A thio-staudinger reaction: Thermolysis of a vinyl azide in the presence of t-butyl mercaptan

Article abstract of DOI:10.1080/713744560

The thermal decomposition of E-3-azido-3-hexene-2,5-dione (1) in protic media gave rise to several novel reactions of the azide 1 including adducts derived from keteneimine 11. Reaction with t-butyl mercaptan yielded two products, keteneimine-derived mercaptan addition product 20 and a sulfenimine 6. Trapping of a vinyl nitrene intermediate or a thio-Staudinger reaction was considered as a possible mechanism for the formation of sulfenimine 6. The absence of the vinyl nitrene addition products 3 and 5 when the thermal decomposition was conducted in either methanol or t-butylamine suggests a thio-Staudinger reaction is operative.

Full text of DOI:10.1080/713744560

This article was downloaded by: [TOBB Ekonomi Ve Teknoloji]
On: 20 December 2014, At: 00:57
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the Related
Elements
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/gpss20
A Thio-Staudinger Reaction: Thermolysis of a Vinyl
Azide in the Presence of t -Butyl Mercaptan
Ronald R. Sauers a & Susan D. Van Arnum a
a Rutgers, The State University of New Jersey , New Brunswick, New Jersey, USA
Published online: 27 Oct 2010.
To cite this article: Ronald R. Sauers & Susan D. Van Arnum (2003) A Thio-Staudinger Reaction: Thermolysis of a Vinyl Azide
in the Presence of t -Butyl Mercaptan, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:10, 2169-2181, DOI:
10.1080/713744560
To link to this article: http://dx.doi.org/10.1080/713744560
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 178:2169–2181, 2003
ꢀC
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500390228792
A THIO-STAUDINGER REACTION: THERMOLYSIS
OF A VINYL AZIDE IN THE PRESENCE
OF t-BUTYL MERCAPTAN
Ronald R. Sauers and Susan D. Van Arnum
Rutgers, The State University of New Jersey,
New Brunswick, New Jersey, USA
(Received February 24, 2003; accepted April 23, 2003)
The thermal decomposition of E-3-azido-3-hexene-2,5-dione (1) in pro-
tic media gave rise to several novel reactions of the azide 1 including
adducts derived from keteneimine 11. Reaction with t-butyl mercaptan
yielded two products, keteneimine-derived mercaptan addition product
20 and a sulfenimine 6. Trapping of a vinyl nitrene intermediate or a
thio-Staudinger reaction was considered as a possible mechanism for
the formation of sulfenimine 6. The absence of the vinyl nitrene addi-
tion products 3 and 5 when the thermal decomposition was conducted
in either methanol or t-butylamine suggests a thio-Staudinger reaction
is operative.
Keywords: Staudinger reaction; sulfenimines; vinyl azides
Sulfenimines1 have been prepared from a variety of starting materials
such as aromatic disulfides,2 sulfenamides,3 thioketenes,4 thioamides,5
and other substrates.6 They also are an important functional con-
stituent of substituted cephalosporins and penicillins.7 Furthermore,
trityl sulfenimine recently has been used as a reagent in a highly di-
astereoselective coupling reaction to prepare an intermediate in the
synthesis of an influenza neuraminidase inhibitor.8 Despite the avail-
ability of different approaches to sulfenimines, the formation of these
compounds by reaction of a mercaptan with an azide has not yet been
We are grateful to the Garden State Fellowship Commission and the J. L. R. Morgan
Fellowship Fund for financial support. We would like to thank Dr. Robert Rosen for the
mass spectral data, Richard Beveridge for the 13C NMR spectrum, and Dr. Dorothy Z.
Denney for the 31P NMR spectrum.
Address correspondence to Ronald R. Sauers, Wright and Rieman Laboratories,
Department of Chemistry and Chemical Biology, Rutgers, The State University of New
Jersey, New Brunswick, NJ 08903. E-mail: sauers@rutchem.rutgers.edu
2169

2170
R. R. Sauers and S. D. Van Arnum
reported. We report on an unexpected reaction when the thermolysis of
E-3-azido-3-hexene-2,5-dione (1) was conducted in t-butyl mercaptan
and to provide evidence that a thio-Staudinger reaction is operative.9
RESULTS
Earlier studies on vinyl azides led us to examine the properties
of E-3-azido-3-hexene-2,5-dione (1) for comparison with the corre-
sponding Z-isomer.10 Of particular interest was the possibility that
thermolysis of the former would produce a vinyl nitrene 2 that could be
trapped with nucleophiles (Eq. 1). A recent review has highlighted the
synthetic
(1)
utility of this concept in the synthesis of heterocycles by intramolec-
ular trapping of nitrenes by heteroatoms.11 For example, ther-
molysis of either the azido benzene, thiophene or furan with a
vinylthiol substituent yielded the corresponding ylide in good yields
(Eq. 2).12
(2)
However, in the case of vinyl azides, calculations have suggested
that the formation of azirines from vinyl azides involves either rate
determining formation of vinyl nitrenes with no activation energy for
the conversion of the nitrene to the azirine or that azirines are formed
from vinyl azides via a concerted losss of nitrogen.13 Kinetic studies
by Hassner have reinforced the latter hypothesis for those vinyl azides
which yield azirines and, in particular, a concerted mechanism is fa-
vored when the α-position is functionalized by substituents that are ca-
pable of stabilizing a positive charge such as aryl, alkyl, heteroatoms, or
alkoylcarboxyl.14 In addition, Hassner’s work also suggests that these
conclusions may not be general, and the mechanism for the decom-
position of an azide will depend on the nature of the substituents.
L’Abbe´ and Matthys also have determined kinetic parameters for

