Application of an isomerization-ring-closing metathesis strategy to the synthesis of unsaturated seven-membered, benzo-fused heterocycles containing two heteroatoms

Article abstract of DOI:10.1016/j.tet.2011.02.035

An isomerization-RCM approach was utilized to synthesize a number of seven-membered benzo-fused heterocycles containing two heteroatoms (N,O, N,S, and S,O). This approach utilized the ruthenium catalyst [RuClH(CO)(PPh ₃)₃] for the is

Full text of DOI:10.1016/j.tet.2011.02.035

Tetrahedron 67 (2011) 2991e2997
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Application of an isomerization-ring-closing metathesis strategy to the synthesis
of unsaturated seven-membered, benzo-fused heterocycles containing two
heteroatoms
Dharmendra B. Yadav, Garreth L. Morgans, Blessing A. Aderibigbe, Lee G. Madeley, Manuel A. Fernandes,
,
1
*
Joseph P. Michael, Charles B. de Koning, Willem A.L. van Otterlo
Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050 Johannesburg, South Africa
a r t i c l e i n f o
a b s t r a c t
Article history:
An isomerization-RCM approach was utilized to synthesize a number of seven-membered benzo-fused
heterocycles containing two heteroatoms (N,O, N,S, and S,O). This approach utilized the ruthenium
catalyst [RuClH(CO)(PPh3)3] for the isomerization of allyl groups, eventually followed by the use of the
Grubbs second generation catalyst for the formation of the desired products. In most instances thermal
RCM conditions were sufficient; however, in a number of cases where this methodology did not give the
desired product a high temperature, short time microwave approach afforded the desired ring-closed
products. In this manner, the following substituted benzo-fused scaffolds were successfully synthesized:
4,5-dihydro-1,5-benzoxazepine, 4,5- and 2,5-dihydro-1,5-benzothiazepine and 2H-1,5-benzoxathiepine.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 25 October 2010
Received in revised form 26 January 2011
Accepted 14 February 2011
Available online 22 February 2011
Keywords:
Isomerization
Ring-closing metathesis
Benzoxazepine
Benzothiazepine
Benzoxathiepine
1. Introduction
H
O
N
S
S
A structure-based literature search soon reveals that benzo-fused
heterocycles are very popular motifs in medicinal chemistry. It is be-
cause of this phenomenon that they have been labeled ‘privileged
structures’.1 Of these, there are a number of known seven-membered
benzannulated compounds containing the heteroatoms oxygen, ni-
trogen, and sulfur. These include the mono-heteroatom containing
compounds 2,3,4,5-tetrahydro-1-benzoxepine 1, 2,3,4,5-tetrahydro-
2
3
1
H
N
O
O
4
N
H
S
6
5
1H-1-benzazepine 2, and 2,3,4,5-tetrahydro-1-benzothiepine
3
O
O
S
(Fig. 1). Examples containing different combinations of two hetero-
atoms in the heterocyclic portion of the annulated molecules
include 3,4-dihydro-2H-1,5-benzodioxepine 4, 2,3,4,5-tetrahydro-
1H-1,5-benzodiazepine 5, 3,4-dihydro-2H-1,5-benzodithiepine 6,
2,3,4,5-tetrahydro-1,5-benzoxazepine 7, 3,4-dihydro-2H-1,5-benzox-
athiepine 8, and 2,3,4,5-tetrahydro-1,5-benzothiazepine 9.2
N
H
S
N
H
8
9
7
Fig. 1. Seven-membered benzo-fused heterocycles with two heteroatoms.
A number of the scaffolds with two heteroatoms, as shown in
Fig. 1, have found utilization in medicinal studies. Examples shown
in Fig. 2 include the benzodiazepine 10 and benzoxazepine 11, both
of which demonstrated activity as non-peptide vasopressin V2
receptor agonists.3 The benzothiazepine class of compounds is
represented by molecule 12, a compound with interesting muscular
contractile activity.4 Finally, benzoxathiepine 13, containing a sul-
fone and an ether functional group in the benzannulated heterocy-
cle, were studied as part of a set of Naþ/Hþ antiporter inhibitors.5
The application of ring-closing metathesis (RCM)6 to the syn-
thesis of benzo-fused seven-membered heteroatom-containing
compounds containing an alkene functionality has been relatively
* Corresponding author. E-mail address: wvo@sun.ac.za (W.A.L. van Otterlo).
