Base-induced coupling of α-azido ketones with aldehydes -an easy and efficient route to trifunctionalized synthons 2-azido-3-hydroxy ketones, 2-acylaziridines, and 2-acylspiroaziridines

Article abstract of DOI:10.1002/1099-0690(20021)2002:2<285::AID-EJOC285>3.0.CO;2-J

An improved synthesis of a-azido ketones under phase-transfer conditions has been developed. The transformation of α-azido ketones into acyclic and heterocyclic 2-azido-3-hydroxy ketones has been demonstrated and the relative configurations of the chroman

Full text of DOI:10.1002/1099-0690(20021)2002:2<285::AID-EJOC285>3.0.CO;2-J

FULL PAPER
Base-Induced Coupling of α-Azido Ketones with Aldehydes ؊ An Easy and
Efficient Route to Trifunctionalized Synthons 2-Azido-3-hydroxy Ketones,
2-Acylaziridines, and 2-Acylspiroaziridines[‡]
[a]
[a]
[b]
´
´
´
´
´
Tamas Patonay,* Eva Juhasz-Toth, and Attila Benyei
´
´
Dedicated to Prof. Pal Sohar on the occasion of his 60th birthday
Keywords: Aldol reactions / Azides / Aziridines / Ketones / Spiro compounds
An improved synthesis of α-azido ketones under phase-trans-
fer conditions has been developed. The transformation of α-
azido ketones into acyclic and heterocyclic 2-azido-3-hy-
mined by X-ray analysis. Treatment of the aldol-type prod-
ucts with triphenylphosphane afforded 2-acylaziridines and
the hitherto unknown spiro[chroman-3,2Ј-aziridin]-4-ones.
droxy ketones has been demonstrated and the relative con- The relative configuration of the spiroaziridines was deter-
figurations of the chromanone derivatives have been deter-
mined by NOE measurements.
Introduction
α-Azido ketones 1 with at least one α-hydrogen atom
have been found to be highly base-sensitive and to undergo
loss of nitrogen from carbanion A, followed by protonation
of imino anion B to give imine 2 (Scheme 1).[1,2] Recently,
we suggested a possible synthetic methodology, based on
the trapping of anions A and B with electrophiles, that
could furnish ketone derivatives 3 and 4.[3]
This kind of trapping was completely unknown in the
literature, the only related transformation has been reported
by Eguchi and co-workers,[4] who synthesized β-(acyloxy)-
vinyl azide by deprotonation of α-azido ketones with LDA
and subsequent treatment with acid chlorides or anhyd-
rides. The product obviously derived from the enolate form
of anion A. In our previous paper[3] we demonstrated that
anions A and B, generated from azides 1 by treatment with
amines, could be trapped with aldehydes or ketones to yield
2-azido-3-hydroxy ketones or 2,5-dihydro-5-hydroxyox-
azoles, depending on the conditions and techniques. Some
examples of the synthetic utility of 2-azido-3-hydroxy ke-
tones were also presented; these valuable 1,2,3-trifunctiona-
lized synthons can be transformed easily and selectively in
many ways, even without protecting groups.
[‡]
α-Azido Ketones, 3. Ϫ Part 2: Ref.[3]; part 1: Ref.[6d]
Scheme 1. Trapping of the anions generated from α-azido ketones
1 by electrophiles
[a]
Department of Organic Chemistry, University of Debrecen,
P. O. Box 20, 4010 Debrecen, Hungary
Fax: (internat.) ϩ 36-52/453-836
E-mail: tpatonay@tigris.klte.hu
Department of Physical Chemistry, Laboratory for X-ray
Diffraction, University of Debrecen,
P. O. Box 7, 4010 Debrecen, Hungary
In this contribution we wish to present further results
in the synthesis and transformations of 2-azido-3-hydroxy
ketones and their α-azido ketone precursors.
[b]
Eur. J. Org. Chem. 2002, 285Ϫ295
WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1434Ϫ193X/02/0102Ϫ0285 $ 17.50ϩ.50/0
285

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T. Patonay, E. Juhasz-Toth, A. Benyei
FULL PAPER
Results and Discussion
Two sets of α-azido ketone substrates were studied. 2-
Azido-1-(4-substituted phenyl)ethanones (phenacyl azides)
6 were chosen to investigate the electronic effect of the sub-
stituents on the deprotonation and coupling reaction of az-
ido ketones. In the cases of 3-azidochromanones 11 and 15
and -1-thiochromanones 12 we wished to survey the pos-
sible extension of the reactions to more complex heterocyc-
lic systems.
A number of methods to synthesize α-azido ketones have
been developed. The most obvious and frequently used ap-
proach utilizes the nucleophilic substitution of a ketone
containing a good leaving group, such as halogeno[2,4,5] or
sulfonyloxy,[6] at the α-position. The main drawback of this
method is the lability of the formed azide under basic con-
ditions; substrates with β-hydrogen atoms, and in particular
with a conjugating group at the β-position, give α-azido ke-
tones in low yields and the major product is the tauto-
merized form of the imine 2.[5eϪ5j] New preparative
methods to overcome this difficulty have been
developed,[7Ϫ10] but these approaches also suffer from lack
of regioselectivity and laborious synthesis required for the
starting material and/or the substrate. Another solution is
to enhance nucleophilic substitution, increasing the rate of
displacement under less basic conditions. The use, in acet-
one solution, of α-nosyloxy ketones with a leaving group of
greater nucleofugacity has been demonstrated.[6d]
We have now established that acetone can also be used
advantageously in the transformations of phenacyl brom-
ides 5aϪd and 5f with sodium azide to afford the corres-
ponding azides 6aϪd and 6f in excellent (81Ϫ94%) yields
(Scheme 2).
Scheme 2. Synthesis of α-azido ketones 6, 11, 12, and 15
At the same time, merely changing the solvent was insuf- sodium azide in DMF at low levels of conversion.[6a] On
ficient to solve the problem of lability in the case of more the other hand, when 3-bromo-2,2-dimethylchromanones
sensitive azido ketones. It was found that the reaction be- 13a and 13b were treated with sodium azide under the
tween sodium azide and 3-bromochromanones 9a, 9e, and standard conditions, no reaction was observed, even after
9f, prepared by the bromination of the corresponding longer periods or at elevated temperatures, due to the steric
chromanones 7a, 7e, and 7f (Scheme 2), takes place very hindrance exerted by the axial methyl group in the β-posi-
slowly in acetone, due to the steric hindrance of the SN2 tion on the rear-side attack of the nucleophile at C-3. This
displacement, with considerable amount of secondary prod- has so far been the only observed limitation of our new
ucts also being detected. In the presence of 10 mol % of 18- method.
crown-6, the reaction was accelerated thanks to the higher
With both sets of α-azido ketones in hand, we systematic-
concentration of azide ions, and the 3-azidochromanones ally investigated their reactions with aldehydes. In continua-
11a, 11e, and 11f were obtained in good to excellent yields tion of our previous work,[3] we treated phenacyl azide 6a
(73Ϫ95%). Even the very sensitive 3-azido-1-thiochrom- with acetaldehyde in the presence of various bases, but all
anone (12a) became available in modest yield (26%) by this attempts to find a deprotonating agent more effective than
methodology. Earlier attempts to prepare azides 11 and 12 the previously used DBU failed. No reaction took place in
by nucleophilic substitution of 3-bromochromanones 9 and the presence of triethylamine or 4-(dimethylamino)pyridine;
3-bromo-1-thiochromanones 10 in more polar solvents such only the use of 1,4-diazabicyclo[2.2.2]octane (DABCO) re-
as DMF, DMSO, alcohols, and mixtures of these with water sulted in the formation of the desired 16a in low yield after
had failed to give any azide, affording only 3-aminochro- an extremely long reaction period (10 d). It is noteworthy
mones and -1-thiochromones,[5eϪ5g] and so our technique that the 1,2-azido alcohol 16a was also obtained in moder-
has notable synthetic value. The use of crown ethers in com- ate yield by use of tetrabutylammonium fluoride (TBAF)
bination with acetone as solvent also enabled trans-3-azido- trihydrate as a base, meaning that the generation of the car-
flavanone (15) to be synthesized from nosylate 14. Previ- banion and the subsequent coupling reaction tolerated the
ously, azide 15 had been prepared in poor yield by quench- presence of small amounts of water. Next, the 2-azido-4Ј-
ing the reaction between trans-3-mesyloxyflavananone and substituted acetophenone series 6aϪd and 6f was treated
286
Eur. J. Org. Chem. 2002, 285Ϫ295

Base-Induced Coupling of α-Azido Ketones with Aldehydes
FULL PAPER
with acetaldehyde and propionaldehyde under the optim- forded the desired 3-azido-3-(1-hydroxyalkyl)chromanones
ized conditions (8 equiv. of electrophile, 0.08 equiv. of 20a, 21a, 21e, 21f, 22a, and 3-azido-3-(1-hydroxyallyl)-1-
DBU) and the corresponding aldol products syn- and anti- thiochromanone 29a in good (60Ϫ74%) yields (Scheme 4,
16aϪd, 16f, 17a, and 17f were obtained in good yields Table 2).
(Scheme 3, Table 1).
Scheme 3. Synthesis of azido alcohols 16 and 17 and their trans-
formation into aziridines 18 and 19
Table 1. Reaction between phenacyl azides 6 and aldehydes
Product[a]
R
H
R1 t [h] Conversion (%)[b] Yield (%) syn/anti
16a
16b
16c
16d
16f
17a
17f
Me 6.5 100
76
80
82
30
67
56
35
56:44
66:34
54:41
59:41
50:50
65:35
63:37
MeO Me 6.5 90
Me 7 89
NO2 Me 17 100
F
Scheme 4. Synthesis of heterocyclic azido alcohols 20؊22, 27, and
29a and their transformation into aziridines 24؊26 and 30a
Cl
H
Cl
Me 22 100
Et 6.5 100
Et
4
100
Table 2. Treatment of 3-azidochromanones 11 and 3-azido-1-
thiochromanone 12a with aldehydes
[a] Reactions performed at 0 °C, with the exceptions of 17a and 17f
(room temperature).
reaction mixture.
[b]
Determined by 1H NMR analysis of the
Starting material[a]
Product
t [h]
Yield (%)
syn/anti
11a
11a
11a
11e
11f
12a
20a
21a
22a
21e
21f
29a
5
3
24
22
2
67
62
60
74
62
65
56:44
58:42
67:33
57:43
57:43
78:22
Incorporation of electron-withdrawing substituents, par-
ticularly the nitro group, into position 4Ј resulted in a signi-
ficant decrease in the yield. This phenomenon may be ex-
plained in terms of the increased stability, and hence the
lower reactivity, of the carbanion A. In accordance with
our previous report,[3] a low diastereoselectivity (0Ϫ32% de)
with a syn preference was observed in the formation of
products 16 and 17.
23
[a]
Reactions were performed at 0 °C.
Products 20, 21, 22, and 29 were isolated as mixtures of
Analogous treatment of 3-azidochromanones 11a, 11e, syn and anti diastereomers, but the determination of their
and 11f and 3-azido-1-thiochromanone (12a) with aliphatic relative configurations in this case was more troublesome
3
aldehydes in the presence of 1 equiv. of triethylamine af- due to the lack of JH,H coupling constant in the 1,2-azido
Eur. J. Org. Chem. 2002, 285Ϫ295
287

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T. Patonay, E. Juhasz-Toth, A. Benyei
FULL PAPER
alcohol unit, and our original tentative assignment[3] based 2-azido-3-hydroxy-1-phenylbutanone (16a) and 2-azido-3-
on 13C chemical shifts had been tenuous because of the con- hydroxy-1-phenylpentanone (17a) into 2-acylaziridines 18a
flicting spectroscopic data. Now, repeated column chroma- and 19a on treatment with triphenylphosphane (TPP). The
tography of the products afforded syn-21a, anti-21a, syn- transformation of vic-azido alcohols into aziridines by
21f, anti-21f, and syn-22a in diastereopure forms and the trivalent phosphorous reagents is well documented in
stereochemistry of syn-21a was unequivocally determined the literature[11] Ϫ examples include the preparation
by X-ray analysis of its p-nitrobenzoate 23 (Figure 1).
of 1H-aziridine-2-carboxylates,[11d,11j] aziridine-2,3-dicarb-
oxylates,[11c,11f,11h] and 2-[2-(ethoxycarbonyl)ethenyl]aziridi-
nes[11i] Ϫ but our method was the first report of the syn-
thesis of 1-unsubstituted-2-acylaziridines. More recently, an
alternative method, based on the base-induced cyclization
of β-(methoxyamino) ketones,[11i] has also been published.
