Synthesis of 5-aryloxazolidines via 1,3-dipolar cycloaddition reaction of a non-stabilized azomethine ylide with aromatic aldehydes

Article abstract of DOI:10.1071/CH07282

The 1,3-dipolar cycloaddition reaction of a non-stabilized azomethine ylide 4a, formed in situ from N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine 5 and a catalytic amount of trifluoroacetic acid, with aromatic aldehydes 3 gives rise to N-benzyl-5-

Full text of DOI:10.1071/CH07282

Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2007, 60, 898–904
www.publish.csiro.au/journals/ajc
Synthesis of 5-Aryloxazolidines via 1,3-Dipolar
Cycloaddition Reaction of a Non-Stabilized
Azomethine Ylide with Aromatic Aldehydes
John H. Ryan,A,C Nadia Spiccia,A Leon S.-M. Wong,A and Andrew B. HolmesB
ACSIRO Molecular and Health Technologies, Bag 10, Clayton South VIC 3169, Australia.
BSchool of Chemistry, Bio21 Institute, University of Melbourne, 30 Flemington Road,
Parkville VIC 3010, Australia.
CCorresponding author. Email: jack.ryan@csiro.au
The 1,3-dipolar cycloaddition reaction of a non-stabilized azomethine ylide 4a, formed in situ from N-(methoxymethyl)-
N-(trimethylsilylmethyl)benzylamine 5 and a catalytic amount of trifluoroacetic acid, with aromatic aldehydes 3 gives
rise to N-benzyl-5-aryloxazolidines 1. Under these conditions, 4-hydroxybenzaldehyde 3p undergoes two-fold addition
of azomethine ylide 4a to afford bis adduct 11.
Manuscript received: 7 August 2007.
Final version: 21 September 2007.
Introduction
sonication at 35◦C in acetonitrile afforded an 80% yield of the
oxazolidine 1a (Scheme 2).[18] Achiwa et al. showed that the
same reactive intermediate 4a could be formed on exposure of
5 to Bronsted or Lewis acid catalysts and found that trifluoro-
acetic acid (TFA) was the most effective catalyst for dipolar
cycloaddition of 4a with alkenes.[16] The reaction of aldehy-
des with the azomethine ylide 4a, generated on treatment with
catalytic trifluoroacetic acid, has not been explored.
Recently, an alternative method for generation of a non-
stabilized azomethine ylide 4b and subsequent addition to aryl
aldehydes was explored by Nyerges et al. (Scheme 3).[19] This
method involves condensation of sarcosine 6 with paraformalde-
hyde under Dean–Stark conditions and concomitant decarboxy-
lation to give the azomethine ylide 4b, which, in the presence
of aryl aldehydes, provided the oxazolidines 7. Although good
yields of 7 were obtained, the forcing conditions (refluxing
benzene for 1 to 15 h) and excess reagents (a 2-fold excess of
The 5-aryloxazolidine substructure is found within several syn-
thetic compounds with interesting biological properties, includ-
ing compounds that have been studied as β3-adrenoceptor
agonists,[1] anti-asthmatics,[2] herbicidal antidotes,[3] and stock-
feed promoters.[4] There are two main approaches to the synthe-
sis of the parent 5-aryloxazolidine structure 1 (Scheme 1). The
most common approach involves condensation of formaldehyde
with 1-aryl-2-aminoalcohols 2,[2,3,5] which in turn are acces-
sible using a variety of methods.[6] An alternative approach
involves 1,3-dipolar cycloaddition reaction of an aromatic alde-
hyde 3 with an azomethine ylide 4.[7,8] An advantage of the
latter approach is that a wide variety of aromatic aldehydes are
commercially available. Therefore, a range of the corresponding
oxazolidines 1 could be generated by parallel synthesis in one
synthetic step.
The 1,3-dipolar cycloaddition to give 5-aryloxazolidines
1 has received little attention except for early studies
of stabilized azomethine ylides formed from the thermo-
lysis of azidirines[9–11] and non-stabilized azomethine ylides
from N-((trimethylsilyl)methyl)-substituted amines.[12–14] One
of the most useful of the silylmethylamine reagents is N-
(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine5,[14–16]
which has been frequently applied with alkenes to the formation
of substituted pyrrolidines.[17] In the case of benzaldehyde as
the dipolarophile, Padwa et al. found that treatment of reagent
5 with lithium fluoride in the presence of benzaldehyde under
O
H
OMe
Bn
O
N
Bn
1 equiv LiF
3a
Nꢁ Bn
N
CH3CN
Sonication, 35°C
TMS
4a
1a
5
80%
[18]
Scheme 2.
OH
O
O
NRꢀ
Nꢁ
NHRꢀ
Rꢀ
ꢁ
H
R
R
R
2
1
3
4
Scheme 1.
© CSIRO 2007
10.1071/CH07282
0004-9425/07/120898

Synthesis of 5-Aryloxazolidines
899
Table 1. Cycloaddition reaction of azomethine ylide 4a with aromatic
aldehydes
O
Ar
H
All products showed satisfactory spectroscopic and analytical data[20]
HN Me
(CH2O)n
O
3
Nꢁ Me
4b
N
Me
O
O
Benzene, ∆
Dean–Stark
Ar
CO2H
5, 0.05 equiv CF3CO2H
N
Bn
H
6
7
R
R
CH2Cl2
0 to 25°C
17 h
[19]
1
3
Scheme 3.
O
Entry
Aldehyde
R
Product
Yield [%]
H
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
H
2-NO2
4-F
2,4-di-F
2-Br
4-Br
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
95
75
89
80
76
86
82
78
93
∼100
78
80
59
54
–
O
NO2
HN Rꢀ
N
(CH2O)n
Rꢀ
3b
Nꢁ Rꢀ
Benzene, ∆
Dean–Stark
CO2H
NO2
6 Rꢀ ꢂ Me
8 Rꢀ ꢂ Bn
4b Rꢀ ꢂ Me
4a Rꢀ ꢂ Bn
7a Rꢀ ꢂ Me, ∼100%
1b Rꢀ ꢂ Bn, 52%
4-CN
4-NMe2
4-OMe
3,4,5-tri-OMe
4-NHAc
2,4,6-tri-Me
4-COOH
2-OH
Scheme 4.
9
10
11
12
13
14
15
16
amino acid and 5-fold excess of paraformaldehyde) required for
high yields would not be suitable for substrates or products that
were sensitive to heat or susceptible to side-reactions with the
reagents.
