Af-
ter 1 h, (monitored by TLC) the reaction was quenched with satd.
NaHCO3 (0.5 mL) and washed with brine (1 mL). The organic
layer was removed and the aqueous layer was extracted with
CH2Cl2 (2×2 mL). The combined organic layers were dried with
MgSO4 and concentrated.
(S)-2-(4-tert-Butyl-2-oxo-1,3-oxazolidin-3-yl)acetyl Chloride (3d):
An aliquot was removed from the crude reaction mixture for 1H
1
NMR analysis. H NMR (300 MHz, CDCl3): δ = 4.87 (ABq, J =
19.0 Hz, 1 H), 4.42 (dd, J = 9.0, 9.0 Hz, 1 H), 4.34 (ABq, J =
19.0 Hz, 1 H), 4.23 (dd, J = 5.1, 9.0 Hz, 1 H), 3.62 (dd, J = 5.1,
8.8 Hz, 1 H), 1.01 (s, 9 H) ppm.
(S)-4-tert-Butyl-3-(3-diazo-2-oxopropyl)-1,3-oxazolidin-2-one (3e):
Purification by flash chromatography (75% EtOAc/hexanes) gave
the diazo ketone 3e (414 mg, 80%) as a yellow solid. Rf = 0.4 (50%
(S)-3-(3-Bromo-2-oxopropyl)-4-phenyl-1,3-oxazolidin-2-one (1):
Bromo ketone 1 (195 mg, 73%) was isolated as a yellow solid. Rf
EtOAc/hexanes). M.p. 76–78 °C. IR (CDCl ): ν = 3107, 2958, 2246,
˜
3
= 0.6 (50% EtOAc/hexanes). M.p. 92–94 °C. IR (CDCl ): ν = 2911,
˜
3
2108, 1744, 1652, 1479, 1422, 1376, 1324, 1244, 1146 cm–1 1H
.
2248, 1753, 1706, 1415, 1357, 910 cm–1 1H NMR (300 MHz,
.
NMR (300 MHz, CDCl3): δ = 5.47 (br. s, 1 H), 4.39 (dd, J = 9.0,
9.0 Hz, 1 H), 4.36 (ABq, J = 17.3 Hz, 1 H), 4.20 (dd, J = 3.9,
9.0 Hz, 1 H), 3.93 (ABq, J = 17.3 Hz, 1 H), 3.57 (dd, J = 3.9,
9.0 Hz, 1 H), 0.99 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
189.5, 160.6, 65.5, 64.9, 54.1, 52.8, 34.9, 25.8 ppm. HRMS calcd.
for C10H15N3O3 [M+] 225.1113, found 225.1117.
CDCl3): δ = 7.42 (m, 3 H), 7.32 (m, 2 H), 5.00 (dd, J = 8.3, 8.3 Hz,
1 H), 4.75 (dd, J = 8.8, 8.8 Hz, 1 H), 4.55 (ABq, J = 19.0 Hz, 1
H), 4.19 (dd, J = 8.8, 8.8 Hz, 1 H), 3.87 (s, 2 H), 3.77 (ABq, J =
19.0 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 196.9, 158.7,
136.9, 129.8, 127.5, 70.6, 60.3, 48.7, 31.2 ppm. HRMS calcd. for
C12H12BrNO3 [M+] 297.0000, found 298.0065. Note: This com-
pound was observed to be unstable.
(4R,5S)-2-(2-Oxo-4,5-[9,10]dimethylanthraceno-1,3-oxazolidin-3-
yl)acetyl Chloride (4d): An aliquot was removed from the crude
(S)-4-Benzyl-3-(3-bromo-2-oxopropyl)-1,3-oxazolidin-2-one (2): The
bromo ketone 2 (210 mg, 75%) was isolated as a yellow solid. Rf
1
1
reaction mixture for H NMR analysis. H NMR (300 MHz): δ =
7.38 (m, 2 H), 7.24 (m, 6 H), 4.72 (d, J = 18.5 Hz, 1 H), 4.58 (d, J
= 9.2 Hz, 1 H), 4.29 (d, J = 18.1 Hz, 1 H), 3.88 (d, J = 9.1 Hz, 1
H), 2.07 (s, 3 H), 2.03 (s, 3 H) ppm.
= 0.6 (50% EtOAc/hexanes). M.p. 99.5–101.5 °C. IR (CDCl ): ν =
˜
3
3005, 2960, 2914, 2242, 1751, 1711, 1426, 1358, 1221, 1090, 1039
1
cm–1. H NMR (300 MHz, CDCl3): δ = 7.42 (m, 3 H), 7.19 (m, 2
(4R,5S)-3-(3-Diazo-2-oxopropyl)-4,5-[9,10]dimethylanthraceno-1,3-
oxazolidin-2-one (4e): Purification by SiO2 column chromatography
(EtOAc/hexanes, 2:3) gave 4e as a highly crystalline yellow solid.
Rf = 0.3 (EtOAc/hexane, 1:2). [α]2D5 = +101.5 (c = 1.1, CHCl3). M.p.
H), 4.48 (ABq, J = 19.0 Hz, 1 H), 4.44 (dd, J = 7.5 Hz, 1 H), 4.27
(dd, J = 7.3 Hz, 1 H), 4.10 (dd, J = 6.6 Hz, 1 H), 4.04 (ABq, J =
18.6 Hz, 1 H), 3.77 (s, 2 H), 3.01 (dd, J = 6.1, 13.4 Hz, 1 H), 2.85
(dd, J = 6.1, 13.4 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
196.9, 158.8, 135.7, 129.3, 129.1, 127.6, 68.1, 56.5, 49.5, 39.5, 31.2
ppm. C13H14BrNO3: calcd. C 50.16, H 4.54, N 4.50; found C 49.66,
H 4.69, N 4.46. HRMS calcd. for C13H14BrNO3 [M+] 311.0157,
found 311.0158.
220–222 °C (dec). IR (neat): ν = 3030, 2970, 2106, 1750, 1644,
˜
1
1524, 1430, 1370, 1228, 920 cm–1. H NMR (300 MHz): δ = 7.38
(m, 2 H), 7.24 (m, 6 H), 5.14 (s, 1 H), 4.55 (d, J = 9.3 Hz, 1 H),
4.00 (d, J = 18.5 Hz, 1 H), 3.94 (d, J = 18.3 Hz, 1 H), 3.84 (d, J =
9.2 Hz, 1 H), 2.08 (s, 3 H), 2.03 (s, 3 H) ppm 13C NMR (75 MHz):
δ = 190.1, 159.8, 142.9, 141.8, 141.0, 140.4, 127.4, 127.3, 127.28,
126.5, 124.4, 123.4, 122.9, 122.6, 81.7, 66.5, 54.7, 53.6, 46.5, 46.0,
16.2, 15.0 ppm. LRMS-FAB: [M+] 348.5.
(S)-3-(3-Bromo-2-oxopropyl)-4-tert-butyl-1,3-oxazolidin-2-one (3):
The bromo ketone 3 (199 mg, 80%) was isolated in as a yellow
solid. Rf = 0.6 (50% EtOAc/hexanes). M.p. 88–90 °C. IR (CDCl3):
ν = 3464, 3405, 2966, 2877, 2253, 1747, 1713, 1480, 1424, 1363,
˜
(1R,2S,6R,7R,8R)-2-[8-tert-Butyl(diphenyl)silanyloxy-4-oxo-3-oxa- 1223, 1188, 1092, 1052 cm–1. 1H NMR (300 MHz, CDCl3): δ =
5-azatricyclo[5.2.1.02,6]dec-5-yl]acetyl Chloride (5d): An aliquot was
4.72 (ABq, J = 18.8 Hz, 1 H), 4.46 (dd, J = 9.0, 9.0 Hz, 1 H), 4.38
(ABq, J = 18.8 Hz, 1 H), 4.24 (dd, J = 4.4, 9.0 Hz, 1 H), 3.94 (m,
removed from the reaction mixture for 1H NMR analysis. 1H NMR
Eur. J. Org. Chem. 2006, 3667–3680
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3675

D. I. MaGee, E. Godineau, P. D. Thornton, M. A. Walters, D. J. Sponholtz
FULL PAPER
1 H), 3.53 (dd, J = 4.4, 9.0 Hz, 1 H), 0.99 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 197.3, 160.4, 65.8, 64.4, 52.7, 34.9, 31.2,
25.8 ppm. C10H16O3NBr: calcd. C 43.18, H 5.80, N 5.04; found C
performed according to the general procedure described above. Pu-
rification by flash chromatography (40% EtOAc/hexanes) followed
by recrystallization (EtOAc/hexanes) gave cycloadduct 6a as a
43.42, H 5.80, N 5.04. HRMS calcd. for C10H16BrNO3 [M+] colourless solid. Rf = 0.3 (50% EtOAc/hexanes). M.p. 166–168 °C.