A Thio-Staudinger Reaction
2171
the thermolysis of vinyl azides that support either a mechanism
involving a concerted loss of nitrogen or a pathway that involves an
intermediate 4H-triazole.15 We report herein the synthesis of vinyl
azide 1 and its thermolysis under a variety of conditions in the pres-
ence of water, methyl alcohol, t-butyl alcohol, t-butylamine, and t-butyl
mercaptan.
The E-vinyl azide 1 was prepared stereospecifically from 3-azido-
2,5-dimethyl furan (8) using a modified Clauson-Kaas method.16,17 The
required furyl azide 8 was synthesized in a 53% yield by a Michael
addition of sodium azide to 5-hydroxy-hex-3-yne-2-one (7) (Eq. 3).18,19
The unstable furyl azide 8 was characterized by preparation of the
(3)
corresponding iminophosphorane by reaction with triphenylphosphine.
After purification by chromatography, the azide 1 was immediately dis-
solved in either an appropriate solvent or in the presence of a reactive
additive in an inert solvent and allowed to thermalize in the dark at
room temperature.
Studies on the thermolysis of the E-3-azido-3-hexene-2,5-dione (1)
in acetonitrile, which contained water or in the presence of alco-
hols or t-butylamine gave rise to three different products: azirine
9,10 Z-acetoxybut-2-enenitrile (10),20 and compounds derived from
keteneimine 11 (Scheme 1).10 The ratios of these products were solvent
dependent. The formation of compound 10 probably involves cycliza-
tion of the azide 1 to form a dihydroxydihydrofuran derivative that
undergoes loss of water and nitrogen. In Hassner’s review of experi-
mental work on vinyl azides which give rise to products derived from a
keteneimine intermediate, a concerted mechanism was favored.14,21,22
By analogy, the keteneimine 11 is believed to arise by a concerted loss
of nitrogen from the vinyl azide 1 via a 1,2-shift of the acetyl group.
Isolation of its derived addition products 12,23 13, 14,∗ and 15 served
to characterize this molecule.
The t-butylamine adduct 15 was isolated from both the decompo-
sition of the E-vinyl azide 1 in t-butylamine and from the photolysis
∗The adduct 14 had 1H NMR data (CDCl3) δ 1.57 (s, 9H), 2.13 (s, 3H), 2.17 (s, 3H),
5.00 (s, 1H), 13.3 (b, 1H).

2172
R. R. Sauers and S. D. Van Arnum
SCHEME 1
of 3-acetyl-5-methylisoxazole 16 in t-butylamine (Eq. 4). The
decomposition of the E-vinyl azide 1 in t-butylamine also
(4)
gave rise to isoxazole ketone 16.24 Under these conditions and the rel-
ative ease by which ene-diones can isomerize,25 the isoxazole ketone
16 probably arises from isomerization of the E-vinyl azide 1 to Z-3-
azido-3-hexene-2,5-dione 17 followed by expulsion of nitrogen (Eq. 5).
Indeed, the significant difference in the semi-quantitative rates for the
(5)
decomposition of the vinyl azides 1 and 17 further suggests that a con-
certed mechanism is operative.∗ In the case of the Z-vinyl azide 17, a
pathway in which the oxygen atom on the γ -carbonyl group functions
∗At room temperature, the thermolysis of the E-vinyl azide 1 required approximately
15 h whereas the decomposition of the Z-vinyl azide 17 was complete in approximately
4 h.