1
Present address: Department of Chemistry and Polymer Sciences, Stellenbosch
University, Stellenbosch 7602, Western Cape, South Africa.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.02.035

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D.B. Yadav et al. / Tetrahedron 67 (2011) 2991e2997
Y
N
S
N
N
N
Mes
Mes
Cl
[RuClH(CO)(PPh3)3]
Ru
Cl
Ph
26
PCy3
O
O
25
O
Me
Me
O
O
N
N
H
Fig. 3. Ruthenium catalysts used in this work.
10 Y = NMe
11 Y = O
12
O
S
addition, Bennasar and co-workers described the formation of tert-
butyl 1,5-benzoxazepine-5(2H)-carboxylate 23 from diene 22,
alongside the formation of the related 4H-1,4-benzoxazine 24, due
to the undesired isomerization of the allyl ether prior to metathesis,
under the reaction conditions employed.11
H2N
H2N
N
13
O
O
O
Fig. 2. Examples of bioactive seven-membered benzo-fused heterocycles with two
heteroatoms.
Over the last number of years, the synthesis of benzo-fused
aromatic systems has been one of the central themes of the re-
search performed in our group. We have made extensive use of the
well-known ruthenium-mediated ring-closing metathesis (RCM)
reaction, utilizing the Grubbs second generation compound 25 as
our catalyst of choice,12 to build a number of benzannulated com-
pounds (Fig. 3).13 In addition, we have successfully applied an
isomerization-RCM14 reaction sequence (sequential or one-pot), to
afford various benzo-fused aromatic systems not always easily
obtained by other synthetic approaches.15,16 To accomplish the
isomerizations we have often applied the robust catalyst 26, with
dependable results (Fig. 3).17
straight-forward. In fact, precursor 14 has regularly been used as
a ‘test substrate’ for novel metathesis catalysts, resulting in the
synthesis of 2,5-dihydro-1-benzoxepine 15 (Scheme 1).7 In addi-
tion, the 2,5-dihydro-1H-1-benzazepine 17 backbone has also been
synthesized in a similar way from compound 16 (R¼Boc,8 R¼Bz9).
To the best of our knowledge however, only two papers have
reported the synthesis of seven-membered benzo-fused com-
pounds containing two heteroatoms, making use of an RCM strat-
egy. In 2004, Guillaumet and co-workers efficiently demonstrated
the synthesis of substituted 2H-1,5-benzodioxepins 20 from pre-
cursors 19, which were readily prepared from 18 (Scheme 2).10 In
In this paper we will disclose the details of the successful ap-
plication of a sequential isomerization-RCM strategy for the syn-
thesis of
a number of novel seven-membered annulated
heterocycles containing two heteroatoms, X and Y, as well as
a carbonecarbon double bond in the heterocyclic ring, as shown in
the disconnection 27/28 (Scheme 3).18 This paper will thus de-
scribe the application of the methodology to systems where X,Y ¼
N,O, S,N, and S,O, respectively.19 It should be clear from the dis-
connection in Scheme 3 that the synthetic strategy will involve the
metathesis of a vinyl group conjugated to a heteroatom, a particular
type of eneeene metathesis reaction seeing increased use over the
last number of years.20
O
O
14
15
R
N
R
N
16
(R = Boc or Bz)
17
X
X
RCM
Scheme 1. Previous RCM approaches.
Y
28
Y
27
OH
O
O
i
R
R
Scheme 3. Retrosynthetic analysis of the work described in this paper.