277.0313, found 277.0311.
IR (CDCl ): ν = 3405, 2969, 2244, 1738, 1712, 1407, 1355, 1215,
˜
3
1100 cm–1. H NMR (300 MHz, CDCl3): δ = 7.42 (m, 3 H), 7.32
1
(+)-(4R,5S)-3-(3-Bromo-2-oxopropyl)-4,5-[9,10]dimethylanthraceno-
1,3-oxazolidin-2-one (4): The bromo ketone 4 (49 mg, 86%) was
isolated as a fine yellow powder. Compound 4 was sensitive to
chromatography so it was used immediately in subsequent cycload-
dition reactions. Rf = 0.4 (EtOAc/hexanes, 2:3). [α]2D5 = +32.3 (c =
(m, 2 H), 6.16 (dd, J = 1.7, 6.1 Hz, 1 H), 5.08 (dd, J = 1.7, 6.1 Hz,
1 H), 4.94 (m, 2 H), 4.82 (dd, J = 4.5, 9.0 Hz, 1 H), 4.78 (dd, J =
1.7, 4.5 Hz, 1 H), 4.73 (dd, J = 8.2, 9.0 Hz, 1 H), 4.13 (dd, J = 4.5,
8.2 Hz, 1 H), 2.88 (dd, J = 5.1, 15.7 Hz, 1 H), 2.46 (d, J = 15.7 Hz,
1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 201.1, 159.6, 140.6,
135.0, 132.0, 129.9, 129.4, 126.5, 80.3, 78.4, 71.4, 67.2, 57.9, 46.0
ppm. C16H15NO4: calcd. C 67.36, H 5.30, N 4.91; found C 67.09,
H 5.21, N 4.93.
1.4, CHCl ). IR (CHCl ): ν = 3036, 2942, 1744, 1542, 1436, 1210,
˜
3
3
1
1010, 926 cm–1. H NMR (300 MHz): δ = 7.38 (m, 2 H), 7.23 (m,
6 H), 4.61 (d, J = 9.3 Hz, 1 H), 4.43 (d, J = 18.5 Hz, 1 H), 4.33 (d,
J = 18.3 Hz, 1 H), 3.94 (d, J = 9.2 Hz, 1 H), 3.83 (s, 2 H), 2.09 (s,
3 H), 2.01 (s, 3 H) ppm. 13C NMR (75 MHz): δ = 196.9, 159.5,
142.8, 141.6, 140.7, 140.1, 127.1, 127.0, 126.7, 124.0, 122.9, 122.8,
122.2, 81.5, 65.1, 52.2, 46.3, 45.7, 31.3, 16.0, 14.9 ppm.
(1S,2R,5S)-2-[(4S)-2-Oxo-4-phenyl-1,3-oxazolidin-3-yl]-8-oxabi-
cyclo[3.2.1]oct-6-en-3-one (6b): Purification by flash chromatog-
raphy (40% EtOAc/hexanes) gave 6b as a mixture with compound
1
6a. Rf = 0.3 (50% EtOAc/hexanes). H NMR (300 MHz, CDCl3):
(–)-(1R,2S,6R,7R,8R)-5-(3-Bromo-2-oxo-propyl)-8-tert-butyl(di-
phenyl)silanyloxy-3-oxa-5-azatricyclo[5.2.1.02,6]decan-4-one (5): The
bromo ketone 5 (507 mg, 93% yield) was isolated as a white-brown
solid. The material obtained was usually of sufficient purity for
direct use in subsequent steps. Purification by flash chromatog-
raphy (CH2Cl2/EtOAc, 5:1) afforded the bromo ketone 5 (464 mg,
85%) as a colourless solid. Rf = 0.47 (CH2Cl2/EtOAc, 20:1). [α]2D5
δ = 7.42 (m, 3 H), 7.32 (m, 2 H), 6.58 (dd, J = 1.7, 6.1 Hz, 1 H),
6.28 (dd, J = 1.7, 6.1 Hz, 1 H), 4.99 (m, 1 H), 4.90 (m, 3 H), 4.75
(m, 1 H), 3.78 (d, J = 4.6 Hz, 1 H), 2.75 (dd, J = 5.1, 15.6 Hz, 1
H), 2.46 (d, J = 15.6 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 200.5, 160.8, 137.4, 133.9, 132.4, 129.9, 129.8, 127.6, 81.0, 78.3,
70.4, 66.4, 64.2, 45.7 ppm.
= –22.5 (c = 0.67, CH Cl ). M.p. 130–132 °C. IR (CDCl ): ν =
˜
2
2
3
(1R,2S,5R)-2-[(4S)-4-Benzyl-2-oxo-1,3-oxazolidin-3-yl]-8-oxabi-
cyclo[3.2.1]oct-6-en-3-one (7a) and (1S,2R,5S)-2-[(4S)-4-Benzyl-2-
oxo-1,3-oxazolidin-3-yl]-8-oxabicyclo[3.2.1]oct-6-en-3-one (7b): Cy-
cloaddition of 2 with furan was performed according to the general
procedure described above. These compounds were isolated as a
mixture in a 2:1 ratio via flash chromatography (40% EtOAc/hex-
anes). Upon recrystallization (EtOAc/hexanes) enhancement of
compound 7a was possible but complete purification was not ob-
tained. Rf = 0.3 (50 % EtOAc/hexanes). 1H NMR (300 MHz,
CDCl3): δ = 7.36 (m, 6 H), 7.24 (m, 4 H), 6.55 (dd, J = 6.1, 1.9 Hz,
1 H 7b), 6.46 (m, 2 H 7a), 6.39 (dd, J = 6.1, 1.7 Hz, 1 H 7b), 5.17
(dd, J = 4.4, 1.2 Hz, 1 H 7a), 5.10 (m, 3 H), 4.66 (d, J = 4.4 Hz, 1
H 7a), 4.28 (m, 3 H), 4.09 (m, 4 H), 2.90 (m, 6 H), 2.54 (m, 2 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 200.6, 158.7, 135.6, 135.4,
133.8, 133.3, 132.3, 129.4, 129.3, 129.2, 129.1, 127.6, 111.7, 111.6,
80.9, 80.4, 78.4, 67.8, 67.7, 67.0, 59.2, 56.4, 45.7, 40.4, 40.8 ppm.
HRMS calcd. for C17H17NO4 [M+] 299.1157, found 299.1157.
2961, 1747, 1428, 1343, 1262, 1111, 1072, 1032, 884, 858, 821 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.60–7.67 (m, 4 H), 7.34–7.47
(m, 6 H), 4.82 (dd, J = 4.9, 10.4 Hz, 1 H), 4.68 (ABq, J = 18.9 Hz,
1 H), 4.29–4.45 (m, 1 H), 4.14 (dd, J = 3.5, 5.8 Hz, 1 H), 4.13 (ddd,
J = 1.6, 4.3, 8.9 Hz, 1 H), 4.11 (ABq, J = 18.9 Hz, 1 H), 3.75 (s, 2
H), 2.49–2.55 (m, 1 H), 2.41–2.47 (m, 1 H), 1.54–1.59 (m, 2 H),
1.18–1.42 (m, 2 H), 1.11 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 197.8, 158.4, 136.1, 135.7, 134.0, 133.4, 131.0, 130.1, 130.0,
128.9, 128.0, 127.9, 76.8, 74.9, 68.3, 58.1, 51.0, 43.9, 40.8, 33.2,
31.2, 29.0, 27.3 (3 C), 19.2 ppm. HRMS (EI) calcd. for
C23H23BrNO4Si79 [M+ –C4H9] 484.0580, found 484.0577.
