Conversions of sulfone-containing vinyl azides to vinyl triazoles and enamides

Article abstract of DOI:10.1016/j.tet.2021.131933

Reported is the efficient conversion of four 3-sulfonyl prop-1-enyl azides into seven 3-sulfonyl prop-1-enyl triazoles. Results demonstrate that the stereochemical integrity of the alkene was maintained during this process. The conversion of (Z)-((3-azido

Full text of DOI:10.1016/j.tet.2021.131933

Tetrahedron 83 (2021) 131933
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Tetrahedron
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Conversions of sulfone-containing vinyl azides to vinyl triazoles and
enamides*
a
a
,
, *
Niall Collins , Goar Sanchez-Sanz b, Paul Evans a
ꢀ
a Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Dublin, D04 N2E5, Ireland
b Irish Centre of High-End Computing, Grand Canal, Quay, Dublin 2, Ireland
a r t i c l e i n f o
a b s t r a c t -
Article history:
Reported is the efficient conversion of four 3-sulfonyl prop-1-enyl azides into seven 3-sulfonyl prop-1-
enyl triazoles. Results demonstrate that the stereochemical integrity of the alkene was maintained
during this process. The conversion of (Z)-((3-azidoallyl)sulfonyl)benzene into the corresponding Z-
enamides proved more challenging and only modest yields of (Z)-N-(3-(phenylsulfonyl)prop-1-en-1-yl)
acetamide and benzamide were obtained using Williams’ thioacid method. Attempts to form these
compounds using Staudinger ligation-type reactions proved unsuccessful.
Received 20 October 2020
Received in revised form
22 December 2020
Accepted 6 January 2021
Available online 21 January 2021
© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).
Keywords:
a,b-unsaturated sulfone
Allyl sulfone
Stereoselectivity
Cis-selectivity
One-pot reaction
1. Introduction
examples demonstrate that if an E-alkene (e.g. 1) is used, synthet-
ically useful levels of Z-selectivity for the new alkene (Z-3) may be
Sulfones represent
a
useful functional group which are
obtained - although it should be mentioned that this does depend
on the substituents present and the reaction conditions employed.
An interesting tandem variant of the general process outlined in
Scheme 1 has been reported where, from intermediate 2, a Ram-
frequently used in the construction of more complex compounds
[1,2] and the varied chemistry sulfones impart have led to them
being referred to as chemical chameleons [3] and pluripotent
€
groups [4]. Representative uses of the sulfone group include:
a
-
berg-Backlund reaction can take place [14].
sulfonyl alkylation, reductive or more traditional sulfinate elimi-
nation, the Julia olefination (including its variants) [5] and the
In relation to this process we have recently studied this type of
transformation and have found that the reaction is particularly
€
Ramberg-Backlund reaction [6]. Unsaturated sulfones also offer
facile and selective when the g-substituent is an azido goup [15].
useful synthetic possibilities.
a
,
b
-Unsaturated sulfones (e.g. 1,
For instance, four differently substituted E-allylic bromides, 4e7
were converted, via a two-step one-pot process, into their vinyl
azides 8e11. Apart from its convenience the one-pot process cir-
cumvented isolation of the intermediate azido vinyl sulfone which,
in the case of 12, proved not to be bench stable. Examples where
R ¼ H gave good to excellent levels of Z-selectivity in the formation
of the new vinyl azide (i.e. compounds 8e10). In the case of R ¼ Me
a reversal in stereochemical outcome was observed in the forma-
tion of predominantly E-11. On the basis of experimental and
computational results it is believed that these isomerisation re-
actions operate under kinetic control and that the selectivity
observed stems from a favoured vinyl sulfone conformer [15].
Because vinyl azides are synthetically useful groups [16] this
indirect, stereocontrolled, method to form the sulfone functional-
ised the vinyl azides is of interest. In this current work reactivity of
Scheme 1), also known as vinyl sulfones, undergo conjugate addi-
tion reactions with a range of soft and hard nucleophiles and also
engage in cycloaddition chemistries [7]. In addition, compounds of
the type 1 can be effectively isomerised into their b,g-unsaturated
counterpart, 3, on treatment with base (Scheme 1) [8].
In the forward sense (1 to 3) this isomerisation reaction serves
to “de-conjugate” the alkene from the electron withdrawing group
and this process is not limited to sulfones [9e13]. Numerous
*
This article is dedicated to Prof. Richard Taylor on the year of his 71st birthday
in acknowledgement for his many contributions to the area of synthetic organic
chemistry and with personal thanks for the knowledge he imparted.
* Corresponding author.
E-mail address: paul.evans@ucd.ie (P. Evans).
https://doi.org/10.1016/j.tet.2021.131933
0040-4020/© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

ꢀ
N. Collins, G. Sanchez-Sanz and P. Evans
Tetrahedron 83 (2021) 131933
Scheme 1. The isomerisation of substituted vinyl and allyl sulfones and the formation of vinyl azides 8e11 from vinyl sulfones 4e7 (B ¼ base; DBU ¼ 1,8-diazobicyclo[5.4.0]undec-
7-ene).
these sulfone containing vinyl azides has been explored. Namely,
the copper promoted azide-alkyne click reaction of vinyl azides 8 to
11 is reported and preliminary work investigating the conversion of
vinyl azides into enamides is also described.
which the trimethylsilyl group had been lost [21]. No alternative
products were detected. Use of the more robust, and bulky triiso-
propylsilyl acetylene led only to the recovery of Z-8 under the same
reaction conditions. Next the isomeric methyl substituted vinyl
azides, 9, 10 and 11 were reacted similarly with phenyl acetylene. In
each case the adducts, 17e19, were isolated in good yields and the
balance of alkene isomers in these adducts matched those found in
the vinyl azide starting materials (Entries 5e7).