O
19
18
O
O
ii
2. Results and discussion
R
2.1. Synthesis of 4,5-dihydro-1,5-benzoxazepines
20
Since Bennasar11 and co-workers had been successful in dem-
onstrating that RCM could be utilized to synthesize the 2,5-dihydro-
1,5-benzoxazepine structure 23 from precursor 22, albeit in a low
yield, it was decided to focus the synthetic efforts on the regioiso-
meric 4,5-dihydro-1,5-benzoxazepine analogue. The readily syn-
thesizedprecursor 29a21 was thereforeexposedtotheisomerization
catalyst [RuClH(CO)(PPh3)3] 26, to give the vinyloxy ether 30a as
a 2:1 mixture of E/Z isomers (Scheme 4). Subsequent allylation of
this product afforded diene 31a, also without any problems. Finally,
RCMusing 10%of catalyst25then readilyafforded thedesired seven-
membered heterocyclic compound tert-butyl 1,5-benzoxazepine-5
(4H)-carboxylate 32a in a reasonable yield of 60%.
O
N
O
iii
Boc
H
Boc
N
O
iv
H
22
21
O
N
O
+
N
Boc
Boc
23
24
Scheme 2. Reagents and conditions: (i) allyl bromide, K2CO3, acetone, 10
h
To demonstrate the versatility of this approach we also syn-
thesized the corresponding benzoyl-protected derivative 32b
(Scheme 4). The synthetic pathway, 29b/30b/31b/32b was
accomplished according to the reaction conditions described in the
(80e86%);10 (ii) Grubbs first generation catalyst or 25 (10e20 mol %), C6H6, 55 ꢀC,
6e17 h (0e82% for Grubbs first generation catalyst, 53e98% for 25);10 (iii) Cp2TiMe2
(1.5 mol equiv), toluene/pyridine, reflux,
4
h;11 (iv) 25 (3ꢁ10%), benzoquinone
(0.3 mol equiv), 80 ꢀC, 58 h, 23/24 (1:3 over two steps, no yield specified).11

D.B. Yadav et al. / Tetrahedron 67 (2011) 2991e2997
2993
NHR
O
NHR
i
ii
O
30a,b
29a,b
R
N
R
N
iii
O
31a,b
O
32a,b
a = Boc, b = C(O)Ph
Scheme 4. Reagents and conditions: (i) (a) R¼Boc, 26 (5 mol %), toluene, Ar,
80e100 ꢀC, 18 h (98%), (b) R¼C(O)Ph, 26 (4 mol %), neat, Ar, 65 ꢀC, 24 h (92%); (ii) NaH,
DMF, allylBr, N2, rt, 18 h, [(a) R¼Boc, 83%; (b) R¼C(O)Ph, 95%]; (iii) (a) R¼Boc, 25
(10 mol %), toluene, 60 ꢀC, Ar, 18 h, (60%), (b) R¼C(O)Ph, 25 (5 mol %), toluene, 80 ꢀC, Ar,
8 h, (50%).
Fig. 4. ORTEP representation of compound 37.
legend of Scheme 4 and afforded the desired benzoyl-protected
4,5-dihydro-1,5-benzoxazepine 32b in reasonable yield of 44% over
three synthetic steps.
metathesis reaction had successfully afforded the seven-membered
2,5-dihydro-1,5-benzothiazepine skeleton, with the double bond
clearly between C3 and C4 (numbering as shown in Fig. 4).
Next, it was decided to synthesize the regiosiomeric 1,5-ben-
zothiazepine skeleton, in which the alkene was now a vinyl sulfide,
by using a modified approach. To this end, 2-(allylsulfanyl)aniline
38 was readily converted into the N-[2-(1-propenylsulfanyl)phenyl]
benzenesulfonamide 39 (Scheme 6) as described before.15a Once
again, this particular compound was converted to the sulfone 40
and when this was treated with the metathesis catalyst 25 under
the previously utilized conditions, none of the desired product was
formed; prolonged reaction times only led to decomposition of the
starting material. Hence, it was decided to apply microwave heat-
ing as described in the literature,25 but unfortunately the usual
moderate conditions described were unsuccessful in providing
desired compound 41. Finally, the application of a high temperature
(145 ꢀC), short duration (10 min) microwave heating regime26
(80 W) did give more satisfactory results with 41 being obtained
in 67% yield. It should be noted that it was found to be necessary to
use higher catalyst loadings (20%) under these conditions to get
a reasonable yield of product. Comparison of the NMR spectra of
this compound with that obtained for regioisomer 37 clearly in-
dicated that the double bond was now between C2 and C3.