General Procedure for Cycloaddition Using CF3CH2OH/Et3N Con-
ditions: The corresponding diene (10 equiv. or 200 equiv.) was
added to a solution of the bromo ketone (0.24 mmol) in 2,2,2-tri-
fluoroethanol (0.92 mL) cooled to 0 °C. Et3N (0.05 mL,
0.39 mmol) was then added dropwise. The resulting mixture was
slowly warmed to room temperature and stirred for 12 h. The or-
ganic layer was diluted with CH2Cl2, washed with brine, dried with
MgSO4 and concentrated in vacuo.
(1R,2S,5R)-2-[(4S)-4-tert-Butyl-2-oxo-1,3-oxazolidin-3-yl]-8-oxabi-
cyclo[3.2.1]oct-6-en-3-one (8a): Cycloaddition of 3 with furan was
performed according to the general procedure described above. Pu-
rification by flash chromatography (40% EtOAc/hexanes) followed
by recrystallization (EtOAc/hexanes) gave cycloadduct 8a as a
colourless solid. Rf = 0.3 (50% EtOAc/hexanes). M.p. 239–241 °C.
General Procedure for Cycloaddition Using LiClO4/Et3N Condi-
tions: The corresponding diene (10 equiv.) was added to a solution
of the bromo ketone (0.23 mmol) and LiClO4 (98 mg, 0.92 mmol)
in freshly distilled acetonitrile (0.92 mL) cooled to 0 °C. Et3N
(0.05 mL, 0.39 mmol) was then added dropwise and the resulting
mixture was slowly warmed to room temperature and stirred for
12 h. The organic layer was diluted with CH2Cl2, washed with
brine, dried with MgSO4 and concentrated in vacuo.
IR (CDCl ): ν = 2966, 2253, 1758, 1713, 1480, 1416, 1363, 1224,
˜
3
1171, 1140 cm–1. 1H NMR (300 MHz, CDCl3): δ = 6.63 (d, J =
6.1 Hz, 1 H), 6.27 (d, J = 6.1 Hz, 1 H), 5.20 (d, J = 4.1 Hz, 1 H),
5.04 (d, J = 4.6 Hz, 1 H), 4.50 (dd, J = 9.0, 9.0 Hz, 1 H), 4.21 (dd,
J = 3.6, 9.0 Hz, 1 H), 4.11 (d, J = 4.1 Hz, 1 H), 3.30 (dd, J = 3.4,
9.0 Hz, 1 H), 2.81 (dd, J = 5.1, 16.1 Hz, 1 H), 2.51 (d, J = 16.3 Hz,
1 H), 1.01 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 200.6,
159.4, 134.1, 131.6, 81.1, 78.4, 71.3, 68.6, 65.3, 45.6, 35.1, 25.5 ppm.
C16H15NO4: calcd. C 63.36, H 7.22, N 5.28; found C 63.19, H 7.32,
N 5.07.
General Procedure for Cycloaddition Using MgBr2/Et3N Conditions:
The corresponding diene (10 equiv.) was added to a solution of
the bromo ketone (0.23 mmol) and MgBr2 (169 mg, 0.92 mmol) in
freshly distilled acetonitrile (0.92 mL) cooled to 0 °C. Et3N
(0.05 mL, 0.39 mmol) was then added dropwise and the resulting
mixture was slowly warmed to room temperature and stirred for
12 h. The organic layer was diluted with CH2Cl2, washed with
brine, dried with MgSO4 and concentrated in vacuo.
(1R,2S,5R)-2-[(4S)-2-Oxo-4-phenyl-1,3-oxazolidin-3-yl]-8-oxabi-
cyclo[3.2.1]oct-6-en-3-one (9a): Cycloaddition of 1 with cyclopenta-
diene was performed according to the general procedure described
(1R,2S,5R)-2-[(4S)-2-Oxo-4-phenyl-1,3-oxazolidin-3-yl]-8-oxabi- above. Purification by flash chromatography (30% EtOAc/hexanes)
cyclo[3.2.1]oct-6-en-3-one (6a): Cycloaddition of 1 with furan was followed by recrystallization (EtOAc/hexanes) gave the cycloadduct
3676
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3667–3680

Cycloadditions of Enantiopure Nitrogen-Stabilized Oxyallyl Cations
FULL PAPER
9a as a colourless solid. Rf = 0.4 (50% EtOAc/hexanes). M.p. 116–
cloadduct 11a as a colourless solid. Rf = 0.4 (50% EtOAc/hexanes).
118 °C. IR (CDCl ): ν = 3066, 2957, 2911, 1750, 1603, 1477, 1411, M.p. 190–191.5 °C. IR (CDCl ): ν = 3173, 2960, 2874, 2253, 1756,
˜
˜
3
3
1
1191, 1043 cm–1. H NMR (300 MHz, CDCl3): δ = 7.42 (m, 3 H), 1716, 1480, 1420, 1362, 1237, 1196, 1115, 1067 cm–1. 1H NMR
7.32 (m, 2 H), 5.98 (dd, J = 2.9, 5.9 Hz, 1 H), 5.02 (dd, J = 2.7,
5.9 Hz, 1 H), 4.91 (d, J = 2.7 Hz, 1 H), 4.74 (m, 2 H), 4.07 (dd, J
= 1.7, 6.1 Hz, 1 H), 2.91 (m, 1 H), 2.79 (m, 1 H), 2.58 (dd, J = 3.4,
(300 MHz, CDCl3): δ = 6.40 (dd, J = 2.9, 5.6 Hz, 1 H), 6.05 (dd,
J = 2.9, 5.6 Hz, 1 H), 4.47 (dd, J = 8.7, 9.0 Hz, 1 H), 4.18 (dd, J
= 3.6, 8.7 Hz, 1 H), 3.89 (d, J = 2.6 Hz, 1 H), 3.24 (m, 2 H), 2.94
15.8 Hz, 1 H), 2.45 (ddd, J = 2.6, 2.9, 15.8 Hz, 1 H), 2.15 (m, 1 (m, 1 H), 2.50 (m, 2 H), 2.33 (m, 1 H), 1.85 (d, J = 10.9 Hz, 1 H)
H), 1.99 (d, J = 11.2 Hz, 1 H) ppm. 13C (75 MHz, CDCl3): δ =
ppm. 13C NMR (75 MHz, CDCl3): δ = 204.0, 159.4, 136.0, 133.8,
204.8, 160.4, 141.6, 137.6, 133.6, 129.5, 128.9, 126.2, 71.6, 68.2,
72.4, 68.9, 65.1, 45.8, 45.3, 45.2, 39.3, 35.2, 25.5 ppm. C17H17NO3:
57.7, 45.2, 44.8, 44.4, 39.8. HRMS calcd. for C17H17NO3 [M+] calcd. C 68.40, H 8.04, N 5.32; found C 68.31, H 8.13, N 5.22.
283.1208, found 283.1205.
(1S,2R,5S)-2-[(4R,5S)-1,5-Dimethyl-2-oxo-4-phenylimidazolidin-3-
(1S,2R,5S)-2-[(4S)-2-Oxo-4-phenyl-1,3-oxazolidin-3-yl]-8-oxabi-
cyclo[3.2.1]oct-6-en-3-one (9b): Purification by flash chromatog-
raphy (30% EtOAc/hexanes) followed by recrystallization (EtOAc/
hexanes) gave cyclaodduct 9b as a colourless solid. Rf = 0.4 (50%
yl]-8-oxabicyclo[3.2.1]oct-6-en-3-one (13a): Cycloaddition of 12
with furan was performed according to the general procedure de-
scribed above. Purification by flash chromatography (EtOAc/hex-
anes, 3:1) afforded cycloadducts 13a (40.6 mg, 21 %) and 13b
EtOAc/hexanes). M.p. 165–167 °C. IR (CDCl ): ν = 3696, 2952, (12.7 mg, 7%) as colourless solids. Rf = 0.41 (EtOAc/hexanes, 3:1).
