Intramolecular cascade rearrangements of enynamine derived ketenimines: Access to acyclic and cyclic amidines

Article abstract of DOI:10.1039/c7ob00499k

Copper-catalyzed reaction of enynamines with sulfonylazides provides acyclic and cyclic amidines. Nucleophilic addition of the tethered amino group on the in situ generated ketenimine forms a six-membered cyclic zwitterionic intermediate which facilitates

Full text of DOI:10.1039/c7ob00499k

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DOI: 10.1039/C7OB00499K
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Intramolecular cascade rearrangements of enynamine derived
ketenimines: Access to acyclic and cyclic amidines
Received 00th January 20xx,
Accepted 00th January 20xx
Dinesh Pratapsinh Chauhan,a Sreejith J. Varma,a,b Mahesh Gudem,a Nihar Panigrahi,a Khushboo
Singh,a,c Anirban Hazra,a and Pinaki Talukdar*a
DOI: 10.1039/x0xx00000x
Copper-catalyzed reaction of enynamines with sulfonylazides provides acyclic and cyclic amidines. Nucleophilic addition of
the tethered amino group on the in situ generated ketenimine forms a six-membered cyclic zwitterionic intermediate
which facilitates migration of the tethered amino group to the C5-center giving the acyclic amidine. On the other hand,
migration of a substituent on the amino group to C2- and C4-centers results in the formation of cyclic amidines.
Computational studies were carried out to validate the mechanism which indicate that the product distribution of the
process depends on the substitutions on the enynamine backbone.
www.rsc.org/
rearrangements.3b,3c,8 For example, N-sulfonyl/phosphoryl
ketenimine undergoes addition reactions with external
nucleophiles e.g. amines, alcohols, pyrroles, indoles,
Introduction
Since the dawn of modern chemistry, reactive intermediates
have served as an inspiration for the development of new
reactions, molecules, and materials. Indeed, the strategies
involving reactive intermediates have made possible the
construction of numerous complex organic frameworks in
easier and shorter routes. In general, reactive intermediates
readily undergo chemical transformations, and their reactions
are typically exothermic.1 Among several reactive entities in
organic chemistry, ketenimines represent an important class of
reactive intermediates which has been applied widely as a
powerful synthon. During last two decades, several
methodologies were developed towards the formation of
ketenimine, and to explore its synthetic applications.2 Because
of the remarkable reactivity, the ketenimine was
comprehensively applied in the synthesis of many complex
compounds.3 Interception of this reactive species with other
functional groups led to novel strategies for the reaction
discovery.4 Going through literature, it is observed that
ketenimine undergoes nucleophilic addition,2i cycloaddition,5
radical addition,6 electrocyclic ring-closure reactions,7 and σ
ammonium salts, etc.2i
In 2014, we reported a novel rearrangement of ketenimine
intermediate, generated from the substituted propargylamine
I, by an internal amine nucleophile forming amidine Ia via the
[1,3]-amino group migration (Scheme 1A).9 Our success in this
area prompted us to investigate the possibilities of new
rearrangement reactions of ketenimine, envisaged through the
incorporation of an additional alkene moiety at the C2-C3
position. Here, we report that such structural modification
leads to not only the formation of acyclic amidine IIa but also
allows the access to highly functionalized cyclic amidines IIb
and IIc from II (Scheme 1B).
a Department of Chemistry, Indian Institute of Science Education and Research
Pune, Dr. Homi Bhabha Road, Pashan, Pune 411008, Maharashtra, India.
Email: ptalukdar@iiserpune.ac.in
b
Present address: Institut de Science et d’Ingénierie Supramoléculaires (ISIS),
Université de Strasbourg, 8 allée Gaspard Monge BP 70028 F-67000, Strasbourg
Cedex, France.
c
Present address: Department of Chemistry, University of Massachusetts Amherst,
Amherst, Massachusetts 01003, United States.
Scheme 1. Reaction of propargylamine I with sulfonylazide under Cu(I) catalyzed
conditions giving amidine Ia as the [1,3]-amino group migration product (A). Reaction
enynamine II with sulfonylazide under Cu(I) catalyzed conditions in the formation of
acyclic and cyclic amidines IIa-IIc (B).
†
We gratefully acknowledge SERB, Govt. of India (EMR/2014/000873B) for
funding our work. DPC thanks CSIR, Govt. of India for research fellowship.
‡ Electronic Supplementary Information (ESI) available: Synthetic procedures and
experimental methods, additional experimental details and NMR spectra. See
DOI: 10.1039/x0xx00000x
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Table 1. Formation of [1,5]-amino group migration products from enynamines.
Results and discussion
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DOI: 10.1039/C7OB00499K
We started our preliminary investigation with the conjugated
enynamine substrate 1, where the amino moiety is the 4-
morpholinyl group. The reaction of 1 with TsN3 (1.1 equiv) in
presence of catalytic CuI (10 mol%) and Et3N (1.5 equiv) in
CHCl3 provided the [1,5]-amino group migration product 1a in
67% yield (Table 1, Entry 1). When substrates 2-4 were used by
introducing phenyl group at either C2- or C3- or both positions,
corresponding [1,5]-amino group migration products 2a-4a
were formed (Entries 2-4). The observations were comparable
when enynamine substrates were decorated with acyclic
amino groups, and C2- and C3-positions were also randomly
substituted with a phenyl group (Entries 5-8).
An interesting twist in the product formation was observed
when the enyne was decorated with the -NBn2 group. Such a
substrate 9 with R3 = R4 = H when reacted with TsN3 under the
CuI catalytic conditions, cyclic amidines 9b (51%) and 9c (16%)
were formed apart from the expected acyclic amidine 9a (23%)
(Table 2, entry 1). The general plausible mechanism of the
process is depicted in Scheme 2. Reaction of enynamine II with
a sulfonylazide under Cu(I) catalytic conditions provides the
triazole intermediate IId which upon releasing a N2 molecule
gives ketenimine IIe.10 Capture of IIe by the internal amino
group leads to the 6-exo-dig cyclization11 to form the
zwitterionic intermediate IIf which has canonical forms IIg and
IIh. The C1–N bond cleavage of the cyclic intermediate IIf via
E1cB process leads to the formation of [1,5]-amino group
migration product IIa. The electrophilic migration of the R1
Entry
1-8
1
2
3
4
5
6
7
8
-NR1R2
-(4-morpholinyl)
-(4-morpholinyl)
-(4-morpholinyl)
-(4-morpholinyl)
-N(Et)2
R3
H
Ph
H
Ph
H
H
R4
H
1a-8a (Yield)a
1a (67%)
2a (76%)
3a (70%)
4a (65%)
5a (67%)
6a (57%)
7a (62%)
8a (62%)
1
2
3
4
5
6
7
8
H
Ph
Ph
Ph
H
H
Ph
-N(iPr)2
-N(nHex)2
H
H
-N(nHex)2
aAll yields are isolated yields.
group of the intermediate IIf to its C2-center gives the cyclic
amidine IIb. On the other hand, an electrophilic migration of
the R1 group to the C4-center facilitates the formation of
adduct IIc.