For amine protecting groups, a benzyl group is generally pre-
ferred over a methyl group owing to the relative ease of removal
of the benzyl group by Pd-catalyzed hydrogenolysis. Therefore,
we repeated Nyerges’ method with 2-nitrobenzaldehyde 3b and
found that although sarcosine 6 afforded a near-quantitative
yield of oxazolidine 7a, the use of N-benzylglycine 8 under
these conditions afforded only a moderate yield of oxazolidine
1b (Scheme 4). The moderate yields using this decarboxyla-
tive method with this model substrate led us to investigate the
cycloaddition reaction of the azomethine ylide 4a, formed from
silylamine 5 and catalytic trifluoroacetic acid, with a wide range
of aromatic and heteroaromatic aldehydes.
3-OH
4-OH
–
sterically demanding (entries 5 and 12), basic (entry 8), and
acidic (entry 13).[21] The lower yield in the case of the carboxylic
acid substituent (entry 13) reflected difficulty in isolation of
the product 1m rather than less efficient cycloaddition chem-
istry. The 1H NMR spectrum of the crude product showed
high conversion into the oxazolidine 1m; however, attempted
chromatographic purification resulted in poor recovery of the
product, which we rationalized was because of its zwitterionic
character. Purification of 1m by crystallization gave a moder-
ate recovery of analytically pure product. The chemoselectivity
of the process was displayed by the 4-cyano example (entry 7),
which gave the corresponding oxazolidine in high yield, as there
was no evidence for competing addition to the nitrile to form an
imidazoline-type structure.[22]
The success with the carboxylic acid-substituted benzalde-
hyde led us to explore whether the presence of a phenolic group
in the benzaldehyde substrate would interfere with the cyclo-
additionprocess.Thus, 2-, 3-, and4-hydroxybenzaldehydeswere
subjected to the reaction conditions (Table 1, entries 14–16).
Salicylaldehyde 3n underwent cycloaddition affording a moder-
ate isolated yield of the expected oxazolidine 1n. In this case,
there were minor side-products in the crude product material,
which resulted in a lower yield of the oxazolidine. In contrast,
3-hydroxybenzaldehyde (3o) gave a complex mixture with no
trace of oxazolidine 1o as evidenced by TLC and 1H NMR
analyses.
In the case of 4-hydroxybenzaldehyde 3p, incomplete con-
version was observed, so more azomethine ylide precursor 5
and trifluoroacetic acid were added. After workup, the major
product isolated exhibited a mass spectral molecular ion of M+•
388, indicating that two equivalents of azomethine ylide 4a
had been added to the starting material. Both the absence of
a strong carbonyl stretch in the infrared spectrum of this product
and a comparison of the NMR spectra of this product with the
analogous oxazolidines 1a–n provided strong evidence that the
azomethine ylide 4a had added to the carbonyl group of 3p to
give an oxazolidine. In addition, the NMR spectra showed that
Results and Discussion
The benefits of generating a non-stabilized azomethine ylide
4a from reagent 5 and a catalytic amount of trifluoroacetic
acid in dry dichloromethane are that the reaction is initiated
at low temperatures (0◦C), usually proceeds to completion at
ambient temperatures (0 to 25◦C) and requires only a small
excess of reagent 5.[16] Also, the reaction workup is straight-
forward, involving concentration of the crude reaction mixture
followed by crystallization or chromatographic purification. On
submission of benzaldehyde 3a to these reaction conditions, we
obtained oxazolidine 1a in 95% yield after chromatographic
purification, a higher yield than that obtained using lithium
fluoride with sonication at 35◦C.[18]
We then applied this method to benzaldehydes substi-
tuted with electron-donating, electron-withdrawing, sterically
demanding, basic, and acidic groups (Table 1). Much of the
chemistry was performed in parallel using a Radley’s Carousel
Reaction Station and, after completion of the reactions, the mix-
tures were concentrated and the products were purified in high-
throughput fashion on pre-packed Isolute normal-phase silica
columns using anArgonaut Flashmaster II automated flash chro-
matography purification system. Notably, 2-nitrobenzaldehyde
3b afforded a 75% yield of oxazolidine 1b after chromato-
graphic purification, a better result than we obtained using the
decarboxylative method. High yields of oxazolidines 1 were
obtained in the cases where the substituents were electron
withdrawing (entries 2–7), electron donating (entries 8–11),

900
J. H. Ryan et al.
O
O
N
3
6
Bn
O
N
N
Bn
Bn
2
Bn
Bn
N
Bn
N
N
4
5
1
O
HO
HO
9
10
11
Fig. 1. Possible structures for the product produced from reaction of azomethine ylide 4a with hydroxyben-
zaldehyde 3p.
Bn
Bn
ꢁN
N
ꢃ
ꢁ
H
R
Bn
R
Bn
R
4a
N
N
R
HO
HO
O
H
O
3p R ꢂ CHO
12 R ꢂ ox*
15 R ꢂ CHO
11 R ꢂ ox*
13 R ꢂ CHO
14 R ꢂ ox*
Bn
O
ox* ꢂ
Me3Si
N
NBn
ꢁ
16
Scheme 5.
the second azomethine ylide 4a had incorporated into the phe-
nol structure as an N-benzyl-N-methyl-aminomethyl moiety. In
principle, the three possibilities for incorporation of the second
azomethine ylide into the phenol structure involved O-alkylation
to give 9 or C-alkylation to give either 10 or 11 (Fig. 1). The
O-alkylation structure 9 was easily discounted owing to evi-
dence for the free phenol hydroxyl group, found in the infrared
and 1H NMR spectra. Furthermore, the disubstituted phenol
ether structure 9 would be expected to exhibit 19 13C NMR
signals; however, 21 13C NMR signals were observed in the
spectrum of the product. A detailed examination of the NMR
spectra (one- and two-dimensional) allowed us to unequivocally
assign structure 11 to this product (for full details, see theAcces-
sory Publication). In the 1H NMR spectrum, the signals at δ 7.15
(dd, J 8.1 and 1.2), 7.02 (br s), and 6.84 (d, J 8.3) were assigned to
H5, H3, and H6 respectively. The signal due to the lone aromatic
proton (H3) showed strong nuclear Overhauser effect correlation
spectroscopy (NOESY) correlations to the signals of the adja-
cent benzylic protons of the groups attached to C2 and C4. In
the 13C NMR spectrum, the upfield aromatic signals at δ 121.9
(quaternary) and 116.2 (methine) were assigned to carbons C2
and C6, respectively, which are strongly shielded through their
ortho relationship to the phenol hydroxyl group. These NMR
data are consistent with structure 11 and cannot be accounted
for by alternative structure 10.