˜
3
1955, 1761, 1602, 1478, 1262, 1106, 1042 cm–1
.
1H NMR
[α]2D5 = –283 (c = 2.03, CH Cl ). IR (CDCl ): ν = 2968, 1733, 1695,
˜
2 2 3
(300 MHz, CDCl3): δ = 7.40 (m, 5 H), 6.27 (dd, J = 2.7, 5.6 Hz, 1 1435, 1403, 1340, 1258, 1040, 966, 845, 703 cm–1
H), 6.05 (dd, J = 2.7, 5.6 Hz, 1 H), 4.89 (dd, J = 8.5, 8.5 Hz, 1 H),
4.68 (dd, J = 8.5, 8.5 Hz, 1 H), 4.12 (dd, J = 8.5, 8.5 Hz, 1 H), 3.71
.
1H NMR
(300 MHz, CDCl3): δ = 7.27–7.42 (m, 5 H), 6.09 (dd, J = 1.7,
6.1 Hz, 1 H), 5.21 (d, J = 4.4 Hz, 1 H), 5.09 (dd, J = 1.8, 6.2 Hz,
(d, J = 2.9 Hz, 1 H) 3.00 (m, 1 H), 2.88 (m, 1 H), 2.46 (m, 2 H), 1 H), 4.93 (dd, J = 0.9, 5.0 Hz, 1 H), 4.68 (dd, J = 1.8, 4.4 Hz, 1
2.18 (m, 1 H), 1.69 (d, J = 10.9 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 204.1, 158.0, 138.0, 135.5, 134.9, 129.5(8), 129.5(1),
127.6, 70.4, 67.7, 64.0, 45.4, 45.3, 44.6, 39.1 ppm. HRMS calcd.
for C17H17NO3 [M+] 283.1208, found 283.1213.
H), 4.48 (d, J = 8.8 Hz, 1 H), 3.97 (dq, J = 2.1, 6.6 Hz, 1 H), 2.82
(d of ABq, J = 5.8, 20.1 Hz, 1 H), 2.74 (s, 3 H), 2.37 (ABq, J =
15.6 Hz, 1 H), 0.72 (d, J = 6.6 Hz, 3 H) ppm. 13C NMR (75 MHz/
CDCl3): δ = 202.9, 162.3, 138.6, 134.4, 132.5, 128.4, 80.9, 78.3,
66.6, 59.7, 57.0, 46.1, 29.2, 15.2 ppm. HRMS (EI) calcd. for
C18H20N2O3 [M+] 312.1474, found 312.1473.
(1R,2S,5R)-2-[(4S)-4-Benzyl-2-oxo-1,3-oxazolidin-3-yl]-8-oxabi-
cyclo[3.2.1]oct-6-en-3-one (10a): Cycloaddition of 2 with cyclopen-
tadiene was performed according to the general procedure de-
scribed above. Purification by flash chromatography (30% EtOAc/
hexanes) followed by recrystallization (EtOAc/hexanes) gave 10a as
a colourless solid. Rf = 0.4 (50 % EtOAc/hexanes). M.p. 136–
(1R,2S,5R)-2-[(4R,5S)-1,5-Dimethyl-2-oxo-4-phenylimidazolidin-3-
yl]-8-oxabicyclo[3.2.1]oct-6-en-3-one (13b): Rf = 0.24 (EtOAc/hex-
anes, 3:1). [α]2D5 = –168 (c = 0.37, CH Cl ). IR (CDCl ): ν = 2962,
˜
2
2
3
2920, 1725, 1694, 1651, 1446, 1403, 1261, 1025, 801 cm–1. 1H NMR
138 °C. IR (CDCl ): ν = 3673, 3409, 2957, 2253, 1747, 1724, 1701, (300 MHz, CDCl3): δ = 7.26–7.43 (m, 5 H), 6.67 (ddd, J = 0.6, 1.9,
˜
3
1604, 1479, 1418, 1351, 1290, 1226, 1089 cm–1
.
1H NMR
6.1 Hz, 1 H), 6.22 (ddd, J = 0.4, 1.8, 6.0 Hz, 1 H), 5.04 (ddd, J =
0.3, 1.8, 4.6 Hz, 1 H), 4.71 (ddd, J = 0.7, 1.4, 5.1 Hz, 1 H), 4.81
(d, J = 8.8 Hz, 1 H), 3.88 (dq, J = 6.6, 8.8 Hz, 1 H), 3.73 (d, J =
4.6 Hz, 1 H), 2.78 (s, 3 H), 2.59 (d of ABq, J = 5.2, 16.2, 1 H),
(300 MHz, CDCl3): δ = 7.32 (m, 3 H), 7.17 (m, 2 H), 6.30 (m, 2
H), 4.61 (d, J = 2.7 Hz, 1 H), 4.09 (m, 3 H), 3.13 (m, 1 H), 3.02 (m,
2 H), 2.69 (dd, J = 9.8, 13.6 Hz, 1 H), 2.58 (dd, J = 3.4, 16.6 Hz, 1
H), 2.52 (ddd, J = 2.7, 2.7, 16.6 Hz, 1 H), 2.40 (m, 1 H), 2.05 (d, 2.42 (ABq, J = 16.2 Hz, 1 H), 0.74 (d, J = 6.6 Hz, 3 H) ppm. 13C
J = 11.2 Hz, 1 H) ppm. 13C (75 MHz, CDCl3): δ = 204.8, 158.7, NMR (75 MHz, CDCl3): δ = 202.5, 160.6, 136.4, 134.7, 131.3,
138.4, 136.4, 134.2, 129.2, 129.1, 127.3, 67.7, 67.3, 57.2, 45.1, 44.9,
44.7, 39.7, 39.1. C18H19NO3: C 7.69; H 6.44, N 4.71; found C 72.13,
H 6.47, N 4.72. HRMS calcd. for C18H19NO3 [M+] 297.1364, found
297.1363.
128.9, 128.7, 81.4, 78.1, 68.0, 65.7, 55.8, 45.8, 28.7, 14.5 ppm.
HRMS (EI) calcd. for C18H20N2O3 [M+] 312.1474, found 312.1465.
(1S,2R,5R)-2-[(4R,5S)-1,5-Dimethyl-2-oxo-4-phenylimidazolidin-3-
yl]bicyclo[3.2.1]oct-6-en-3-one (14a): Cycloaddition of 12 with cy-
clopentadiene was performed according to the general procedure
described above. Purification by flash chromatography (EtOAc/
hexanes, 1:1) afforded cycloadducts 14a (65 mg, 36 %) and 14b
(36 mg, 20%) as colourless solids. Rf = 0.30 (EtOAc/hexanes, 1:1).
(1S,2R,5S)-2-[(4S)-4-Benzyl-2-oxo-1,3-oxazolidin-3-yl]-8-oxabi-
cyclo[3.2.1]oct-6-en-3-one (10b): Purification by flash chromatog-
raphy (30% EtOAc/hexanes) gave 10b as a colourless oil. Rf = 0.4
(50% EtOAc/hexanes). IR (CDCl ): ν = 2954, 2871, 1949, 1745,
˜
3
1715, 1603, 1496, 1478, 1290, 1255, 1190, 1102, 1012 cm–1
.
1H [α]2D5 = –120.6 (c = 2.32, CH Cl ). IR (CDCl ): ν = 2949, 1720,
˜
2 2 3
NMR (300 MHz, CDCl3): δ = 7.32 (m, 3 H), 7.17 (m, 2 H), 6.28 1694, 1435, 1403, 1351, 1253, 1193, 1099, 735 cm–1
.