A Thio-Staudinger Reaction
2173
as an internal nucleophile, via SN2 attack on the C-terminus nitrogen
of the azide group, is a likely mechanism.26
An authentic sample of Z-3-acetoxybut-2-enenitrile (10) was pre-
pared by the acetylation of the anion of 3-oxo-butanenitrile (18) to afford
a mixture of E- and Z-isomers 19 and 10. The anion of cyanoacetone
(18) was prepared in situ by the base-catalyzed cleavage of the isoxazole
ketone 16 (Eq. 6).
(6)
In contrast, decomposition of the E-vinyl azide 1 in t-butyl mercaptan
at room temperature yielded two products, the expected keteneimine
addition product 20 and a new product, which is assigned as sulfenimine
6. No azirine 9 or acrylonitrile 10 were detected. Compounds 20 and
6 were isolated respectively in yields of 17% and 19% based on the
furyl azide 8 (Eq. 7). The spectral properties of the mercaptan adduct
(7)
20 were in agreement with the product obtained from the photolysis of
the isoxazole ketone 16 in the presence of t-butyl mercaptan (Eq. 8).
(8)
The structural assignment of the sulfenimine 6, isolated as a single
stereoisomer, was based on the correct exact mass for C10H17NO2S. The
IR spectrum had two intense carbonyl absorbances at 1720 and 1690
cm−1 and another absorbance at 1360 cm−1, which was assigned to the
1
imine stretch.27,∗ The H NMR spectrum had resonances at 1.43 ppm
(s, 9H, t-Bu), 2.20 ppm (s, 3H, CH3), 2.43 ppm (s, 3H, CH3), and
∗The IR imine stretch of nonconjugated thiooximes occurs between 1618 and 1622
cm−1
.

2174
R. R. Sauers and S. D. Van Arnum
3.70 ppm (s, 2H, CH2).28 The mercaptan adduct 20 also had a correct
exact mass for C10H17NO2S. The IR spectrum displayed a broad ab-
sorbance at 2900–2850 cm−1, two strong carbonyl absorbances at 1700
and 1620 cm−1, and two other intense absorbances at 1550 and 1220
cm−1. The 1H NMR spectrum for the adduct 20 had resonances at 1.67
ppm (s, 9H, t-Bu), 2.20 ppm (s, 6H, 2 × CH3), 5.60 ppm (s, 1H, CH), and
13.3 ppm (b, 1H, NH).
DISCUSSION
In the case of the thermolysis of vinyl azide 1, the formation of the
sulfenimine 6 is most likely explained by attack of t-butyl mercaptan
on the N-terminus of the azide in a similar manner as in the Staudinger
reaction.9,14 Migration of the mercapto group to the C-terminus nitro-
gen, followed by expulsion of nitrogen, affords an ene-sulfenamine that
gives rise to sulfenimine 6 on tautomerization (Eq. 9).29
(9)
As an alternative mechanism, we considered the possibility that
sulfenimine 6 might be formed by trapping of a vinyl nitrene intermedi-
ate. However, when the thermolysis of the vinyl azide 1 was conducted
in either methanol or t-butylamine, there was no evidence for the analo-
gous insertion products, 3 and 5. For comparison purposes in this study,
an authentic sample of the 3-O-methyl oxime of 2,3,5-hexanetrione (3)
was prepared by the addition of methoxyamine to 3-hex-yne-2,5-dione
(21) (Eq. 10).30
(10)
These findings are consistent with the proposal by Hassner et al.
that vinyl nitrenes are not intermediates in the thermolysis of vinyl
azides.14 In contrast, the photolytic production of 20 from the isoxa-
zole ketone 16 is believed to involve the singlet state of the incipient
Z-nitrene, which may be stabilized by the lone pairs on sulfur. As a

A Thio-Staudinger Reaction
2175
consequence, the importance of the triplet state, the source of rear-
rangement products for compounds such as azirine 9 is reduced with
concomitant formation of 20.10,31
CONCLUSION
In summary, the decomposition of the E-vinyl azide 1 in t-butyl mer-
captan affords the t-butyl mercaptan addition product 20 and an unex-
pected product, sulfenimine 6. The absence of the vinyl nitrene-like ad-
dition products 3 and 5 when the thermal decomposition was conducted
in either methanol or t-butylamine suggests that a thio-Staudinger
reaction is operative as opposed to trapping of a vinyl nitrene inter-
mediate. Aside from the potential utility of this chemistry to prepare
sulfenimines, this thio-Staudinger reaction may have applicability as a
method to probe active sites in enzymes. In a similar way that aromatic
azides are used in photoaffinity labeling studies, the selectivity in this
reaction for mercaptans may allow for specific identification of cysteine
residues in enzymes.32
EXPERIMENTAL
Melting points were taken on a Mel-Temp apparatus and are uncor-
1
rected. H NMR spectra were recorded on a Varian Model T-60 spec-
trophotometer in deuterochloroform using tetramethylsilane as an in-
ternal standard. 13C NMR spectra were recorded on a Varian XL-400
spectrophotometer in deuterochloroform using tetramethylsilane as an
internal standard. IR spectra were obtained on a Perkin-Elmer Model
727 IR spectrophotometer. Low resolution mass spectra were obtained
on a VG Analytical model and high resolution spectra were obtained on
a 7070 EQ high resolution mass spectrophotometer. UV spectra were
taken on either a Perkin-Elmer UV-VIS or a Cary 17D spectrophotome-
ter. The 31P NMR spectrum was taken on a Varian Model FT 80 NMR
using a broad band probe operating at 32.203 MHz. An external
standard of 85% H3PO4 was used. Elemental analyses were done by
Robertson Laboratories, Florham Park, NJ.
Preparation of 3-Azido-2,5-dimethylfuran (7)
To 4.23 g (0.038 mmol) of 5-hydroxy-hex-3-yne-2-one (7)30,33 in 90 mL
of acetic acid was added a solution of 2.64 g (0.041 mmol) of sodium
azide in 20 mL of water. The solution was placed in a freezer at