We further investigated the effects of R and R1‒R4 groups
on product distribution to obtain greater insight on observed
rearrangement processes. All conjugated enynamine
substrates were prepared according to three general
sequences outlined in Schemes S1, S3, S5 and S7.12 The -NBn2
substituted enynamine 10 (R3 = Ph, R4 = H), when treated with
TsN3, cyclic amidines 10b (50%) and 10c (40%) were
Table 2. Scope of Cu(I) catalyzed reaction of enynamine and sulfonylazide.
Entry
1
2
3
4
5
6
7
8
9-24
9
R
R1
Bnb
Bn
Bn
R2
Bn
Bn
Bn
R3
H
Ph
H
Ph
H
Ph
H
Ph
H
Ph
H
Ph
H
Ph
H
R4
H
9a-26a (Yield)a
9a (23%)
9b-26b (Yield)a
9b (51%)
10b (50%)
11b (5%)
9c-26c (Yield)a
9c (16%)
10c (40%)
11c (0%)
12c (0%)
13c (23%)
14c (32%)
15c (0%)
16c (0%)
17c (12%)
18c (11%)
19c (6%)
20c (0%)
21c (23%)
22c (25%)
23c (0%)
24c (0%)
25c (34%)
26c (0%)
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
Me
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
10
11
H
10a (0%)
Ph
Ph
H
11a (84%)
12a (48%)
13a (13%)
14a (0%)
15a (77%)
16a (73%)
17a (0%)
18a (0%)
19a (8%)
20a (0%)
21a (14%)
22a (0%)
Bn
Bn
12b (30%)
13b (37%)
14b (51%)
15b (0%)
16b (18%)
17b (63%)
18b (60%)
19b (70%)
20b (68%)
21b (39%)
22b (50%)
23b (0%)
4-CNBnc
4-CNBn
4-CNBn
4-CNBn
4-MeOBnd
4-MeOBn
4-MeOBn
4-MeOBn
Bn
4-CNBn
4-CNBn
4-CNBn
4-CNBn
4-MeOBn
4-MeOBn
4-MeOBn
4-MeOBn
4-CNBn
4-CNBn
4-CNBn
4-CNBn
Bn
H
Ph
Ph
H
9
10
11
12
13
14
15
16
17
18
H
Ph
Ph
H
Bn
Bn
Bn
Bn
H
Ph
Ph
H
23a (86%)
24a (46%)
25a (0%)
Ph
Ph
H
24b (29%)
25b (52%)
26b (25%)
4-NO2C6H4
Bn
Bn
Ph
26a (49%)
aAll yields are isolated yields. bBn = Benzyl, c4-CNBn = 4-cyanobenzyl, d4-MeOBn = 4-methoxybenzyl.
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Fig. 1 Single crystal XRD structures of cyclic amidine 10b (A) and acyclic amidine 11a (B)
presented as stick model.
Calculations on the enynamine II with R1 = R2 = Bn, and
different combinations of H and Ph for R3, R4 corresponding to
substrates 9-12 were performed using DFT (B3LYP/6-31G). In
these cases, obtaining the transition state structures using the
MP2 method, which is significantly more computationally
demanding than DFT, is impractical. The transition state
structures and consequently barrier heights using DFT
corresponding to products IIa and IIb were obtained (Table
S2). The transition state for IIc proved elusive in spite of using
several techniques and initial structures to search for it. Since
the MP2 barriers are more reliable, we applied a correction to
the DFT barriers to estimate them better using the results of
the simplified enynamine III where both MP2 and DFT barriers
were calculated. Assuming that there are similar differences in
MP2 and DFT calculated barrier heights in the present case as
in III, we applied the calculated difference in III as a correction
to the present case (Table S2). The corrected barrier heights
uniformly predict the trends in the observed product
distribution, thus supporting the proposed mechanism.
Inspection of the intermediate structures suggests that a
phenyl group at the C2-center (i.e. for substrate 10) increases
the contributions of IIg and IIh through further delocalization
of the negative charge. Enhancement of negative charge at C2-
and C4-centers further favors the attacks on the R1 group from
these sites thereby, stabilizing corresponding transition states.
In case of 11, the phenyl group at C3-center does not
contribute significantly to the stabilization of the negative
charge on the intermediate IIf. Therefore, IIf facilitates a C1-N
bond cleavage leading to the formation of [1,5]-migration
product. For 12, the substitution of phenyl groups at C2-center
again opens the scope of R1 group migration.
Scheme 2. Proposed general mechanism for the formation of IIa, IIb and IIc from II.
obtained as rearranged products (Entry 2). Corresponding
acyclic amidine 10a could not be traced from the reaction
mixture. On the contrary, the substrate 11 (R3 = H, R4 = Ph)
under similar reaction conditions provided 11a (84%) as the
major isomer (Entry 3). In this case, the isomer 11b was
isolated as the minor product, and formation of 11c could not
be detected. Similar reaction of 12 (R3 = R4 = Ph) gave two
products 12a (48%) and 12b (30%) (Entry 4). Apart from one
1
dimensional H and 13C NMR studies, the molecular structures
acyclic and cyclic amidines were further confirmed using either
single crystal X-ray diffraction (e.g. Fig. 1 for 10b and 11a) or
1
1
two-dimensional NMR spectroscopic (e.g. H-1H COSY and H-
13C HETCOR for 9c, 21c and 25c) analysis (see ESI).
Quantum chemical calculations were done to validate the
proposed mechanism and rationalize the product distribution.
For a simplified version of enynamine III with R1 = R2 = Me, R3 =
R4 = H (Fig. S7), optimized structures of the cyclic intermediate
IIIf (Fig. 2), and corresponding products IIIa, IIIb, and IIIc were
obtained using the MP2 and DFT (B3LYP) methods with the 6-
31G basis set (Fig. S7). Transition state structures IIIa′, IIIb′ and
IIIc′ corresponding to these products (Fig. 2), and the reaction
barrier of each process were also obtained (Table S1). Small
differences in the barrier heights between MP2 and DFT for a
given product were observed. The MP2 method is known to be
more reliable than DFT (B3LYP) for calculating reaction
barriers,[13] but the former is computationally more expensive
than the latter.
Having established the effect of substituents at C2- and C3-
centers, we next evaluated the effects of different p-
substituted arylmethylene groups at R1 and R2 positions in
controlling the product distribution. For enynamines 13-16,
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designed with R1 = R2 = 4-CNBn, and varying R3 and R4 groups
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among and Ph, the distributions of products were
H
comparable to that observed with 9-12 (Entries 5-8). However,
for substrates 17-20 with of R1 = R2 = 4-MeOBn, an interesting
bias of product distribution towards cyclic systems was
observed (Entries 9-12). For example, the substrate 17 (R3 = R4
= H) upon reaction with TsN3 gave only cyclic products 17b
(63%) and 17c (12%). Therefore, the electron rich aromatic
moiety of 4-MeOBn contributes significantly in shifting the
course of rearrangement towards cyclic products due to the
higher migratory aptitude of the 4-OMeBn group.