The observation of a complex reaction product emanating
from the reaction with 3-hydroxybenzaldehyde 3o is thought
to be a result of competing side-reactions involving Mannich-
type substitution of 3o with the incipient iminium moiety within
the azomethine ylide.[23] These side reactions are less likely
for 2- and 4-hydroxybenzaldehydes (3n and 3p, respectively)
as these species have fewer sites available, ortho and para to
the phenol group, for electrophilic aromatic substitution. In
addition, 3n and 3p are less reactive towards electrophilic aro-
matic substitution owing to conjugation of the phenol group
with the electron-withdrawing aldehyde group. The reactions
with 2-hydroxybenzaldehyde (salicylaldehyde, 3n) are relatively
clean, indicating little if any Mannich-type side reactions. The
reactivity of 2-hydroxybenzaldehyde towards such electrophilic
aromatic substitutions would be further reduced by the
hydrogen-bonding stabilization of the ortho-phenolic residue by
the aldehyde group.[24]
Compound 11 is a formal bis adduct of 4-hydroxybenzal-
dehyde 3p and two equivalents of azomethine ylide 4a. The
product results from the expected 1,3-dipolar cycloaddition
reaction of the aldehyde group with one azomethine ylide inter-
mediate and a formal Mannich-type reaction of the phenol group
withasecondazomethineylideintermediate.Themechanismfor
the Mannich-type reaction is not clear; however, one could envis-
age a stepwise or concerted process involving Mannich reaction
and deprotonation of the phenol 3p (or derived oxazolidine 12)
with azomethine ylide 4a to give intermediate 13 (or 14), which
would readily undergo aromatization to the observed ortho alky-
latedproduct15(or 11)(Scheme5). Similarprocesses, involving
an intermediate silyliminium species 16 (formed in situ from 5
andTFA) as the reactive species in the Mannich reaction, cannot
be discounted at this stage. It is yet to be determined whether
the Mannich-type azomethine ylide reaction occurs before or
after the dipolar cycloaddition with the aldehyde of the starting
material 3p; however, the presence of the deactivating aldehyde
group on 3p may be expected to slow down the Mannich-
type reaction through inductive effects. Mannich reactions of
iminium ions with phenols are well known; however, the analo-
gous reaction of an azomethine ylide with a phenol has not been
reported.[25] The scope and mechanism of this transformation
are under investigation and will be reported in due course.
The reaction scope was further explored by subjection
of a range of heteroaromatic aldehydes to the cycloaddition
conditions (Table 2). 2-Furan-, 2-thiophene-, and 3-pyridine-
carboxaldehydes 17–19 were successfully converted into
the corresponding oxazolidines 23–25 (entries 1–3). For 2-
pyrrolecarboxaldehyde 20, none of the expected oxazolidine
26 was detected in the reaction product (entry 4). Instead the
product was a complex intractable mixture containing an appre-
ciable amount of starting aldehyde. The presence of starting
material indicated a much retarded reaction rate was at least
partly the cause of the reaction failure, although competitive
electrophilic aromatic substitution side-reactions could not be
ruled out. We explored this effect through subjection of nitrogen-
substituted pyrrole-2-carboxaldehyde analogues to the standard

Synthesis of 5-Aryloxazolidines
901
Table 2. Reaction of heteroaromatic aldehydes with azomethine
ylide 4a
adduct formed via azomethine ylide cycloaddition and a formal
azomethine ylide electrophilic aromatic substitution reaction.
There is continued interest in the 1,3-dipolar cycloaddition
chemistry of azomethine ylides and carbonyl compounds[27] and
in revelations that this chemistry may be involved in biological
processes.[28]
Entry
Aldehyde
Product
Yield [%]
O
O
N
Bn
Bn
Bn
O
O
S
1
100
Experimental
Proton (1H) and carbon (13C) NMR spectra were recorded on a
BrukerAV400spectrometerat400and100 MHz, respectively, or
a Bruker AV200 spectrometer at 200 and 50 MHz, respectively.
Chemical shifts were recorded as δ values in parts per million
(ppm). Spectra were acquired in deuterated chloroform (CDCl3)
at 20◦C. For 1H NMR spectra recorded in CDCl3, the peak due
to residual CDCl3 (δH 7.26) was used as the internal reference,
whereasforproton-decoupled13CNMRspectra, thecentralpeak
17
23
O
O
N
N
S
2
3
92
73
18
24
O
O
1
(δC 77.16) of the CDCl3 triplet was used as the reference. H
NMR spectroscopic data are recorded as follows: chemical shift
(δH) (relative integral, multiplicity, coupling constant(s) J (Hz))
whereby multiplicity is defined as: s for singlet; d for doublet; t
for triplet; q for quartet or quintet; m for multiplet, or combina-
tions thereof. Elemental analyses were performed by Campbell
Microanalytical Laboratory, University of Otago, New Zealand.
Melting points were recorded on an Electrothermal IA9300 digi-
tal melting point apparatus and are uncorrected. Infrared spectra
were recorded on a Perkin Elmer SPECTRUM 2000 FTIR
Spectrometer. Oils were analyzed neat as thin films on sodium
chloride plates, whereas solids were dissolved in chloroform
and deposited on sodium chloride plates with the solvent being
allowed to evaporate before measurement of the spectra. Positive
ionelectronimpact(EI)massspectrawererunonaThermoQuest
MAT95XL mass spectrometer using ionization energy of 70 eV.
Accurate mass measurements were obtained on the same instru-
ment with a resolution of 5000–10000 using perfluorokerosene
(PFK) as the reference compound. Positive and negative ion
atmospheric pressure chemical ionization (APCI) mass spec-
tra were acquired with a VG Platform mass spectrometer using
a cone voltage of 50V, and the source was maintained at 100◦C.
Nitrogen was used as the nebuliser and sheath gas, and the probe
temperature was 400◦C. The solvent system used was aceto-
nitrile with a flow rate of 0.3 mL min−1. Positive and negative
ion electrospray mass spectra were acquired with a VG Platform
mass spectrometer using a cone voltage of 50V and the source
was maintained at 80◦C. The solvent system used was aceto-
nitrile with a flow rate of 0.04 mL min−1. Flash chromatography
was carried out on an Argonaut FlashMaster II purification sys-
tem with FC 204 Fraction Collector, using Isolute normal-phase
silica gel. Analytical TLC was conducted on Merck Kieselgel
60 F254 on aluminium sheets. All starting materials, reagents,
and solvents were obtained from commercial sources and used
as supplied unless otherwise noted. Dichloromethane was dried
by passage through two sequential columns of activated neutral
alumina. 2-Furaldehyde was distilled twice before use.