2176
R. R. Sauers and S. D. Van Arnum
−10 to 5◦C for 17 h during which time the mixture eventually froze.
Chloroform (250 mL) and water (100 mL) were added. The organic layer
was washed with aqueous sodium bicarbonate solution (3 × 150 mL)
and saturated sodium chloride solution (150 mL). Drying over magne-
sium sulfate was followed by evaporation of the solvent at room temper-
ature. There was obtained 5.84 g of crude product. Flash chromatogra-
phy on silica gel using a mixture of 65% hexane and 35% ethyl acetate
as the eluent yielded 2.71 g (53% yield) of the furyl azide 8 as a bright
yellow oil. 1H NMR (CDCl3) δ 2.06 (s, 3H), 2.17 (s, 3H), 5.83 (s, 1H); IR
(film) 4.65 (vs), 6.06 (m), 7.69 (s), 13.33 (m) µm. The furyl azide 8 is not a
stable compound and decomposes on standing. The azide 8 was further
characterized by the preparation of the corresponding phosphinimine
by reaction with triphenylphosphine. Under a nitrogen atmosphere and
in glassware, which had been washed with concentrated ammonium hy-
droxide and dried in an oven overnight at 120◦C, a solution of 0.1500 g
(1.09 mmol) of freshly chromatographed furyl azide 8 in 2 mL of anhy-
drous diethyl ether was prepared. A solution of 0.286 g (1.09 mmol) of
triphenylphosphine in 2 mL of anhydrous ether was added. Additional
ether was added and, under a nitrogen atmosphere, the product was
filtered and the solid was washed with anhydrous ether. This phos-
phinimine had m.p. 134–136◦C (dec); 1H NMR (CDCl3) δ 2.06–2.17 (d,
6H), 5.30 (s, 1H), 6.83–7.90 (m, 15H); 31P NMR (CH2Cl2) δ 4.45; IR (KBr)
6.17 (s), 6.97 (m), 7.07 (m), 7.69 (m), 9.01 (s), 14.3 (s) µm. Anal. Calcd.
for C24H22NOP: C, 77.62; H, 5.97; N, 3.77; P, 8.34. Found: C, 77.49; H,
6.17; N, 4.03; P, 8.23.
Preparation of E-Azido-hex-3-ene-2,5-dione (1)
To 2.07 g (0.015 mmol) of 3-azido-2,5-dimethylfuran (8) in 130 mL of ace-
tone and 20 mmL of water was added 4.78 g (0.060 mmol) of pyridine.17
The solution was cooled to −20◦C in a dry-ice/carbon tetrachloride bath.
A solution of bromine (2.43 g, 0.015 mmol) in 13 mL of acetone and
3 mL of water was added over a 10-min period. After 20 min, the reac-
tion was complete as shown by TLC. Ether (140 mL) and saturated
sodium chloride solution (70 mL) were added, and the layers were sep-
arated. The ether layer was washed with saturated aqueous cupric sul-
fate (2 × 70 mL) and dried over magnesium sulfate. The solvent was
removed at room temperature under reduced pressure. The E-azide 1
was immediately purified by flash chromatography on silica gel using
a mixture of 65% hexane and 35% ethyl acetate as the eluent. The
E-azide 1 decomposed explosively when neat upon standing. Solutions
containing the E-vinyl azide 1 were not evaporated to dryness. 1H NMR