Subsequently, the migratory aptitudes of Bn and 4-CNBn
groups were compared by considering enynamines 21-24.
Compound 21 (R3 = R4 = H) when reacted with TsN3,
compounds 21a-21c were formed in 14%, 39% and 23% yields,
respectively (Entry 13). Structural analysis of 21b and 21c
clearly indicated the migration of the benzyl group to either
C2- or C4-position (see ESI). For the substrates 21-24, the
trends in product distribution are similar to the corresponding
substrates 9-12 as might have been expected (Entries 14, 16).
Substrate 23 (R3 = H and R4 = Ph) however, gave only 23a
(86%) as expected (Entry 15). As anticipated, the substitutions
on the sulfonyl group did not have any contribution in
changing the product distribution for substrates 10 and 11
(Entries 17, 18).
Scheme 3. Synthesis of bridged bicycloamidine 28 (A). [2+2] Cycloaddition of 11a with
in situ generated benzyne (B).
To get an experimental evidence of the zwitterionic cyclic
Fig. 3 Single crystal XRD structures of cyclic amidine 28 (A) and acyclic amidine 30 (B)
intermediate, a 2-vinylpiperidine substituted enynamine 27 presented as stick model.
was designed. Reaction of 27 with TsN3 gave bicycloamidine 28
as single product (Scheme 3A) and this structure was
unambiguously confirmed by X-ray crystallographic data
analysis (Fig. 3A). Therefore, the ketenimine intermediate 27a
forms the cyclic intermediate 27b which subsequently
undergoes aza-Claisen rearrangement14 by an attack from C4-
to C4'-position followed by migration of the double bond from
when reacted with highly reactive benzyne, generated from
29, compound 30 was formed as an exclusive [2+2]
cycloaddition15 product (Scheme 3B). Such observation is
unique because a thermal [4+2] cycloaddition16 is more
common under the applied conditions. The structure of 30 was
confirmed by X-ray crystallographic data analysis (Fig. 3B).
C4'=C3' to the C3'=C2', and cleavage of the C2'N bond (Scheme
S9). Compound 11a, a representative conjugated acyclic diene,
Conclusions
In conclusion, we have demonstrated the reaction of
substituted enynamines with sulfonylazides under Cu(I)
catalytic conditions providing acyclic and cyclic amidines.
Structures of these products were confirmed by NMR and
single crystal X-ray diffraction studies. The central carbon of in
situ formed ketenimine was attacked by tethered amino group
in the 6-exo-dig cyclization mode followed by breaking of C-N
bond in the E1cB fashion gives acyclic amidines. On the other
hand, the delocalization of negative charge on the cyclic
zwitterionic intermediate facilitated the transfer of a nitrogen
substituent to C3- and C5-centers leading to the formation of
cyclic amidines. The mechanism and the product distribution
of these reactions were evaluated by computational studies.
Two interesting applications of the strategy were illustrated
through the formation of a bridged bicycloamidine and a [2+2]
cycloaddition reaction.
Fig. 2 Structures of the intermediate IIIf (A), and transition states IIIa′, IIIb′ and IIIc′ (B-
D) for the formation of IIIa, IIIb and IIIc calculated at the MP2/6-31G level.
Experimental
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General Information
47.6, 44.1, 29.8, 21.6; HRMS (ESI): Calc. for C22H25N2O3S [M+H]+:
397.1586; Found: 397.1584.
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DOI: 10.1039/C7OB00499K
All the chemicals were purchased from commercial sources
and used as received unless stated otherwise. All reactions
were carried out under the nitrogen atmosphere. Solvents:
dichloromethane (DCM), ethyl acetate (EtOAc), methanol
(MeOH) and petroleum ether, were distilled prior to thin layer
and column chromatography. Column chromatographic
purification was performed on silica gel (100–200 mesh). TLC
was carried out with silica gel 60-F-254 plates.
3a: Isolated yield: 70%, 122 mg. Colorless semi-solid, IR (neat):

max/cm-1 2967, 2920, 2860, 1721, 1597, 1521, 1443, 1344, 1344,
1
1275, 1225, 1150, 1113, 1088, 1029; H NMR (400 MHz, CDCl3): δ
7.74 (d, J = 8.3 Hz, 2H), 7.44 – 7.35 (m, 5H), 7.18 (d, J = 7.9 Hz, 2H),
6.25 (s, 1H), 6.20 (dd, J = 17.3, 10.8 Hz, 1H), 5.30 (dt, J = 10.8, 1.2
Hz, 1H), 5.20 (d, J = 17.3 Hz, 1H), 3.96 – 3.89 (m, 2H), 3.80 – 3.75 (m,
2H), 3.72 – 3.67 (m, 2H), 3.62 – 3.56 (m, 2H), 2.38 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 163.3, 145.2, 142.1, 140.4, 137.7, 132.1, 129.1,
128.7, 128.6, 128.5, 126.9, 122.8, 119.7, 66.7, 66.3, 47.8, 44.8, 29.8,
21.5; HRMS (ESI): Calc. for C22H25N2O3S [M+H]+: 397.1586; Found:
397.1584.
1
The H and 13C NMR spectra were recorded on 400 MHz Jeol
400 MHz (or 100 MHz for 13C) spectrometers using either
residual solvent signal as an internal reference or from internal
tetramethylsilane on the δ scale (CDCl3: δH 7.24 ppm, δC 77.0
ppm). The chemical shifts (δ) are reported in ppm and coupling
constants (J) in Hz. The following abbreviations are used: m
(multiplet), s (singlet), br s (broad singlet), d (doublet), t
(triplet) dd (doublet of doublet), dt (doublet of triplet), q
(quartet), sex (sextet), and sept (septet). High-resolution mass
spectra were recorded using Micro Mass ESTOF MS
spectrometer. (FT-IR) spectra were recorded using Bruker: α
ALPHA spectrophotometer (neat) and reported in cm-1. Crystal
structures were recorded on a Bruker single crystal X-Ray
diffractometer.
4a: Isolated yield: 65%, 101 mg. Colorless semi-solid. IR (neat):

max/cm-1 2967, 2920, 2860, 1721, 1597, 1521, 1443, 1344, 1344,
1
1275, 1225, 1150, 1113, 1088, 1029; H NMR (400 MHz, CDCl3): δ
7.72 (d, J = 8.3 Hz, 2H), 7.43 – 7.39 (m, 2H), 7.34 (m, 3H), 7.26 (dd, J
= 6.7, 3.3 Hz, 2H), 7.23 – 7.19 (m, 3H), 7.17 (d, J = 8.0 Hz, 2H), 6.79
(s, 1H), 5.86 (d, J = 0.6 Hz, 1H), 5.34 (s, 1H), 3.58 (s, 4H), 3.40 (s, 2H),
3.25 (s, 2H), 2.40 (s, 3H); 13C NMR (101 MHz, CDCl3): δ 162.49,
148.81, 143.98, 142.01, 140.37, 139.06, 137.34, 129.04, 128.76,
128.65, 128.54, 128.18, 128.06, 127.96, 127.41, 126.88, 126.56,
119.30, 119.03, 66.11, 65.68, 48.12, 44.53, 21.49; HRMS (ESI): Calc.
for C28H29N2O3S [M+H]+: 473.1899; Found: 473.1894.