Related aziridine-2-carboxamides have been prepared from
α,β-unsaturated amides and diaziridine.[12] 1-Sulfonyl-2-
acyl- or 1,2-diacylaziridines have been obtained by elec-
trophilic amination of α,β-unsaturated ketones with (N-tos-
ylimino)phenyliodinane[13] and by treatment of monocar-
bonyl iodonium ylides with sulfonyl- or acylimines.[14] Since
2-acylaziridines and related derivatives are useful synthetic
building blocks,[11Ϫ14] we investigated the transformation of
our 2-azido-3-hydroxy ketones 16, 17, 20؊22, and 29 into
these valuable compounds.
Treatment of 1,2-azido alcohols 16aϪd, 16f, and 17a with
TPP in benzene solution yielded the corresponding trans-
aziridines 18aϪc, 18f, and 19a in poor (3.1Ϫ21%) yields
Figure 1. Crystal structure of p-nitrobenzoate 23
This allowed us to assign the isomers in the whole series, (Scheme 3), and all attempts (change of stoichiometry and
on the basis of their characteristic spectral differences. The solvent, use of other phosphanes or triethyl phosphite in-
1
characteristic feature in the H NMR spectra of the more stead of TPP) failed to improve the yields. A marked sub-
polar anti diastereomers was the well-separated AX doub- stituent effect was observed; the presence of an electron-
lets of the 2-methylene group of the chromanone ring (δ ϭ withdrawing substituent in position 4Ј significantly lowered
4.32Ϫ4.36 and 4.66Ϫ4.70, respectively), whereas the less the yield of the ring-closure and the nitro derivative 18d was
polar syn isomers showed a very tight AB system (∆δAB
ϭ
unavailable in this way. However, much better (29Ϫ63%)
0.02Ϫ0.03). Another diagnostic tool was the chemical shift yields were achieved for the analogous treatment of syn-
of the C-1Ј carbon signal, which appeared at lower field and anti-3-azido-3-(1-hydroxyalkyl)chromanones and -1-
(∆δ ϭ 1.8Ϫ2.1) in the 13C NMR spectrum of the syn isomer thiochromanone 20a, 21a, 21e, 21f, 22a, and 29a, which af-
than in that of the anti diastereomer.
forded the desired cis- and trans-aziridines 24a, 25a, 25e,
As before, low diastereoselectivity with syn preference 25f, 26a, and 30a (Scheme 4). The relative configurations of
was observed in most cases, the diastereomeric excesses the aziridine rings were determined by 2D {1H}-1H NOE
varying between 12 and 16% for products 20a, 21a, 21e, measurements. Irradiation of the chromanone ring 2-Heq
and 21f. However, the selectivity depended significantly on hydrogen atom resulted in an NOE difference on the 3Ј-
steric factors, since 1,2-azido alcohol 22a, obtained from methyl group of trans-24a, but on the 3Ј-methine proton in
valeraldehyde, with a longer alkyl chain, and aldol product the case of the isomeric cis-24a. This type of spiroaziridines
29a, obtained from 3-azido-1-thiochromanone (12a), a sub- (24؊26, 30) was almost unknown in the literature, the only
strate with a more distorted heterocycle, afforded higher synthesis, reported by Piva,[15] being based on the photoin-
syn/anti ratios (34 and 56% de, respectively).
Treatment of trans-3-azidoflavanone (15) with acetalde-
duced cyclization of 2-aminocyclohexenone derivatives.
The stereochemical outcome of the cyclization was an-
hyde yielded the anticipated but highly unstable product 27, other point of interest. The phosphane-induced transforma-
which decomposed by retro-aldol reaction during the at- tion of 1,2-azido alcohols into aziridines is generally re-
tempted purification by silica gel chromatography. Treat- garded[11] as a diastereospecific and diastereoselective reac-
ment of the crude reaction mixture with trimethylsilyl tion with inversion at the carbon atom bearing the hydroxy
chloride afforded the protected derivative 28 in 13% over- group, although some controversial data have also been
all yield.
published by Zwanenburg et. al.[11c] In our case, the reac-
These results clearly show the generality of this new CϪC tions of diastereomerically pure chromanone derivatives
bond-forming reaction, both for aliphatic and for cyclic α- syn-21a, anti-21a, and syn-22a displayed complete diaster-
azido ketones. 2-Azido-3-hydroxy ketones, available from eospecificity and diastereoselectivity. The syn-1,2-azido al-
the reaction between various α-azido ketones and alde- cohols yielded cis-aziridines, and the anti-1,2-azido alcohol
hydes, are useful trifunctionalized synthons. We have re- a trans-aziridine exclusively, in accordance with the earlier
ported[3] some preliminary results on the transformation of findings and the proposed mechanism.[11] At the same time,
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Eur. J. Org. Chem. 2002, 285Ϫ295

Base-Induced Coupling of α-Azido Ketones with Aldehydes
FULL PAPER
2-Bromo-1-(4-fluorophenyl)ethanone (5c): This compound was pro-
duced from 1-(4-fluorophenyl)ethanone (3.16 g), giving 3.25 g
(66%) of 5c. White crystals. M.p. 43Ϫ45 °C (hexane; ref.[17] 49 °C).
treatment of a syn/anti mixture of acyclic derivatives 16 and
17 gave trans-aziridines 18 and 19 as the only products, with
no cis-aziridines detected or isolated. Surprisingly, treat-
ment of syn-16f with TPP resulted in the formation of the
trans-18f, although the yield was considerably lower (7.3%)
than that of the analogous ring-closure of anti-16f (32%).
The reason for this anomaly is unclear. Fast decomposition
of cis-aziridines may explain the lack of this isomer in the
reaction mixtures, but formation of the trans-aziridine in
the reaction of the syn-1,2-azido alcohol remains unex-
plained. Its relative configuration, which contradicts the
suggested mechanism,[11] may indicate incomplete diaster-
eoselectivity in the ring-forming step. However, we cannot
rule out epimerization of the starting material in a preequi-
librium either through α-deprotonationϪreprotonation or
even by a retro-aldolϪaldol reaction sequence.
1H NMR: δ ϭ 4.42 (s, 2 H, 2-H), 7.18 (dd, Jortho ϭ 8.9 Hz, JHF
ϭ
8.7 Hz, 2 H, 3Ј,5Ј-H), 7.18 (dd, Jortho ϭ 8.9 Hz, JHF ϭ 5.3 Hz, 2
H, 2Ј,6Ј-H).
2-Bromo-1-(4-chlorophenyl)ethanone (5f): This compound was pro-
duced from 1-(4-chlorophenyl)ethanone (4.50 g), giving 4.52 g
(66%) of 5f. White crystals. M.p. 92Ϫ94 °C (hexane; ref.[17] 78 °C,
1
ref.[18] 77Ϫ79 °C). H NMR: δ ϭ 4.41 (s, 2 H, 2-H), 7.48 (d, J ϭ
8.8 Hz, 2 H, 3Ј,5Ј-H), 7.94 (d, J ϭ 8.8 Hz, 2 H, 2Ј,6Ј-H).
General Procedure for the Synthesis of Phenacyl Azides 6: A mixture
of the appropriate α-bromoacetophenone 5 (14.00 mmol) and so-
dium azide (1.82 g, 28.00 mmol) in acetone (250 mL) was stirred
at room temperature until completion of the reaction (TLC). The
mixture was poured into water and extracted with CH2Cl2 (3 ϫ
80 mL), and the organic layer was dried (MgSO4), concentrated
under reduced pressure, and purified by crystallization or column
chromatography.
Conclusion
2-Azido-1-phenylethanone (6a): Compound 6a (2.61 g, 81%) was
obtained from 5a (3.98 g). Purification was by column chromato-
graphy (eluent: hexane/ethyl acetate, 4:1, v/v). Yellow oil which so-
lidifies in the refrigerator (ref.[19] 17 °C). Spectroscopic data have
been reported previously.[6d]
We have improved the synthesis of α-azido ketones and
demonstrated the usefulness of the obtained azides in the
synthesis of acyclic and heterocyclic 2-azido-3-hydroxy ke-
tones, which are valuable trifunctionalized synthons. Treat-
ment of 2-azido-3-hydroxy ketones with triphenylphos-
phane resulted in the formation of 2-acylaziridines. The
hitherto unknown spiro[chroman-3,2Ј-aziridin]-4-ones have
also been prepared in moderate to good yields and with
complete diastereoselectivity.
2-Azido-1-(4-methoxyphenyl)ethanone (6b): Compound 6b (3.61 g,
94%) was obtained from 5b (4.60 g). Purification was by crystalliza-
˜
tion from hexane. Yellowish-white crystals. M.p. 68Ϫ69 °C. IR: ν ϭ
2124 (N3), 1684 (CϭO), 1600, 1240 (CϪOϪC), 1178, 826 cmϪ1
.
1H NMR: δ ϭ 3.89 (s, 3 H, 4Ј-OMe), 4.52 (s, 2 H, 2-H), 6.98 (d,
J ϭ 9.0 Hz, 2 H, 3Ј,5Ј-H), 7.90 (d, J ϭ 9.0 Hz, 2 H, 2Ј,6Ј-H). 13C
NMR: δ ϭ 54.4 (C-2), 55.4 (4Ј-OMe), 114.0 (C-3Ј,5Ј), 127.2 (C-
1Ј), 130.1 (C-2Ј,6Ј), 164.1 (C-4Ј), 191.5 (C-1). C9H9N3O2 (191.2):
C 56.54, H 4.74, N 21.98; found C 56.39, H 4.70, N 22.09.
Experimental Section
General: All chemicals were used as purchased unless otherwise
stated. THF was distilled from benzophenone ketyl, triethylamine
was distilled from LAH. Column chromatography was performed
on Kieselgel 60 or Kieselgel 40, TLC was performed on Kieselgel
60 F254 (Merck) plates. Melting points: Boetius hot-stage, uncorrec-
ted values. IR: PerkinϪElmer 16 PC-FT-IR; KBr pellets unless
otherwise stated. NMR: Varian Gemini 200, Bruker WP 200 SY,
2-Azido-1-(4-fluorophenyl)ethanone (6c): Compound 6c (2.30 g,
93%) was obtained from 5c (3.00 g). Purification was by crystalliza-
˜
tion from hexane. Yellow crystals. M.p. 47.5Ϫ48.5 °C. IR: ν ϭ 2100
(N3), 1689 (CϭO), 1594, 1226, 1217, 834 cmϪ1. 1H NMR: δ ϭ 4.54
(s, 2 H, 2-H), 7.18 (dd, Jortho ϭ 9.0 Hz, JHF ϭ 8.9 Hz, 2 H, 3Ј,5Ј-
H), 7.97 (dd, Jortho ϭ 9.0 Hz, JHF ϭ 5.4 Hz, 2 H, 2Ј,6Ј-H). 13C
NMR: δ ϭ 54.7 (C-2), 116.3 (d, JCF ϭ 22.2 Hz, C-3Ј,5Ј), 130.8 (d,
JCF ϭ 9.5 Hz, C-2Ј,6Ј), 130.9 (C-1Ј), 166.5 (d, JCF ϭ 256 Hz, C-
4Ј), 192.0 (C-1). C8H6FN3O (179.2): C 53.63, H 3.38, N 23.45;
found C 53.49, H 3.22, N 23.22.
1
Bruker AM 360 (200 or 360 MHz for H; 50 or 90 MHz for 13C).
Recorded in CDCl3 solution unless otherwise stated. Chemical
shifts are given in δ relative to an internal standard TMS (δ ϭ 0)
1
or to the residual CHCl3 (δ ϭ 7.26 for H NMR and δ ϭ 77.0 for
13C NMR). Elemental analysis: CarloϪErba 1108 CHN analyzer.