2.2. Synthesis of 4,5-dihydro-1,5-benzothiazepine, 2,5-
dihydrobenzo[b][1,4]thiazepine and derivatives
The RCM of substrates containing sulfur atoms has become more
important in the last few years.22 In addition, the application of
RCM to synthesize benzo-fused S-containing heterocycles has seen
more investigation.8,23 We thus decided to test whether we could
synthesize the seven-membered benzo-fused ring systems con-
taining sulfur, in addition to nitrogen or oxygen.
To this end, aminothiol 33 was thus readily converted into
compound 34 (Scheme 5).15a This substrate was then oxidized to
the corresponding sulfone 35 using mCPBA at ꢂ5 ꢀC. We were then
able to perform a selective alkene isomerization on 35 to obtain
compound 36, in which only the N-allyl group had been isomerized.
ꢀ
Kuznik and co-workers have shown that allyl sulfones can be iso-
merized to the thermodynamically more stable internal form,24 but
under our reaction conditions only the N-allyl group was affected
by the ruthenium catalyst 26. Subsequently, when compound 36
was treated with Grubbs catalyst 25, the seven-membered 1,5-
benzothiazepine 37 was obtained, although the reaction was par-
ticularly slow. This led to the desired product 37 being isolated in
41% yield, in addition to unreacted starting material 36 in 59%
yield.13e
We were delighted to observe that the sulfide 39 (Scheme 6),
when subjected to the short time, high temperature metathesis
A single-crystal X-ray diffraction study confirmed the structure
of compound 37, with the sulfonamide-protected enamine func-
tionality clearly in place. In addition, it was evident that the
S
NH2
38
Steps[15a]
Steps[15a]
S
SH
i
N
Ts
NH2
S
N
S
iii
33
34
O
S
O O
S
O
N
Ts
42
39
Ts
ii
i
N
N
Ts
Ts
35
36
O
S
O
S
O
O O
S
O
ii
iii
N
Ts
N
Ts
N
Ts
40
37
41
Scheme 5. Reagents and conditions: (i) mCPBA (2.2 equiv), CH2Cl2, ꢂ5 ꢀC, N2, 48 h
(71%); (ii) 26 (10 mol %), toluene, Ar, 105 ꢀC, 24 h (84%); (iii) 25 (5 mol %), toluene,
50 ꢀC, Ar, 24 h, then further 25 (5 mol %), 80 ꢀC, Ar, 24 h, 37 (41%) and 36 (59%).
Scheme 6. Reagents and conditions: (i) mCPBA (2.2 equiv), CH2Cl2, ꢂ5 ꢀCe0 ꢀC, N2,
24 h (84%); (ii) 25 (20 mol %), toluene, MW, Ar, 145 ꢀC, 80 W, 10 min (67%); (iii) 25
(20 mol %), toluene, MW, Ar, 145 ꢀC, 80 W, 10 min (92%).

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D.B. Yadav et al. / Tetrahedron 67 (2011) 2991e2997
microwave conditions,26 furnished the desired product 42 in an
excellent yield of 92% (of note is that under the milder metathesis
conditions no cyclized product was formed). It would thus appear
that these harsh conditions allow for the metathesis of the more
hindered propenyl derivatives, as well as overcoming potential
catalyst disrupting chelations from donor atoms, such as sulfur,
whichcould beproblematic under ‘normal’thermal RCMconditions.
Infra-red spectra were recorded on either a Bruker IFS 25 Fourier
Transform spectrometer or on a Bruker Vector 22 Fourier Transform
spectrometer. Mass spectra were recorded on a Kratos MS 9/50, VG
70E MS or VG 70 SEQ mass spectrometer or a WatersAPI Q-TOF
Ultima or Waters GCT Premier mass spectrometer. Macher-
eyeNagel kieselgel 60 (particle size 0.063e0.200 mm) was used for
conventional silica gel chromatography. All solvents used for re-
actions and chromatography were distilled prior to use. Reactions
were performed under a blanket of inert gas (Ar or N2) unless
specified. All microwave reactions were performed in a CEM Cor-
poration Discover Focused Microwave Synthesis system using CEM
microwave reactor vials, which were sealed with the CEM Discover
pressure/infra red attenuator.