The conversion of sulfonyl containing Z-vinyl azide 8 into the
corresponding enamide was subsequently considered. Enamides
represent an interesting functional group and are present in a va-
riety of natural products of both structural and biological interest
[22]. For instance, pamerolide A, crocacin A, TMC-95 A, the mem-
bers of the ceanothine family and salicylihalamide A all contain a
stereodefined enamide with a 1,2-disubstitution pattern on the
carbon-carbon double bond. As outlined in Scheme 3, using Wil-
liams’ method [23] 8 (E:Z ¼ 5:95) was converted into N-acetyl Z-
enamide 20 using thioacetic acid and lutidine. Although the reac-
tion did not proceed to completion Z-20 was successfully isolated in
33% yield. Unlike the CuAAC reactions (Scheme 2) in this reaction
some alkene isomerisation was observed and the small amounts of
the minor E-isomer was formed, which was chromatographically
separable from the major Z-isomer. Starting material (8) was
additionally recovered (25%) and trace amounts of a material
tentatively assigned to mixed N,S-acetal (22), resulting from the
reaction of 20 with thioacetic acid, was also detected.
2. Results and discussion
Compounds 8 to 11 were accessed according to our previously
published procedure [15] and their copper promoted azide-alkyne
click (CuAAC) chemistry was considered [17]. As shown in Scheme
2, firstly azide 8 was reacted with several terminal alkynes, using
typical reaction conditions [18]. Use of phenyl acetylene, oct-1-yne
and methyl propiolate gave the expected triazoles, 13e15 in good
yields (Scheme 2, Entries 1e3). It should be noted that no changes
in alkene geometry were observed in these reactions [19] and in the
case of Z-13 a single crystal X-ray structure was obtained [20]. Use
of trimethylsilyl acetylene gave a moderate yield of triazole Z-16 in
Unfortunately, attempts to use thiobenzoic acid in the reaction
were more disappointing. Although the reaction did work the
conversion and consequent yields of the N-benzoyl enamide 21
Scheme 2. Use of vinyl azides 8e11 in the CuAAC reaction to form vinyl triazoles
13e19. Single crystal X-ray structure of Z-13 (thermal ellipsoids shown on the 50%
probability level) [20].
Scheme 3. Conversion of vinyl azides 8 into Z-enamides 20 and 21.
2

ꢀ
N. Collins, G. Sanchez-Sanz and P. Evans
Tetrahedron 83 (2021) 131933
were poorer than in the case of thioacetic acid, although 39% of
unreacted Z-8 was recovered. Compound 22 (R ¼ Me and Ph)
proved to have similar polarity to the E-enamides 20 and 21 but
could be clearly detected by diagnostic NMR spectroscopic signals
and mass spectrometry (see SI).
Staudinger-functionalisation chemistry was also briefly inves-
tigated as a potential means to directly convert a vinyl azide into an
enamide [24]. Using either 2-(diphenylphosphaneyl)phenyl acetate
[25] or S-[(diphenylphosphaneyl)methyl]ethanethioate [26] evo-
lution of gaseous nitrogen was detected, however, in both cases no
20 was isolated.
chloroform. Assignment was aided by two-dimensional NMR ex-
periments (g-COSY and HSCQ). High resolution mass spectra were
carried out with a Waters/Micromass LCT ESI mass spectrometer
under electrospray ionisation conditions (ESI) and a time-of-flight
(TOF) analyser. Infrared spectra were recorded on a Bruker Alpha
FTIR spectrometer. Melting points were recorded on a Gallenkamp
electrothermal melting point apparatus and are uncorrected. Thin-
layer chromatography was performed on silica coated aluminium
sheets and compounds were visualised with UV light and aqueous
potassium permanganate, followed by heating. Merck silica gel
(0.040e0.063 mm) was used for flash column chromatography.
Compounds 8e11 and 24 were prepared according to procedures
previously described in the literature [15].
In order to further explore the preparation of sulfonyl contain-
ing enamides the synthesis of 21 was also considered using an
alternative route (Scheme 4). Hippuric acid was converted in 70% to
known Weinreb amide 23 using a carbodiimide coupling [27].
4.2. (Z)-4-Phenyl-1-[3-(phenylsulfonyl)prop-1-en-1-yl]-1H-1,2,3-
triazole 13
Thereafter,
a reduction-Horner-Wadsworth-Emmons sequence
give 25 in a poor overall yield as a single geometrical isomer.
Nevertheless, from 25, compound 21 can be accessed via the vinyl
sulfone to allyl sulfone transposition outlined in general terms in
Scheme 1. It should be noted that, in contrast to the azide-based
route, following this isomerisation method 21 is formed as a
mixture of stereoisomers within which the E-isomer predominates.
Sodium ascorbate (71 mg, 0.36 mmol, 0.8 equiv.) was added to a
stirred solution of vinyl azide 8 (100 mg, 0.45 mmol, 1.0 equiv.),
phenylacetylene (50 mg, 0.49 mmol, 1.1 equiv.) and CuSO4$5H2O
(34 mg, 0.13 mmol, 0.3 equiv.) in DMF (4 mL). This mixture was
stirred at room temperature for 18 h. Solvent was removed in vacuo,
the residue was re-dissolved in EtOAc (20 mL) and washed with
water (20 mL). The aqueous layer was back extracted with EtOAc (2
x 20 mL) and the combined organic layers were washed with brine
(60 mL), dried over MgSO4 and solvent was removed in vacuo to
give crude product. Purification by column chromatography (c-
Hex:EtOAc, 2:1) yielded triazole 13 (115 mg, 79%) as a white crys-
talline solid. X-Ray quality crystals were grown from the slow
infusion of pentane into a saturated solution of 13 in DCM.