2-Azido-1-(4-nitrophenyl)ethanone (6d): Compound 6d (2.12 g,
93%) was obtained from 5d (2.70 g). Purification was by crystalliza-
tion from a hexane/ethyl acetate mixture (10:1, v/v). Pale brownish
General Procedure for the Synthesis of Phenacyl Bromides 5: After
dropwise addition, at room temperature over 5 min, of a solution of
bromine (1.7 mL, 33.00 mmol) in diethyl ether (40 mL) to a stirred
solution of the corresponding acetophenone (30.30 mmol) in diox-
ane (50 mL), the reaction mixture was heated and stirred at 40 °C
for 1Ϫ2 h, and then allowed to cool to room temperature. The mix-
ture was washed with water (5 ϫ 50 mL), and the organic layer was
dried (Na2SO4) and concentrated in vacuo. Recrystallization gave
pure 5.
˜
crystals. M.p. 91Ϫ93 °C. IR: ν ϭ 2114 (N3), 1706 (CϭO), 1524
1
(NO2), 1344 (NO2), 1212, 854 cmϪ1. H NMR: δ ϭ 4.62 (s, 2 H,
2-H), 8.10 (d, J ϭ 8.8 Hz, 2 H, 2Ј,6Ј-H), 8.37 (d, J ϭ 8.8 Hz, 2 H,
3Ј,5Ј-H). 13C NMR: δ ϭ 55.2 (C-2), 124.3 (C-3Ј,5Ј), 129.2 (C-2Ј,6Ј),
138.9 (C-1Ј), 151.1 (C-4Ј), 192.3 (C-1). C8H6N4O3 (206.2): C 46.61,
H 2.93, N 27.18; found C 46.88, H 3.07, N 26.99.
2-Azido-1-(4-chlorophenyl)ethanone (6f): Compound 6f (3.22 g,
89%) was obtained from 5f (4.30 g). Purification was by crystalliza-
2-Bromo-1-(4-methoxyphenyl)ethanone (5b): This compound was
produced from 1-(4-methoxyphenyl)ethanone (4.55 g), giving
tion from hexane. Yellow crystals. M.p. 60Ϫ64 °C. IR: ν˜ ϭ 2107
1
4.89 g (71%) of 5b. White crystals. M.p. 66Ϫ69 °C (diethyl ether; (N3), 1694 (CϭO), 1595, 1220, 1093 (Ar-Cl) cmϪ1. H NMR: δ ϭ
1
ref.[16] 70Ϫ72 °C). H NMR: δ ϭ 3.89 (s, 3 H, 4Ј-OMe), 4.41 (s, 2 4.53 (s, 2 H, 2-H), 7.48 (d, J ϭ 8.6 Hz, 2 H, 3Ј,5Ј-H) 7.86 (d, J ϭ
H, 2-H), 6.97 (d, J ϭ 9.0 Hz, 2 H, 3Ј,5Ј-H), 7.98 (d, J ϭ 9.0 Hz, 2
H, 2Ј,6Ј-H).
8.6 Hz, 2 H, 2Ј,6Ј-H). 13C NMR: δ ϭ 54.7 (C-2), 129.2 (C-
2Ј,3Ј,5Ј,6Ј) 132.6 (C-1Ј), 140.5 (C-4Ј), 192.0 (C-1). C8H6ClN3O
Eur. J. Org. Chem. 2002, 285Ϫ295
289

´
´
´
´
T. Patonay, E. Juhasz-Toth, A. Benyei
FULL PAPER
(195.6): C 49.12, H 3.09, N 21.48; found C 48.92, H 3.25, N 21.32.
(47 mg, 0.18 mmol), and acetone (20 mL) was stirred at room tem-
perature until completion of the reaction (TLC). It was then poured
into water, extracted with CH2Cl2 (3 ϫ 40 mL), dried (MgSO4),
and concentrated in vacuo. The residue was purified by column
chromatography (eluent: hexane/ethyl acetate, 6:1, v/v).
General Procedure for the Synthesis of 3-Bromochroman-4-ones 9
and 13: Bromine (1.6 mL, 31.20 mmol) was added at reflux temper-
ature to a stirred solution of the appropriate chromanone 7
(26.00 mmol) in diethyl ether (22 mL) and the mixture was heated
for 3 h. It was then stirred overnight and extracted with water (5
ϫ 25 mL), and the organic layer was dried (MgSO4) and concen-
trated in vacuo. The residue was either purified by crystallization
or submitted to column chromatography.
3-Azido-4-chromanone (11a): Compound 11a (364 mg, 73%) was
obtained from 9a (600 mg). Spectroscopic data have been re-
ported previously.[6d]
3-Azido-6-methyl-4-chromanone (11e): Compound 11e (1.20 g,
95%) was obtained from 9e (1.50 g). Pale yellow crystals. M.p.
3-Bromo-4-chromanone (9a): Compound 9a (4.63 g, 75%) was ob-
tained from 7a (4.00 g). Purification was by crystallization from
˜
57Ϫ58.5 °C. IR: ν ϭ 2138 (N3), 1696 (CϭO), 1616, 1490, 1220,
1
hexane. White crystals. M.p. 66Ϫ68 °C (ref.[20] 70 °C). H NMR:
1
822 cmϪ1. H NMR: δ ϭ 2.32 (s, 3 H, 6-Me) 4.21 (dd, J ϭ 11.4,
δ ϭ 4.57Ϫ4.69 (m, 2 H, 2,3-H), 7.04 (d, J ϭ 8.6 Hz, 1 H, 8-H),
7.09 (dd, J ϭ 7.8, 6.9 Hz, 1 H, 6-H), 7.54 (dd, J ϭ 8.6, 6.9 Hz, 1
H, 7-H), 7.95 (d, J ϭ 7.8 Hz, 1 H, 5-H).
10.5 Hz, 1 H, 2-Hax), 4.35 (dd, J ϭ 10.5, 4.5 Hz, 1 H, 3-H), 4.47
(dd, J ϭ 11.4, 4.5 Hz, 1 H, 2-Heq), 6.89 (d, J ϭ 8.6 Hz, 1 H, 8-H),
7.33 (d, J ϭ 8.6 Hz, 1 H, 7-H), 7.70 (br. s, 1 H, 5-H). 13C NMR:
δ ϭ 20.3 (Me), 60.1 (C-3), 68.8 (C-2), 117.6 (C-8), 118.9 (C-4a),
127.0 (C-5), 131.7 (C-6), 137.8 (C-7), 159.4 (C-8a), 188.6 (C-4).
C10H9N3O2 (203.2): C 59.11, H 4.46, N 20.68; found C 59.34, H
4.32, N 20.43.
3-Bromo-6-methyl-4-chromanone (9e): Compound 9e (3.96 g, 82%)
was obtained from 7e (3.24 g). Purification was by column chroma-
tography (eluent: toluene/hexane, 2:3, v/v). Pale yellow crystals.
1
M.p. 68Ϫ70 °C (ref.[21] 74 °C). H NMR: δ ϭ 2.33 (s, 3 H, Me),
4.50Ϫ4.69 (m, 3 H, 2,3-H), 6.94 (d, J ϭ 8.3 Hz, 1 H, 8-H), 7.36
(dd, J ϭ 8.3, 1.7 Hz, 1 H, 7-H), 7.72 (br. s, 1 H, 5-H).
3-Azido-6-chloro-4-chromanone (11f): Compound 11f (690 mg,
81%) was obtained from 9f (1.00 g). Yellow crystals. M.p. 85Ϫ86
°C. IR: ν˜ ϭ 2133, 2100 (N3), 1683 (CϭO), 1650, 1558, 1287, 830
3-Bromo-6-chloro-4-chromanone (9f): Compound 9f (4.41 g, 85%)
was obtained from 7f (3.65 g). Purification was by crystallization
1
cmϪ1. H NMR: δ ϭ 4.40 (m, 3 H, 2,3-H), 6.97 (d, J ϭ 8.7 Hz, 1
H, 8-H), 7.47 (dd, J ϭ 8.7, 2.5 Hz, 1 H, 7-H), 7.88 (d, J ϭ 2.5 Hz,
1 H, 5-H). 13C NMR: δ ϭ 59.7 (C-3), 68.9 (C-2), 119.6 (C-8), 120.1
(C-4a), 126.7 (C-5), 127.7 (C-6), 136.5 (C-7), 159.7 (C-8a), 187.4
(C-4). C9H6ClN3O2 (223.6): C 48.34, H 2.70, N 18.79; found C
48.53, H 2.55, N 18.57.
˜
from hexane. Yellow crystals. M.p. 93Ϫ96 °C. IR: ν ϭ 1698 (Cϭ
1
O), 1473, 1419, 1269, 1182, 1163, 1012, 830 cmϪ1. H NMR: δ ϭ
4.57Ϫ4.71 (m, 3 H, 2,3-H), 7.01 (d, J ϭ 8.8 Hz, 1 H, 8-H), 7.48
(dd, J ϭ 8.8, 2.5 Hz, 1 H, 7-H), 7.88 (d, J ϭ 2.5 Hz, 1 H, 5-H).
13C NMR: δ ϭ 44.5 (C-3), 71.3 (C-2), 119.6 (C-4a), 119.8 (C-8),
127.5 (C-5), 128.6 (C-6), 136.7 (C-7), 159.3 (C-8a), 184.4 (C-4).
C9H6BrClO2 (261.5): C 41.34, H 2.31; found C 41.11, H 2.42.
3-Azido-1-thiochroman-4-one (12a): Compound 12a (433 mg, 26%)
was obtained from 10a (2.00 g). Toluene/ethyl acetate (9:1, v/v) was
used as eluent. Yellow crystals. M.p. 85Ϫ86 °C. IR: ν˜ ϭ 2108 (N3),
1678 (CϭO), 1436, 1266, 1216, 736 cmϪ1. 1H NMR: δ ϭ 3.15 (dd,
J ϭ 13.2, 4.4 Hz, 1 H, 2-Heq), 3.38 (dd, J ϭ 13.2, 12.5 Hz, 1 H, 2-
Hax), 4.54 (dd, J ϭ 12.5, 4.4 Hz, 1 H, 3-H), 7.20Ϫ7.29 (m, 2 H,
6,8-H), 7.44 (m, 1 H, 7-H), 8.14 (dd, J ϭ 8.1, 1.6 Hz, 1 H, 5-H).
13C NMR: δ ϭ 30.7 (C-2), 63.5 (C-3), 125.4 (C-6), 127.2 (C-8),
130.0 (C-5), 133.9 (C-7), 141.0 (C-8a), 190.3 (C-4). C9H7N3OS
(205.2): calcd. C 52.67, H 3.44, N 20.47; found C 52.82, H 3.19, N
20.70. 1-Thiochromone (599 mg, 45%), m.p. 72Ϫ73 °C (ref.[6d]
74Ϫ76 °C) and 3-amino-1-thiochromone (60 mg, 8.7%), m.p.
125Ϫ128 °C (ref.[24] 127Ϫ129 °C) were isolated from the fractions
eluting subsequently.