2.3. Synthesis of 2H-1,5-benzoxathiepine and derivatives
The final set of substrates used in this approach required the
conversion of 2-mercaptophenol 43 into bis-alkene 44 according to
established procedures. This compound was then oxidized to the
corresponding sulfone 45 but unfortunately we were unable to
accomplish the desired RCM reaction to yield 46, even under the
high temperature-short time microwave conditions. We are unable
to explain this result in light of the other successes with this
methodology. However, treatment of substrate 44 under the high
temperature microwave conditions did give the benzoxathiepine
47 in acceptable yield (62%), although the use of a larger than
normal amount of catalyst 25 was required (2ꢁ20%) to ensure
depletion of all the starting material 44 (Scheme 7).
4.1.1. tert-Butyl 2-(1-propenyloxy)phenylcarbamate 30a. tert-Butyl
2-(allyloxy)phenylcarbamate27 29a (0.20 g, 0.80 mmol) was dis-
solved in toluene (8 mL) and [RuClH(CO)(PPh3)3] 26 (5 mol %,
0.038 g, 0.40 mmol) was added. The reaction was then heated at
80e100 ꢀC for 18 h, under Ar. H2O (20 mL) was then added and the
crude product was extracted with EtOAc (2ꢁ100 mL). The solvent
was removed under vacuum and silica gel column chromatography
(10% EtOAc/hexane) was performed on the crude product to afford
the product 30a as a brown oil (0.19 g, 98%). NMR spectroscopy
showed that the compound was a mixture of E/Z isomers (2:1). Rf
(10% EtOAc/hexanes) 0.73; IR: vmax (film)/cmꢂ1 3442, 2987, 1732,
1671, 1606, 1524, 1478, 1450, 1393, 1368, 1328; 1H NMR (300 MHz,
SH
CDCl3): d (ppm) 1.53 and 1.54 [9H, s, C(CH3)3], 1.67 and 1.73 (3H, d, J
OH
43
6.7 Hz, OCHCHCH3), 4.95e5.00 and 5.35e5.46 (1H, m, OCHCHCH3),
6.17e6.34 (1H, m, OCHCHCH3), 6.88e7.01 (4H, m, 4ꢁ ArH), 8.09
Steps[15a]
(1H, br s, NH); 13C NMR (75 MHz, CDCl3):
d (ppm) 9.4 and 12.1
S
S
iii
(CH3), 28.3 [C(CH3)3], 80.5 [C(CH3)3],108.8 and 109.2 (CH),114.2 and
114.7 (CH), 118.6 (CH), 122.3 and 122.4 (CH), 122.9 and 123.0 (CH),
128.6 (C), 140.7 and 141.8 (CH), 145.3 and 145.5 (C), 152.0 (C]O);
m/z (EI): 249 (Mþ, 9%), 193 (60), 149 (31), 120 (37), 108 (19), 57
(100); HRMS, required for C14H19NO3 249.1365, found 249.1356.
O
O
44
47
i
O
ii
O
O O
S
4.1.2. tert-Butyl allyl[2-(1-propenyloxy)phenyl]carbamate 31a.
Carbamate 30a (0.13 g, 0.52 mmol) was dissolved in DMF (10 mL)
and NaH (60% in oil, 0.025 g, 0.63 mmol) was added, followed by
allyl bromide (0.050 mL, 0.63 mmol). The reaction was stirred at rt,
under N2, for 18 h, after which H2O (20 mL) was added. The crude
product was subsequently extracted with EtOAc (4ꢁ100 mL), which
was removed under reduced pressure. Column chromatography
(5% EtOAc/hexane) was then performed to afford the product 31a as
a yellow oil (0.12 g, 83%). The product was found to be a mixture of
E/Z isomers by NMR spectroscopy in a ratio 2:1. Rf (5% EtOAc/hex-
anes) 0.35; IR: vmax (film)/cmꢂ1 1701, 1526, 1499, 1454, 1386; 1H
S
RCM
O
O
45
46
Scheme 7. Reagents and conditions: (i) mCPBA (2.2 equiv), CH2Cl2, ꢂ5 ꢀCe0 ꢀC, N2,
24 h (70%); (ii) 25 (20þ20 mol %), toluene, MW, Ar, 145e225 ꢀC, 80e150 W, 30 min, no
product obtained; (iii) 25 (20þ20 mol %), toluene, MW, Ar, 150 ꢀC, 100 W, 20 min,
(62%).