General procedure for the copper catalyzed reaction of 1 with
tosyl azide
General procedure for the copper catalyzed reaction of 9 with
tosyl azide
The reaction conditions and results are shown in Tables 1. A typical
procedure is given for the reaction of 1 with tosyl azide (Table 1,
entry 1). To the solution of enynamine 1 (100 mg, 0.6 mmol) in
chloroform (3.0 mL) was added tosyl azide (156 mg, 0.8 mmol), Et3N
(108 mg, 1.0 mmol) followed by CuI (12 mg, 10 mol%) and stirred
for 30 minutes at room temperature. The reaction was quenched by
saturated NH4Cl and compound was extracted in chloroform (15 mL
× 2). Solvent was evaporated and obtained crude product was
purified by column chromatography (Eluent: 30% EtOAc in hexane)
to afford the desired acyclic amidine product 1a (142 mg, 67% yield)
as a colorless semi-solid.
The reaction conditions and results are shown in Tables 2. To the
solution of enynamine 9 (100 mg, 0.3 mmol) in chloroform (3.0 mL)
was added tosyl azide (90 mg, 0.4 mmol), Et3N (50 mg, 0.5 mmol)
followed by CuI (6.0 mg, 10 mol%) and stirred for 30 minutes at
room temperature. The reaction was quenched by sat. NH4Cl and
compound was extracted in chloroform (15 mL × 2). Solvent was
evaporated and obtained crude product was purified by column
chromatography (Eluent: 20% EtOAc in hexane) to afford amidine
products 9a (38 mg, 23% yield), 9b (84 mg, 51% yield) and 9c (26
mg, 16% yield) as colorless semi-solids.
1a: IR (neat): max/cm-1 3743, 3678, 3648, 3619, 2967, 2921, 2861,
9a: Isolated yield: 23%, 38 mg. Colorless semi-solid, IR (neat):

max/cm-1 3744, 3027, 2925, 2864, 1739, 1692, 1639, 1533, 1484,
2319, 1740, 1693, 1643, 1595, 1519, 1476, 1444, 1346, 1273, 1190,
1
1
1383, 1342, 1273, 1139, 1083, 1026; H NMR (400 MHz, CDCl3): δ
7.76 (d, J = 8.2 Hz, 2H), 7.40 – 7.31 (m, 6H), 7.24 (m, 2H), 7.20 (d, J =
8.0 Hz, 2H), 7.12 (d, J = 6.5 Hz, 2H), 6.33 (m, 2H), 6.08 (m, 1H), 5.35
(dt, J = 16.7 Hz, 0.7 Hz, 1H), 5.22 (d, J = 10 Hz, 1H), 4.72 (br.s, 2H),
4.5 (s, 2H), 2.4 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 165.3, 141.8,
137.1, 135.2, 130.2, 129.1, 128.7, 128.1, 128.1, 126.5, 126.2, 121.9,
53.2, 48.2, 21.5; HRMS (ESI): Calc. for C26H27N2O2S [M+H]+:
431.1793.
1141, 1114, 1087; H NMR (400 MHz, CDCl3): δ 7.71 (d, J = 8.2 Hz,
2H), 7.17 (d, J = 8.2 Hz, 2H), 6.30 (t, J = 11.4 Hz, 1H), 6.16 (d, J = 11.5
Hz, 1H), 5.96 (dt, J = 16.7 Hz, 10.7 Hz, 1H), 5.32 (d, J = 16.9 Hz, 1H),
5.21 (d, J = 10.0 Hz, 1H), 3.81 ( t, J = 4.5 Hz, 2H), 3.68 (t, J = 5.0 Hz,
2H), 3.59 (t, J = 5.0 Hz, 2H), 3.46 (t, J = 5.0 Hz, 2H), 2.33(s, 3H); 13C
NMR (100 MHz, CDCl3): δ 163.1, 142.1, 140.2, 135.4, 131.3, 129.1,
126.9, 123.6, 120.3, 66.7, 66.3, 47.9, 44.7, 21.5; HRMS (ESI): Calc.
for C16H21N2O3S [M+H]+: 321.1273; Found: 321.1281.
9b: Isolated yield: 51%, 84 mg. Colorless semi-solid, IR (neat):
2a: Isolated yield: 76%, 132 mg. Colorless semi-solid, IR (neat):
max/cm-1 3742, 3029, 2924, 2863, 1740, 1691, 1638, 1531, 1481,

max/cm-1 2967, 2920, 2860, 1721, 1597, 1521, 1443, 1344, 1344,

1
1
1382, 1340, 1270, 1137, 1081, 1025; H NMR (400 MHz, CDCl3): δ
7.85 (d, J = 8.2 Hz, 2H), 7.33 (m, 3H), 7.24 – 7.20 (m, 9H), 6.84 (dd, J
= 7.7 Hz, 2.3 Hz, 2H), 6.58 (dd, J = 9.8 Hz, 4.16 Hz, 1H), 4.92 (d, J =
14.4 Hz, 1H), 4.51 (d, J = 14.4 Hz, 1H), 3.37 (dd, J = 12.8 Hz, 5.6 Hz,
1H), 3.17 (dd, J = 12.7 Hz, 5.8 Hz, 1H), 2.67 (m, 2H), 2.41 (dd, J =
11.4, 4.6 Hz, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 157.9,
144.0, 142.1, 141.2, 137.7, 135.9, 129.2, 128.9, 128.9, 128.7, 128.6,
1275, 1225, 1150, 1113, 1088, 1029; H NMR (400 MHz, CDCl3): δ
7.83 (d, J = 8.2 Hz, 2H), 7.34 (dd, J = 6.6, 3.3 Hz, 3H), 7.32 – 7.22 (m,
7H), 6.71 (dd, J = 12.4, 0.8 Hz, 1H), 6.48 (d, J = 12.5 Hz, 1H), 5.52 (s,
1H), 5.44 (s, 1H), 3.46 (dd, J = 11.3, 6.4 Hz, 4H), 3.34 (s, 2H), 2.39 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 162.2, 143.8, 142.2, 140.6, 138.2,
136.4, 129.2, 128.5, 128.4, 126.7, 126.7, 120.7, 120.4, 66.3, 65.7,
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Journal Name
128.1, 126.8, 126.4, 119.9, 52.8, 48.9, 37.3, 35.7, 21.6; HRMS (ESI): 3.16 Hz, 1H), 2.39 (s, 3H), 2.31 (dd, J = 14.0 Hz, 11.V0iewHzA,rti1clHe )O;n1li3nCe
Calc. for C26H27N2O2S [M+H]+: 431.1793; Found: 431.1790.