N
N
19
25
O
O
O
H
N
H
N
N
Bn
Bn
N
4
5
–
–
20
26
O
N
N
21
27
O
S O
O
S O
O
N
O
6
90
N
Bn
N
22
28
reaction conditions (entries 5 and 6). The N-methyl analogue
21 also resulted in a complex intractable mixture that contained
some starting material but no oxazolidine (entry 5), whereas,
for the N-benzenesulfonyl analogue 22, an excellent yield of
the cycloadduct 28 resulted (entry 6). We rationalize the lack of
success for the pyrrole aldehydes 20 and 21 as being a result
of the electron-rich nature of the heterocycle, which has two
effects: reducing the reactivity of the aldehyde towards cyclo-
addition and increasing the reactivity of the heterocycle towards
potential electrophilic aromatic substitution side-reactions. The
reduction in reactivity of electron-rich aldehydes towards such
cycloadditions would be due to a raised carbonyl lowest unoccu-
pied molecular orbital (LUMO) energy and an overall increase
in the azomethine ylide highest unoccupied molecular orbital
(HOMO)-carbonyl LUMO energy gap.[14,26]
3-Methyl-5-(2ꢀ-nitrophenyl)oxazolidine 7a[19a]
Conclusions
A mixture of 2-nitrobenzaldehyde (0.76 g, 5.0 mmol), sarcosine
(0.90 g, 10.0 mmol), and paraformaldehyde (0.75 g, 25.0 mmol)
in toluene (50 mL) was heated at reflux for 1 h with azeotropic
removal of water using a Dean–Stark trap. The mixture was con-
centrated, dissolved in acetone, and passed through a plug of
silica, with acetone as eluent. Concentration of the acetone wash-
ings afforded the title compound (0.83 g, ∼100%) as an oil. The
1H NMR spectrum was consistent with reported data.[19a]
In summary, the 1,3-dipolar cycloaddition of a non-stabilized
azomethine ylide 4a with aromatic and heteroaromatic alde-
hydes proceeds under mild conditions to afford high isolated
yields of the corresponding oxazolidines. In the case of pheno-
lic aromatics or pyrrolic aldehydes, slower cycloaddition rates
and competing side-reactions were observed. In the case of
4-hydroxybenzaldehyde 3p, the major product isolated was a bis

902
J. H. Ryan et al.
3-Benzyl-5-(2ꢀ-nitrophenyl)oxazolidine 1b
(1H, dd, J 11.3 and 7.7). δC (100 MHz) 162.3 (d, JCF• 245), 138.7,
138.0 (d, JCF•3), 128.8, 128.6, 127.4 (d, JCF• 5), 127.3, 115.4 (d,
JCF• 21), 87.6, 76.2, 60.7, 58.4. m/z (EI) 256 (1%, [M − H]+),
133 (100%), 91 (76%).
A mixture of 2-nitrobenzaldehyde (0.76 g, 5.0 mmol), N-
benzylglycine hydrochloride (2.01 g, 10.0 mmol), sodium car-
bonate (2.65 g, 25.0 mmol), and paraformaldehyde (0.75 g,
25.0 mmol) in toluene (70 mL) was heated at reflux for 5 h
with azeotropic removal of water using a Dean–Stark trap.
The mixture was concentrated, then dissolved in acetone and
passed through a plug of silica eluting with acetone. The acetone
washings were concentrated, then purified by automated flash
chromatography using a gradient (100% hexanes to 50:50 hex-
anes/dichloromethane) and afforded the title compound (0.74 g,
3-Benzyl-5-(2ꢀ,4ꢀ-difluorophenyl)oxazolidine 1d
2,4-Difluorobenzaldehyde 3d: 565 mg, 3.98 mmol. Product
1d (878 mg, 80%) isolated as a colourless oil. RF 0.18 (5:95
EtOAc:hexanes). (Found: [M − H]+ 274.1033. C16H14F2NO
requires [M − H]+ 274.1038.) νmax (neat)/cm−1 3029, 2928,
2878, 2802, 1606, 1501, 1272. δH (400 MHz) 7.53 (1H, ddd,
J 8.6, 8.6 and 6.8), 7.40–7.27 (5H, m), 6.90 (1H, td, J 8.5 and
2.4), 6.79 (1H, ddd, J 10.8, 8.8 and 2.4), 5.24 (1H, m), 4.58 (2H,
m), 3.83 (2H, s), 3.52 (1H, dd, J 11.6 and 6.7), 2.83 (1H, dd, J
11.5 and 7.6). δC (100 MHz) 162.4 (dd, JCF 242 and 12), 159.8
(dd, JCF 242 and 12), 138.7, 128.8, 128.6, 127.8 (dd, JCF 10 and
6), 127.5, 125.6 (dd, JCF• 14 and 4), 111.3 (dd, JCF 21 and 4),
103.8 (t, JCF 25), 87.2, 71.0 (d, JCF 2), 59.5, 58.4. m/z (EI) 274
(4%, [M − H]+), 184 (2%), 133 (100%), 91 (96%).
1
52%) as an oil. The H NMR spectrum was identical to that
obtained for 1b produced by the alternative method reported
below.
General Procedure for the Reaction of Aromatic
and Heteroaromatic Aldehydes with Reagent 5
and Catalytic Trifluoroacetic Acid
3-Benzyl-5-phenyloxazolidine 1a[12,13]
3-Benzyl-5-(2ꢀ-bromophenyl)oxazolidine 1e
The reaction of benzaldehyde 3a is representative. To a
solution of 3a (420 mg, 3.96 mmol) in dichloromethane (8 mL)
at 0◦C under an atmosphere of nitrogen gas, was added
2-Bromobenzaldehyde 3e: 739 mg, 3.99 mmol. Product
1e (960 mg, 76%) as a white amorphous solid, mp 33–
34◦C. RF 0.18 (5:95 EtOAc/hexanes). (Found: [M(79Br) − H]+
316.0332. C16H15BrNO requires [M(79Br) − H]+ 316.0332.)
νmax (neat)/cm−1 2923, 2870, 2802, 1588, 1464, 1127, 1019. δH
(400 MHz) 7.61 (1H, dd, J 7.9 and 1.6), 7.51 (1H, dd, J 7.9 and
1.0), 7.38–7.25 (6H, m), 7.13 (1H, td, J 7.9 and 1.7), 5.28 (1H,
m), 4.63 (2H, m), 3.83 (2H, dd, J 15.4 and 13.0), 3.70 (1H, dd, J
11.7 and 7.0), 2.76 (1H, dd, J 11.9 and 7.1). δC (100 MHz) 142.2,
138.8, 132.7, 128.9, 128.7, 128.6, 127.8, 127.5, 126.5, 121.3,
87.6, 75.9, 59.6, 58.7. m/z (EI) 318 (<1%, [M(81Br) − H]+),
316 (<1%, [M(79Br) − H]+), 133 (100%), 91 (83%).