3-Bromo-2,2-dimethyl-4-chromanone (13a): Compound 13a
(906 mg, 57%) was obtained from 2,2-dimethyl-4-chromanone
(1.00 g). Purification was by column chromatography (eluent: hex-
ane/ethyl acetate, 5:1, v/v). Pale yellow crystals. M.p. 56Ϫ58 °C
1
(ref.[22] 62Ϫ63 °C). H NMR: δ ϭ 1.54, 1.63 (2 ϫ s, 2 ϫ 3 H, 2,2-
Me2), 4.39 (s, 2 H, 3-H), 6.98 (d, J ϭ 8.3 Hz, 1 H, 8-H), 7.05 (m,
1 H, 6-H), 7.53 (m, 1 H, 7-H), 7.92 (d, J ϭ 7.2 Hz, 1 H, 5-H).
3-Bromo-7-methoxy-2,2-dimethyl-4-chromanone (13b): Compound
13b (254 mg, 37%) was obtained from 7-methoxy-2,2-dimethyl-4-
chromanone (500 mg). Purification was by column chromato-
graphy (eluent: toluene). White crystals. M.p. 37Ϫ38 °C (hexane;
1
ref.[23] 40Ϫ41 °C). H NMR: δ ϭ 1.52, 1.62 (2 ϫ s, 2 ϫ 3 H, 2,2-
trans-3-Azidoflavanone (15): A mixture of 3-nosyloxyflavanone
(14)[6a] (2.50 g, 5.50 mmol), sodium azide (715 mg, 11.00 mmol),
and 18-crown-6 (145 mg, 0.55 mmol) in dry acetone (150 mL) was
stirred at room temperature for 100 h, poured into water, extracted
with CH2Cl2 (3 ϫ 30 mL), dried (MgSO4), and concentrated in
vacuo. The residue was purified by column chromatography (elu-
ent: hexane/ethyl acetate, 3:1, v/v) to give 733 mg (50%) of azide 15
Me2), 3.84 (s, 3 H, 7-OMe), 4.33 (s, 2 H, 3-H), 6.42 (d, J ϭ 2.1 Hz,
1 H, 8-H), 6.61 (dd, J ϭ 8.9, 2.1 Hz, 1 H, 6-H), 7.84 (d, J ϭ 8.9 Hz,
1 H, 5-H).
3-Bromo-1-thiochroman-4-one
(10a):
Bromine
(1.03 mL,
19.99 mmol) was added dropwise to a stirred solution of 1-thioch-
roman-4-one (3.28 g, 20.00 mmol) in chloroform (80 mL) and the
mixture was stirred for 3 h at room temperature. It was washed
with 10% NaHCO3 solution (50 mL) and water (30 mL), and then
dried (MgSO4). Concentration and crystallization from hexane af-
forded pure 10a (4.42 g, 91%) as yellow crystals. M.p. 70Ϫ73 °C
˜
as pale yellow crystals. M.p. 77Ϫ80 °C (hexane). IR: ν ϭ 2114 (N3),
1698 (CϭO), 1608, 1464, 1278, 1232, 760 cmϪ1 1H NMR: δ ϭ
.
4.55 (d, J ϭ 12.0 Hz, 1 H, 2-H), 5.15 (d, J ϭ 12.0 Hz, 1 H, 3-H),
7.02Ϫ7.20 (m, 2 H, 6,8-H) 7.45Ϫ7.69 (m, 6 H, 7-H, Ph) 7.96 (dd,
J ϭ 7.6, 1.9 Hz, 1 H, 5-H). C15H11N3O2 (265.3): C 67.92, H 4.18,
N 15.84; found C 67.85, H 4.02, N 15.62.
1
(ref.[24] 76 °C). H NMR: δ ϭ 3.50 (dd, J ϭ 14.1, 8.5 Hz, 1 H, 2-
Hax), 3.67 (dd, J ϭ 14.1, 3.1 Hz, 1 H, 2-Heq), 4.98 (dd, J ϭ 8.5,
3.1 Hz, 1 H, 3-H), 7.21Ϫ7.30 (m, 2 H, 6,8-H), 7.44 (m, 1 H, 7-H),
8.15 (dd, J ϭ 7.9, 1.5 Hz, 1 H, 5-H).
General Procedure for the Synthesis of 1-Aryl-2-azido-3-hydroxy-1-
alkanones 16 and 17: A mixture of α-azido ketone 6 (6.21 mmol),
the appropriate aldehyde (24.74 mmol), and DBU (77.8 µL,
0.52 mmol) in dry THF (50 mL) was stirred for 1 h. Another batch
General Procedure for the Synthesis of 3-Azidochromanones 11 and
Thio Derivative 12a: A mixture of the appropriate bromide 9 or
10a (1.76 mmol), sodium azide (229 mg, 3.52 mmol), 18-crown-6 of aldehyde (24.74 mmol) was then added and the mixture was
290 Eur. J. Org. Chem. 2002, 285Ϫ295

Base-Induced Coupling of α-Azido Ketones with Aldehydes
FULL PAPER
stirred until completion of the reaction (TLC). The mixture was
195.3 (C-1); syn-16d: δ ϭ 20.1 (C-4), 68.3, 68.5 (C-2,3), 139.5 (C-
poured into water, extracted with CH2Cl2 (6 ϫ 40 mL), and dried 1Ј), 195.0 (C-1); inseparable signals: δ ϭ 124.0 (C-3Ј,5Ј), 129.8 (C-
(MgSO4), the solvent was evaporated under reduced pressure, and
the residue was submitted to column chromatography.
2Ј,6Ј), 150.6 (C-4Ј); NMR spectroscopic data were taken from the
spectra of the diastereomeric mixture. C10H10N4O4 (250.2): calcd.
C 48.00, H 4.03, N 22.39; found C 48.21, H 3.79, N 22.23.
2-Azido-3-hydroxy-1-phenyl-1-butanone (16a): Compound 16a
(960 mg, 76%) was obtained from 6a (1.00 g) (reaction period:
6.5 h; temperature: 0 °C). Spectroscopic data have been reported
previously.[3] Compound 16a (40 mg, 28%) was also obtained from
6a (112 mg) with 0.08 equiv. of DABCO as base (reaction period:
10 d; temperature: 0 °C). Compound 16a (50 mg, 37%) was also
obtained from 6a (106 mg) with 0.085 equiv. of TBAF·3H2O as
base (reaction period: 5 h; temperature: 0 °C).
2-Azido-1-(4-chlorophenyl)-3-hydroxy-1-butanone (16f): Compound
16f [1.17 g, 67%; reaction period: 22 h; temperature: 0 °C; elution
with toluene/ethyl acetate (8:1, v/v) mixture] was obtained from 6f
(1.42 g). Yellow oil, 50:50 mixture of the syn/anti diastereomers
1
˜
(based on H NMR). IR (neat): ν ϭ 3452 (OH), 2112 (N3), 1684
(CϭO), 1588, 1284, 1252, 1216, 822 cmϪ1. Fractional crystalliza-
tion from diisopropyl ether afforded pure diastereomers. anti-16f:
White prisms. M.p. 100Ϫ103 °C. 1H NMR: δ ϭ 1.35 (d, J ϭ
6.3 Hz, 3 H, 4-H), 2.03 (br. s, 1 H, OH), 4.35 (m, 1 H, 3-H), 4.48
(d, J ϭ 6.2 Hz, 1 H, 2-H), 7.49 (d, J ϭ 8.6 Hz, 2 H, 3Ј,5Ј-H), 7.93
(d, J ϭ 8.6 Hz, 2 H, 2Ј,6Ј-H). 13C NMR: δ ϭ 19.5 (C-4), 67.0, 68.0
(C-2,3), 129.2 (C-3Ј,5Ј), 130.2 (C-2Ј,6Ј), 133.6 (C-1Ј), 140.8 (C-4Ј),
195.0 (C-1). C10H10ClN3O2 (239.7): calcd. C 50.12, H 4.21, N
17.53; found C 50.21, H 4.23, N 17.39. syn-16f: Yellowish prisms.
M.p. 37Ϫ41 °C. 1H NMR: δ ϭ 1.35 (d, J ϭ 6.5 Hz, 3 H, 4-H),
2.20 (br. s, 1 H, OH), 4.33Ϫ4.41 (m, 2 H, 2,3-H), 7.49 (d, J ϭ
9.0 Hz, 2 H, 3Ј,5Ј-H), 7.92 (d, J ϭ 9.0 Hz, 2 H, 2Ј,6Ј-H). 13C NMR:
δ ϭ 19.9 (C-4), 67.5, 68.4 (C-2,3), 129.2 (C-3Ј,5Ј), 130.1 (C-2Ј,6Ј),
133.1 (C-1Ј), 140.7 (C-4Ј), 195.0 (C-1). C10H10ClN3O2 (239.7):
calcd. C 50.12, H 4.21, N 17.53; found C 50.26, H 4.18, N 17.43.
2-Azido-3-hydroxy-1-(4-methoxyphenyl)-1-butanone (16b): Com-
pound 16b (445 mg, conversion: 90%; yield: 80%, normalized to
100% conversion) was obtained from 6b [500 mg, reaction period:
6.5 h; temperature: 0 °C; elution with hexane/ethyl acetate (3:1,
v/v) mixture]. Yellow oil, 66:34 mixture of the syn/anti diastereo-
1
˜
mers (based on H NMR). IR (neat): ν ϭ 3462 (OH), 2104 (N3),
1680 (CϭO), 1598, 1512, 1310, 1264, 1174, 1028, 848 cmϪ1 1H
.
NMR: anti-16b: δ ϭ 4.48 (d, J ϭ 6.2 Hz, 1 H, 2-H), 7.98 (d, J ϭ
8.7 Hz, 2 H, 2Ј,6Ј-H); syn-16b: δ ϭ 7.97 (d, J ϭ 8.7 Hz, 2 H, 2Ј,6Ј-
H); inseparable signals: δ ϭ 1.33 (d, J ϭ 6.7 Hz, 3 H, 4-H), 3.89
(s, 3 H, 4Ј-OMe), 4.32Ϫ4.38 [m, 1 H, 3-H (anti) ϩ m, 2 H, 2,3-H
(syn)], 6.95Ϫ7.00 (m, 2 H, 3Ј,5Ј-H); NMR spectroscopic data were
taken from the spectra of the diastereomeric mixture. 13C NMR:
anti-16b: δ ϭ 19.1 (C-4), 66.7, 68.1 (C-2,3), 128.1 (C-1Ј), 194.2 (C-
1); syn-16b: δ ϭ 19.8 (C-4), 66.8, 68.5 (C-2,3), 127.6 (C-1Ј), 194.5
(C-1); inseparable signals: δ ϭ 55.4 (4Ј-OMe), 114.0 (C-3Ј,5Ј), 131.1
(C-2Ј,6Ј), 164.3 (C-4Ј); NMR spectroscopic data were taken from
the spectra of the diastereomeric mixture. C11H13N3O3 (235.2): C
56.16, H 5.57, N 17.86; found C 55.98, H 5.71, N 17.76.
2-Azido-3-hydroxy-1-phenyl-1-pentanone (17a): Compound 17a
[766 mg, 56%; reaction period: 6.5 h; temperature: 25 °C; elution
with hexane/ethyl acetate (3:1, v/v) mixture] was obtained from 6a
(1.00 g). Spectroscopic data have been reported previously.[3]
2-Azido-1-(4-chlorophenyl)-3-hydroxy-1-pentanone (17f): Com-
pound 17f [455 mg, 35%; reaction period: 4 h; temperature: 25 °C;
elution with toluene/ethyl acetate (4:1, v/v) mixture] was obtained
from 6f (1.00 g). Yellow oil, 63:37 mixture of the syn/anti diastereo-
2-Azido-1-(4-fluorophenyl)-3-hydroxy-1-butanone (16c): Compound
16c (450 mg; conversion: 89%; yield: 82%, normalized to 100% con-
version) was obtained from 6c [500 mg, reaction period: 7 h; tem-
perature: 0 °C; elution with hexane/ethyl acetate (3:1, v/v) mixture].
Yellow oil, 59:41 mixture of the syn/anti diastereomers (based on
1H NMR). IR (neat): ν˜ ϭ 3444 (OH), 2104 (N3), 1682 (CϭO),
1
mers (based on H NMR). IR (neat): ν˜ ϭ 3444 (OH), 2108 (N3),
1682 (CϭO), 1588, 1402, 1210, 1180, 1012, 984, 822 cmϪ1 1H
.
NMR: anti-17f: δ ϭ 4.48 (d, J ϭ 6.6 Hz, 1 H, 2-H), 7.93 (d, J ϭ
8.1 Hz, 2 H, 2Ј,6Ј-H); syn-17f: δ ϭ 4.47 (d, J ϭ 3.0 Hz, 1 H, 2-H),
7.90 (d, J ϭ 7.8 Hz, 2 H, 2Ј,6Ј-H); inseparable signals: δ ϭ 1.03 (t,
J ϭ 7.3 Hz, 3 H, 5-H), 1.66 (m, 2 H, 4-H), 2.35 (br. s, 1 H, OH),
4.08 (m, 1 H, 3-H), 7.49 (d, J ϭ 8.9 Hz, 2 H, 3Ј,5Ј-H); NMR spec-
troscopic data were taken from the spectra of the diastereomeric
mixture. 13C NMR: anti-17f: δ ϭ 9.7 (C-5), 26.5 (C-4), 65.3 (C-2),
73.1 (C-3), 133.8 (C-1Ј); syn-17f: δ ϭ 10.1 (C-5), 27.1 (C-4), 66.0
(C-2), 73.8 (C-3), 133.1 (C-1Ј); inseparable signals: δ ϭ 129.3, 130.2
(C-2Ј,3Ј,5Ј,6Ј), 140.8 (C-4Ј), 195.1 (C-1); NMR spectroscopic data
were taken from the spectra of the diastereomeric mixture.