DOI: 10.1039/C7OB00499K
NMR (100 MHz, CDCl3): δ 158.5, 153.7, 142.0, 141.5, 138.3, 136.1,
135.9, 130.5, 129.3, 129.2, 129.1, 129.0, 128.9, 128.7, 128.2, 127.0,
9c: Isolated yield: 16%, 26 mg. Colorless semi-solid. IR (neat):

max/cm-1 3743, 3030, 2925, 2859, 1708, 1647, 1597, 1552, 1516,
126.7, 126.4, 114.7, 52.6, 47.2, 38.0, 36.1, 21.5; HRMS (ESI): Calc.
for C32H31N2O2S [M+H]+: 507.2106; Found: 507.2110.
1495, 1450, 1341, 1270, 1141, 1084, 1029; 1H NMR (400 MHz,
CDCl3): δ 7.80 (d, J = 8.24 Hz, 2H), 7.28 – 7.21 (m, 10H), 7.09 (dd, J = 12a: Isolated yield: 48%, 68 mg. Colorless semi-solid. IR (neat):
7.16 Hz, 1.6 Hz, 2H), 5.74 (m, 2H), 4.91 (d, J = 14.54 Hz, 1H), 4.74 (m, /cm-1 3744, 3035, 2933, 2866, 1723, 1688, 1645, 1538, 1481, 1382,
1H), 4.26 (d, J = 14.6 Hz, 1H), 3.50 (m, 1H), 3.35 (dd, J = 13 Hz, 7.7 1342, 1275, 1138, 1088, 1021; 1H NMR (400 MHz, CDCl3): δ 7.77 (d,
Hz, 1H), 3.06 (d, J = 17.5 Hz, 1H), 2.41 (s, 3H); 13C NMR (101 MHz, J = 8.3 Hz, 2H), 7.40 – 7.34 (m, 6H), 7.31 (m, 6H), 7.19 (d, J = 8.0 Hz,
CDCl3): δ 165.3, 141.7, 141.6, 137.0, 135.2, 130.1, 129.1, 128.7, 2H), 7.17 – 7.01 (m, 10H), 6.90 (s, 1H), 5.69 (d, J = 0.6 Hz, 1H), 5.37
128.0, 128.0, 127.8, 126.6, 126.4, 126.1, 121.7, 53.1, 48.1, 40.4, (d, J = 0.5 Hz, 1H), 2.41 (s, 3H); 13C NMR (101 MHz, CDCl3): δ 163.9,
40.2, 21.4; HRMS (ESI): Calc. for C26H27N2O2S [M+H]+: 431.1793; 148.0, 142.7, 141.9, 140.6, 138.8, 137.1, 135.5, 135.3, 129.1, 129.1,
Found: 431.1792.
129.0, 128.9, 128.6, 128.4, 128.3, 128.1, 127.8, 127.7, 127.2, 127.1,
126.8, 126.7, 119.6, 119.3, 52.2, 49.6, 21.5; HRMS (ESI): Calc. for
C38H35N2O2S [M+H]+: 583.2419; Found: 583.2430.
10b: Isolated yield: 50%, 75 mg. Colorless semi-solid. IR (neat):
/cm-1 3008, 2931, 2838, 1621, 1577, 1534, 1514, 1467, 1441, 1381,
1275, 1246, 1174, 1140, 1113, 1084, 1032; 1H NMR (400 MHz, 12c: Isolated yield: 30%, 43 mg. Colorless semi-solid. IR (neat):
CDCl3): δ 7.79 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 10.2 Hz, 1H), 7.28 – /cm-1 3738, 3032, 2925, 2867, 1722, 1687, 1638, 1531, 1483, 1382,
7.08 (m, 11H), 7.04 (d, J = 6.9 Hz, 2H), 6.98 (dd, J = 8.1, 1.5 Hz, 2H), 1344, 1277, 1133, 1077, 1032; 1H NMR (400 MHz, CDCl3): δ 7.73 (d,
6.79 (d, J = 10.2 Hz, 1H), 6.65 (d, J = 6.8 Hz, 2H), 4.81 (d, J = 14.6 Hz, J = 8.0 Hz, 4H), 7.63 (s, 2H), 7.42 – 7.31 (m, 7H), 7.28 – 7.13 (m,
1H), 4.54 (d, J = 14.6 Hz, 1H), 3.58 (s, 2H), 3.04 (d, J = 13.5 Hz, 1H), 23H), 7.13 – 7.02 (m, 8H), 6.76 (d, J = 7.5 Hz, 4H), 6.61 (d, J = 7.4 Hz,
2.92 (d, J = 13.5 Hz, 1H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 4H), 4.92 (d, J = 14.7 Hz, 2H), 4.06 (d, J = 14.7 Hz, 2H), 3.91 (d, J =
157.8, 146.6, 142.0, 141.2, 140.8, 135.3, 135.2, 130.4, 129.2, 128.7, 13.0 Hz, 2H), 3.46 (d, J = 14.3 Hz, 2H), 3.39 (d, J = 13.0 Hz, 2H), 3.26
128.4, 128.1, 127.8, 127.4, 127.0, 126.5, 126.4, 120.1, 56.2, 52.9, (d, J = 14.3 Hz, 2H), 2.41 (s, 6H); 13C NMR (101 MHz, CDCl3): δ
44.7, 44.0, 21.6; HRMS (ESI): Calc. for C32H31N2O2S [M+H]+: 157.52, 156.04, 141.74, 141.46, 141.31, 137.96, 135.91, 134.88,
507.2106; Found: 507.2115.
130.55, 129.29, 129.01, 128.73, 128.49, 128.46, 128.37, 128.02,
128.01, 127.45, 127.33, 127.14, 126.90, 126.37, 121.50, 57.74,
52.28, 47.61, 42.00, 21.46; HRMS (ESI): Calc. for C38H35N2O2S
[M+H]+: 583.2419; Found: 583.2420.