A Thio-Staudinger Reaction
2177
(CDCl3) δ 2.23 (s, 3H), 2.36 (s, 3H), 5.87 (s, 1H); IR (CCl4) 4.76 (s), 6.10
(m), 7.19 (m), 9.17 (m) µm. UV (CH3CN) λ = 400 nm (ε = ca. 14); λ =
280 (ε = ca. 2700).
Thermolysis of E-Azido-hex-3-ene-2,5-dione (1)
in t-Butyl Mercaptan
To approximately 4.4 mmol of the E-vinyl azide 1, based on 0.60 g (4.4
mmol) of the furyl azide 8 was added 30 mL of t-butyl mercaptan and the
solution was stirred overnight at room temperature. The solvent was
removed, and the products were purified to yield 0.16 g (17%) of the
t-butyl mercaptan adduct 20 and 0.18 g (19%) of the sulfenimine 6. The
adduct 20, isolated as a pale yellow solid, had the following properties:
m.p. 50–52◦C. Exact mass calcd for C10H17NO2S: 215.0980007. Found:
1
215.0978200. MS, m/z 159 (55%), 116 (100%), 102 (25%), 84 (29%). H
NMR (CDCl3) δ 1.67 (s, 9H), 2.20 (s, 6H), 5.60 (s, 1H), 13.3 (b, 1H). IR
(KBr) 3.45–3.51 (b), 5.88 (s), 6.17 (s), 6.45 (s), 8.20 (s) µm. The sulfen-
imine 6 had the following properties: Exact mass calcd for C10H17NO2S:
215.0980007. Found: 215.0974100. MS, m/z 215 (8%), 159 (100%), 116
(65%), 89 (35%), 74 (28%). 1H NMR (CDCl3) δ 1.43 (s, 9H), 2.20 (s, 3H),
2.43 (s, 3H), 3.70 (s, 2H); IR (film) 5.81 (s), 5.91 (s), 7.35 (s), 8.62 (m),
13.5 (m) µm.
Photolysis of 3-Acetyl-5-methylisoxazole (16)
in t-Butyl Mercaptan
A nitrogen degassed solution of 3-acetyl-5-methylisoxazole (16) (0.50
g, 0.4 mmol)24 in 10 mL of t-butyl mercaptan was irradiated in quartz
NMR tubes at 254 nm in a Rayonet photochemical reactor (Southern
New England Ultraviolet Co.) for 16 h. The solvent was removed under
vacuum, and the residue was filtered through silica gel using methylene
chloride as the eluent. The fractions containing the t-butyl mercaptan
adduct 20 were combined and purified again via flash chromatography
on silica gel using a mixture of 65% hexane and 35% ethyl acetate as
the eluent to yield 0.07 g (8.1%) of the adduct 20. The spectral proper-
ties of this compound were in agreement with those obtained from the
thermolysis of the E-vinyl azide 1.
Thermolysis of E-Azido-hex-3-ene-2,5-dione (1)
in Acetonitrile
To the E-vinyl azide 1 prepared from 2.07 g (15.1 mmol) of furyl azide
8 was added to 100 mL of acetonitrile which contained approximately

2178
R. R. Sauers and S. D. Van Arnum
0.1% water. The solution was wrapped in aluminum foil and held at
room temperature for 17 h. Solvent was removed under vacuum to yield
a yellow oil. 1H NMR integration revealed the products to be a mixture
of imide 12 (61%),23 azirine 9 (6%),10 and enol ester 10 (33%).10 This oil
darkened very rapidly when neat upon standing. Anhydrous ether was
added, and imide 12 (0.25 g, 12%) was filtered and air dried. The imide
1
12 had m.p. 89–91◦C (lit.23 m.p. 86–86.5◦C); H NMR (CDCl3) δ 2.00
(s, 3H enol), 2.23 (s, 3H), 2.33 (s, 3H, keto), 3.82 (s, 2H, enol), 5.82
(s, 1H enol), 9.60 (b, 1H), 13.6 (b, 1H enol), keto:enol ratio 5:1; IR (KBr)
3.05 (s), 5.75 (s), 5.88 (sh), 6.62 (s), 7.94 (s), 8.62 (m) µm. The filtrate
was concentrated and the residue was chromatographed on silica gel
using a mixture of 65% hexane and 35% ethyl acetate as the eluent to
yield 0.07g (3.7%) of the Z-enol ester 10.20 1H NMR (CDCl3) δ 2.13 (d,
3H), 2.23 (s, 3H), 4.95 (q, 1H); IR (film) 4.50 (s), 5.65 (s), 6.02 (s), 8.33
(s), 8.47 (s), 12.5 (m) µm; Anal. Calcd. for C6H7NO2: C, 57.59; H, 5.64;
N, 11.19. Found: C, 57.37; H, 5.55; N, 11.01.
Thermolysis of E-Azido-hex-3-ene-2,5-dione (1)
in Methanol
E-vinyl azide 1 was prepared from 2.07 g (15.1 mmol) of the furyl azide
8 and was dissolved in 100 mL of methanol. The solution was held in
the dark at room temperature for 17 h. Solvent was removed under
1
vacuum to yield 0.80 g of product. H NMR integration revealed the
mixture to contain 70% of enol ether 13 and 30% of enol ester 10. An
analytical sample of the enol ether 13 was prepared via a distillation at
50–55◦C (0.1 mm), followed by flash chromatography on silica gel using
a mixture of 65% hexane and 35% ethyl acetate as the eluent. The enol
ether 13 had 1H NMR (CDCl3) δ 2.12 (s, 3H), 2.13 (s, 3H), 4.90 (s, 1H),
12.40 (b, 1H); IR (film) 2.82–3.51 (b), 5.78–6.33 (b), 6.67 (s), 6.90 (s),
7.25 (s), 7.58 (s), 8.26 (s) µm; Anal. Calcd. for C7H11NO3: C, 53.49; H,
7.06; N, 8.90. Found: C, 52.98; H, 7.40; N, 9.05. To a sample of the enol
ether 13 in CDCl3, was added an aqueous overlay of trifluoroacetic acid
and the two-phase system was held at room temperature for 2 days.
1
The course of the hydrolysis was monitored by H NMR analysis and
indicated that the enol ether 13 had yielded the imide 12 under these
conditions.
Thermolysis of E-Azido-hex-3-ene-2,5-dione (1)
in t-Butylamine
Azide 1 was prepared from 1.00 g (7.3 mmol) of furyl azide 8 and was
dissolved in 50 mL of freshly distilled t-butylamine. After 15 h in the