3. Conclusion
NMR (300 MHz, CDCl3):
d (ppm) 1.34 and 1.50 [9H, br s, C(CH3)3],
This paper has demonstrated that the utilization of an isomer-
ization-RCM approach is of specific use in the synthesis of seven-
membered benzo-fused heterocycles containing two heteroatoms
in the heterocyclic ring. In particular, the approach produced
examples of compounds containing N,O- (viz. a substituted
4,5-dihydro-1,5-benzoxazepine), N,S- (viz. a substituted 4,5- and
1.64 and 1.70 (3H, d, J 6.7 Hz, CHCHCH3), 4.13 (2H, br s,
NCH2CHCH2), 4.84e4.88 and 5.27e5.36 (1H, m, OCHCHCH3),
5.02e5.11 (2H, m, NCH2CHCH2), 5.80e5.95 (1H, m, NCH2CHCH2),
6.31e6.34 (1H, m, OCHCHCH3), 6.96e7.01 (2H, m, 2ꢁ ArH),
7.11e7.26 (2H, m, 2ꢁ ArH); 13C NMR (75 MHz, CDCl3, 1 carbon signal
not observed):
d (ppm) 9.4 and 12.1 (CH3), 28.1 [C(CH3)3], 52.2
2,5-dihydro-1,5-benzothiazepine), and also
a S,O-containing
(NCH2), 79.7 (CeO),107.2 and 108.0 (CH), 115.7 and 116.3 (CH),116.8
(CH), 122.3 (CH), 128.0 (CH), 129.6 and 129.7 (CH), 131.9 (C), 134.2
(CH), 140.9 and 142.2 (C), 154.7 and 159.8 (C]O); m/z (EI): 289 (Mþ,
9%), 233 (11), 189 (20), 163 (35), 160 (25), 148 (11), 120 (13), 57
(100); HRMS, required for C17H23NO3 289.1678, found 289.1670.
compound (viz. 2H-1,5-benzoxathiepine). In addition, it was found
that with certain substrates the application of a short duration-
high temperature microwave protocol was required for the for-
mation of the desired cyclized products.
4. Experimental
4.1. General
4.1.3. tert-Butyl 1,5-benzoxazepine-5(4H)-carboxylate 32a. Carbamate
31a (0.097 g, 0.33 mmol) was dissolved in toluene (5 mL) and Grubbs
second generation catalyst 25 (10 mol %, 0.014 g, 0.04 mmol) was
added under Ar. The reaction was then stirred at 60 ꢀC for 18 h. The
solvent was removed under vacuum and column chromatography
(10% EtOAc/hexane) was performed on the crude residue to afford the
1H NMR and 13C NMR spectra were recorded either on a Bruker
300 or Bruker DRX 400 spectrometer at the frequency indicated.

D.B. Yadav et al. / Tetrahedron 67 (2011) 2991e2997
2995
cyclized compound 32a as a brown solid (0.036 g, 60%). Mp:
59e61 ꢀC; Rf (10% EtOAc/hexanes) 0.25; IR: vmax (film)/cmꢂ1 1703,
80 ꢀC for 8 h under Ar. After cooling, the reaction mixture was
diluted with a 10% EtOAc/hexane mixture (20 mL) and filtered
through a compacted Celite plug (3ꢁ20 mL) to remove the catalyst;
the solvent was then removed under reduced pressure. The
resulting crude residue was passed through a silica gel column (10%
EtOAc/hexane) to afford the cyclized 32b as a low melting point
solid (0.13 g, 50%). Mp 27e28 ꢀC; Rf (10% EtOAc/hexanes) 0.14; IR:
vmax (ATR)/cmꢂ1: 1657, 1593, 1537, 1469, 1414, 1364, 1325, 1287,
1264, 1202; 1H NMR (300 MHz, CDCl3, one proton for NCH2 not
observed in spectrum due to very broad peaks caused by amide
1612, 1498, 1454, 1380; 1H NMR (300 MHz, CDCl3):
d (ppm) 1.38 [9H,
br s, C(CH3)3], 4.22 (2H, br s, NCH2), 4.80e4.85 (1H, m, NCH2CHCH),
6.42 (1H, d, J 6.0 Hz, OCHCH), 7.07 (2H, br s, 2ꢁ ArH), 7.17e7.20 (2H,
m, 2ꢁ ArH); 13C NMR (75 MHz, CDCl3):
d (ppm) 28.2 [C(CH3)3], 45.2
(CH2), 80.6 (CeO), 105.2 (CH), 121.0 (CH), 123.7 (C), 123.9 (CH), 127.9
(CH),129.8 (CH),133.2 (C), 142.7 (CH),154.3 (C]O); m/z (EI): 247 (Mþ,
20%), 214 (5), 191 (50), 174 (12), 147 (16), 146 (16), 120 (21), 91 (6), 57
(100); HRMS, required for C14H17NO3 247.1208, found 247.1204.