10c: Isolated yield: 40%, 60 mg. Colorless semi-solid. IR (neat):
/cm-1 3018, 2935, 2831, 1624, 1575, 1535, 1511, 1471, 1444, 1382,
1271, 1244, 1184, 1148, 1121, 1094, 1038; 1H NMR (400 MHz,
CDCl3): δ 7.88 (d, J = 8.3 Hz, 2H), 7.35 – 7.30 (m, 3H), 7.29 – 7.17 (m, 13a: Isolated yield: 13%, 20 mg. Colorless semi-solid. IR (neat):
11H), 7.13 (m, 4H), 6.05 (dd, J = 5.6, 2.7 Hz, 1H), 4.94 (d, J = 14.5 Hz, /cm-1 3022, 2918, 2218, 1713, 1625, 1545, 1488, 1441, 1412, 1338,
2H), 4.33 (d, J = 14.6 Hz, 1H), 3.77 (dd, J = 17.1, 1.7 Hz, 1H), 3.56 1276, 1225, 1178, 1141, 1083, 1021;1H NMR (400 MHz, CDCl3): δ
(dd, J = 13.1, 7.2 Hz, 1H), 3.29 (dd, J = 13.1, 3.5 Hz, 1H), 3.20 (dt, J = 7.73 – 7.67 (m, 4H), 7.60 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H),
17.1, 2.9 Hz, 1H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 165.0, 7.23 (d, J = 7.9 Hz, 4H), 6.43 (t, J = 11.4 Hz, 1H), 6.24 (d, J = 11.6 Hz,
141.8, 141.6, 136.9, 135.0, 133.4, 130.2, 129.1, 128.7, 128.7, 128.2, 1H), 6.05 (dt, J = 16.8, 10.6 Hz, 1H), 5.42 (d, J = 16.7 Hz, 1H), 5.31 (d,
128.1, 128.0, 127.8, 126.7, 126.2, 124.9, 122.3, 53.3, 49.9, 40.8, J = 10.1 Hz, 1H), 4.77 – 4.66 (m, 2H), 4.61 (s, 2H), 2.42 (s, 3H); 13C
40.4, 21.4; HRMS (ESI): Calc. for C32H31N2O2S [M+H]+: 507.2106; NMR (100 MHz, CDCl3): δ 164.6, 142.6, 140.8, 140.1, 139.7, 136.1,
Found: 507.2115.
133.0, 132.6, 130.9, 129.1, 129.0, 127.8, 126.7, 124.4, 119.9, 52.2,
50.3, 29.7, 21.5; HRMS (ESI): Calc. for C28H25N4O2S [M+H]+:
481.1698; Found: 481.1702.
11a: Isolated yield: 84%, 126 mg. Colorless semi-solid. IR (neat):
/cm-1 3740, 3025, 2922, 2862, 1733, 1690, 1635, 1530, 1480, 1381,
1341, 1271, 1135, 1081, 1022; 1H NMR (400 MHz, CDCl3): δ 7.77 (d, 13b: Isolated yield: 37%, 57 mg. Colorless semi-solid. IR (neat):
J = 8.2 Hz, 2H), 7.39 – 7.28 (m, 13H), 7.20 (d, J = 8.0 Hz, 2H), 7.16 /cm-1 3013, 2927, 2238, 1711, 1609, 1552, 1491, 1452, 1422, 1345,
1
(dd, J = 8.1 Hz, 1.7 Hz, 2H), 6.33 (s, 1H), 6.22 (dd, J = 17.2 Hz, 10.8 1273, 1218, 1171, 1141, 1086, 1021; H NMR (400 MHz, CDCl3): δ
Hz, 1H), 5.21 (dt, J = 10.8 Hz, 1.2 Hz, 1H), 5.13 (dd, J = 17.2 Hz, 0.84 7.76 (d, J = 8.3 Hz, 2H), 7.59 (dd, J = 8.4, 3.4 Hz, 4H), 7.29 (dd, J =
Hz, 1H), 4.59 (br.s, 2H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 13.3, 8.4 Hz, 6H), 7.10 (d, J = 8.3 Hz, 2H), 6.56 (dd, J = 10.0, 4.0 Hz,
164.8, 144.8, 142.0, 140.7, 137.9, 135.8, 135.2, 132.1, 129.2, 129.1, 1H), 4.77 (d, J = 15.0 Hz, 1H), 4.64 (d, J = 15.0 Hz, 1H), 3.44 (dd, J =
128.9, 128.9, 128.7, 128.5, 128.4, 128.3, 128.1, 127.4, 126.9, 122.5, 12.9, 5.5 Hz, 1H), 3.18 (dd, J = 12.8, 6.6 Hz, 1H), 2.86 – 2.75 (m, 2H),
120.5, 51.9, 50.0, 21.5; HRMS (ESI): Calc. for C32H31N2O2S [M+H]+: 2.63 (td, J = 10.6, 3.9 Hz, 1H), 2.44 (s, 3H); 13C NMR (100 MHz,
507.2106; Found: 507.2106.
CDCl3): δ 157.70, 143.30, 142.87, 141.22, 140.65, 138.71, 132.67,
132.63, 129.67, 129.34, 128.90, 128.67, 126.34, 120.38, 118.74,
111.20, 55.88, 52.91, 50.07, 37.67, 35.18, 21.59; HRMS (ESI): Calc.
for C28H25N4O2S [M+H]+: 481.1698; Found: 481.1699.
11b: Isolated yield: 5%, 8 mg. Colorless semi-solid. IR (neat):

max/cm-1 3740, 3025, 2921, 2861, 1743, 1693, 1635, 1535, 1485,
1
1384, 1342, 1273, 1135, 1085, 1021; H NMR (400 MHz, CDCl3): δ
7.91 (d, J = 8.2 Hz, 2H), 7.60 (m, 3H), 7.43 (m, 3H), 7.32 (m, 3H), 7.26 13c: Isolated yield: 23%, 35 mg. Colorless semi-solid. IR (neat):
(m, 5H), 7.11 (m, 3H), 6.53 (dd, J = 7.2 Hz, 3.7 Hz, 2H), 5.09 (d, J = /cm-1 3018, 2925, 2226, 1702, 1601, 1554, 1491, 1447, 1414, 1344,
1
14.3 Hz, 1H), 4.39 (d, J = 14.3 Hz, 1H), 3.47 (dd, J = 13.2 Hz, 5.0 Hz, 1269, 1209, 1174, 1149, 1088, 1011; H NMR (400 MHz, CDCl3): δ
1H), 3.23 (d, J = 13.2 Hz, 1H), 3.02 (m, 1H), 2.59 (dd, J = 14.0 Hz, 8.03 (s, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 7.9 Hz, 2H), 7.51 (d, J
6 | J. Name., 2012, 00, 1-3
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OrgaPnleicas&e dBoionmotoaledcjuuslatrmCahrgeimnsistry
Journal Name
ARTICLE
= 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 7.9 Hz, 2H), 7.14 (d, 126.4, 119.1, 118.5, 112.4, 111.8, 52.7, 50.2, 21.5; HRVMieSw (AErtSicIl)e:OCnalilnce.
+
DOI: 10.1039/C7OB00499K
for C40H34N4O2S [M+H] : 633.2324; Found: 633.2317.
J = 8.0 Hz, 2H), 5.83 (dd, J = 10.0, 4.1 Hz, 1H), 5.77 (dd, J = 8.6, 4.0
Hz, 1H), 4.94 (d, J = 15.1 Hz, 1H), 4.77 (s, 1H), 4.18 (d, J = 15.1 Hz,
1H), 3.64 (d, J = 15.7 Hz, 1H), 3.38 (m, 3H), 2.98 (s, 3H), 2.90 (s, 3H),
2.43 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 164.5, 142.7, 142.4,
140.8, 140.5, 132.5, 131.9, 130.7, 129.2, 128.2, 126.1, 126.0, 121.9,
118.8, 118.3, 111.7, 110.8, 53.1, 49.0, 40.5, 39.9, 21.5; HRMS (ESI):
Calc. for C28H25N4O2S [M+H]+: 481.1698; Found: 481.1697.