M.p. ¼ 153e155 ꢀC (DCM). Rf ¼ 0.25 (c-Hex:EtOAc, 2:1). IR (neat):
3. Conclusion
In conclusion, described is the use of a series of sulfonyl
substituted vinyl azides (8e11) in CuAAC reactions in order to
prepare novel sulfonyl functionalised 1-vinyl substituted 1,2,3-
triazoles (13e19). These were isolated in reasonable to good
yields. In all cases the stereochemistry of the initial double bond
was maintained in the formation of 13e19. A preliminary study of
the reactivity of the azido group in 8 under conditions aimed at
converting it into an amido group was studied. This type of
Staudinger-functionalisation chemistry was also briefly investi-
gated and using thioacid conditions the Z-vinyl azide could be
converted into the corresponding Z-enamide (although the con-
version was poor).
3091, 3050, 1730, 1582, 1560, 1361,1238, 1150, 1071, 1018 cmꢁ1
HRMS (ESþ) C17H16N3O2S (MHþ) calcd. 326.0977; found
326.0963.1H NMR (400 MHz, CDCl3):
.
d
¼ 4.62 (dd, J ¼ 8.0, 1.5 Hz,
2H, CH2), 5.76 (dt, J ¼ 9.5, 8.0 Hz, 1H, CH), 7.05 (dt, J ¼ 9.5, 1.5 Hz,1H,
CH), 7.34e7.40 (m, 1H, ArH), 7.41e7.52 (m, 4H, ArH), 7.54e7.60 (m,
1H, ArH), 7.69 (s, 1H, CH), 7.76e7.80 (m, 2H, ArH), 7.89e7.93 (m, 2H,
ArH) ppm. 13C NMR (100 MHz, CDCl3):
120.2 (CH),125.8 (CH),127.1 (CH),128.3 (CH),128.7 (CH),129.0 (CH),
129.1 (CH), 129.5 (C), 133.9 (CH), 138.4 (C), 147.2 (C) ppm.
d
¼ 55.0 (CH2), 111.1 (CH),
4. Experimental section
4.1. General directions
4.3. (Z)-4-Hexyl-1-[3-(phenylsulfonyl)prop-1-en-1-yl]-1H-1,2,3-
Reagents from commercial suppliers were used without further
purification. 1H, 1H-decoupled 13C NMR spectra were recorded on
Varian Unity 300, 400 and 500 MHz spectrometers and coupling
constants (J) are quoted in Hertz. All values are reported in ppm and
were referenced to either tetramethylsilane, or residual protonated
triazole 14
In a procedure identical to triazole 52 above (but with stirring
for 18 h), azide 8 (203 mg, 0.91 mmol, 1.0 equiv.), 1-octyne (110 mg,
1.00 mmol, 1.1 equiv.), CuSO4$5H2O (68 mg, 0.27 mmol, 0.3 equiv.)
Scheme 4. Synthesis of enamide 21 from hippuric acid.
3

ꢀ
N. Collins, G. Sanchez-Sanz and P. Evans
Tetrahedron 83 (2021) 131933
and sodium ascorbate (145 mg, 0.73 mmol, 0.8 equiv.) were stirred
at room temperature in DMF (10 mL) for 18 h. The mixture was
worked-up as described above and was further purified by column
chromatography (c-Hex:EtOAc, 2:1) which yielded triazole 14
(197 mg, 65%) as a white crystalline solid. M.p. ¼ 88e90 ꢀC.
Rf ¼ 0.30 (c-Hex:EtOAc, 2:1). IR (neat): 3075, 3014, 2923, 2878,
1583, 1379, 1246, 1151, 1086, 954 cmꢁ1. HRMS (ESþ): C17H24N3O2S
(MHþ) calcd. 334.1589; found 334.1599.1H NMR (400 MHz, CDCl3):
4.6. (E/Z)-4-phenyl-1-[4-(phenylsulfonyl)but-2-en-2-yl]-1H-1,2,3-
triazole 17
As described above, azide 9 (77 mg, 0.325 mmol, 1.0 equiv.),
phenylacetylene (36 mg, 0.36 mmol, 1.1 equiv.), CuSO4$5H2O
(24 mg, 0.10 mmol, 0.3 equiv.) and sodium ascorbate (51 mg,
0.26 mmol, 0.8 equiv.) in DMF (5 mL) were stirred at room tem-
perature for 24 h. At this stage some 17 was evident by TLC so
phenylacetylene (36 mg, 0.36 mmol, 1.1 equiv.) was added and
stirring maintained for 16 h. Work-up as described and purification
by column chromatography (c-Hex:EtOAc, 1:1) yielded triazole 17
(83 mg, 75%) as a white solid with an E:Z ratio of 20:80. Rf ¼ 0.25 (c-
Hex:EtOAc, 2:1). IR (neat): 3139, 3056, 2926, 1684, 1387, 1212, 995,
777, 686, 431 cmꢁ1. HRMS (ESþ): C18H18N3O2S (MHþ) calcd.