N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine
5
(1.55 mL, 6.06 mmol). To the resulting solution was added a
solution of trifluoroacetic acid (1 M in dichloromethane, 0.2 mL,
0.2 mmol), dropwise with stirring. The resulting solution was
allowed to warm to room temperature, and the reaction mixture
was stirred untilTLC indicated consumption of starting material
(17 h). Solvent was removed under vacuum before purification
by flash chromatography (silica; hexanes grading to 1:9 ethyl
acetate/hexanes) to give the title compound (904 mg, 95%) as a
white solid, mp 42–43◦C. RF 0.16 (1:9 EtOAc/hexanes). (Found:
[M − H]+ 238.1223. C16H16NO requires [M − H]+ 238.1226.)
νmax/cm−1 3058, 3028, 2924, 2874, 2801, 1494, 1453, 998. δH
(400 MHz) 7.51–7.19 (10H, m), 5.08 (1H, m), 4.63 (2H, s),
3.85 (2H, s), 3.45 (1H, dd, J 11.4 and 6.7), 2.85 (1H, dd, J
11.3 and 8.1). δC (100 MHz) 142.3, 138.8, 128.8, 128.6, 128.6,
127.5, 127.4, 125.7, 87.7, 76.7, 60.8, 58.5. m/z (EI) 238 (<1%,
[M − H]+), 133 (100%), 91 (80%).
3-Benzyl-5-(4ꢀ-bromophenyl)oxazolidine 1f
4-Bromobenzaldehyde 3f: 506 mg, 2.73 mmol. Product 1f
(752 mg, 86%) isolated as a white crystalline solid, mp 66–
67◦C. RF 0.27 (15:85 EtOAc/exanes). (Found: C 60.5, H 5.1, N
4.4; [M(79Br) − H]+ 316.0321. C16H15BrNO requires C 60.4,
H 5.1, N 4.4%; [M(79Br) − H]+ 316.0332.) νmax (neat)/cm−1
2919, 2879, 1489, 1453, 1042. δH (400 MHz) 7.47 (2H, d, J
8.4), 7.38–7.25 (5H, m), 7.22 (2H, d, J 8.2), 5.01 (1H, m), 4.58
(2H, s), 3.81 (2H, s), 3.41 (1H, dd, J 11.3 and 6.7), 2.77 (1H, dd,
J 11.4 and 7.7). δC (100 MHz) 141.5, 138.7, 131.7, 128.8, 128.6,
127.5, 127.4, 121.3, 87.8, 76.1, 60.6, 58.5. m/z (EI) 318 (<1%,
[M(81Br) − H]+), 316 (<1%, [M(79Br) − H]+).
3-Benzyl-5-(2ꢀ-nitrophenyl)oxazolidine 1b
2-Nitrobenzaldehyde 3b: 602 mg, 3.99 mmol. Product 1b
(860 mg, 75%) isolated as a colourless oil. RF 0.27 (25:75
EtOAc/hexanes). (Found: M+• 284.1143. C16H16N2O3 requires
M
+• 284.1155.) νmax (neat)/cm−1 3029, 2923, 2873, 2807, 1609,
1529, 1346, 995. δH (400 MHz) 8.06 (1H, dd, J 8.2 and 1.2), 7.93
(1H, br d, J 7.8), 7.66 (1H, ddd, J 8.8, 8.8 and 1.2), 7.42 (1H, m),
7.37–7.25 (5H, m), 5.58 (1H, m), 4.68 (1H, d, J 5.7), 4.61 (1H,
d, J 5.7), 3.83 (2H, dd, J 17.7 and 13.1), 3.78 (1H, dd, J 12.0
and 7.1), 2.85 (1H, dd, J 12.1 and 6.7). δC (100 MHz) 147.1,
139.6, 138.6, 134.1, 128.9, 128.5, 128.0, 127.4, 127.3, 124.9,
87.7, 73.6, 60.4, 58.6. m/z (EI) 284 (<1%, M+•), 148 (22%),
133 (95%), 91 (100%).
4-(3ꢀ-Benzyloxazolidin-5ꢀ-yl)benzonitrile 1g
4-Cyanobenzaldehyde 3g: 523 mg, 3.99 mmol. Product 1g
(869 mg, 82%) isolated as white amorphous crystals, mp 65–
66◦C. RF 0.21 (25:75 EtOAc/hexanes). (Found: [M − H]+
263.1177. C17H15N2O requires [M − H]+ 263.1179.) νmax
(neat)/cm−1 2924, 2879, 2806, 2228, 1609, 1493, 1451, 910.
δH (400 MHz) 7.63 (2H, d, J 8.3), 7.45 (2H, d, J 8.3), 7.36–7.25
(5H, m), 5.08 (1H, m), 4.60 (2H, s), 3.80 (2H, s), 3.45 (1H, dd, J
11.4 and 6.9), 2.78 (1H, dd, J 11.4 and 7.4). δC (100 MHz) 148.1,
138.4, 132.5, 128.8, 128.6, 127.6, 126.2, 118.9, 111.3, 87.9,
75.9, 60.4, 58.3. m/z (EI) 263 (<1%, [M − H]+), 133 (84%),
91 (100%).
3-Benzyl-5-(4ꢀ-fluorophenyl)oxazolidine 1c
4-Fluorobenzaldehyde 3c: 496 mg, 4.00 mmol. Product 1c
(918 mg, 89%) isolated as white crystals, mp 29–30◦C. RF
0.16 (10:90 EtOAc/hexanes). (Found: [M − H]+ 256.1127.
C16H15FNO requires [M − H]+ 256.1132.) νmax (neat)/cm−1
3025, 2924, 2875, 2801, 1605, 1509, 1224, 834. δH (400 MHz)
7.42–7.25 (7H, m), 7.04 (2H, dd, J 8.7 and 8.7), 5.04 (1H, m),
4.60 (2H, s), 3.83 (2H, s), 3.41 (1H, dd, J 11.3 and 6.7), 2.80
[4-(3ꢀ-Benzyloxazolidin-5ꢀ-yl)phenyl]dimethylamine 1h
4-(Dimethylamino)benzaldehyde 3h: 160 mg, 1.05 mmol.