C11H12ClN3O2 (253.7): calcd. C 52.08, H 4.77, N 16.56; found C
51.99, H 4.72, N 16.52.
1598, 1504, 1410, 1300, 1234, 1160, 1104, 852 cmϪ1 1H NMR:
.
anti-16c: δ ϭ 4.48 (d, J ϭ 6.5 Hz, 1 H, 2-H); inseparable signals:
δ ϭ 1.38 (d, J ϭ 6.2 Hz, 3 H, 4-H), 4.40Ϫ4.46 [m, 1 H, 3-H (anti)
ϩ m, 2 H, 2,3-H (syn)], 7.12Ϫ7.28 (m, 2 H, 3Ј,5Ј-H), 7.98Ϫ8.10
(m, 2 H, 2Ј,6Ј-H). NMR spectroscopic data were taken from the
spectra of the diastereomeric mixture. 13C NMR: anti-16c: δ ϭ 19.5
(C-4), 67.0, 68.0 (C-2,3); syn-16c: δ ϭ 19.9 (C-4), 67.3, 68.5 (C-
2,3); inseparable signals: δ ϭ 116.1 (d, JCF ϭ 22.0 Hz, 3Ј,5Ј-C),
131.6 (d, JCF ϭ 9.9 Hz, 2Ј,6Ј-C), 131.1 (C-1Ј), 166.3 (d, JCF
ϭ
258 Hz, 4Ј-C), 194.6 (C-1). NMR spectroscopic data were taken
from the spectra of the diastereomeric mixture. C10H10FN3O2
(223.2): C 53.81, H 4.52, N 18.83; found C 54.00, H 4.25, N 18.62.
General Procedure for the Synthesis of 3-Azido-3-(1-hydroxyalk-
yl)chromanones 20؊22 and Thio Derivative 29a: A mixture of the
appropriate α-azido ketone (1.48 mmol), aldehyde (143 mmol), and
TEA (0.21 mL, 1.48 mmol) was allowed to stand at 0 °C until com-
pletion of the reaction (TLC). The mixture was poured into water
and extracted with CH2Cl2 (4 ϫ 40 mL), the organic layer was
dried (MgSO4), the solvent was removed under reduced pressure,
and the residue was submitted to column chromatography.
2-Azido-3-hydroxy-1-(4-nitrophenyl)-1-butanone (16d): Compound
16d [181 mg, 30%; reaction period: 17 h; temperature: 0 °C; elution
with toluene/ethyl acetate (4:1, v/v) mixture] was obtained from 6d
(500 mg). Brownish oil, 59:41 mixture of the syn/anti diastereomers
1
(based on H NMR). IR (neat): ν˜ ϭ 3446 (OH), 2114 (N3), 1652
(CϭO), 1522 (NO2), 1348 (NO2), 852 cmϪ1 1H NMR: anti-16d:
.
δ ϭ 4.50 (d, J ϭ 6.4 Hz, 1 H, 2-H); syn-16d: δ ϭ 4.45 (d, J ϭ
3.8 Hz, 1 H, 2-H); inseparable signals: δ ϭ 1.37 (d, J ϭ 6.3 Hz, 3 3-Azido-3-(1-hydroxyethyl)-4-chromanone (20a): Compound 20a
H, 4-H), 4.38 (m, 1 H, 3-H), 8.13 (overlapping d’s, J ϭ 8.4 Hz, 2 (230 mg, 67%) was obtained from 11a (280 mg; reaction period:
H, 2Ј,6Ј-H), 8.34 (d, J ϭ 8.4 Hz, 2 H, 3Ј,5Ј-H); NMR spectroscopic
5 h; elution with hexane/ethyl acetate (3:1, v/v) mixture]. Yellow oil,
data were taken from the spectra of the diastereomeric mixture. 13
C
56:44 mixture of the syn/anti diastereomers[26] (based on 1H NMR).
NMR: anti-16d: δ ϭ 19.8 (C-4), 67.6, 68.0 (C-2,3), 140.0 (C-1Ј), 1H NMR: anti-20a: δ ϭ 1.30 (d, J ϭ 6.6 Hz, 3 H, 2Ј-H), 2.28
Eur. J. Org. Chem. 2002, 285Ϫ295
291

´
´
´
´
T. Patonay, E. Juhasz-Toth, A. Benyei
FULL PAPER
(deuterable s, 1 H, OH), 4.36, 4.68 (AB q, J ϭ 11.6 Hz, 2 H, 2-H); 3-Azido-3-(1-hydroxypentyl)-4-chromanone (22a): Compound 22a
syn-20a: δ ϭ 1.34 (d, J ϭ 6.2 Hz, 3 H, 2Ј-H), 2.98 (br. deuterable
(450 mg, 60%) was obtained from 11a [520 mg; reaction period:
s, 1 H, OH), 4.29 (s, 2 H, 2-H); detailed spectroscopic data have 24 h; elution with hexane/acetone (12:1, v/v) mixture]. Yellow oil,
1
been reported previously.[3]
67:33 mixture of the syn/anti diastereomers (based on H NMR).
˜
IR (neat): ν ϭ 3478 (OH), 2112 (N3), 1682 (CϭO), 1608, 1480,
1466, 1312, 1270, 1218, 1148, 1038, 760 cmϪ1. The pure syn diaster-
eomer was obtained by repeated column chromatography with
toluene/ethyl acetate (9:1, v/v) mixture as eluent. syn-22a: Yellow
3-Azido-3-(1-hydroxypropyl)-4-chromanone (21a): Compound 21a
(1.63 g, 62%) was obtained from 11a [2.00 g; reaction period: 3 h;
elution with toluene/ethyl acetate (9:1, v/v) mixture]. Yellow oil,
58:42 mixture of the syn/anti diastereomers[26] (based on 1H NMR).
Pure diastereomers were obtained by repeated column chromato-
graphy, with a toluene/ethyl acetate (9:1, v/v) mixture as eluent. 1H
NMR: anti-21a: δ ϭ 1.03 (t, J ϭ 7.3 Hz, 3 H, 3Ј-H), 1.39Ϫ1.72
(m, 2 H, 2Ј-H), 4.11 (m, 1 H, 1Ј-H), 4.34, 4.68 (AB q, J ϭ 12.0 Hz,
2 H, 2-H); syn-21a: δ ϭ 1.06 (t, J ϭ 7.2 Hz, 3 H, 3Ј-H), 1.40Ϫ1.74
(m, 2 H, 2Ј-H), 4.10 (m, 1 H, 1Ј-H), 4.31, 4.35 (AB q, J ϭ 12.2 Hz,
2 H, 2-H); detailed spectroscopic data have been reported previ-
ously.[3]
1
oil. H NMR: δ ϭ 0.92 (t, J ϭ 7.0 Hz, 3 H, 5Ј-H), 1.20Ϫ1.61 (m,
6 H, 2Ј,3Ј,4Ј-H), 4.18 (m, 1 H, 1Ј-H), 4.35 (s, 2 H, 2-H), 7.00 (d,
J ϭ 8.4 Hz, 1 H, 8-H), 7.11 (m, 1 H, 6-H), 7.56 (m, 1 H, 7-H),
7.97 (dd, J ϭ 7.6, 1.6 Hz, 1 H, 5-H). 13C NMR: δ ϭ 13.8 (C-5Ј),
22.3, 28.1, 30.7 (C-2Ј,3Ј,4Ј), 67.4 (C-3), 69.6 (C-2), 72.3 (C-1Ј),
117.8 (C-8), 119.2 (C-4a), 122.2 (C-6), 127.9 (C-5), 136.8 (C-7),
160.9 (C-8a), 190.1 (C-4). C14H17N3O3 (275.3): C 61.08, H 6.22, N
15.26; found C 60.90, H 6.25, N 15.34. anti-22a: 1H NMR: δ ϭ
4.19 (m, 1 H, 1Ј-H), 4.35, 4.70 (AB q, J ϭ 12.1 Hz, 2 H, 2-H), 7.01
(d, J ϭ 8.4 Hz, 1 H, 8-H), 7.09 (t, J ϭ 8.4 Hz, 1 H, 6-H); insepar-
able signals: δ ϭ 0.88Ϫ0.93 (m, 3 H, 5Ј-H), 1.34Ϫ1.67 (m, 6 H,
2Ј,3Ј,4Ј-H), 7.55 (m, 1 H, 7-H), 7.94 (d, J ϭ 8.1, 1.7 Hz, 1 H, 5-
H); NMR spectroscopic data were taken from the spectra of the
diastereomeric mixture. 13C NMR: δ ϭ 13.8 (C-5Ј), 22.3, 28.3, 30.1,
(C-2Ј,3Ј,4Ј), 67.8 (C-3), 69.1 (C-2), 70.2 (C-1Ј), 117.9 (C-8), 119.5
(C-4a), 122.0 (C-6), 127.9 (C-5), 136.8 (C-7), 160.9 (C-8a), 189.1
(C-4); NMR spectroscopic data were taken from the spectra of the
diastereomeric mixture. C14H17N3O3 (275.3): C 61.08, H 6.22, N
15.26; found C 60.95, H 6.26, N 15.03.
3-Azido-3-(1-hydroxypropyl)-6-methyl-4-chromanone (21e): Com-
pound 21e (761 mg, 74%) was obtained from 11e [800 mg; reaction
period: 22 h; elution with toluene/ethyl acetate (9:1, v/v) mixture].
Yellow oil, 57:43 mixture of the syn/anti diastereomers (based on
1
˜
H NMR). IR (neat): ν ϭ 3456 (OH), 2110 (N3), 1682 (CϭO),
1616, 1494, 1418, 1294, 1220, 1138, 824 cmϪ1. H NMR: anti-21e:
1
δ ϭ 1.04 (t, J ϭ 7.2 Hz, 3 H, 3Ј-H), 4.32, 4.66 (AB q, J ϭ 11.5 Hz,
2 H, 2-H), 6.91 (d, J ϭ 8.4 Hz, 1 H, 8-H); syn-21e: δ ϭ 1.07 (t,
J ϭ 7.4 Hz, 3 H, 3Ј-H), 4.29, 4.33 (AB q, J ϭ 12.1 Hz, 2 H, 2-H),
6.90 (d, J ϭ 8.1 Hz, 1 H, 8-H); inseparable signals: δ ϭ 1.48Ϫ1.68
(m, 2 H, 2Ј-H), 2.33 (s, 3 H, 6-Me), 4.08 (m, 1 H, 1Ј-H), 7.36
(overlapping d’s, 1 H, 7-H), 7.73 (overlapping d’s, 1 H, 5-H); NMR
spectroscopic data were taken from the spectra of the diastereom-
eric mixture. 13C NMR: anti-21e: δ ϭ 10.8 (C-3Ј), 23.7 (C-2Ј), 68.0
(C-3), 69.3 (C-2), 72.1 (C-1Ј), 117.8 (C-8), 119.2 (C-4a), 127.3 (C-
5), 131.7 (C-6), 189.3 (C-4); syn-21e: δ ϭ 10.6 (C-3Ј), 24.1 (C-2Ј),
67.4 (C-3), 69.8 (C-2), 74.1 (C-1Ј), 117.7 (C-8), 118.9 (C-4a), 127.4
(C-5), 131.9 (C-6), 190.3 (C-4); inseparable signals: δ ϭ 20.4 (6-
Me), 138.2 (C-7), 159.1 (C-8a); NMR spectroscopic data were
taken from the spectra of the diastereomeric mixture. C13H15N3O3
(261.3): C 59.76, H 5.79, N 16.08; found C 59.89, H 5.55, N 16.05.