d
¼ 0.89 (t, J ¼ 7.0 Hz, 3H, CH3), 1.25e1.39 (m, 6H, CH2), 1.63 (p,
J ¼ 7.5 Hz, 2H, CH2), 2.67 (t, J ¼ 7.5 Hz, 2H, CH2), 4.59 (dd, J ¼ 8.0,
1.5 Hz, 2H, CH2), 5.66 (dt, J ¼ 9.5, 8.0 Hz, 1H, CH), 6.96 (dt, J ¼ 9.5,
1.5 Hz, 1H, CH), 7.22 (s, 1H, CH), 7.47e7.53 (m, 2H, ArH), 7.56e7.62
(m, 1H, ArH), 7.87e7.93 (m, 2H, ArH). 13C NMR (100 MHz, CDCl3):
d
¼ 14.1 (CH3), 22.5 (CH2), 25.6 (CH2), 28.8 (CH2), 29.2 (CH2), 31.5
(CH2), 55.0 (CH2), 110.0 (CH), 121.5 (CH), 127.2 (CH), 128.3 (CH),
129.0 (CH), 133.8 (CH), 138.5 (C), 147.9 (C).
340.1120; found 340.1129.1H NMR (400 MHz, CDCl3):
d
¼ 2.11 (s,
0.6H, CH3),* 2.31 (s, 2.4H, CH3),y 4.01 (d, J ¼ 8.5 Hz, 0.4H, CH2),*
4.09e4.17 (m, 1.6H, CH2),y 5.69 (td, J ¼ 8.0, 1.25 Hz, 0.8H, CH),y 6.06
(td, J ¼ 8.5, 1.0 Hz, 0.2H, CH),* 7.32e7.39 (m, 1H, ArH), 7.40e7.50 (m,
3.4H, ArH), 7.52e7.62 (m, 1H, ArH), 7.64 (t, J ¼ 8.0 Hz, 0.2H, ArH),*
7.69 (s, 0.8H, ArH),y 7.77e7.86 (m, 4H, ArH), 7.81 (d, J ¼ 8.0 Hz, 0.4H,
ArH),* 7.95 (s, 0.2H, ArH)* ppm; 13C NMR (100 MHz, CDCl3):
4.4. Methyl (Z)-1-[3-(phenylsulfonyl)prop-1-en-1-yl]-1H-1,2,3-
triazole-4-carboxylate 15
d
¼ 14.8 (CH3), 22.8 (CH3), 55.2 (CH2), 55.4 (CH2), 106.5 (CH), 111.0
In a procedure identical to that described above for the synthesis
of triazole 13, azide 8 (178 mg, 0.79 mmol, 1.0 equiv.), methyl
propiolate (74 mg, 0.88 mmol, 1.1 equiv.), CuSO4$5H2O (60 mg,
0.24 mmol, 0.3 equiv.) and sodium ascorbate (130 mg, 0.64 mmol,
0.8 equiv.) in DMF (10 mL) were stirred at room temperature for
3.5 h. After work-up as described the crude reaction product was
purified by flash column chromatography (c-Hex:EtOAc, 1:1) which
yielded triazole 15 (170 mg, 69%) as a white crystalline solid.
M.p. ¼ 123e125 ꢀC. Rf ¼ 0.30 (c-Hex:EtOAc, 1:1). IR (neat): 3099,
3062, 1713, 1584, 1346, 1264, 1243, 1156, 1073, 1032 cmꢁ1. HRMS
(ESþ): C14H13N3O4S (MHþ) calcd. 308.0705; found 308.0695.1H
(CH), 117.1 (CH), 119.4 (CH), 125.8 (CH), 125.9 (CH), 128.2 (CH), 128.5
(CH),128.6 (CH),129.0 (CH),129.1 (CH),129.4 (CH),129.6 (CH),129.9
(C), 130.0 (C), 134.0 (CH), 134.3 (CH), 138.2 (C), 138.3 (C), 138.6 (C),
139.7 (C), 147.4 (C), 150.0 (C) ppm. *Denotes signals for E-17;
yDenotes signals for Z-17.
4.7. (Z)-1-[2-methyl-3-(phenylsulfonyl)prop-1-en-1-yl]-4-phenyl-
1H-1,2,3-triazole 18
In an identical procedure to that described above, azide 10
(75 mg, 0.32 mmol, 1.0 equiv.), phenylacetylene (36 mg, 0.36 mmol,
1.1 equiv.), CuSO4$5H2O (24 mg, 0.10 mmol, 0.3 equiv.) and sodium
ascorbate (50 mg, 0.25 mmol, 0.8 equiv.) were stirring at room
temperature in DMF (5 mL) for 21 h. Work-up and purification by
column chromatography (c-Hex:EtOAc, 2:1) yielded triazole 18
(87 mg, 81%) as a white crystalline solid. M.p. ¼ 141e142 ꢀC.