rotamers):
d
(ppm) 3.76 and 5.36 (1H, 2ꢁ br s, NCH2), 4.94 (1H, d, J
4.1.4. N-[2-(1-Propenyloxy)phenyl]benzamide 30b. N-[2-(Allyloxy)
phenyl]benzamide28 29b (0.401 g, 1.58 mmol) and [RuClH(CO)
(PPh3)3] 26 (4 mol %, 0.060 g, 0.063 mmol) were stirred under neat
(solventless) conditions. The reaction mixture was subsequently
heated at 65 ꢀC for 24 h under Ar. The reaction solution was then
diluted with a 5% EtOAc/hexane mixture (20 mL) and filtered
through a compacted Celite plug (3ꢁ20 mL) to remove the catalyst;
the solvent was then removed under reduced pressure. The
resulting crude residue was passed through a silica gel column (10%
EtOAc/hexane) to afford the desired product 30b as a yellow oil
(0.37 g, 92%) as a mixture of E/Z isomers (ratio 3:1). Rf (20% EtOAc/
hexanes) 0.57; IR: vmax (ATR)/cmꢂ1: 1672, 1604, 1525, 1477, 1453,
3.1 Hz, NCH2CH), 6.51e6.58 (1H, m, OCH), 6.70 (1H, br s, ArH), 6.80
(1H, br s, ArH), 7.10e7.31 (7H, m, 7ꢁ ArH); 13C NMR (75 MHz,
CDCl3):
d (ppm) 44.5 (br, NCH2), 105.0 (NCH2CH), 121.1 (CH), 124.5
(CH),127.8 (CH),128.0 (CH),128.4 (CH),129.5 (CH),129.9 (CH),134.8
(C), 135.4 (C), 142.9 (CH), 153.2 (C), 169.8 (C]O); m/z (EI): 252
(MþþH, 94%), 251 (Mþ, 30%), 196 (8), 154 (40), 136 (38), 131 (15),
120 (9), 105 (100); HRMS, required for C16H14NO2 252.1025, found
252.1012.