Product 1h (230 mg, 78%) isolated as white flaky crystals, mp

Synthesis of 5-Aryloxazolidines
903
73–74◦C. RF 0.29 (20:80 EtOAc/CH2Cl2). (Found: C 76.6, H
7.9, N 10.0, M+ 282.1703. C18H22N2O requires C 76. 6, H 7.9,
N 9.9%, M+ 282.1727.) νmax (neat)/cm−1 3029, 2981, 2876,
2796, 1615, 1523, 1449, 1348, 818. δH (400 MHz) 7.43–7.23
(7H, m), 6.75 (2H, d, J 8.8), 5.01 (1H, m), 4.59 (2H, m), 3.85
(2H, s), 3.37 (1H, dd, J 11.1 and 6.8), 2.96 (6H, s), 2.86 (1H,
dd, J 11.3 and 8.1). δC (100 MHz) 150.3, 139.0, 129.5, 128.8,
128.5, 127.3, 127.0, 112.7, 87.4, 76.9, 60.5, 58.5, 40.8. m/z (EI)
282 (35%, M+), 133 (100%), 91 (40%).
4-(3-Benzyloxazolidin-5-yl)benzoic Acid 1m
Benzaldehyde-4-carboxylic acid 3m: 152 mg, 1.01 mmol. A
first crop was obtained by filtration of the crude reaction mix-
ture. The filtrate was reduced and a second crop was obtained
by recrystallization from dichloromethane.The crops were com-
bined to give the title compound 1m (105 mg, 59%) as a white
solid, mp 139–140◦C. (Found: C 71.9, H 6.0, N 5.0. C17H17NO3
requires C 72.1, H 6.1, N 4.9%.) νmax (neat)/cm−1 3001, 2980,
2880, 2847, 2677, 2554, 1680, 1610, 1431, 1317, 1293, 1044,
994, 903, 853. δH (400 MHz) 8.09 (2H, d, J 8.1), 7.45 (2H, d, J
8.2), 7.39–7.24 (5H, m), 5.14 (1H, m), 4.64 (2H, s), 3.85 (2H, s),
3.50 (1H, m), 2.84 (1H, m). δC (100 MHz) 171.2, 148.4, 138.2,
130.6, 129.0, 128.7, 127.7, 125.6, 87.6, 76.3, 60.3, 58.4. m/z
(ES+) 284 (5%, [M + H]+), 91 (100%).
3-Benzyl-5-(4ꢀ-methoxyphenyl)oxazolidine 1i
4-Methoxybenzaldehyde 3i: 547 mg, 4.02 mmol. Product 1i
(1.01 g, 93%) isolated as a white amorphous solid, mp 46–47◦C.
RF 0.25 (25:75 EtOAc/hexanes). (Found: C 75.6, H 7.1, N 5.3,
M+ 269.1403. C17H19NO2 requires C 75.8, H 7.1, N 5.2%,
M+ 269.1410.) νmax (neat)/cm−1 2873, 2829, 1612, 1513, 1454,
1246, 1036, 830. δH (400 MHz) 7.42–7.25 (7H, m), 6.90 (2H,
d, J 8.8), 5.03 (1H, m), 4.59 (2H, m), 3.84 (2H, s), 3.81 (3H,
s), 3.39 (1H, dd, J 11.3 and 6.7), 2.83 (1H, dd, J 11.3 and 8.0).
δC (100 MHz) 159.2, 138.9, 134.1, 128.8, 128.5, 127.4, 127.1,
114.0, 87.5, 76.6, 60.7, 58.5, 55.4. m/z (EI) 269 (<1%, M+),
133 (100%), 91 (67%).
2-(3-Benzyloxazolidin-5-yl)phenol 1n
Salicylaldehyde 3n: 110 µL, 1.03 mmol. Product 1n:
colourless waxy solid (142 mg, 54%). RF 0.27 (2.5:97.5
EtOAc/CH2Cl2). Mp 64–65◦C. (Found: C 75.1, H 6.7, N 5.5.
C16H17NO2 requires C 75.3, H 6.7, N 5.5%.) νmax (neat)/cm−1
3313, 3060, 3023, 2928, 2834, 2712, 1583, 1487, 1455, 1261.
δH (400 MHz) 10.96 (1H, br s), 7.44–7.37 (4H, m), 7.37–7.30
(1H, m), 7.24 (1H, ddd, J 8.1, 7.4 and 1.7), 7.06 (1H, dd, J 7.5
and 1.7), 6.96 (1H, dd, J 8.1 and 1.1), 6.81 (1H, ddd, J 7.4, 7.4
and 1.2), 5.15 (1H, dd, J 7.9 and 2.4), 4.80 (1H, d, J 3.0), 4.06
(1H, d, J 3.0), 3.82 (1H, m), 3.28 (1H, dd, J 10.0 and 2.4), 2.99
(1H, dd, J 9.9 and 7.9). δC (100 MHz) 155.9, 136.2, 130.1, 129.9,
128.8, 128.6, 127.9, 125.6, 118.7, 117.5, 86.5, 79.5, 56.3, 55.4.
m/z (ES+) 256 (20%, [M + H]+), 224 (100%).
3-Benzyl-5-(3ꢀ,4ꢀ,5ꢀ-trimethoxyphenyl)oxazolidine 1j
3,4,5-Trimethoxybenzaldehyde 3j: 197 mg, 1.00 mmol.
Product 1j (331 mg, ∼100%) isolated as a colourless oil. RF 0.15
(25:75 EtOAc/hexanes). (Found: M+ 329.1614. C19H23NO4
requires M+ 329.1622.) νmax (neat)/cm−1 2937, 2875, 2833,
1591, 1232, 1127, 1006. δH (400 MHz) 7.38–7.18 (5H, m), 6.56
(2H, s), 4.98 (1H, m), 4.56 (2H, m), 3.82 (6H, s), 3.81 (3H, s),
3.79 (2H, s), 3.36 (1H, dd, J 11.3 and 6.6), 2.80 (1H, dd, J 11.3
and 7.5). δC (100 MHz) 153.2, 138.5, 137.8, 137.0, 128.5, 128.3,
127.1, 102.2, 87.3, 76.4, 60.6, 60.2, 58.1, 55.9. m/z (EI) 329 (2%,
M+), 298 (8%), 133 (100%), 91 (88%).
2-((Benzyl(methyl)amino)methyl)-4-
(3-benzyloxazolidin-5-yl)phenol 11
4-Hydroxybenzaldehyde 3p: 123 mg, 1.01 mmol; 5: 0.78 mL,
3.03 mmol; TFA (1 M in dichloromethane): 0.1 mL, 0.1 mmol.