16b: Isolated yield: 18%, 25 mg. Colorless semi-solid. IR (neat):
/cm-1 3018, 2920, 2216, 1711, 1612, 1542, 1491, 1438, 1410, 1339,
1268, 1251, 1179, 1133, 1085, 1013; δ 7.65 (d, J = 5.8 Hz, 6H), 7.62
(s, 3H), 7.38 – 7.29 (m, 17H), 7.23 (d, J = 8.2 Hz, 8H), 7.22 – 7.16 (m,
19H), 7.14 (d, J = 7.9 Hz, 6H), 6.69 (dd, J = 8.1, 5.8 Hz, 12H), 5.13 (d,
J = 15.1 Hz, 3H), 3.95 (d, J = 12.7 Hz, 3H), 3.81 (d, J = 15.1 Hz, 3H),
14b: Isolated yield: 51%, 73 mg. Colorless semi-solid. IR (neat): 3.51 (d, J = 14.3 Hz, 3H), 3.37 (d, J = 12.8 Hz, 3H), 3.30 (d, J = 14.4
/cm-1 3019, 2926, 2228, 1703, 1605, 1555, 1498, 1446, 1415, 1343, Hz, 3H), 2.40 (s, 10H); 13C NMR (101 MHz, CDCl3): δ 142.30, 141.37,
1
1270, 1215, 1173, 1140, 1083, 1019; H NMR (400 MHz, CDCl3): δ 140.92, 140.71, 140.43, 137.43, 132.12, 131.72, 131.22, 129.88,
7.67 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 10.2 Hz, 1H), 7.39 (d, J = 8.1 Hz, 129.14, 129.03, 128.86, 128.26, 128.13, 127.99, 127.01, 126.30,
2H), 7.34 (d, J = 8.2 Hz, 2H), 7.29 – 7.15 (m, 6H), 6.92 (t, J = 7.4 Hz, 121.59, 118.53, 118.43, 111.12, 111.00, 58.58, 52.07, 47.83, 42.07,
4H), 6.76 (d, J = 8.2 Hz, 2H), 6.69 (d, J = 10.3 Hz, 1H), 5.02 (d, J = 15.1 21.49; HRMS (ESI): Calc. for C40H34N4O2S [M+H]+: 633.2324; Found:
633.2321.
Hz, 1H), 4.21 (d, J = 15.1 Hz, 1H), 3.64 (d, J = 12.9 Hz, 1H), 3.56 (d, J =
12.9 Hz, 1H), 3.13 (d, J = 13.4 Hz, 1H), 2.96 (d, J = 13.4 Hz, 1H), 2.40
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 157.5, 145.3, 142.4, 140.5,
140.5, 139.8, 132.3, 131.9, 130.9, 129.2, 128.9, 128.5, 127.9, 126.4,
126.3, 120.7, 118.4, 111.5, 111.2, 57.5, 52.7, 44.53, 44.1, 21.5;
HRMS (ESI): Calc. for C34H29N4O2S [M+H]+: 557.2011; Found:
557.2012.
Crystallography
Crystal structure of compound 11a (CCDC 1525177):
C26H26N2O2S; Compound 11a was crystallized from slow
evaporation of CH2Cl2/hexane at room temperature.
colorless cubic shaped crystal with approximate dimensions
0.185 x 0.161 x 0.058 mm gave an Orthorhombic with space
group C2/c; a = 27.148(6) b = 6.2305(14) c = 27.401(6) Å, α =
90o β = 92.154o γ = 90o; V = 4631.5(18) Å3; T = 296 (2) K; Z = 8;
ρcalc = 1.235 Mgm-3; θmax= 26.37o; MoKαλ = 0.71073 Å. Fine-
focus sealed tube source with graphite monochromator. R =
0.0514 (for 2576 reflection I>2σ(I)), wR = 0.1764 which was
A
14c: Isolated yield: 32%, 46 mg. Colorless semi-solid. IR (neat):
/cm-1 3024, 2922, 2222, 1706, 1603, 1551, 1495, 1444, 1411, 1347,
1
1277, 1214, 1173, 1142, 1085, 1012; H NMR (400 MHz, CDCl3): δ
7.71 (d, J = 8.3 Hz, 2H), 7.52 (d, J = 8.2 Hz, 2H), 7.48 (d, J = 8.3 Hz,
2H), 7.39 (d, J = 8.2 Hz, 2H), 7.36 – 7.31 (m, 3H), 7.21 (d, J = 8.2 Hz,
2H), 7.17 – 7.10 (m, 4H), 6.02 (dd, J = 5.5, 2.6 Hz, 1H), 4.96 (d, J =
15.2 Hz, 2H), 4.24 (d, J = 15.1 Hz, 1H), 3.89 (dd, J = 17.1, 1.7 Hz, 1H),
3.55 (dt, J = 17.1, 2.8 Hz, 1H), 3.44 (qd, J = 13.0, 5.7 Hz, 2H), 2.41 (s,
3H); 13C NMR (100 MHz, CDCl3): 164.31, 142.84, 142.55, 140.76,
140.42, 136.10, 133.27, 132.62, 132.00, 130.86, 129.30, 129.09,
128.87, 128.33, 126.11, 124.81, 121.66, 118.85, 118.41, 111.92,
111.03, 53.29, 50.71, 40.74, 40.40, 21.58; HRMS (ESI): Calc. for
C34H29N4O2S [M+H]+: 557.2011; Found: 557.2012.
refined against ׀F2׀ and S = 0.941 for 281 parameters and 4739
unique reflections. The structure was obtained by direct
methods using SHELXS-97. All non-hydrogen atoms were
refined isotropically. The hydrogen atoms were fixed
geometrically in the idealized position and refined in the fil
cycle of refinement as riding over atoms to which they are
bonded. μ = 0.164 mm-1.
Crystal structure of compound 10b (CCDC 1525176):
15a: Isolated yield: 77%, 110 mg. Colorless semi-solid. IR (neat): C32H30N2O2S; Compound 10b was crystallized from slow
/cm-1 3022, 2924, 2226, 1703, 1605, 1555, 1498, 1444, 1414, 1343, evaporation of CH2Cl2/hexane at room temperature.