3-Azido-3-(1-hydroxyethyl)-1-thiochroman-4-one (29a): Compound
29a (198 mg, 65%) was obtained from 12a [250 mg; reaction period:
23 h; elution with hexane/ethyl acetate (3:1, v/v) mixture]. Yellow
oil, 78:22 mixture of the syn/anti diastereomers (based on 1H
˜
NMR). IR (neat): ν ϭ 3479 (OH), 2109 (N3), 1695 (CϭO), 1590,
1
1436, 1267, 903, 738 cmϪ1. H NMR: anti-29a: δ ϭ 1.24 (d, J ϭ
6.4 Hz, 3 H, 2Ј-H), 3.37, 3.58 (AB q, J ϭ 13.6 Hz, 2 H, 2-H); syn-
29a: δ ϭ 1.36 (d, J ϭ 6.3 Hz, 3 H, 2Ј-H), 3.08, 3.41 (AB q, J ϭ
14.0 Hz, 2 H, 2-H); inseparable signals: δ ϭ 4.59 (overlapping q’s,
1 H, 1Ј-H), 7.20Ϫ7.24 (m, 2 H, 6,8-H), 7.41 (m, 1 H, 7-H), 8.09 (m,
1 H, 5-H); NMR spectroscopic data were taken from the spectra of
the diastereomeric mixture. 13C NMR: anti-29a: δ ϭ 17.2 (C-2Ј),
31.3 (C-1Ј), 69.1 (C-2), 125.5 (C-6), 127.3 (C-8), 130.7 (C-5), 134.2
(C-7), 141.6 (C-8a), 191.1 (C-4); syn-29a: δ ϭ 17.6 (C-2Ј), 32.1 (C-
1Ј), 69.0 (C-2), 125.7 (C-6), 127.1 (C-8), 131.0 (C-5), 134.1 (C-7),
141.0 (C-8a), 192.0 (C-4); inseparable signals: δ ϭ 66.8 (C-3), 129.6
(C-4a); NMR spectroscopic data were taken from the spectra of
the diastereomeric mixture. C11H11N3O2S (249.3): C 53.00, H 4.45,
N 16.86; found C 53.21, H 4.57, N 14.88.
3-Azido-6-chloro-3-(1-hydroxypropyl)-4-chromanone (21f): Com-
pound 21f (236 mg, 62%) was obtained from 11f [300 mg; reaction
period: 2 h; elution with toluene/ethyl acetate (9:1, v/v) mixture].
Yellow oil, 57:43 mixture of the syn/anti diastereomers (based on
1H NMR). IR (neat): ν˜ ϭ 3438 (OH), 2112 (N3), 1682 (CϭO),
1606, 1470, 1418, 1270, 1100, 824 cmϪ1. Pure diastereomers were
obtained by repeated column chromatography with toluene/ethyl
1
acetate (9:1, v/v) mixture as eluent. anti-21f: Yellow oil. H NMR:
δ ϭ 1.06 (t, J ϭ 7.2 Hz, 3 H, 3Ј-H), 1.46Ϫ1.68 (m, 2 H, 2Ј-H), 4.09
syn-3-Azido-3-[1-(p-nitrobenzoyloxy)propyl]-4-chromanone (23): p-
(dd, J ϭ 10.6, 2.6 Hz, 1 H, 1Ј-H), 4.36, 4.70 (AB q, J ϭ 12.1 Hz, Nitrobenzoyl chloride (295 mg, 1.59 mmol) was added to a stirred
2 H, 2-H), 6.98 (d, J ϭ 8.7 Hz, 1 H, 8-H), 7.48 (dd, J ϭ 8.7, 2.6 Hz, and cooled (0 °C) solution of syn-3-azido-3-(1-hydroxypropyl)-4-
1 H, 7-H), 7.89 (d, J ϭ 2.6 Hz, 1 H, 5-H). 13C NMR: δ ϭ 10.8 (C- chromanone (syn-21a; 328 mg, 1.33 mmol) in dry pyridine (9 mL)
3Ј), 23.7 (C-2Ј), 67.6 (C-3), 69.4 (C-2), 72.0 (C-1Ј), 119.8 (C-8), and the reaction mixture was allowed to warm to ambient temper-
120.4 (C-4a), 127.1 (C-5), 127.8 (C-6), 136.9 (C-7), 159.5 (C-8a), ature. After 18 h, the reaction mixture was poured into water and
188.1 (C-4). C12H12ClN3O3 (281.7): C 51.17, H 4.29, N 14.92; extracted with CH2Cl2 (3 ϫ 30 mL). The organic layer was dried
found C 51.09, H 4.42, N 14.83. syn-21f: Yellow oil. 1H NMR: δ ϭ
(MgSO4), concentrated under reduced pressure, and purified by
1.07 (t, J ϭ 7.4 Hz, 3 H, 3Ј-H), 1.51Ϫ1.72 (m, 2 H, 2Ј-H), 4.06 (dd, short column chromatography (eluent: hexane/ethyl acetate, 3:1, v/v)
J ϭ 9.4, 3.3 Hz, 1 H, 1Ј-H), 4.30, 4.35 (AB q, J ϭ 12.3 Hz, 2 H, to give 420 mg (80%) of ester 23 as colorless crystals. M.p. 78Ϫ80
˜
°C. IR: ν ϭ 2114 (N3), 1732 (CϭO, ester), 1696 (CϭO, ketone),
2-H), 6.95 (d, J ϭ 8.6 Hz, 1 H, 8-H), 7.46 (dd, J ϭ 8.6, 2.3 Hz, 1
H, 7-H), 7.88 (d, J ϭ 2.3 Hz, 1 H, 5-H). 13C NMR: δ ϭ 10.5 (C- 1608, 1524 (NO2), 1478, 1344 (NO2), 1260 (CϪOϪC), 1098, 718
1
3Ј), 24.2 (C-2Ј), 67.3 (C-3), 69.8 (C-2), 73.8 (C-1Ј), 119.6 (C-8), cmϪ1. H NMR: δ ϭ 1.02 (t, J ϭ 7.3 Hz, 3 H, 3Ј-H), 1.99 (m, 2
120.1 (C-4a), 127.1 (C-5), 127.9 (C-6), 136.7 (C-7), 159.4 (C-8a), H, 2Ј-H), 4.22, 4.40 (AB q, J ϭ 12.0 Hz, 2 H, 2-H), 5.78 (dd, J ϭ
189.1 (C-4). C12H12ClN3O3 (281.7): C 51.17, H 4.29, N 14.92;
found C 51.02, H 4.51, N 15.11.
7.7, 5.5 Hz, 1 H, 1Ј-H), 6.98 (d, J ϭ 8.1 Hz, 1 H, 8-H), 7.10 (m, 1
H, 6-H), 7.55 (m, 1 H, 7-H), 7.85 (dd, J ϭ 7.6, 1.5 Hz, 1 H, 5-H),
292
Eur. J. Org. Chem. 2002, 285Ϫ295

Base-Induced Coupling of α-Azido Ketones with Aldehydes
FULL PAPER
8.16 (d, J ϭ 8.8 Hz, 2 H, 2ЈЈ,6ЈЈ-H), 8.28 (d, J ϭ 8.8 Hz, 2 H, mers of 16a [170 mg; reaction period: 24 h; elution with hexane/
3ЈЈ,5ЈЈ-H). 13C NMR: δ ϭ 10.1 (C-3Ј), 22.8 (C-2Ј), 66.6 (C-3), 70.1 ethyl acetate (1:3, v/v) mixture]. Spectroscopic data have been re-
(C-2), 75.8 (C-1Ј), 117.8 (C-8), 119.2 (C-4a), 122.7 (C-6), 123.6 (C-
3ЈЈ,5ЈЈ), 128.0 (C-5), 131.0 (C-2ЈЈ,6ЈЈ), 134.4 (C-1ЈЈ), 136.9 (C-7),
150.7 (C-4ЈЈ), 160.7 (C-8a), 163.8 (CϭO, ester), 189.5 (C-4).
C19H16N4O6 (396.4): C 57.58, H 4.07, N 14.14; found C 57.41, H
4.11, N 14.19.
ported previously.[3]
trans-2-(4-Methoxybenzoyl)-3-methylaziridine (18b): Compound
18b (34 mg, 21%) was obtained from a 66:34 mixture of the syn/
anti diastereomers of 16b [200 mg; reaction period: 7 h; elution
with hexane/ethyl acetate (1:3, v/v) mixture]. Yellow oil. IR (neat):
ν˜ ϭ 3264 (NH), 1660 (CϭO), 1600, 1512, 1424, 1254, 1172, 942,
Crystal Data of 23: Colorless hexagonal block of twinned crystals
(0.65 ϫ 0.3 ϫ 0.12 mm) of C19H16N4O6, M ϭ 396.36, trigonal, a ϭ
848, 722 cmϪ1 1H NMR: δ ϭ 1.35 (d, J ϭ 5.4 Hz, 3 H, 3-Me),
.
˚
˚
˚
15.8076(10) A, b ϭ 15.8076(10) A, c ϭ 14.0709(10) A, α ϭ 90°,
2.12Ϫ2.21 (m, 2 H, NH, 3-H), 3.18 (d, J ϭ 2.1 Hz, 1 H, 2-H), 3.89
(s, 3 H, 4Ј-MeO), 6.98 (d, J ϭ 8.6 Hz, 2 H, 3Ј,5Ј-H), 8.01 (d, J ϭ
8.6 Hz, 2 H, 2Ј,6Ј-H). 13C NMR: δ ϭ 18.4 (3-Me), 37.6 (C-3), 40.1
(C-2), 55.4 (4Ј-MeO), 114.0 (C-3Ј,5Ј), 129.4 (C-1Ј), 130.6 (C-2Ј,6Ј),
164.2 (C-4Ј), 195.7 (CϭO). C11H13NO2 (191.2): C 69.09, H 6.85,
N 7.32; found C 69.23, H 7.01, N 7.31.
3
˚
V ϭ 3045.0(3) A , Z ϭ 6, space group: P3bar, ρcalcd. ϭ 1.297 g
cmϪ3. Data were collected at 293(1) K, EnrafϪNonius MACH3
˚
diffractometer, Mo-Kα radiation λ ϭ 0.71073 A, ω-2θ motion,
θmax ϭ 25.23°, 3677 measured, unique reflections of which 1141
with I Ͼ 2σ(I), decay: 7%. The structure was solved by SIR-92
software[27] and refined on F2 with the SHELX-97[28] program,
publication material was prepared with the WINGX-97 suite,[29]
R(F) ϭ 0.1453 and wR(F2) ϭ 0.4475 for 3677 reflections, 263 para-
trans-2-(4-Fluorobenzoyl)-3-methylaziridine (18c): Compound 18c
(5 mg, 3.1%) was obtained from a 59:41 mixture of the syn/anti
diastereomers of 16c [200 mg; reaction period: 23 h; elution with
3
˚
meters. Residual electron density: 1.266/Ϫ0.268 e/A . Crystal struc-
ture data for the structure have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC-144756. Copies of the data can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [Fax: (internat.) ϩ 44-1223/336-033; E-mail: deposit@ccdc.ca-
m.ac.uk].
˜
hexane/ethyl acetate (1:3, v/v) mixture]. Yellow oil. IR (neat): ν ϭ
3268 (NH), 1670 (CϭO), 1598, 1422, 1258, 1232, 852 cmϪ1 1H
.
NMR: δ ϭ 1.36 (d, J ϭ 5.4 Hz, 3 H, 3-Me), 2.16Ϫ2.37 (m, 2 H,
NH, 3-H), 3.22 (d, J ϭ 2.2 Hz, 1 H, 2-H), 7.16Ϫ7.24 (m, 2 H,
3Ј,5Ј-H), 8.08 (dd, Jortho ϭ 8.7 Hz, JHF ϭ 5.5 Hz, 2 H, 2Ј,6Ј-H).
C10H10FNO (179.2): C 67.03, H 5.62, N 7.82; found C 66.80, H
5.79, N 8.02.