Rf ¼ 0.25 (c-Hex:EtOAc, 2:1). IR (neat): 2995, 2926, 1678, 1368,
1260, 1146, 1018, 854, 593 cmꢁ1. HRMS (ESþ): C18H18N3O2S (MHþ)
NMR (400 MHz)):
d
¼ 3.97 (s, 3H, CH3), 4.53 (dd, J ¼ 8.0, 1.5 Hz, 2H,
CH2), 5.88 (dt, J ¼ 9.0, 8.0 Hz, 1H, CH), 7.04 (dt, J ¼ 9.0, 1.5 Hz, 1H,
CH), 7.48e7.54 (m, 2H, ArH), 7.58e7.64 (m, 1H, ArH), 7.87e7.93 (m,
2H, ArH). 13C NMR (100 MHz):
d
¼ 52.6 (CH3), 55.0 (CH2),113.6 (CH),
126.9 (CH), 128.2 (CH), 128.4 (CH), 129.4 (CH), 134.2 (CH), 138.4 (C),
139.6 (C), 160.6 (C) ppm.
calcd. 340.1120; found 340.1136.1H NMR (400 MHz, CDCl3):
d
¼ 2.21
(d, J ¼ 1.5 Hz, 3H, CH3), 4.46 (s, 2H, CH2), 6.90 (d, J ¼ 1.5 Hz, 1H),
4.5. (Z)-1-[3-(Phenylsulfonyl)prop-1-en-1-yl]-1H-1,2,3-triazole 16
7.34e7.52 (m, 6H, ArH, CH), 7.73e7.81 (m, 5H, ArH) ppm. 13C NMR
(100 MHz, CDCl3):
124.9 (C), 125.8 (CH), 128.3 (CH), 128.6 (CH), 129.1 (CH), 129.3 (CH),
129.9 (C), 133.8 (CH), 138.7 (C), 147.2 (C) ppm.
d
¼ 22.1 (CH3), 58.6 (CH2), 120.4 (CH), 124.5 (CH),
Azide 8 (55 mg, 0.25 mmol, 1.0 equiv.), ethynyltrimethylsilane
(27 mg, 0.27 mmol, 1.1 equiv.), CuSO4$5H2O (18 mg, 0.07 mmol, 0.3
equiv.) and sodium ascorbate (40 mg, 0.19 mmol, 0.8 equiv.) were
stirred at room temperature in DMF (4 mL) for 7 days. Work-up as
described above followed by purification by column chromatog-
raphy (c-Hex:EtOAc,1:1) yielded triazole 16 (23 mg, 36%, 46% based
on recovered starting material) as a white crystalline solid.
M.p. ¼ 140e142 ꢀC. Rf ¼ 0.25 (c-Hex:EtOAc, 1:1). IR (neat): 3116,
3057, 3020, 1734, 1583, 1390, 1237, 1152, 1074, 1014 cmꢁ1. HRMS
(ESþ): C11H12N3O2S (MHþ) calcd. 250.0650; found 250.0640.1H
4.8. (E/Z)-4-phenyl-1-[3-(phenylsulfonyl)but-1-en-1-yl]-1H-1,2,3-
triazole 19
In an identical procedure to that described above for the syn-
thesis of triazole 13, azide 11 (46 mg, 0.19 mmol, 1.0 equiv.), phe-
nylacetylene (19 mg, 0.21 mmol, 1.1 equiv.), CuSO4$5H2O (13 mg,
0.06 mmol, 0.3 equiv.) and sodium ascorbate (31 mg, 0.16 mmol, 0.8
equiv.) were stirred in DMF (4 mL) at room temperature for 16 h.
TLC analysis indicated 11 remained, therefore, phenylacetylene
(19 mg, 0.21 mmol, 1.1 equiv.) was added and stirring maintained
for a further 8 h. Work-up and purification by column chromatog-
raphy (c-Hex:EtOAc, 1:1) yielded triazole 19 (57 mg, 86%) as a white
crystalline solid in an E:Z ratio of 80:20. M.p. ¼ 137e140 ꢀC.
NMR (400 MHz, CDCl3):
d
¼ 4.58 (dd, J ¼ 8.0, 1.5 Hz, 2H, CH2), 5.73
(dt, J ¼ 9.5, 8.0 Hz, 1H, CH), 7.04 (dt, J ¼ 9.5, 1.5 Hz, 1H, CH),
7.46e7.52 (m, 2H, ArH), 7.55 (d, J ¼ 1.0 Hz, 1H, CH), 7.56e7.62 (m,
1H, ArH), 7.64 (d, J ¼ 1.0 Hz, 1H, CH), 7.86e7.91 (m, 2H, ArH) ppm.
13C NMR (100 MHz, CDCl3):
d
¼ 55.1 (CH2), 111.1 (CH), 124.7 (CH),
127.2 (CH), 128.4 (CH), 129.2 (CH), 133.4 (CH), 134.1 (CH), 138.6 (C)
ppm.