1H NMR
(dd, J = 2.7, 5.6 Hz, 1 H), 6.18 (dd, J = 2.7, 5.6 Hz, 1 H), 4.77 (d, (300 MHz, CDCl3): δ = 7.26–7.44 (m, 4 H), 6.97–7.11 (m, 1 H),
J = 2.7 Hz, 1 H), 4.28 (dd, J = 8.5, 8.5 Hz, 1 H), 4.08 (dd, J = 4.4, 5.92 (dd, J = 2.8, 5.9 Hz, 1 H), 5.11 (dd, J = 2.6, 5.8 Hz, 1 H), 5.03
8.5 Hz, 1 H), 3.87 (m, 1 H), 3.22 (m, 1 H), 3.05 (m, 2 H), 2.71 (dd,
J = 10.5, 13.6 Hz, 1 H), 2.56 (dd, J = 3.2, 15.8 Hz, 1 H), 2.47 (ddd,
(d, J = 2.7 Hz, 1 H), 4.39 (d, J = 8.9 Hz, 1 H), 3.96 (dq, J = 2.3,
6.6 Hz, 1 H), 2.81–2.87 (m, 1 H), 2.72 (s, 3 H), 2.63 (quint, J =
J = 2.4, 2.7, 15.8 Hz, 1 H), 2.37 (m, 1 H), 2.09 (d, J = 11.2 Hz, 1 2.7 Hz, 1 H), 2.51 (d of ABq, J = 2.6, 15.8 Hz, 1 H), 2.37 (t of
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 200.3, 155.7, 134.8
131.6, 128.6, 124.9, 124.8, 123.1, 64.1, 63.5, 50.3, 40.7, 40.6, 40.4,
36.4, 35.5 ppm. HRMS calcd. for C18H19NO3 [M+] 297.1364,
found 297.1367.
ABq, J = 2.9, 15.9 Hz, 1 H), 2.03–2.12 (m, 1 H), 1.95–2.09 (ABq,
J = 12.4 Hz, 1 H), 0.70 (d, J = 6.6 Hz, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 206.5, 163.0, 139.1, 136.8, 134.3, 128.6,
128.1, 128.0, 127.5, 67.2, 59.7, 57.2, 45.3, 44.8, 44.6, 39.7, 29.3, 15.2
ppm. HRMS (EI) calcd. for C19H22N2O2 [M+] 310.1681, found
310.1687.
(1R,2S,5R)-2-[(4S)-4-tert-Butyl-2-oxo-1,3-oxazolidin-3-yl]-8-oxa-
bicyclo[3.2.1]oct-6-en-3-one (11a): Cycloaddition of 3 with cyclo-
pentadiene was performed according to the general procedure de-
scribed above. Purification by flash chromatography (30% EtOAc/
(1R,2S,5S)-2-[(4R,5S)-1,5-Dimethyl-2-oxo-4-phenylimidazolidin-3-
yl]bicyclo[3.2.1]oct-6-en-3-one (14b): Rf = 0.24 (EtOAc/hexanes,
hexanes) followed by recrystallization (EtOAc/hexanes) gave cy- 1:1). IR (CDCl ): ν = 2944, 1699, 1435, 1402, 1362, 1261, 1028,
˜
3
Eur. J. Org. Chem. 2006, 3667–3680
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3677

D. I. MaGee, E. Godineau, P. D. Thornton, M. A. Walters, D. J. Sponholtz
FULL PAPER
762, 704 cm–1. H NMR (300 MHz, CDCl3): δ = 7.26–7.43 (m, 5
H), 6.34 (dd, J = 2.6, 5.6 Hz, 1 H), 5.99 (dd, J = 2.4, 5.5 Hz, 1 H),
4.77 (d, J = 8.9 Hz, 1 H), 3.90 (dq, J = 6.6, 8.9 Hz, 1 H), 3.65 (d,
J = 2.9 Hz, 1 H), 3.08 (quint, J = 2.7 Hz, 1 H), 2.86–2.88 (m, 1
H), 2.78 (s, 3 H), 2.37–2.40 (m, 2 H), 2.17 (broad quint, J = 5.7 Hz,
1 H), 1.67 (d, J = 11.2 Hz, 1 H), 0.71 (d, J = 6.6 Hz, 3 H) ppm.
= 1.5, 4.1, 10.4 Hz, 1 H), 2.70 (d of ABq, J = 4.9, 14.6 Hz, 1 H),
2.66–2.74 (m, 1 H), 2.43–2.49 (m, 1 H), 2.35 (d of ABq, J = 1.2,
14.6 Hz, 1 H), 1.61 (dd of ABq, J = 3.2, 5.0, 13.8 Hz, 1 H), 1.28–
1.47 (m, 2 H), 1.21–1.23 (m, 1 H), 1.11 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 201.6, 157.9, 136.1, 135.9, 134.0, 133.8,
133.7, 133.5, 130.0, 129.8, 127.9, 127.8, 80.1, 78.7, 75.1, 68.9, 60.4,
1
13C NMR (75 MHz, CDCl3): δ = 206.0, 161.1, 136.9, 133.9, 128.3 47.0, 44.7, 40.8, 33.5, 29.5, 27.4 (3 C), 19.2 ppm. HRMS (EI) calcd.
(2 C), 128.3 (2 C), 68.8, 65.5, 63.9, 56.0, 45.6, 45.4, 44.6, 39.0, 28.8,
14.5 ppm. HRMS (EI) calcd. for C19H22N2O2 [M+] 310.1681,
found 310.1675.
for C27H26NO5Si [M+ –C4H9] 472.1580, found 472.1587.
(1S,2R,5R)-2-[(1R,2S,6R,7R,8R)-8-tert-Butyl(diphenyl)silanyloxy-
4-oxo-3-oxa-5-azatricyclo[5.2.1.02,6]dec-5-yl]-8-oxabicyclo[3.2.1]oct-
(1S,2R,5S)-2-[(4R,5S)-2-Oxo-4,5-[9,10]dimethylanthraceno-1,3- 6-en-3-one (16b): R = 0.43 (CH Cl /EtOAc, 5:1). IR (CDCl ): ν =
˜
f
2
2
3
oxazolidin-3-yl]-8-oxabicyclo[3.2.1]oct-6-en-3-one (15a): Cycload-
dition of 4 with furan was performed according to the general pro-
cedure described above. Purification by flash chromatography
(EtOAc/hexanes, 2:3) afforded cycloadducts 15a (145 mg, 83%),
15b (6 mg, 3%) and 15c (4.5 mg, 2.6%) as colourless solids. Rf =
0.22 (EtOAc/hexanes, 2:3). [α]2D5 = +44.2 (c = 1.0, CH2Cl2). M.p.
3070, 2953, 2850, 2249, 1748, 1725, 1594, 1472, 1262, 1111, 1075
1
cm–1. H NMR (400 MHz, CDCl3): δ = 7.62–7.67 (m, 4 H), 7.33–
7.46 (m, 6 H), 6.38 (dd, J = 1.8, 6.1 Hz, 1 H), 6.25 (dd, J = 1.6,
6.1 Hz, 1 H), 5.26 (dd, J = 1.6, 4.4 Hz, 1 H), 5.00–5.03 (m, 1 H),
4.95 (d, J = 4.4 Hz, 1 H), 4.86 (ddd, J = 1.2, 4.0, 10.6 Hz, 1 H),
4.34 (m, 1 H), 3.65 (ddd, J = 1.6, 4.0, 10.6 Hz, 1 H), 2.87 (d of
ABq, J = 5.0, 15.1 Hz, 1 H), 2.48–2.54 (m, 1 H), 2.39 (ABq, J =
14.4 Hz, 1 H), 2.33–2.38 (m, 1 H), 1.59–1.74 (m, 1 H), 1.17–1.45
199–201 °C. IR (CHCl ): ν = 3054, 2966, 1762, 1715, 1526, 1412,
˜
3
1362, 1210, 1011, 924 cm–1. H NMR (300 MHz): δ = 7.38 (m, 4
1
H), 7.25 (m, 4 H), 6.14 (ddd, J = 1.5, 3.1, 5.4 Hz, 2 H), 5.03 (dd, (m, 3 H), 1.11 (s, 9 H) ppm.