A Thio-Staudinger Reaction
2179
dark at room temperature, solvent was removed under vacuum to af-
1
ford a black tar. By H NMR analysis, the mixture contained nearly
equal amounts of isoxazole ketone 1626 and the t-butylamine adduct 15.
The tar was triturated in ether, and the supernatant was decanted. An
analytical sample of the t-butylamine adduct 15 was prepared by flash
chromatography on silica gel using a mixture of 65% hexane and 35%
ethyl acetate as the eluent. The adduct 15, isolated as a yellow oil, had
exact mass calcd. for C10H18N2O2: 198.1368280. Found: 198.1355100.
MS, m/z 198 (80%), 127 (87%), 101 (80%), 85 (100%), 57 (55%). 1H NMR
(CDCl3) δ 1.40 (s, 9H), 2.03 (s, 3H), 2.13 (s, 3H), 4.80 (s, 1H), 9.15 (b,
1H), 14.17 (b, 1H). IR (film) 3.13 (b), 5.95 (m), 6.17 (s), 6.33 (s), 7.25 (m),
8.20 (m). 13C NMR (CDCl3)δ 25.22, 28.94, 30.83, 51.29, 83.14, 155.66,
173.15, 180.28, 192.95.
Preparation of the 3-O-Methyloxime
of 2,3,5-Hexanetrione (3)
To a magnetically stirred solution of 0.33 g (5.00 mmol) of potassium hy-
droxide in 2 mL of water was added 10 mL of chloroform. Methoxyamine
hydrochloride (0.42 g, 5 mmol) was added, and the mixture was stirred
for 5 min. 3-Hex-yne-2,5-dione (21) (0.55 g, 5.0 mmol) was added.30
1
After the addition, the reaction was complete as shown by H NMR
analysis. Drying over magnesium sulfate was followed by evaporation
of the solvent. There was obtained 0.70 g (90%) of the 3-O-methyloxime
(3) of 2,3,5-hexanetrione. An analytical sample was prepared by flash
chromatography using a mixture of 65% hexane and 35% ethyl acetate
1
as the eluent; H NMR δ 2.17 (s, 3H), 2.40 (s, 3H), 3.62 (s, 2H), 4.05
(s, 3H); IR (film) 5.81(s), 5.92 (s), 6.25 (w), 7.35 (m) µm. Anal. Calcd.
For C7H11NO3: C, 53.49; H, 7.06; N, 8.90. Found: C, 53.30; H, 7.44; N,
8.89.
Preparation of E-3-Acetoxybut-2-enenitrile (19)
and Z-3-Acetoxybut-2-enenitrile (10)
Under a nitrogen atmosphere, 0.23 g (0.01 mmol) of sodium was added
to 25 mL of methanol. A solution of 1.25 g (0.01 mmol) of 3-acetyl-5-
methylisoxazole (16)24 in 5 mL of methanol was added. The reaction
was stirred at room temperature overnight, and the solvent was re-
moved under reduced pressure to yield a reddish-brown solid. The salt
was suspended in 50 mL of acetonitrile, and 1.0 mL (0.014 mmol) of
acetyl chloride was added. The reaction was exothermic, and the precip-
itation of sodium chloride occurred immediately. Solvent was removed
under vacuum, and water (50 mL) and ether (100 mL) were added. The