4

ꢀ
N. Collins, G. Sanchez-Sanz and P. Evans
Tetrahedron 83 (2021) 131933
Rf ¼ 0.25 (c-Hex:EtOAc, 2:1). IR (neat): 3135, 2988, 2934, 1669,
1285, 1258, 1084, 1000, 940, 687 cmꢁ1. HRMS (ESþ): C18H18N3O2S
(MHþ) calcd. 340.1120; found 340.1136.1H NMR (400 MHz, CDCl3):
1.2 equiv.), N,O-dimethylhydroxylamine hydrochloride (0.84 g,
8.62 mmol, 1.2 equiv.) and diisopropylethylamine (1.15 mL,
8.64 mmol, 1.2 equiv.) was added last (note: exotherm!). The
resulting solution was stirred at room temperature for 27 h and
quenched with 1 M HCl (30 mL), the organic layer was washed with
brine (30 mL), dried over MgSO4, filtered and solvent was removed
in vacuo. Purification by flash column chromatography (c-Hex:-
EtOAc, 2:1) afforded Weinreb amide 23 (1.12 g, 70%) as a colourless
crystalline solid. Rf ¼ 0.20 (c-Hex:EtOAc, 1:2). 1H NMR (400 MHz,
E-19:
d
¼ 1.55e1.62 (m, 3H, CH3), 3.87e3.96 (m, 1H, CH), 6.23 (dd,
J ¼ 14.5, 8.5 Hz, 1H, CH), 7.15 (dd, J ¼ 14.5, 1.0 Hz, 1H, CH), 7.35e7.40
(m, 1H, ArH), 7.42e7.49 (m, 2H, ArH), 7.52e7.60 (m, 2H, ArH),
7.65e7.71 (m, 1H, ArH), 7.82e7.91 (m, 4H, ArH), 7.97 (s, 1H, CH). Z-
19:
d
¼ 1.55e1.62 (m, 3H, CH3), 5.16e5.29 (m, 1H, CH), 5.60 (dd,
J ¼ 10.5, 9.5 Hz, 1H, CH), 6.95 (dd, J ¼ 9.5, 0.5 Hz, 1H, CH), 7.35e7.40
(m, 1H, ArH), 7.42e7.49 (m, 2H, ArH), 7.52e7.60 (m, 2H, ArH), 7.64
(s, 1H, CH), 7.65e7.71 (m, 1H, ArH), 7.82e7.91 (m, 4H, ArH). 13C NMR
CDCl3):
d
¼ 3.22 (s, 3H, CH3), 3.74 (s, 3H, CH3), 4.36 (d, J ¼ 3.5 Hz, 2H,
CH2), 7.11 (bs, 1H, NH), 7.38e7.44 (m, 2H, ArH), 7.44e7.50 (m, 1H,
(100 MHz, CDCl3):
d
¼ 13.8 (CH3), 13.9 (CH3), 58.7 (CH), 61.5 (CH),
ArH), 7.79e7.84 (m, 2H, ArH) ppm. 13C NMR (100 MHz, CDCl3):
114.5 (CH), 116.7 (CH), 118.7 (CH), 120.40 (CH), 125.9 (CH), 125.9
(CH), 126.0 (CH),128.8 (CH), 128.9 (CH), 129.1 (CH), 129.1 (CH), 129.1
(CH), 129.2 (CH) 129.4 (CH), 129.4 (CH), 129.8 (CH), 133.9 (CH), 134.4
(CH), 136.5 (C), 137.4 (C), 148.4 (C) ppm.
d
¼ 32.5 (CH3), 41.3 (CH2), 61.7 (CH3), 127.1 (CH), 128.6 (CH), 131.7
(CH), 134.0 (C), 167.4 (C), 169.8 (C) ppm. Data are consistent with that
reported in the literature. [27].
4.12. (E)-N-[3-(Phenylsulfonyl)allyl]benzamide 25
4.9. (Z)-N-[3-(Phenylsulfonyl)prop-1-en-1-yl]acetamide 20
Weinreb amide 23 (246 mg, 1.12 mmol, 1.0 equiv.) was added
dropwise as a solution in THF (3 mL) to a flame dried flask con-
taining LiAlH4 (44 mg, 1.16 mmol, 1.04 equiv.) in THF (3 mL)
at ꢁ78 ꢀC. The mixture was warmed to 0 ꢀC (ice-water bath). After
20 min, the solution was again cooled to ꢁ78 ꢀC and aq. sat. NH4Cl
(10 mL) was added. The mixture was allowed warm to room tem-
perature, diluted with H2O (10 mL) and extracted with EtOAc (3 x
10 mL). Combined organic extracts were washed with brine
(30 mL), dried over Na2SO4, filtered and solvent was removed in
vacuo to afford crude aldehyde. This was then dissolved in THF
(6 mL) and added to 0 ꢀC solution of phosphonate 24 (324 mg,
1.11 mmol,1.0 equiv.) and 60% NaH (40 mg,1.00 mmol, 0.9 equiv.) in
THF (6 mL) which had been stirred at this temperature for 0.5 h. The
mixture was stirred and gradually warmed to room temperature
over 16 h H2O (10 mL) was added and the organics were extracted
with EtOAc (3 x 10 mL). Combined organic layers were washed with
brine (30 mL), dried over Na2SO4, filtered and solvent was removed
in vacuo. Purification by column chromatography afforded vinyl
sulfone 25 (40 mg, 14%) as a viscous colourless oil. Rf ¼ 0.25 (c-
Hex:EtOAc, 2:1). IR (neat): 3334, 3058, 2919, 1643, 1528, 1141, 999,
To a stirred solution of vinyl azide 8 (224 mg, 1.00 mmol, 1.0
equiv.) in CHCl3 (1 mL) at room temperature, was added thioacetic
acid (176 mg, 2.31 mmol, 2.3 equiv.) and 2,6-lutidine (247 mg,
2.31 mmol, 2.3 equiv.) sequentially by syringe. The mixture was
heated to reflux for 48 h, cooled to room temperature and solvent
was removed in vacuo to afford a crude residue. The residue was
purified by column chromatography (gradient elution; c-Hex:-
EtOAc, 6:1 to EtOAc) affording starting material 8 (56 mg, 25%, E:Z;
5:95) and Z-enamide 20 (79 mg, 33%) as a white crystalline solid.
M.p. ¼ 117e119 ꢀC. Rf ¼ 0.40 (EtOAc). IR (neat): 3345, 3207, 1679,
1652, 1583, 1366, 1122, 998, 727, 521 cmꢁ1 HRMS (ESþ):
.