3-Azido-3-(1-trimethylsilyloxyethyl)flavanone (28): A mixture of
trans-3-azido-flavanone (15, 198 mg, 0.74 mmol), acetaldehyde
(5.00 mL, 88.6 mmol), and TEA (0.10 mL, 0.74 mmol) was stirred
at room temperature for 24 h. The solvent was removed under re-
duced pressure and hexamethyldisilazane (0.05 mL, 0.25 mmol)
was then added to the stirred solution of the residue in hexane
(2 mL). A solution of chlorotrimethylsilane (0.03 mL, 0.25 mmol)
in hexane (5 mL) was added dropwise over 15 min at room temper-
ature. The reaction mixture was refluxed and stirred. Two batches
of HMDS (0.25 mmol) and TMSCl (0.25 mmol) were added to the
reaction mixture after 4 and 17 h. When the reaction was complete
(29 h), the mixture was filtered and the precipitate was washed with
hexane (2 ϫ 10 mL). The combined organic layers were concen-
trated in vacuo and the residue was purified by column chromato-
graphy (eluent: hexane/ethyl acetate, 3:1, v/v) to give pure 28
trans-2-(4-Chlorobenzoyl)-3-methylaziridine (18f): Compound 18f
(26 mg, 32%) was obtained from anti-16f [100 mg; reaction period:
18 h; elution with hexane/ethyl acetate (1:3, v/v) mixture]. Yellow
˜
oil. IR (neat): ν ϭ 3255, 3186 (NH), 1682 (CϭO), 1588, 1402, 1226,
1
1092, 1012, 850 cmϪ1. H NMR: δ ϭ 1.36 (d, J ϭ 5.8 Hz, 3 H, 3-
Me), 2.24 (dq, J ϭ 5.8, 2.7 Hz, 1 H, 3-H), 2.40 (br. s, 1 H, NH),
3.18 (d, J ϭ 2.7 Hz, 1 H, 2-H), 7.48 (d, J ϭ 8.4 Hz, 2 H, 3Ј,5Ј-H),
7.95 (d, J ϭ 8.4 Hz, 2 H, 2Ј,6Ј-H). C10H10ClNO (195.6): C 61.39,
H 5.15, N 7.16; found C 61.12, H 4.98, N 7.32. When the reaction
was repeated with syn-16f (100 mg; reaction period: 26 h), 6 mg
(7.3%) of trans-aziridine 18f was obtained.
trans-2-Benzoyl-3-ethylaziridine (19a): Compound 19a (15 mg,
9.4%) was obtained from a 65:35 mixture of the syn/anti diastereo-
mers of 17a [200 mg; reaction period: 29 h; elution with hexane/
(51 mg, 13%) as a yellow oil, 74:26 mixture of the diastereomers
˜
ethyl acetate (1:3, v/v) mixture]. Yellow oil. IR (neat): ν ϭ 3270
1
˜
28/28Ј (based on H NMR). IR (neat): ν ϭ 2112 (N3), 1694 (Cϭ
1
(NH), 1668 (CϭO), 1450, 1258, 700 cmϪ1. H NMR: δ ϭ 1.07 (t,
O), 1606, 1252, 1464, 842 cmϪ1. H NMR: 28: δ ϭ 0.19 (s, 9 H,
1
J ϭ 7.4 Hz, 3 H, CH2CH3), 1.50Ϫ1.72 (m, 2 H, CH2CH3),
2.09Ϫ2.29 (m, 2 H, NH, 3-H), 3.28 (d, J ϭ 2.2 Hz, 1 H, 2-H),
7.40Ϫ7.70 (m, 3 H, 3Ј,4Ј,5Ј-H), 7.98Ϫ8.10 (dd, J ϭ 8.0, 1.6 Hz, 2
H, 2Ј,6Ј-H). 13C NMR: δ ϭ 11.0 (CH2CH3), 26.3 (CH2CH3), 39.5
(C-3), 44.5 (C-2), 128.3, 128.8, 128.9 (C-2Ј,3Ј,5Ј,6Ј), 133.8 (C-4Ј),
196.8 (CϭO). C11H13NO (175.2): C 75.40, H 7.48, N 7.99; found
C 75.41, H 7.29, N 8.05.
Me3Si), 1.04 (d, J ϭ 6.5 Hz, 1 H, 2Ј-H), 4.61 (q, J ϭ 6.5 Hz, 1 H,
1Ј-H), 5.81 (s, 1 H, 2-H), 7.00 (d, J ϭ 8.3 Hz, 1 H, 8-H), 7.09 (m,
1 H, 6-H), 7.93 (dd, J ϭ 8.2, 1.6 Hz, 1 H, 5-H). 28Ј: δ ϭ Ϫ0.06 (s,
9 H, Me3Si), 1.52 (d, J ϭ 6.0 Hz, 1 H, 2Ј-H), 4.53 (q, J ϭ 6.0 Hz,
1 H, 1Ј-H), 5.35 (s, 1 H, 2-H), 6.98 (d, J ϭ 8.3 Hz, 1 H, 8-H), 7.08
(m, 1 H, 6-H), 7.91 (dd, J ϭ 8.0, 1.7 Hz, 1 H, 5-H); inseparable
signals: δ ϭ 7.26Ϫ7.44 (m, 5 H, 2-Ph), 7.55 (m, 1 H, 7-H); NMR
spectroscopic data were taken from the spectra of the diastereom-
eric mixture. C20H23N3O3Si (381.5): C 62.97, H 6.08, N 11.01;
found C 62.83, H 5.96, N 10.93.
3Ј-Methylspiro[chroman-3,2Ј-aziridin]-4-one (24a): Compound 24a
(65 mg, 37%) was obtained from a 56:44 mixture of the syn/anti
diastereomers of 20a [220 mg; reaction period: 4d; elution with hex-
ane/ethyl acetate (1:3, v/v) mixture] as a 51:49 mixture of the cis/
trans diastereomers (based on 1H NMR). Analytical samples of
pure cis and trans diastereomers were obtained by repeated column
chromatography with a hexane/ethyl acetate (1:3, v/v) mixture as
General Procedure for the Synthesis of Aziridines 18, 19, 24؊26,
30a: A mixture of the appropriate α-azido-β-hydroxy ketone 16,
17, 20؊22, or 29a (0.90 mmol) and triphenylphosphane (236 mg,
0.90 mmol) in dry benzene (10 mL) was stirred at room temper-
ature until completion of the reaction (TLC). The reaction mixture
was concentrated in vacuo and the residue was purified by col-
umn chromatography.
˜
eluent. trans-24a: Yellowish oil. IR (neat): ν ϭ 3269 (NH), 1684
(CϭO), 1608, 1477, 1317, 1212, 1100, 792 cmϪ1 1H NMR: δ ϭ
.
1.36 (d, J ϭ 5.3 Hz, 3 H, CH3), 2.08 (s, 1 H, NH), 2.45 (q, J ϭ
5.3 Hz, 1 H, 3Ј-H), 4.27, 4.68 (AB q, J ϭ 11.9 Hz, 2 H, 2-H),
6.99Ϫ7.09 (m, 2 H, 6,8-H), 7.52 (m, 1 H, 7-H), 7.89 (dd, J ϭ 7.5,
1.6 Hz, 1 H, 5-H). 13C NMR: δ ϭ 14.2 (CH3), 41.8 (C-3Ј), 42.9 (C-
trans-2-Benzoyl-3-methylaziridine (18a): Compound 18a (27 mg,
20%) was obtained from a 56:44 mixture of the syn/anti diastereo-
Eur. J. Org. Chem. 2002, 285Ϫ295
293

´
´
´
´
T. Patonay, E. Juhasz-Toth, A. Benyei
FULL PAPER
3/2Ј), 67.9 (C-2), 118.3 (C-8), 120.9 (C-4a), 121.7 (C-6), 127.0 (C-
3Ј-Ethylspiro[6-chlorochroman-3,2Ј-aziridin]-4-one (25f): Com-
5), 136.5 (C-7), 162.1 (C-8a), 192.2 (C-4). C11H11NO2 (189.2): C pound 25f (63 mg, 44%) was obtained from a 57:43 mixture of the
69.83, H 5.86, N 7.40; found C 69.66, H 5.99, N 7.23. cis-24a: syn/anti diastereomers of 21f [170 mg; reaction period: 4 d; elution
1
Yellowish oil. H NMR: δ ϭ 1.26 (d, J ϭ 5.5 Hz, 3 H, CH3), 2.04 with hexane/ethyl acetate (2:1, v/v) mixture] as a 66:34 mixture of
(s, 1 H, NH), 2.54 (q, J ϭ 5.5 Hz, 1 H, 3Ј-H), 3.99, 4.74 (AB q, the cis and trans diastereomers (based on 1H NMR). Analytical
J ϭ 11.7 Hz, 2 H, 2-H), 6.99Ϫ7.09 (m, 2 H, 6,8-H), 7.52 (m, 1 H,
samples of pure cis and trans diastereomers were obtained by re-
7-H), 7.92 (dd, J ϭ 7.4, 1.9 Hz, 1 H, 5-H). 13C NMR: δ ϭ 13.0 peated column chromatography with hexane/ethyl acetate (2:1, v/
˜
(CH3), 43.7 (C-3/2Ј), 44.6 (C-3Ј), 73.0 (C-2), 118.2 (C-8), 121.6 (C- v) mixture as eluent. trans-25f: Yellow oil. IR (neat): ν ϭ 3271
6), 126.9 (C-5), 136.4 (C-7), 162.0 (C-8a), 190 3 (C-4). C11H11NO2 (NH), 1684 (CϭO), 1605, 1474, 1260, 860 cmϪ1 1H NMR: δ ϭ
.
(189.2): C 69.83, H 5.86, N 7.40; found C 70.11, H 5.69, N 7.47.
1.06 (t, J ϭ 7.4 Hz, 3 H, CH2CH3), 1.44Ϫ1.73 (m, 2 H,
CH2CH3), ഠ1.8 (br. s, 1 H, NH), 2.35 (br. s, 1 H, 3Ј-H), 4.24, 4.65
(AB q, J ϭ 12.4 Hz, 2 H, 2-H), 6.99 (d, J ϭ 8.3 Hz, 1 H, 8-H),
7.46 (dd, J ϭ 8.3, 2.7 Hz, 1 H, 7-H), 7.86 (d, J ϭ 2.7 Hz, 1 H, 5-
H). 13C NMR: δ ϭ 11.4 (CH2CH3), 22.4 (CH2CH3), 42.8 (C-3/2Ј),
48.9 (C-3Ј), 68.1 (C-2), 120.0 (C-8), 121.7 (C-4a), 126.3 (C-5), 127.3
(C-6), 136.2 (C-7), 160.5 (C-8a), 191.4 (C-4). C12H12ClNO2 (237.7):
C 60.64, H 5.09, N 5.89; found C 60.43, H 4.97, N 5.64. cis-25f:
cis-3Ј-Ethylspiro[chroman-3,2Ј-aziridin]-4-one (cis-25a): Compound
cis-25a (68 mg, 62%) was obtained from syn-21a [133 mg; reaction
period: 7 d; elution with hexane/ethyl acetate (1:1, v/v) mixture].
˜
Yellow oil. IR (neat): ν ϭ 3254 (NH), 1682 (CϭO), 1606, 1470,
1288, 1210, 760 cmϪ1 1H NMR: δ ϭ 0.38 (t, J ϭ 7.4 Hz, 3 H,
.
CH2CH3), 1.28Ϫ1.71 (m, 2 H, CH2CH3), 1.80 (br. s, 1 H, NH),
2.34 (m, 1 H, 3Ј-H), 3.92, 4.71 (AB q, J ϭ 11.6 Hz, 2 H, 2-H),
6.96Ϫ7.05 (m, 2 H, 6,8-H), 7.48 (m, 1 H, 7-H), 7.90 (dd, J ϭ 7.7,
1.9 Hz, 1 H, 5-H). 13C NMR: δ ϭ 11.8 (CH2CH3), 20.8 (CH2CH3),
43.5 (C-3/2Ј), 51.0 (C-3Ј), 73.0 (C-2), 118.2 (C-8), 121.6 (C-6), 126.9
(C-5), 136.5 (C-7), 162.1 (C-8a), 190.7 (C-4). C12H13NO2 (203.2):
C 70.92, H 6.45, N 6.89; found C 70.73, H 6.69, N 6.63.