2180
R. R. Sauers and S. D. Van Arnum
layers were separated and the organic layer was washed with satu-
rated aqueous sodium bicarbonate solution (3 × 50 mL) and saturated
sodium chloride solution (50 mL). Drying over magnesium sulfate was
followed by evaporation of the solvent to yield 1.20 g of crude product.
Distillation at 20–25◦C (0.1 mm) [lit20a b.p. 85◦C (13 mm)] yielded 0.22 g
(22%) of a mixture of E- and Z-3-acetoxybut-2-enenitriles (19 and 10).
1
By H NMR analysis, the mixture contained 75% of the E-isomer 19
1
and 25% of the Z-isomer 10. The E-isomer 19 had H NMR (CDCl3) δ
2.27 (s, 6H), 5.40 (s, 1H). The Z-isomer 10 had 1H NMR (CDCl3) δ 2.13
(d, 3H), 2.23 (s, 3H), 4.95 (q, 1H). IR (film) (mixture) 4.50 (s), 5.65 (s),
6.02 (s), 8.33 (s), 8.47 (s), 11.1 (m), 12.5 (m) µm.
REFERENCES
[1] a) G. M. Robertson, Comprehensive Organic Functional Group Transformations,
edited by A. R. Katrizky, O. Meth-Cohn, and C. W. Rees (Elsevier, Oxford, UK,
1995) Vol. 3, pp. 425-441, 733–856; b) P. K. Claus, Chemistry of Sulphenic Acids
and Their Derivatives, edited by S. Patai (Wiley, Chichester, UK, 1990).
[2] a) T. Fuchigami, S. Ichikawa, and A. Konno, Chem. Lett., 2405 (1992); b) D. G.
Brenner, K. M. Cavolowsky, and K. L. Shepard, J. Heterocycl. Chem., 22, 805 (1985);
c) S. Torri, H. Tanaka, S. Hamano, et al., Chem. Lett., 1823 (1984); d) D. H. R.
Barton, P. D. Magnus, and S. I. Pennanen, J. Chem. Soc., Chem. Comm., 1007 (1974);
e) F. A. Davis, W. A. R. Slegeir, S. Evans, et al., J. Org. Chem., 38, 2809 (1973);
f) F. A. Davis, W. A. R. Slegeir, and J. M. Kaminski, J. Chem. Soc. Chem. Comm., 634
(1972).
[3] a) M. D. Refvik and A. L. Schwan, Tetrahedron., 52, 8387 (1996); b) W. Franek
and P. K. Claus, Montash. Chem., 121, 539 (1990); c) O. Ruel, J. B. Baudin, and
S. A. Julia, Syn. Comm., 20, 2151 (1990); d) T. Morimoto, Y. Nezu, K. Achiwa, and
M. Sekiya, J. Chem. Soc. Chem. Comm., 22, 1584 (1985); e) F. A. Davis and P. A.
Mancinell, J. Org. Chem., 43, 1797 (1978).
[4] E. Schaumann, O. Bolte, and H. Behr, J. Chem. Soc., Perkin Trans 1., 182 (1990).
[5] B. P. Branchaud, J. Org. Chem., 48, 3531 (1983).
[6] a) Y. Li, W. Zhu, Z. Cheng, and G. Yang, Syn. Comm., 29, 2645 (1999); b) R. G. Lovey
and A. B. Cooper, Synlett, 167 (1994); c) R. Reck and J. C. Jochims, Chem. Ber., 115,
1494 (1982); d) S. Pike and D. R. M. Walton, Tetrahedron Lett., 21, 4989 (1980);
e) E. M. Gordon and J. Pluscec, J. Org. Chem., 44, 1218 (1979); f) H. Dj-Forudan,
R. F. Hudson, and K. A. F. Record, J. Chem. Soc., Chem. Comm., 503 (1976); g) R. J.
G. Searle, B. Cross, and R. E. Woodall, J. Chem. Soc. C., 1833 (1971).
[7] a) T. P. Smyth, M. E. O’Donnell, M. J. O’Connor, and J. O. St. Ledger, Tetrahedron.,
56, 5699 (2000); b) T. P. Smyth, M. J. O’Connor, and M. E. O’Donnell, J. Org. Chem.,
64, 3132 (1999); c) T. P. Smyth, M. E. O’Donnell, M. J. O’Connor, and J. O. St. Ledger,
J. Org. Chem., 63, 7600 (1998).
[8] D. M. Barnes, M. A. McLaughlin, T. Oie, et al., Org. Lett., 4, 1427 (2002).
[9] a) A. W. Johnson, Ylides and Imines of Phosphorous (John Wiley & Sons, New York,
1993), pp. 403–407; b) Y. G. Gololobov and L. F. Kasukhin, Tetrahedron., 48, 1353
(1992).
[10] R. R. Sauers and S. D. Van Arnum, Tetrahedron Lett., 28, 5797 (1987).