C
11H13NO3NaS (MNaþ) calcd. 262.0514; found 262.0525.1H NMR
(400 MHz, CDCl3):
d
¼ 2.08 (s, 3H, CH3), 3.90e3.93 (m, 2H, CH2),
4.45 (app. q, J ¼ 8.5 Hz, 1H, CH), 6.97e7.05 (m, 1H, CH), 7.54e7.60
(m, 2H, ArH), 7.64e7.71 (m, 1H, ArH), 7.86e7.91 (m, 2H, ArH), 8.47
(d, J ¼ 10.0 Hz, 1H, NH) ppm. 13C NMR (100 MHz, CDCl3):
d
¼ 23.4
(CH3), 54.6 (CH2), 95.1 (CH), 128.5 (CH),129.4 (CH), 130.2 (CH), 134.3
(CH), 138.0 (C), 168.6 (C) ppm. Further elution gave a mixture of E-
20 and 22 (R ¼ Me) (25 mg).
710, 559, 533 cmꢁ1 HRMS (ESþ): C16H16NO3S (MHþ) calcd.
.
4.10. (Z)-N-[3-(Phenylsulfonyl)prop-1-en-1-yl]benzamide 21
302.0851; found 302.0857.1H NMR (400 MHz, CDCl3): 4.28 (ddd,
J ¼ 6.5, 4.5, 2.0 Hz, 2H, CH2), 6.48 (dt, J ¼ 15.0, 2.0 Hz, 1H, CH), 6.98
(bs, 1H, NH), 7.02 (dt, J ¼ 15.0, 4.5 Hz, 1H, CH), 7.35e7.41 (m, 2H,
ArH), 7.45e7.54 (m, 3H, ArH), 7.58e7.63 (m, 1H, ArH), 7.76e7.80 (m,
2H, ArH), 7.81e7.86 (m, 2H, ArH) ppm. 13C NMR (100 MHz, CDCl3):
In an identical procedure to that described above, vinyl azide 8
(201 mg, 0.90 mmol, 1.0 equiv.), 2,6-lutidine (222 mg, 2.07 mmol,
2.3 equiv.) and thiobenzoic acid (286 mg, 2.07 mmol, 2.3 equiv.)
were heated to reflux for 48 h in CHCl3 (1 mL). Purification by
column chromatography using gradient elution (c-Hex:EtOAc, 6:1
to 1:1) gave starting material 8 (78 mg, 39%, E:Z; 5:95) and 21 with
a co-running contaminant. Additional purification of the latter
fraction by column chromatography (DCM) afforded 21 (30 mg,
d
¼ 39.9 (CH2), 127.2 (CH), 127.8 (CH), 128.7 (CH), 129.5 (CH), 131.0
(CH), 132.0 (CH), 133.6 (C), 133.7 (CH), 139.9 (C), 143.3 (CH), 167.6 (C)
ppm.
4.13. (E/Z)-N-[3-(Phenylsulfonyl)prop-1-en-1-yl]benzamide 21
11%e18% based on RSM) as
a
white crystalline solid.
M.p. ¼ 86e88 ꢀC. Rf ¼ 0.50 (c-Hex:EtOAc,1:1). IR (neat): 3401, 2899,
To a stirred solution of vinyl sulfone 25 (34 mg, 0.11 mmol, 1.0
equiv.) in MeCN (1 mL), was added DBU (9 mg, 0.06 mmol, 0.5
equiv.). The mixture was quenched by addition of 1 M HCl (2 mL)
after 1 h and subsequently diluted with H2O (2 mL) and extracted
with EtOAc (3 x 3 mL). The combined organic layers were washed
with brine (10 mL), dried over MgSO4, filtered and solvent was
removed in vacuo to give (E/Z)-21 (22 mg, 65%) as an off-white solid
1651, 1383, 1130, 1080, 999, 797, 688, 525 cmꢁ1. HRMS (ESþ):
C
16H16NO3S (MHþ) calcd. 302.0851; found 302.0846.1H NMR
(400 MHz, CDCl3):
d
¼ 3.96e3.99 (m, 2H, CH2), 4.59 (q, J ¼ 8.0 Hz,
1H, CH), 7.22e7.30 (m, 1H, CH), 7.47e7.53 (m, 2H, ArH), 7.55e7.62
(m, 3H, ArH), 7.66e7.72 (m, 1H, ArH), 7.90e7.94 (m, 2H, ArH),
7.95e8.00 (m, 2H, ArH), 9.49 (d, J ¼ 9.5 Hz, 1H, NH) ppm. 13C NMR
(100 MHz, CDCl3):
d
¼ 55.1 (CH2), 96.1 (CH), 127.7 (CH), 128.6 (CH),
in
an
E:Z
ratio
of
65:35.1H
NMR
(400
MHz,
129.0 (CH), 129.5 (CH), 131.2 (CH), 132.6 (CH), 132.8 (C), 134.4 (CH),
137.9 (C), 165.2 (C) ppm.
DMSO‑d6):*
d
¼ 4.10e4.17 (m, 2H, CH2), 5.32 (dt, J ¼ 14.0, 8.0 Hz, 1H,
CH), 6.99e7.05 (m, 1H, CH), 7.47e7.53 (m, 2H, ArH), 7.55e7.77 (m,
5H, ArH), 7.85e7.92 (m, 3H, ArH), 10.50 (d, J ¼ 10 Hz, 1H, NH) ppm.