˜
Pale yellow oil. IR (neat): ν ϭ 3257 (NH), 1684 (CϭO), 1604, 1474,
1261, 859 cmϪ1. 1H NMR: δ ϭ 0.87 (t, J ϭ 7.7 Hz, 3 H, CH2CH3),
1.35 (m, 1 H, one of CH2CH3), 1.63 (m, 1 H, other CH2CH3), 1.76
(br. s, 1 H, NH), 2.39 (br. t, J ϭ 6.1 Hz, 1 H, 3Ј-H) 3.95, 4.72 (AB
q, J ϭ 11.5 Hz, 2 H, 2-H), 6.98 (d, J ϭ 8.9 Hz, 1 H, 8-H), 7.45
(dd, J ϭ 8.9, 2.6 Hz, 1 H, 7-H), 7.87 (d, J ϭ 2.6 Hz, 1 H, 5-H).
13C NMR: δ ϭ 12.1 (CH2CH3), 21.1 (CH2CH3), 43.5 (C-3/2Ј), 51.5
(C-3Ј), 73.2 (C-2), 119.9 (C-8), 122.2 (C-4a), 126.1 (C-5), 127.2 (C-
6), 136.2 (C-7), 160.4 (C-8a), 189.4 (C-4). C12H12ClNO2 (237.7): C
60.64, H 5.09, N 5.89; found C 60.63, H 5.05, N 5.98.
trans-3Ј-Ethylspiro[chroman-3,2Ј-aziridin]-4-one (trans-25a): Com-
pound trans-25a (17 mg, 26%) was obtained from anti-21a [80 mg,
reaction period: 7 d; elution with hexane/ethyl acetate (1:1, v/v)
˜
mixture]. Yellow oil. IR: (neat): ν ϭ 3269 (NH), 1676 (CϭO), 1608,
1
1457, 1325, 1212, 757 cmϪ1. H NMR: δ ϭ 1.06 (t, J ϭ 7.5 Hz, 3
cis-3Ј-Butylspiro[chroman-3,2Ј-aziridin]-4-one (cis-26a): Compound
cis-26a (46 mg, 39%) was obtained from syn-22a [140 mg; reaction
period: 14 d; elution with hexane/ethyl acetate (2:1, v/v) mixture].
Yellow oil. IR (neat): ν˜ ϭ 3255 (NH), 1684 (CϭO), 1607, 1477,
H, CH2CH3), 1.47Ϫ1.77 (m, 2 H, CH2CH3), 2.34 (br. s, 2 H, 3Ј-
H, NH), 4.23, 4.66 (AB q, J ϭ 12.1 Hz, 2 H, 2-H), 7.00Ϫ7.10 (m,
2 H, 6,8-H), 7.53 (m, 1 H, 7-H), 7.90 (dd, J ϭ 8.1, 1.9 Hz, 1 H, 5-
H). 13C NMR: δ ϭ 11.3 (CH2CH3), 22.2 (CH2CH3), 42.8 (C-3/2Ј),
48.5 (C-3Ј), 68.0 (C-2), 118.4 (C-8), 121.0 (C-4a), 121.8 (C-6), 127.2
(C-5), 136.6 (C-7), 162.4 (C-8a), 192.6 (C-4). C12H13NO2 (203.2):
C 70.92, H 6.45, N 6.89; found C 71.07, H 6.31, N 6.77.
1
1283, 1211, 1027, 760 cmϪ1. H NMR: δ ϭ 0.78 (t, J ϭ 6.9 Hz, 3
H, CH3), 1.19Ϫ1.57 (m, 6 H, (CH2)3CH3), 1.99 (br. s, 1 H, NH),
2.38 (t, J ϭ 6.3 Hz, 1 H, 3Ј-H), 3.95, 4.74 (AB q, J ϭ 11.7 Hz, 2
H, 2-H), 7.00Ϫ7.09 (m, 2 H, 6,8-H), 7.52 (m, 1 H, 7-H), 7.92 (dd,
J ϭ 8.0, 1.4 Hz, 1 H, 5-H). 13C NMR: δ ϭ 13.7 (CH3), 22.0, 27.1,
29.8 (CH2CH2CH2CH3), 43.5 (C-3/2Ј), 49.8 (C-3Ј), 73.1 (C-2),
118.1 (C-8), 121.5 (C-6), 126.7 (C-5), 136.3 (C-7), 161.9 (C-8a),
190.4 (C-4). C14H17NO2 (231.3): C 72.70, H 7.41, N 6.06; found C
72.58, H 7.65, N 5.92.
3Ј-Ethylspiro[6-methylchroman-3,2Ј-aziridin]-4-one (25e): Com-
pound 25e (303 mg, 63%, normalized to 100% conversion) was ob-
tained from a 57:43 mixture of the syn/anti diastereomers of 21e
[700 mg; reaction period: 6 d; elution with hexane/ethyl acetate
(2:1, v/v) mixture; conversion: 83%] as a 58:42 mixture of the cis/
trans diastereomers (based on 1H NMR). Analytical samples of the
pure cis and trans diastereomers were obtained by repeated column
chromatography with hexane/ethyl acetate (2:1, v/v) mixture as elu-
ent. trans-25e: Yellowish-brown oil. IR (neat): ν˜ ϭ 3268 (NH), 1683
3Ј-Butylspiro[chroman-3,2Ј-aziridin]-4-one (26a): Compound 26a
(122 mg, 52%) was obtained from a 67:33 mixture of the syn/anti
diastereomers of 22a [280 mg; reaction period: 9 d; elution with
hexane/ethyl acetate (2:1, v/v) mixture], as a 70:30 mixture of the
cis/trans diastereomers (based on 1H NMR). Analytical samples of
the pure cis and trans diastereomers were obtained by repeated col-
umn chromatography with hexane/ethyl acetate (2:1, v/v) mixture
(CϭO), 1618, 1492, 1299, 876 cmϪ1 1H NMR: δ ϭ 1.06 (t, J ϭ
.
7.3 Hz, 3 H, CH2CH3), 1.72Ϫ1.94 (m, 2 H, CH2CH3), 2.32 (over-
lapping s and t, 5 H, 6-Me, 3Ј-H, NH), 4.20, 4.62 (AB q, J ϭ
12.2 Hz, 2 H, 2-H), 6.91 (d, J ϭ 8.3 Hz, 1 H, 8-H), 7.33 (dd, J ϭ
8.3, 2.9 Hz, 1 H, 7-H), 7.68 (d, J ϭ 2.9 Hz, 1 H, 5-H). 13C NMR:
δ ϭ 11.4 (CH2CH3), 20.2 (6-Me), 22.3 (CH2CH3), 42.8 (C-3/2Ј),
48.4 (C-3Ј), 67.9 (C-2), 117.9 (C-8), 120.4 (C-4a), 126.5 (C-5), 131.1
(C-6), 137.4 (C-7), 160.1 (C-8a), 192.3 (C-4). C13H15NO2 (217.3):
C 71.87, H 6.96, N 6.45; found C 71.99, H 7.12, N 6.24. cis-25e:
˜
as eluent. trans-26a: Yellow oil. IR (neat): ν ϭ 3268 (NH), 1683
(CϭO), 1607, 1477, 1324, 1034, 759 cmϪ1 1H NMR: δ ϭ 0.89
.
(t, J ϭ 7.1 Hz, 3 H, CH3), 1.34Ϫ1.59 (m, 6 H, (CH2)3CH3), 2.34
(overlapping t and s, J ϭ 6.2 Hz, 2 H, 3Ј-H, NH), 4.23, 4.65 (AB
q, J ϭ 12.0 Hz, 2 H, 2-H), 6.98Ϫ7.08 (m, 2 H, 6,8-H), 7.49 (m, 1
H, 7-H), 7.89 (dd, J ϭ 8.4, 1.3 Hz, 1 H, 5-H). 13C NMR: δ ϭ 13.8
(CH3), 22.4, 28.6, 29.4 (CH2CH2CH2CH3), 42.8 (C-3/2Ј), 47.1 (C-
3Ј), 68.0 (C-2), 118.2 (C-8), 120.8 (C-4a), 121.6 (C-6), 127.0 (C-5),
136.4 (C-7), 162.0 (C-8a), 192.2 (C-4). C14H17NO2 (231.3): C 72.70,
H 7.41, N 6.06; found C 72.79, H 7.69, N 6.24.
˜
Brownish oil. IR (neat): ν ϭ 3254 (NH), 1680 (CϭO), 1618, 1492,
1286, 873 cmϪ1. 1H NMR: δ ϭ 0.87 (t, J ϭ 7.5 Hz, 3 H, CH2CH3),
1.35Ϫ1.67 (m, 2 H, CH2CH3), 2.07 (br. s, 1 H, NH), 2.32 (s, 3 H,
6-Me), 2.38 (t, J ϭ 6.8 Hz, 1 H, 3Ј-H) 3.92, 4.71 (AB q, J ϭ
11.7 Hz, 2 H, 2-H), 6.91 (d, J ϭ 8.3 Hz, 1 H, 8-H), 7.33 (dd, J ϭ
8.3, 2.2 Hz, 1 H, 7-H), 7.70 (s, 1 H, 5-H). 13C NMR: δ ϭ 12.0 3Ј-Methylspiro[1-thiochroman-3,2Ј-aziridin]-4-one (30a): Com-
(CH2CH3), 20.3 (6-Me), 20.9 (CH2CH3), 43.6 (C-3/2Ј), 51.0 (C-3Ј), pound 30a (26 mg, 44%, normalized to 100% conversion) was ob-
73.0 (C-2), 117.8 (C-8), 121.0 (C-4a), 126.2 (C-5), 130.9 (C-6), 137.3 tained from a 78:22 mixture of the syn/anti diastereomers of 29a
(C-7), 160.0 (C-8a), 190.4 (C-4). C13H15NO2 (217.3): C 71.87, H [110 mg; reaction period: 10 d; elution with hexane/ethyl acetate
6.96, N 6.45; found C 71.66, H 7.00, N 6.58.
294
(1:1, v/v) mixture; conversion: 65%] as a 65:35 mixture of the cis/
Eur. J. Org. Chem. 2002, 285Ϫ295

Base-Induced Coupling of α-Azido Ketones with Aldehydes
FULL PAPER
V. Z. Zhdankin, C. J. Kuehl, A. P. Krasutsky, M. S. Formaneck,
[9]
trans diastereomers (based on 1H NMR). Analytical samples of the
pure cis and trans diastereomers were obtained by repeated column
chromatography with hexane/ethyl acetate (1:1, v/v) mixture as elu-
ent. trans-30a: Yellow oil. IR (neat): ν˜ ϭ 3262 (NH), 1666 (CϭO),
J. T. Boltz, Tetrahedron Lett. 1994, 35, 9677Ϫ9680.
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1588, 1438, 1306, 1212, 744 cmϪ1 1H NMR: δ ϭ 1.42 (d, J ϭ
.
´
Thang, M. A. Laborde, A. Olesker, G. Lukacs, J. Chem. Soc.,
5.9 Hz, 3 H, CH3), 2.31 (q, J ϭ 5.4 Hz, 1 H, 3Ј-H), 2.79, 3.87 (AB
q, J ϭ 14.1 Hz, 2 H, 2-H), 7.20Ϫ7.41 (m, 3 H, 6,7,8-H), 8.08 (dd,
J ϭ 9.5, 1.4 Hz, 1 H, 5-H). C11H11NOS (205.3): C 64.36, H 5.40,
N 6.82; found C 64.04, H 5.29, N 6.52. cis-30a: Yellow oil. IR
(neat): ν˜ ϭ 3250 (NH), 1666 (CϭO), 1590, 1438, 1350, 1212, 1082,
914, 744 cmϪ1. 1H NMR: δ ϭ 1.19 (d, J ϭ 5.5 Hz, 3 H, CH3), 2.55
(q, J ϭ 5.8 Hz, 1 H, 3Ј-H), 2.49, 3.94 (AB q, J ϭ 14.1 Hz, 2 H, 2-
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5-H). C11H11NOS (205.3): C 64.36, H 5.40, N 6.82; found C 64.29,
H 5.45, N 6.63.
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Received April 27, 2000
[O01209]
Eur. J. Org. Chem. 2002, 285Ϫ295
295