Product 11: colourless oil (209 mg, 53%). RF 0.2 (15:85
EtOAc/CH2Cl2). (Found: M+ 388.2136. C25H28N2O2 requires
M+ 388.2145.) νmax (neat)/cm−1 3061, 3028, 2844 (br s), 1601,
1494, 1453, 1355, 1258, 1149, 1116, 1074, 1017, 907, 856, 827,
745, 699. δH (200 MHz) 10.9 (1H, br s), 7.42–7.25 (m, 10H),
7.15 (1H, dd, J 8.1 and 1.2), 7.02 (1H, br s), 6.84 (1H, d, J 8.3),
4.97 (1H, m), 4.60–4.57 (2H, m), 3.84 (2H, s), 3.76 (2H, br s),
3.61 (2H, br s), 3.36 (1H, dd, J 11.2 and 6.5), 2.81 (1H, dd, J 11.2
and 8.1), 2.25 (3H, s). δC (50 MHz) 157.5, 138.7, 136.8, 132.3,
129.4 (2), 128.8 (2), 128.7 (2), 128.6 (2), 127.8, 127.4, 126.6,
126.3, 121.9, 116.2, 87.5, 76.9, 61.6, 61.0, 60.5, 58.5, 41.4. m/z
(EI) 388 (10%, [M]+•), 134 (76%), 132 (100%), 120 (51%).
N-[4-(3ꢀ-Benzyloxazolidin-5ꢀ-yl)phenyl]acetamide 1k
4-Acetamidobenzaldehyde 3k: 202 mg, 1.24 mmol. Product
1k (287 mg, 78%) isolated as a white crystalline solid, mp 121–
123◦C. RF 0.20 (60:40 EtOAc/CH2Cl2). (Found: C 72.3, H 6.8,
N 9.4, [M − 2H]+• 294.1363. C18H20N2O2 requires C 73.0,
H 6.8, N 9.5%, [M − 2H]+• 294.1363.) νmax (neat)/cm−1 3254,
3192, 3124, 3059, 2888, 1664, 1602, 1547, 1514, 1318, 834. δH
(400 MHz) 7.47 (2H, d, J 8.4), 7.38–7.24 (7H, m), 7.17 (1H, br s),
5.02 (1H, m), 4.58 (2H, s), 3.81 (2H, s), 3.39 (1H, dd, J 11.3 and
6.8), 2.79 (1H, dd, J 11.3 and 7.8), 2.17 (3H, s). δC (100 MHz)
168.3, 138.8, 138.3, 137.2, 128.9, 128.6, 127.5, 126.5, 120.1,
87.7, 76.4, 60.7, 58.5, 24.8. m/z (APCI) 297 (39%, [M + H]+),
267 (100%). m/z (EI) 294 (8%, [M − 2H]+•), 133 (100%),
91 (63%).
3-Benzyl-5-(furan-2-yl)oxazolidine 23
2-Furaldehyde 17 (distilled before use): 100 µL, 1.21 mmol.
Product 23: colourless oil (277 mg, 100%). RF 0.27 (2.5:97.5
EtOAc/CH2Cl2). νmax (neat)/cm−1 2931, 2879, 1558, 1506,
1496, 1456, 1149, 1008, 737. δH (400 MHz) 7.44–7.25 (6H, m),
6.35 (1H, dd, J 3.2 and 1.8), 6.32 (1H, d, J 3.1), 5.03 (1H, m),
4.52 (2H, dd, J 9.9 and 5.8), 3.85 (2H, dd, J 18.5 and 13.1),
3.33 (1H, dd, J 11.9 and 7.1), 3.18 (1H, dd, J 11.8 and 7.5).
δC (100 MHz) 153.9, 142.8, 138.9, 128.9, 128.6, 127.4, 110.4,
107.7, 87.0, 69.7, 58.5, 56.4. m/z (EI) 229 (2%, M+), 133 (78%),
91 (100%).
3-Benzyl-5-(2ꢀ,4ꢀ,6ꢀ-trimethylphenyl)oxazolidine 1l
2,4,6-Trimethylbenzaldehyde 3l: 592 mg, 3.99 mmol. Prod-
uct 1l (903 mg, 80%) isolated as a white amorphous solid, mp
36–37◦C. RF 0.16 (5:95 EtOAc/hexanes). (Found: [M − 2H]+•
279.1612. C19H23NO requires [M − 2H]+• 279.1618.) νmax
(neat)/cm−1 3023, 2922, 2870, 2796, 1612, 1453, 1355, 1074.
δH (400 MHz) 7.48–7.29 (5H, m), 6.87 (2H, s), 5.51 (1H, dd, J
9.8 and 6.4), 4.70 (1H, d, J 4.6), 4.63 (1H, d, J 4.6), 3.92 (2H, s),
3.26 (1H, dd, J 11.0 and 6.3), 2.89 (1H, m), 2.43 (6H, s), 2.30
(3H, s). δC (100 MHz) 138.8, 136.7, 136.3, 132.3, 130.3, 128.8,
128.6, 127.4, 86.9, 75.4, 58.6, 56.8, 20.9, 20.8. m/z (APCI) 282
(46%, [M + H]+), 252 (100%), 133 (30%). m/z (EI) 279 (<1%,
[M − 2H]+•), 133 (100%), 91 (77%).
3-Benzyl-5-(thiophen-2-yl)oxazolidine 24
2-Thiophenecarboxaldehyde 18: 100 µL, 1.07 mmol. Prod-
uct 24: colourless oil (241 mg, 92%). RF 0.27 (5:95 EtOAc/

904
J. H. Ryan et al.
CH2Cl2). (Found: M+ 245.0866. C14H15NOS requires M+
245.0869.) νmax (neat)/cm−1 3025, 2918, 2875, 2806, 1669,
1493, 1451, 909. δH (400 MHz) 7.41–7.24 (6H, m), 7.01–6.96
(2H, m), 5.29 (1H, m), 4.59 (1H, d, J 5.2), 4.51 (1H, d, J 5.2),
3.85 (2H, s), 3.42 (1H, dd, J 11.5 and 6.9), 3.02 (1H, dd, J 11.5
and 7.1). δC (100 MHz) 145.7, 138.7, 128.9, 128.6, 127.5, 126.9,
125.1, 124.4, 87.0, 72.9, 60.5, 58.4. m/z (EI) 245 (<1%, M+),
133 (100%).
[7] 1,3-Dipolar Cycloaddition Chemistry (Ed. A. Padwa) 1984, Vols 1, 2
(Wiley–Interscience: New York, NY).
[8] For a recent review, see: L. M. Harwood, R. J. Vickers, in Synthetic
Applications of 1,3-Dipolar Cycloaddition ChemistryToward Hetero-
cycles and Natural Products in Chemistry of Heterocyclic Compounds
(Eds A. Padwa, W. H. Pearson) 2003, Vol. 59, Ch. 3, pp. 169–252
(Wiley: New York, NY).
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(b) G. Dallas, J. W. Lown, J. P. Moser, J. Chem. Soc. C 1970, 2383.