4.11. N-{2-[Methoxy(methyl)amino]-2-oxoethyl}benzamide 23
13C NMR (100 MHz, DMSO‑d6):*
d
¼ 56.9 (CH2), 98.7 (CH), 127.7
(CH), 128.0 (CH), 128.6 (CH), 129.4 (CH), 131.6 (CH), 132.2 (CH), 133.0
(C), 133.8 (CH), 138.9 (C), 164.0 (C) *Data for E-isomer only, for Z-21
data see above.
To a stirred solution of hippuric acid (1.29 g, 7.20 mmol, 1.0
equiv.) in CHCl3 (35 mL), was added EDCI$HCl (1.66 g, 8.64 mmol,
5

ꢀ
N. Collins, G. Sanchez-Sanz and P. Evans
Tetrahedron 83 (2021) 131933
(b) N.S. Simpkins, Tetrahedron 46 (1990) 6951e6984;
(c) J.E. Backvall, R. Chinchilla, C. Najera, M. Yus, Chem. Rev. 98 (1998)
2291e2312;
(d) T.G. Back, Tetrahedron 57 (2001) 5263e5301;
(e) D.C. Meadows, J. Gervay-Hauge, Med. Res. Rev. 26 (2006) 793e814;
(f) Y. Fang, Z. Luo, X. Xu, RSC Adv. 6 (2016) 59661e59676.
Declaration of competing interest
€
ꢀ
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
[8] D.E. O’Connor, W.J. Lyness, J. Am. Chem. Soc. 86 (1964) 3840e3846.
[9] See for example:. (a) E.-P. Krebs, Helv. Chim. Acta 64 (1981) 1023e1025;
(b) Y. Ikeda, J. Ukai, N. Ikeda, H. Yamamoto, Tetrahedron 43 (1987) 743e753.
[10] For a review, see:, K. Inomata, J. Synth. Org. Chem., Jpn. 67 (2009) 1172e1182.
[11] For an example of the isomerisation of a vinyl sulfone in natural product
synthesis, see:, S.V. Ley, A. Armstrong, D. Díez-Martín, M.J. Ford, P. Grice,
J.G. Knight, H.C. Kolb, A. Mardin, C.A. Marby, S. Mukherjee, A.N. Shaw,
A.M.Z. Slawin, S. Vile, A.D. White, D.J. Williams, M. Woods, J. Chem. Soc.,
Perkin Trans. 1 (1991) 667e692.
Acknowledgements
We thank the Irish Research Council for a Postgraduate Schol-
arship (GOIPG/2017/648). Drs Helge Muller-Bunz and Yannick Ortin
are thanked for X-ray crystallography and NMR spectroscopy
respectively and Amber Harrison (UCD) is thanked for the synthesis
of compound 22 and contributions from Drs. William Doherty and
Robert Connon are acknowledged.
[12] (a) R.W. Hoffmann, S. Goldmann, N. Maak, R. Gerlach, F. Frickel, G. Steinbach,
Chem. Ber. 113 (1980) 819e830;
(b) K. Burgess, J. Cassidy, J. Henderson, J. Org. Chem. 56 (1991) 2050e2058.
[13] A.M. Modro, T.A. Modro, Can. J. Chem. 66 (1988) 1541e1545.
[14] E. Block, M. Aslam, K. Eswarakrishnan Gebreyes, J. Hutchinson, R. Iyer, J.-
A. Laffitte, A. Wall, J. Am. Chem. Soc. 108 (1986) 4568e4580.
Appendix A. Supplementary data
ꢀ
[15] N. Collins, R. Connon, G. Sanchez-Sanz, P. Evans, Eur. J. Org Chem. (2020)
6228e6235.
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2021.131933.
[16] For reviews focussing on vinyl azide synthesis and chemistry, see:. (a)
S. Chiba, Synlett (2012) 21e44;
(b) B. Hu, S.G. DiMagno, Org. Biomol. Chem. 13 (2015) 3844e3855;
(c) H. Hayashi, A. Kaga, S. Chiba, J. Org. Chem. 82 (2017) 11981e11989.
[17] J.E. Hein, V.V. Fokin, Chem. Soc. Rev. 39 (2010) 1302e1315.
[18] For examples of the synthesis of vinyl traizoles, see:. (a) D. Caprioglio,
S. Torretta, M. Ferrari, C. Travelli, A.A. Grolla, F. Condorelli, A.A. Genazzani,
A. Minassi, Bioorg. Med. Chem. 24 (2016) 140e152;
(b) L.L. Baldassari, E.A. Cechinatto, A.V. Moro, Green Chem. 21 (2019)
3556e3560.
[19] Note, for 1,2-disubstituted Vinyl Triazoles (13-15) the Z-Stereochemistry Can
Be Inferred from the 3J-Values (9.0 to 9.5 Hz). For Trisubstituted Vinyl Tri-
azoles (17 and 18) a Combination of Chemical Shift and NOESY Data Support
the Assignments.
[20] CCDC deposition number 2039566 contains the supplementary crystallo-
graphic data. These data are available free of charge by the joint Cambridge
Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access
Structure services [www.ccdc.cam.ac.uk/structures].
[21] For a similar example featuring the loss of a TMS group in a CuAAC reaction,
see:, S.-Q. Bai, L. Jiang, T.S.A. Hor, Dalton Trans. 44 (2015) 6075e6081.
[22] For a review, see:, Y.-L. Zhang, Y.-F. Li, B. Yu, L.-H. Shan, H.-M. Liu, Synth.
Commun. 45 (2015) 2159e2180. For a recent stereocontrolled synthesis of a
Z-enamide see: Geldsetzer, J.; Kalesse, M. Beilstein J. Org. Chem. 2020, 16,
670-673.
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6