J = 1.4, 4.5 Hz, 1 H), 4.99 (dt, J = 0.98, 5.35 Hz, 1 H), 4.58 (d, J
(1R,2R,5S)-2-[(1R,2S,6R,7R,8R)-8-tert-Butyl(diphenyl)silanyloxy-
= 9.2 Hz, 1 H), 4.05 (d, J = 4.5 Hz, 1 H), 3.67 (d, J = 9.2 Hz, 1
H), 2.75 (dd, J = 5.3, 16.6 Hz, 1 H), 2.44 (d, J = 16.6 Hz, 1 H),
2.11 (s, 3 H), 2.06 (s, 3 H) ppm. 13C NMR (75 MHz): δ = 199.5,
158.0, 142.6, 141.7, 140.7, 140.3, 133.6, 131.5, 127.2, 127.1, 127.0,
126.7, 124.3, 124.1, 122.7, 122.3, 81.0, 80.9, 78.2, 69.6, 68.6, 46.4,
45.9, 45.4, 16.0, 14.8 ppm. HRMS (EI) calcd. for C26H23NO4 [M+]
413.1627, found 413.1622.
4-oxo-3-oxa-5-azatricyclo[5.2.1.02,6]dec-5-yl]-8-oxabicyclo[3.2.1]oct-
6-en-3-one (16c): Rf = 0.32 (CH2Cl2/EtOAc, 5:1). [α]2D5 = +83.3 (c
= 0.018, CH Cl ). IR (CDCl ): ν = 2928, 1749, 1427, 1260, 1223,
˜
2
2
1
3
1075, 802 cm–1. H NMR (300 MHz, CDCl3): δ = 7.61–7.68 (m, 4
H), 7.36–7.45 (m, 6 H), 6.68 (dd, J = 1.8, 7.7 Hz, 2 H), 6.60 (dd,
J = 1.8, 7.7 Hz, 2 H), 6.29 (ddd, J = 0.7, 1.8, 6.0 Hz, 1 H), 5.49
(dd, J = 1.6, 6.0 Hz, 1 H), 5.41–5.42 (m, 1 H), 4.97 (dd, J = 1.8,
(1R,2S,5R)-2-[(4R,5S)-2-Oxo-4,5-[9,10]dimethylanthraceno-1,3- 5.7 Hz, 1 H), 4.75 (ddd, J = 0.8, 4.6, 10.3 Hz, 1 H), 4.45–4.49 (m,
oxazolidin-3-yl]-8-oxabicyclo[3.2.1]oct-6-en-3-one (15b): Rf = 0.2
1 H), 4.21 (s, 1 H), 3.86 (ddd, J = 1.5, 4.0, 10.4 Hz, 1 H), 2.75 (dd
of ABq, J = 1.0, 5.8, 17.8 Hz, 1 H), 2.68–2.73 (m, 1 H), 2.55 (broad
t, J = 5.0 Hz, 1 H), 2.44 (ABq, J = 17.8 Hz, 1 H), 1.73 (dd of ABq,
(EtOAc/hexanes, 2:3). IR (CHCl ): ν = 3054, 2966, 1764, 1715,
˜
3
1534, 1408, 1360, 924 cm–1. H NMR (300 MHz): δ = 7.38 (m, 4
1
H), 7.24 (m, 4 H), 6.28 (dd, J = 1.6, 6.0 Hz, 1 H), 6.22 (dd, J = J = 3.0, 5.0, 13.6 Hz, 1 H), 1.61 (dd of ABq, J = 1.2, 5.1, 13.5 Hz,
1.5, 6.0 Hz, 1 H), 4.98 (dd, J = 0.84, 5.3 Hz, 1 H), 4.93 (dd, J = 1 H), 1.49 (m, 1 H), 1.41 (m, 1 H), 1.23–1.31 (m, 1 H), 1.10 (s, 9
1.5, 5.5 Hz, 1 H), 4.57 (d, J = 8.7 Hz, 1 H), 4.36 (d, J = 4.5 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 204.6, 159.5, 136.1,
H), 3.73 (dd, J = 0.86, 8.7 Hz, 1 H), 2.83 (dd, J = 5.4, 16.5 Hz, 1
H), 2.50 (d, J = 16.5 Hz, 1 H), 2.07 (s, 3 H), 1.97 (s, 3 H) ppm.
13C NMR (75 MHz): δ = 198.4, 143.7, 141.5, 140.4, 139.2, 132.9,
127.1, 127.0, 126.5, 124.7, 123.3, 122.9, 122.0, 81.1, 80.3, 78.1, 77.4,
69.0, 66.3, 46.9, 45.8, 15.7, 15.2 ppm.
136.0, 135.7, 134.3, 133.4, 131.6, 130.2, 129.8, 128.1, 127.9, 79.5,
77.4, 75.1, 72.2, 61.9, 58.5, 47.1, 44.9, 40.7, 34.1, 29.7, 27.3 (3 C),
19.4 ppm. HRMS (EI) calcd. for C27H26NO5Si [M+ – C4H9]
472.1580, found 472.1584.
(1S,2R,5S)-2-[(4R,5S)-2-Oxo-4,5-[9,10]dimethylanthraceno-1,3-
(1S,2S,5S)-2-[(4R,5S)-2-Oxo-4,5-[9,10]dimethylanthraceno-1,3- oxazolidin-3-yl]bicyclo[3.2.1]oct-6-en-3-one (17a): Cycloaddition of
oxazolidin-3-yl]-8-oxabicyclo[3.2.1]oct-6-en-3-one (15c): Rf = 0.18
(EtOAc/hexanes, 2:3). IR (CDCl ): ν = 3050, 2972, 1761, 1716,
4 with cyclopentadiene was performed according to the general
procedure described above. Purification by flash chromatography
˜
3
1522, 1416, 1350, 1212, 1015, 926 cm–1. H NMR (300 MHz): δ = (EtOAc/hexanes, 2:3) afforded cycloadducts 17a (167 mg, 89 %)
1
7.37 (m, 2 H), 7.22 (m, 6 H), 6.48 (ddd, J = 0.85, 4.1, 18.6 Hz, 2
H), 5.00 (t, J = 0.5 Hz, 2 H), 4.55 (d, J = 9.3 Hz, 1 H), 3.87 (d, J
= 9.5 Hz, 1 H), 3.27 (s, 1 H), 3.07 (dd, J = 7.1, 19.1 Hz, 2 H), 2.06
(s, 3 H), 1.98 (s, 3 H) ppm.
and 17b (9 mg, 5%) as a colourless solids. Rf = 0.33 (EtOAc/hex-
anes, 2:3). [α]2D5 = +23.0 (c = 1.25, CHCl3). M.p. 168–170 °C. IR
(CDCl ): ν = 3052, 2968, 1760, 1716, 1526, 1416, 1364, 1212, 1011,
˜
3
1
926 cm–1. H NMR (300 MHz): δ = 7.32–7.26 (m, 4 H), 7.25–7.21
(m, 4 H), 5.95 (dd, J = 1.2, 0.3 Hz, 2 H), 4.56, (d, J = 9.2 Hz, 1
H), 3.84, (d, J = 2.8 Hz, 1 H), 3.61 (d, J = 9.2 Hz, 1 H), 3.11–3.07
(m, 1 H), 2.92–2.86 (m, 1 H), 2.42 (t, J = 2.8 Hz, 2 H), 2.35–2.30
(m, 1 H), 2.07 (s 3 H), 2.05 (s, 3 H), 1.86 (d, J = 11.1, 1 H) ppm.
13C NMR (75 MHz): δ = 223.1, 158.2, 143.1, 142.0, 141.0, 140.3,
135.7, 133.8, 127.1, 126.9, 126.0, 124.1, 123.1, 122.3, 80.8, 71.2,
69.3, 46.5, 46.0, 45.1, 44.8, 39.1, 15.9, 15.0 ppm. HRMS (EI) calcd.
for C27H26NO5Si [M+ –C4H9] 472.1580, found 472.1579.