A Thio-Staudinger Reaction
2181
[11] B. C. G. So¨derberg, Curr. Org. Chem., 4, 727 (2000).
[12] R. S. Gairns, R. D. Grant, C. J. Moody, C. W. Rees, and S. C. Tsoi, J. Chem. Soc.,
Chem. Commun., 483 (1986).
[13] T. Yamabe, M. Kaminoyama, T. Minato, et al., Tetrahedron., 40, 2095 (1984).
[14] A. Hassner, N. H. Wiegand, and H. G. Gottlieb, J. Org. Chem., 51, 3176 (1986).
[15] G. L’Abbe´ and G. Matthys, J. Org. Chem., 39, 1778 (1974).
[16] P. Nedenskov, N. Elming, J. T. Nielsen, and N. Clauson-Kaas, Acta Chem. Scand.,
9, 17 (1955).
[17] J. Jurczak and P. Stanistan, Tetrahedron Lett., 25, 3039 (1985).
[18] D. Obrecht, Helv. Chim. Acta., 72, 447 (1989).
[19] D. M. Sammond and T. Sammakia, Tetrahedron Lett., 37, 6065 (1996).
[20] a) N. Goasdoue and M. Gaudemar, J. Organomet. Chem., 39, 29 (1972); b) H.
Vorbrueggen, Tetrahedron Lett., 1631 (1968).
[21] Y. Tamura, Y. Yoshimura, T. Nishamura, S. Kato, and Y. Kita, Tetrahedron Lett.,
351 (1973).
[22] K. Friedrich, Angew. Chem. 79, 980 (1967).
[23] a) M. Sato, N. Kanuma, and T. Kato, Chem. Pharm. Bull., 30, 1315 (1982);
b) Y. Yamanoto, S. Ohnishi, and Y. Azuma, Synthesis., 122 (1981); c) Y. Yamamoto
and H. Kimura, Chem. Pharm. Bull., 24, 1236 (1976).
[24] R. R. Sauers, A. A. Hagedorn, III, S. D. Van Arnum, R. P. Gomez, and R. V. Moquin,
J. Org. Chem., 52, 5501 (1987).
[25] a) D. D. Williams and E. Legoff, J. Org. Chem., 46, 4143 (1981); b) A. Hassner,
G. L’Abbe´, and M. J. Miller, J. Am. Chem. Soc., 93, 981 (1971); c) J. A. Hirsch and
A. J. Szur, J. Heterocycl. Chem., 9, 523 (1972).
[26] U. Turck and H. Behringer, Chem. Ber., 98, 3020 (1965).
[27] J. A. Barltrop and K. J. Morgan, J. Chem. Soc., 3072 (1957).
[28] C. Brown, B. T. Grayson, and R. F. Hudson, Tetrahedron Lett., 4925 (1970).
[29] a) S. I. Yakimovich and I. V. Zerova, Zh. Org. Khim., 27, 1630 (1991); Chem. Abstr.,
116, 151038 (1992); b) S. I. Yakimovich, I. V. Zerova, and T. E. Gabis, Zh. Org.
Khim., 26, 2510 (1990); Chem. Abstr., 115, 135416 (1991); c) S. I. Yakimovich, V.
N. Nikolaev, and O. A. Afonina, Zh. Org. Khim., 15, 922 (1979); Chem. Abstr., 91,
456126 (1979); d) H. Simon, and W. Moldenhauer, Chem. Ber., 100, 1949 (1967); e)
J. Buckingham, Quart. Rev. (London) 23, 37 (1969).
[30] a) P. Li, W.-M. Fong, L. C. F. Chao, S. H. C. Fung, and I. D. Williams, J. Org. Chem.,
66, 4087 (2001); b) S. Goldschmidt and A. Zoebelein, Chem. Ber., 94, 169 (1961).
[31] R. R. Sauers, L. M. Hadel, A. A. Scimone, and T. A. Stevenson, J. Org. Chem., 55,
4011 (1990).
[32] a) J. L. Spletstoser, P. T. Flahert, G. I. Georg, and R. H. Himes, Book of Abstracts,
224th ACS National Meeting, Boston, MA (American Chemical Society. Washington,
DC, 1999), MEDI-134; b) T. G. Back and K. Minksztym, Synlett, 201 (1999); c) S. A.
Fleming, J. Young, and K. Weenig, Book of Abstracts, 218th ACS National Meeting,
New Orleans, LA (American Chemical Society. Washington, DC, 1999), ORGN-276;
d) J.-P. Gotteland, C. Dax, and S. Halazy, Bioorg. Med. Chem. Lett., 7, 1153 (1997);
e) P. J. A. Weber and A. G. Beck-Sickinger, J. Peptide Res., 49, 375 (1997); f) B. Smith
and C. J. Cramer, Book of Abstracts, 214th ACS National Meeting, Las Vegas, NE
(American Chemical Society. Washington, DC, 1997), COMP-107; g) E. F. V. Scriven,
ed., Azides and Nitrenes: Reactivity and Utility (Academic Press, Inc. Orlando, FL,
1984).
[33] a) D. D. Enchev, Phosphorus, Sulfur and Silicon and the Related Elements, 134/135,
187 (1998); b) L. Palombi, L. Arista, A. Lattanzi, et al., Tetrahedron Lett., 37, 7849
(1996); c) A. F. Thomas and H. Damm, Tetrahedron Lett., 27, 505 (1986).