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[10] H. W. Heine, R. P. Henzel, J. Org. Chem. 1969, 34, 171.
doi:10.1021/JO00838A037
[11] F. Texier, R. Carrié, C. R. Acad. Sci. Ser. C 1969, 269, 709.
[12] A. Padwa, Y.-Y. Chen, U. Chiacchio, W. Dent, Tetrahedron 1985, 41,
3529. doi:10.1016/S0040-4020(01)96706-7
[13] A. Padwa, W. Dent, H. Nimmesgern, M. K. Venkatramanan,
G. S. K. Wong, Chem. Ber. 1986, 119, 813. doi:10.1002/CBER.
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JO00378A013
[15] A. Hosomi, Y. Sakata, H. Sakurai, Chem. Lett. (Jpn.) 1984, 13, 1117.
doi:10.1246/CL.1984.1117
[16] Y. Terao, H. Kotaki, N. Imai, K. Achiwa, Chem. Pharm. Bull. (Tokyo)
1985, 33, 2762.
[17] G. Pandey, P. Banerjee, S. R. Gadre, Chem. Rev. 2006, 106, 4484.
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[18] (a) A. Padwa, W. Dent, Org. Synth. Collect. 1993, 8, 231.
(b) A. Padwa, W. Dent, Org. Synth. 1989, 67, 133.
3-(3-Benzyloxazolidin-5-yl)pyridine 25
3-Pyridinecarboxaldehyde 19: 100 µL, 1.06 mmol. Prod-
uct 24: colourless oil (186 mg, 73%). RF 0.09 (5:94.5:0.5
EtOAc/CH2Cl2/Et3N).
(Found:
[M − H]+
239.1181.
C15H15N2O requires [M − H]+ 239.1179.) νmax (neat)/cm−1
3029, 2918, 2876, 2802, 1577, 1453, 1427, 1354. δH (400 MHz)
8.55 (1H, d, J 2.0), 8.48 (1H, dd, J 4.8 and 1.6), 7.63 (1H, br
d, J 8.0), 7.35–7.18 (6H, m), 5.01 (1H, m), 4.54 (2H, m), 3.76
(2H, s), 3.38 (1H, dd, J 11.3 and 6.8), 2.78 (1H, dd, J 11.3 and
7.5). δC (100 MHz) 148.9, 147.5, 138.4, 137.6, 133.2, 128.6,
128.4, 127.3, 123.3, 87.6, 74.4, 60.2, 58.1. m/z (EI) 239 (4%,
[M − H]+), 133 (100%).
3-Benzyl-5-(1ꢀ-phenylsulfonyl-1H-pyrrol-2ꢀ-yl)-
oxazolidine 28
1-(Phenylsulfonyl)-1H-pyrrole-2-carboxaldehyde22:239 mg,
1.02 mmol. Product 28: colourless oil (338 mg, 90%). RF 0.16
(25:75 EtOAc/hexanes). (Found: M+ 368.1153. C20H20N2O3S
requires M+ 368.1189.) νmax (neat)/cm−1 3063, 3028, 2928,
2875, 2815, 1448, 1368, 1178, 1152, 1090, 1050, 726, 685, 605,
590, 565. δH (400 MHz) 7.79 (2H, d, J 7.6), 7.57 (1H, dd, J 7.4
and 7.4), 7.47 (2H, m), 7.37–7.24 (6H, m), 6.39–6.35 (1H, m),
6.27 (1H, dd, J 3.3 and 3.3), 5.35 (1H, m), 4.46 (2H, m), 3.81
(2H, s), 3.44 (1H, dd, J 11.8 and 6.9), 2.96 (1H, dd, J 11.8 and
6.7). δC (100 MHz) 139.4, 138.7, 136.3, 133.9, 129.4, 128.8,
128.5, 127.4, 126.7, 123.4, 112.2, 112.0, 86.7, 70.1, 59.5, 58.5.
m/z (EI) 368 (<1%, M+), 133 (100%), 91 (59%).
[19] (a) M. Nyerges, I. Fejes, A. Virányi, P. W. Groundwater, L. Töke, Syn-
thesis 2001, 1479. doi:10.1055/S-2001-16077
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Commun. 2006, 36, 3581. doi:10.1080/00397910600943568
[20] The oxazolidine products are unstable under electron-impact ioniza-
tion conditions and show very low-intensity or no M+ ions. For those
compounds that didn’t show M+ ions, high-resolution mass spectro-
metry (electron impact) were obtained on [M − H]+ (see: J. Xu, G.
Zuo, Rapid Commun. Mass Spectrom. 2003, 17, 1651; or G. L. Eggle-
ton, B. A. Cooper, C. L. Sturch, J. C. Trentt, II, R. B. Walker, Org.
Mass Spectrom. 1989, 24, 1022) or [M − 2H]+• fragment ions.
[21] For entries 1–12 (Table 1), high conversions were observed by 1H
NMR analysis of the crude product. The lower yields obtained in
some cases, e.g. 75% for 1b (entry 2), were due to losses during
chromatographic purification of the crude product. The purification
was automated and not optimized for each product.
[22] Foranexampleofanitrileactingasadipolarophilewithanazomethine
ylide, see: C. W. Derstine, D. N. Smith, J. A. Katzenellenbogen, J. Am.
Chem. Soc. 1996, 118, 8485. doi:10.1021/JA9614833
[23] F. F. Blicke, Org. React. 1942, 1, 303.
[24] (a) I. D. Sadekov, V. I. Minkin, A. E. Lutskii, Russ. Chem. Rev. 1970,
39, 179. doi:10.1070/RC1970V039N03ABEH001950
(b) F. Hibbert, J. Emsley, in Advances in Physical Organic Chemistry
(Ed. D. Bethell) 1990,Vol. 26, pp. 255–379 (Academic Press Limited:
London).
Accessory Publication
An Accessory Publication containing 1H and 13C JMOD NMR
spectra for compound 11, as well as full assignment of these
spectra, is available from the authors or available from the
Australian Journal of Chemistry until December 2012.
Acknowledgements
We thank the CSIRO (Australia), the Australian Research Council, and the
Victorian Endowment for Science, Knowledge and Innovation (VESKI) for
financial support. Nadia Spiccia was the recipient of a CSIRO Summer
Vacation Scholarship. We also thank Dr Roger Mulder and Dr Jo Cosgriff
for assistance with collection of NMR data, and Dr Carl Braybrook for
interpretation of MS data.
[25] We thank a referee for pointing out a related example of α-alkylation
of a ketone with ylide 4a [M. Rudus, I. Fejes, M. Nyerges,A. Szöllõzy,
L. Tokë, P. Groundwater, J. Chem. Soc., Perkin Trans. 1 1999, 1167].
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