(1R,2S,5S)-2-[(1R,2S,6R,7R,8R)-8-tert-Butyl(diphenyl)silanyloxy-4-
oxo-3-oxa-5-azatricyclo[5.2.1.02,6]dec-5-yl]-8-oxabicyclo[3.2.1]oct-6-
en-3-one (16a): Cycloaddition of 5 with furan (200 equiv.) was per-
formed according to the general procedure described above. Purifi-
cation by flash chromatography (EtOAc/hexanes gradient, 1:5, 1:4,
1:3, 1:2 and 1:1) afforded cycloadducts 16a (50.1 mg, 82%), 16b
(1.6 mg, 3%) and 16c (2.8 mg, 5%) all as colourless solids. Rf =
0.35 (CH2Cl2/EtOAc, 10:1). [α]2D5 = +0.4 (c = 1.05, CH2Cl2). M.p.
81–84 °C. IR (CDCl ): ν = 3072, 2963, 2858, 2249, 1748, 1725,
(1R,2S,5R)-2-[(4R,5S)-2-Oxo-4,5-[9,10]dimethylanthraceno-1,3-
˜
3
1589, 1472, 1262, 1111, 1077, 1029 cm–1
CDCl3): δ = 7.63–7.71 (m, 4 H), 7.37–7.47 (m, 6 H), 6.47 (dd, J =
1.7, 6.0 Hz, 1 H), 6.23 (dd, J = 1.7, 6.0 Hz, 1 H), 5.65 (dd, J = 1.8, 1354, 1210, 1015, 926 cm–1. 1H NMR (300 MHz): δ = 7.37–7.34
.
1H NMR (300 MHz, oxazolidin-3-yl]bicyclo[3.2.1]oct-6-en-3-one (17b): Rf = 0.31 (EtOAc/
hexanes, 2:3). IR (CDCl ): ν = 3051, 2970, 1760, 1716, 1524, 1414,
˜
3
4.4 Hz, 1 H), 4.96 (dt, J = 1.5, 4.9 Hz, 1 H), 4.64 (ddd, J = 1.2,
4.9, 10.4 Hz, 1 H), 4.57 (s, 1 H), 4.33–4.37 (m, 1 H), 4.21 (ddd, J
(m, 4 H), 7.27–7.23 (m, 4 H), 6.22 (ddd, J = 2.8, 5.5, 15.9 Hz, 2
H), 4.55 (d, J = 9.3 Hz, 1 H), 3.82 (d, J = 9.2 Hz, 1 H), 3.18, (s, 1
3678
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Eur. J. Org. Chem. 2006, 3667–3680

Cycloadditions of Enantiopure Nitrogen-Stabilized Oxyallyl Cations
FULL PAPER
H), 2.91 (dd, J = 2.9, 4.2 Hz, 1 H), 2.79 (br. q, J = 1.5 Hz, 1 H),
2.62 (dd, J = 5.1, 18.8 Hz, 1 H), 2.58 (d, J = 11.2 Hz, 1 H), 2.31
1 H), 3.90 (ddd, J = 1.5, 4.0, 10.3 Hz, 1 H), 3.70 (s, 3 H), 2.79–
2.84 (m, 1 H), 2.68 (d of ABq, J = 4.4, 15.7 Hz, 1 H), 2.45–2.51
(d, J = 18.4 Hz, 1 H), 2.04 (s, 6 H), 1.80–1.77 (m, 1 H) ppm. 13C (m, 1 H), 2.42 (d of ABq, J = 1.5, 15.7 Hz, 1 H), 1.32–1.60 (m, 3
NMR (75 MHz): δ = 208.1, 158.8, 143.0, 142.1, 141.2, 140.5, 140.3,
135.3, 127.3, 127.2, 127.17, 126.8, 124.5, 123.0, 122.9, 122.5, 81.6,
H), 1.22–1.29 (m, 1 H), 1.11 (s, 9 H) ppm. 13C NMR (75 MHz,
DMSO, 80 °C): δ = 199.7, 157.7, 152.1, 135.1 (2 C), 134.9 (2 C),
69.8, 65.3, 46.6, 46.0, 45.99, 45.4, 37.1, 36.6, 15.9, 15.0 ppm. 133.1, 133.4, 133.2, 132.8, 129.3, 129.1, 127.2 (2 C), 127.1 (2 C),
HRMS (EI) calcd. for C27H26NO5Si [M+ –C4H9] 472.1580, found
472.1580.
76.1, 74.5, 67.1, 60.8, 59.5, 56.4, 51.9, 44.2, 44.0, 33.6, 30.4, 29.0,
26.7 (3 C), 18.2 ppm. HRMS (EI) calcd. for C29H29N2O6Si [M+ –
C4H9] 529.1795, found 529.1800.
(1S,2R,5R)-2-[(1S,2R,6S,7S,8S)-8-tert-Butyl(diphenyl)silanyloxy-4-
oxo-3-oxa-5-azatricyclo[5.2.1.02,6]dec-5-yl]bicyclo[3.2.1]oct-6-en-3-
one (18a): Cycloaddition of 5 with cyclopentadiene (200 equiv.) was
performed according to the general procedure described above. Pu-
rification by flash column chromatography (EtOAc/hexanes gradi-
ent, 1:7, 1:5, 1:4, 1:2 and 1:1) afforded cycloadducts 18a (30.8 mg,
76% yield) and 18c (6.1 mg, 14%) as colourless solids. Rf = 0.45
(CH2Cl2/EtOAc, 20:1). [α]2D5 = –21.4 (c = 0.22, CH2Cl2). M.p. 71–
Methyl (1R,2R,5S)-2-[(1R,2S,6R,7R,8R)-8-tert-Butyl(diphenyl)sil-
anyloxy-4-oxo-3-oxa-5-azatricyclo[5.2.1.02,6]dec-5-yl]-3-oxo-8-aza-
bicyclo[3.2.1]oct-6-ene-8-carboxylate (21): Rf = 0.44 (EtOAc/hex-
anes, 2:1). [α]2D5 = +7.3 (c = 0.15, CH Cl ). IR (CDCl ): ν = 2961,
˜
2
2
3
2857, 1747, 1731, 1699, 1455, 1410, 1261, 1105, 1071, 1031 cm–1.
1H NMR (300 MHz, DMSO, 80 °C): δ = 7.69–7.78 (m, 4 H), 7.38–
7.51 (m, 6 H), 6.46 (dd, J = 2.3, 6.0 Hz, 1 H), 6.10 (dd, J = 2.5,
6.1 Hz, 1 H), 5.59 (t, J = 2.0 Hz, 1 H), 4.88 (t, J = 2.2 Hz, 1 H),
4.71 (dd, J = 5.0, 9.9 Hz, 1 H), 4.24 (quint, J = 4.2 Hz, 1 H), 3.94
(s, 1 H), 3.84 (ddd, J = 1.4, 4.1, 10.2 Hz, 1 H), 3.69 (s, 3 H), 2.99
(d of ABq, J = 4.5, 16.5 Hz, 1 H), 2.35–2.41 (m, 2 H), 2.24 (m, 2
H), 1.14–1.41 (m, 3 H), 1.07 (s, 9 H) ppm.