A
1
1275, 1210, 1170, 1145, 1085, 1018; H NMR (400 MHz, CDCl3): δ colorless cubic shaped crystal with approximate dimensions
7.69 (d, J = 8.1 Hz, 4H), 7.62 (d, J = 8.1 Hz, 2H), 7.41 – 7.36 (m, 4H), 0.185 x 0.161 x 0.058 mm gave an Orthorhombic with space
7.35 (s, 1H), 7.31 (dd, J = 6.6, 3.0 Hz, 2H), 7.26 (d, J = 8.3 Hz, 2H), group P21/c; a = 8.0697(3) b = 32.4621(12) c = 9.8721(4) Å, α =
7.21 (d, J = 8.2 Hz, 2H), 6.27 (s, 1H), 6.20 (dd, J = 17.2, 10.8 Hz, 1H), 90o β = 90.5490o γ = 90o; V = 2585.97(17) Å3; T = 296 (2) K; Z =
5.29 (d, J = 10.8 Hz, 1H), 5.23 (d, J = 17.3 Hz, 1H), 4.68 (s, 3H), 2.42 4; ρcalc = 1.301 Mgm-3; θmax = 68.384o; MoKαλ = 0.71073 Å.
(s, 3H); 13C NMR (101 MHz, CDCl3): δ 164.86, 145.69, 142.59, Fine-focus sealed tube source with graphite monochromator.
140.78, 140.31, 139.84, 137.36, 133.01, 132.56, 131.82, 129.16, R = 0.0434 (for 4143 reflection I>2σ(I)), wR = 0.1365 which was
128.85, 128.51, 128.45, 127.83, 126.75, 123.41, 119.20, 118.31, refined against ׀F2׀ and S = 1.101 for 335 parameters and 4726
118.07, 112.54, 112.08, 52.41, 50.57, 21.50; HRMS (ESI): Calc. for unique reflections. The structure was obtained by direct
C34H29N4O2S [M+H]+: 557.2011; Found: 557.2018.
methods using SHELXS-97. All non-hydrogen atoms were
refined isotropically. The hydrogen atoms were fixed
geometrically in the idealized position and refined in the final
16a: Isolated yield: 73%, 100 mg. Colorless semi-solid. IR (neat):
/cm-1 3025, 2921, 2227, 1708, 1601, 1554, 1496, 1432, 1411, 1348,
1
cycle of refinement as riding over atoms to which they are
1275, 1213, 1173, 1141, 1088, 1011; H NMR (400 MHz, CDCl3): δ
bonded. μ = 1.364 mm-1.
7.69 (d, J = 8.3 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 8.4 Hz,
2H), 7.34 (m, 6H), 7.23 – 7.13 (m, 10H), 7.10 (d, J = 8.3 Hz, 2H), 6.86
Crystal structure of compound 28 (CCDC 1525520):
(s, 1H), 5.79 (d, J = 0.5 Hz, 1H), 5.40 (s, 1H); 13C NMR (101 MHz,
C25H28N2O2S; Compound 28 was crystallized from slow
evaporation of CH2Cl2/hexane at room temperature.
A
CDCl3): δ 164.2, 149.1, 143.1, 142.6, 140.5, 140.4, 139.8, 138.3,
136.6, 132.9, 132.2, 129.2, 129.2, 128.8, 128.6, 127.5, 127.1, 126.7,
colorless cubic shaped crystal with approximate dimensions
0.185 x 0.161 x 0.058 mm gave an Orthorhombic with space
group P-1; a = 9.0423(4) b = 10.9846(5) c = 11.4374(5) Å, α =
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91.995o β = 100.164o γ = 103.818o; V = 2128.3(8) Å3; T = 0 (2) K;
Z = 2; ρcalc = 1.291 Mgm-3; θmax = 54.76o; MoKαλ = 0.71073 Å.
Fine-focus sealed tube source with graphite monochromator.
R = 0.0361 (for 4159 reflection I>2σ(I)), wR = 0.0820 which was
Targets Heterocycl. Syst., 2000, 4, 293; (f) H. PerVsite,wSAcrit.iclSeyOnntlhin.e,
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refined against ׀F2׀ and S = 0.935 for 258 parameters and 4839
3
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unique reflections. The structure was obtained by direct
methods using SHELXS-97. All non-hydrogen atoms were
refined isotropically. The hydrogen atoms were fixed
geometrically in the idealized position and refined in the final
cycle of refinement as riding over atoms to which they are
bonded. μ = 0.174 mm-1.
Crystal structure of compound 30 (CCDC 1525179):
C38H34N2O2S; Compound 30 was crystallized from slow
evaporation of CH2Cl2/hexane at room temperature.
A
colorless cubic shaped crystal with approximate dimensions
0.185 x 0.161 x 0.058 mm gave an Orthorhombic with space
group P21/c; a = 12.375(4) b = 17.958(7) c = 14.179(6) Å, α =
90o β = 91.594o γ = 90o; V = 3150(2) Å3; T = 296 (2) K; Z = 4; ρcalc
= 1.229 Mgm-3; θmax= 28.282o; MoKαλ = 0.71073 Å. Fine-focus
sealed tube source with graphite monochromator. R = 0.0805
(for 2133 reflection I>2σ(I)), wR = 0.2471 which was refined
4
5
against ׀F2׀ and S = 0.912 for 389 parameters and 5734 unique
6
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reflections. The structure was obtained by direct methods
using SHELXS-97. All non-hydrogen atoms were refined
isotropically. The hydrogen atoms were fixed geometrically in
the idealized position and refined in the final cycle of
refinement as riding over atoms to which they are bonded. μ =
0.139 mm-1.
Crystal structure of compound 22b (CCDC 1525178):
C33H29N3O2S; Compound 22b was crystallized from slow
evaporation of CH2Cl2/hexane at room temperature.
A
colorless cubic shaped crystal with approximate dimensions
0.185 x 0.161 x 0.058 mm gave an Orthorhombic with space
group P-1; a = 8.7353(11) b = 10.2521(13) c = 15.765(2) Å, α =
101.925o β = 98.258o γ = 93.270o; V = 1361.6(3) Å3; T = 296 (2)
K; Z = 2; ρcalc = 1.334 Mgm-3; θmax = 77.283o; MoKαλ = 0.71073
Å. Fine-focus sealed tube source with graphite
monochromator. R = 0.0948 (for 4453 reflection I>2σ(I)), wR =
8
9
0.2636 which was refined against ׀F2׀ and S = 1.782 for 353
parameters and 5550 unique reflections. The structure was
obtained by direct methods using SHELXS-97. All non-hydrogen
atoms were refined isotropically. The hydrogen atoms were
fixed geometrically in the idealized position and refined in the
final cycle of refinement as riding over atoms to which they are
bonded. μ = 1.334 mm-1.
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Notes and references
1
(a) T. T. Tidwell, Pure Appl. Chem., 1997, 69, 211; (b) J. E. Leffler,
The Reactive Intermediates of Organic Chemistry, Interscience
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2
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Wang, Synlett, 2010, 165; (e) M. Alajarin, A. Vidal and F. Tovar,
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15 (a) H. Heaney and S. V. Ley, J. Chem. Soc., Perkin Trans. 1, 1974,
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View Article Online
DOI: 10.1039/C7OB00499K
16 The compound 11a was also inert to dienophiles e.g.
diphenylacetylene and ethyl vinyl ether even under refluxed
conditions.
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