74 °C. IR (CDCl ): ν = 2956, 2858, 1748, 1589, 1471, 1427, 1439,
˜
3
1260, 1111, 1076, 911, 860 cm–1. 1H NMR (300 MHz, CDCl3): δ
= 7.64–7.71 (m, 4 H), 7.33–7.54 (m, 6 H), 6.13 (dd, J = 2.7, 5.8 Hz,
1 H), 6.05 (dd, J = 2.6, 6.0 Hz, 1 H), 4.74 (ddd, J = 0.9, 5.0,
10.3 Hz, 1 H), 4.51 (d, J = 2.9 Hz, 1 H), 4.36 (ddt, J = 1.3, 4.6,
8.8 Hz, 1 H), 4.05 (ddd, J = 1.5, 4.0, 10.3 Hz, 1 H), 3.55 (quint, J
= 2.7 Hz, 1 H), 2.90 (br. t, J = 4.0 Hz, 1 H), 2.80–2.86 (m, 1 H),
2.47 (broad t, J = 4.6 Hz, 1 H), 2.30 (dd, J = 1.6, 3.0 Hz, 1 H),
1.97 (quint, J = 5.8 Hz, 1 H), 1.68 (dd of ABq, J = 3.3, 4.7, 13.7 Hz,
1 H), 1.43–1.53 (m, 2 H), 1.29 (dt of ABq, J = 1.4, 11.2 Hz, 1 H),
1.16 (quint of ABq, J = 1.6 Hz, 11.3 Hz, 1 H), 1.07 (s, 9 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 204.1, 158.3, 136.7, 136.1, 136.0,
134.3, 129.9, 129.6, 127.8, 127.7, 76.8, 74.9, 69.3, 60.8, 46.4, 45.3,
44.1, 40.8, 40.2, 33.6, 29.9, 27.3 (3 C), 19.2 ppm. HRMS (EI) calcd.
for C28H28NO4Si [M+ –C4H9] 470.1788, found 470.1800.
(1R,2S,5S)-6-Bromo-2-[(1R,2S,6R,7R,8R)-8-tert-butyl(diphenyl)-
silanyloxy-4-oxo-3-oxa-5-azatricyclo[5.2.1.02,6]dec-5-yl]-8-oxabi-
cyclo[3.2.1]oct-6-en-3-one (22): Cycloaddition of 5 with 3-bromofu-
ran (200 equiv.) was performed according to the general procedure
described above. Purification by flash chromatography (EtOAc/
hexanes gradient, 1:4, 1:3 and 1:2) afforded cycloadduct 22
(20.8 mg, 21% yield) as an orange solid. Rf = 0.51 (EtOAc/hexanes,
1:3). [α]2D5 = +2.72 (c = 0.25, CH2Cl2). M.p. 140–142 °C. IR
(CDCl ): ν = 2962, 2858, 1748, 1728, 1600, 1471, 1427, 1260, 1112,
˜
3
1073, 806 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.68 (dd, J =
1.5, 7.8 Hz, 2 H), 7.63 (dd, J = 1.7, 7.6 Hz, 2 H), 7.34–7.47 (m, 6
H), 6.57 (d, J = 2.0 Hz, 1 H), 5.63 (dd, J = 2.0, 4.2 Hz, 1 H), 4.73–
4.81 (m, 2 H), 4.47 (d, J = 4.2 Hz, 1 H), 4.37 (quint, J = 5.3 Hz, 1
H), 4.27 (ddd, J = 1.5, 4.1, 10.4 Hz, 1 H), 2.60–2.70 (m, 3 H), 2.45–
2.50 (m, 1 H), 1.61 (dd of ABq, J = 3.2, 4.6, 13.7 Hz, 1 H), 1.45
(dd of ABq, J = 5.0, 10.7, 13.7 Hz, 1 H), 1.34 (ABq, J = 11.4 Hz,
1 H), 1.18 (ABq, J = 11.6 Hz, 1 H), 1.11 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 200.7, 157.8, 136.0, 135.8, 133.9, 133.7,
132.5, 130.1, 129.9, 127.9, 127.8, 123.6, 82.4, 81.3, 75.1, 67.2, 60.3,
45.3, 44.6, 40.8, 33.5, 29.4, 27.5 (3 C), 19.3 ppm. HRMS (EI) calcd.
for C27H25O5NSi81Br [M+ –C4H9] 552.0665, found: 552.0660.
(1S,2S,5R)-2-[(1S,2R,6S,7S,8S)-8-tert-Butyl(diphenyl)silanyloxy-4-
oxo-3-oxa-5-azatricyclo[5.2.1.02,6]dec-5-yl]bicyclo[3.2.1]oct-6-en-3-
one (18c): R = 0.42 (CH Cl /EtOAc, 20:1). IR (CDCl ): ν = 2956,
˜
f
2
2
3
2856, 1746, 1594, 1470, 1440, 1266, 1114, 1076, 910 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 7.59–7.69 (m, 4 H), 7.35–7.47 (m, 6 H),
6.27 (dd, J = 2.7, 5.8 Hz, 1 H), 6.12 (dd, J = 2.3, 5.6 Hz, 1 H), 4.76
(dd, J = 4.8, 10.0 Hz, 1 H), 4.56 (d, J = 2.6 Hz, 1 H), 4.39 (quint,
J = 4.9 Hz, 1 H), 4.33 (d, J = 3.0 Hz, 1 H), 4.18 (ddd, J = 1.7, 4.4,
10.7 Hz, 1 H), 3.59–3.65 (m, 1 H), 3.16–3.23 (m, 1 H), 2.83–2.90
(m, 1 H), 2.49–2.56 (m, 1 H), 2.00 (dt, J = 5.6, 12.1 Hz, 1 H), 1.62–
1.79 (m, 1 H), 1.45–1.47 (m, 5 H), 1.08 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 195.4, 157.9, 137.3, 136.1 (2 C), 135.9 (2 C),
134.8, 134.5, 133.6, 130.0, 129.8, 127.9 (2 C), 127.8 (2 C), 75.0,
69.6, 60.4, 60.3, 50.5, 45.6, 45.4, 43.6, 40.9, 33.5, 30.0, 27.4 (3 C),
19.4 ppm. HRMS (EI) calcd. for C28H28NO4Si [M+ – C4H9]
470.1788, found 470.1788.
CCDC-607138 to -607140 contain the complete crystallographic
data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgments
Methyl (1R,2S,5S)-2-[(1R,2S,6R,7R,8R)-8-tert-Butyl(diphenyl)sil-
anyloxy-4-oxo-3-oxa-5-azatricyclo[5.2.1.02,6]dec-5-yl]-3-oxo-8-aza-
bicyclo[3.2.1]oct-6-ene-8-carboxylate (20): Cycloaddition of 5 with
methyl 1H-pyrrole-1-carboxylate (200 equiv.) was performed ac-
cording to the general procedure described above. Purification by
flash chromatography (EtOAc/hexanes gradient, 1:5, 1:3, 1:1 and
2:1) afforded cycloadducts 20 (30.6 mg, 32%) and 21 (2.9 mg, 3%)
as colourless solids. Rf = 0.46 (EtOAc/hexanes, 2:1). [α]2D5 = –0.5 (c
Financial support from the Natural Sciences and Engineering Re-
search Council of Canada (NSERC) for a Discovery grant, the
National Science Foundation (CHE9421077), the Pittsburgh Su-
percomputing Centre (CHE970007P), sponsored by the National
Science Foundation (NSF) and the University of New Brunswick
is gratefully acknowledged. Helpful discussions with Professor Ro-
bert Ditchfield (Dartmouth College) and Dr. Larry Calhoun
(UNB) are gratefully acknowledged. We would like to thank Mr.
Gilles Vautour with assistance in running the mass spectra and Dr.
Andreas Decken for X-ray analysis.
= 1.47, CH Cl ). M.p. 96–98 °C. IR (CDCl ): ν = 2957, 2880, 2858,
˜
2
2
3
1750, 1728, 1708, 1449, 1392, 1293, 1214, 1113, 1075 cm–1 1H
.
NMR (300 MHz, DMSO, 80 °C): δ = 7.76 (dd, J = 1.7, 7.6 Hz, 2
H), 7.67 (dd, J = 1.6, 7.9 Hz, 2 H), 7.41–7.54 (m, 6 H), 6.45 (dd,
J = 2.5, 6.2 Hz, 1 H), 6.33 (dd, J = 2.4, 6.1 Hz, 1 H), 5.09 (dd, J
= 2.4, 3.9 Hz, 1 H), 4.89 (ddd, J = 4.3, 10.3 Hz, 1 H), 4.77 (quint,
J = 2.3 Hz, 1 H), 4.54 (d, J = 4.0 Hz, 1 H), 4.45 (quint, J = 5.5 Hz,
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D. I. MaGee, E. Godineau, P. D. Thornton, M. A. Walters, D. J. Sponholtz
FULL PAPER
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Received: April 14, 2006
Published Online: June 7, 2006
3680
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3667–3680