4.1.7. N-Allyl-N-[2-(allylsulfonyl)phenyl]-4-methyl-benzenesulfona-
mide 35. The diene 3415a (0.471 g, 1.31 mmol) was dissolved in dry
CH2Cl2 (15 mL) and cooled to ꢂ5 ꢀC under N2. mCPBA (70%, 0.497 g,
2.88 mmol) was added in one portion and stirring was continued
for 36 h at 0 ꢀC. The reaction mixture was then poured into a sat-
urated solution of NaHCO3 (20 mL) and extracted with additional
CH2Cl2 (20 mL). The organic extracts were washed with brine
(20 mL), dried over Na2SO4, filtered, and evaporated to afford
a thick yellow oil. Column chromatography (20% EtOAc/hexane)
subsequently afforded the desired product 35 (0.364 g, 71% yield)
as a pale yellow oil that started to solidify on standing. Rf (40%
1332, 1256, 1205; 1H NMR (300 MHz; CDCl3):
d (ppm) 1.68 and 1.75
(3H, dd and dd, J 6.9, 1.4 Hz and J 6.9, 1.6 Hz, OCHCHCH3), 4.92e5.10
and 6.33e6.43 (1H, 2ꢁ m, OCHCHCH3), 6.34e6.40 (1H, m,
OCHCHCH3), 6.98e7.10 (3H, m, 3ꢁ ArH), 7.43e7.58 (3H, m, 3ꢁ ArH),
7.89 (2H, dd, J 6.5, 1.6 Hz, 2ꢁ ArH), 8.46e8.59 (2H, m, ArH and NH);
13C NMR (75 MHz; CDCl3):
d (ppm) 9.3 and 12.0 (CH3), 108.7 and
109.6 (CH), 114.0 and 114.6 (CH), 120.3 (CH), 122.9 (CH), 123.8 (CH),
126.8 (2ꢁ CH), 128.3 (C), 128.7 (2ꢁ CH), 131.7 (CH), 135.0 (C), 140.4
and 141.5 (CH), 146.0 (C), 165.0 (C]O); m/z (EI): 253 (Mþ, 34%), 196
(35), 105 (100), 77 (23), 51 (8); HRMS, required for C16H15NO2
253.1103, found 253.1091.
EtOAc/hexanes) 0.48; 1H NMR (300 MHz, CDCl3):
d (ppm) 2.49 (3H,
s, CH3), 4.16e4.58 (4H, m, 2ꢁ CH2), 4.87e5.03 (2H, m, CH2CHCH2),
5.37e5.46 (2H, m, CH2CHCH2), 5.63e5.74 (1H, m, CH2CHCH2),
5.77e5.93 (1H, m, CH2CHCH2), 6.90e6.96 (1H, m, ArH), 7.38 (2H, d, J
8.1 Hz, 2ꢁ ArH), 7.49e7.56 (2H, m, 2ꢁ ArH), 7.38 (2H, d, J 8.1 Hz, 2ꢁ
4.1.5. N-Allyl-N-[2-(1-propenyloxy)phenyl]benzamide 31b. Benzamide
30b (0.297 g, 1.17 mmol) was dissolved in dry DMF (30 mL) under N2,
and the temperature of the mixture lowered to 0 ꢀC, followed by the
sequential addition of NaH (60% in oil, 0.054 g, 1.4 mmol) and allyl
bromide (0.28 g, 2.3 mmol, 0.20 mL). The reaction mixture was then
stirred at rt for 24 h under N2. H2O (80 mL) was then added to quench
the reaction mixture, after which it was extracted with EtOAc
(3ꢁ50 mL) and the combined fractions dried (MgSO4). The solvent
was then removed under reduced pressure. The resulting crude res-
idue was passed through a silica gel column (20% EtOAc/hexane) to
afford compound 31b as a pale yellow oil (0.33 g, 95%) and as
a mixture of E/Z isomers (ratio 65:35). Rf (10% EtOAc/hexanes) 0.17; IR:
vmax (ATR)/cmꢂ1: 1639, 1496, 1384, 1255, 1213; 1H NMR (300 MHz;
ArH), 8.05e8.10 (1H, m, ArH); 13C NMR (75 MHz, CDCl3):
d (ppm)
21.6 (CH3), 56.1 (CH2), 60.2 (CH2),120.5, (CH),124.5 (CH),125.1 (CH),
128.4 (2 CH), 128.9 (CH), 129.8 (2 CH), 131.5 (CH), 131.6 (CH), 133.2
(CH), 133.9 (CH), 136.5 (C), 138.5 (C), 139.0 (C), 144.4 (C); m/z (ESI):
282 (MþþH, 100%), 235 (15); HRMS, required for C19H22NO4S2
392.0984, found 392.0985.
4.1.8. N-[2-(Allylsulfonyl)phenyl]-4-methyl-N-(1-propenyl)benzene-
sulfonamide 36. The sulfone 35 (0.11 g, 0.29 mmol) was dissolved in
a degassed solution (Ar) of toluene-d8 (0.50 mL) in an NMR tube
containing the isomerization catalyst 26 (0.003 g, 0.003 mmol,
1 mol %). The tube was then sealed and heated in an oil bath at 95 ꢀC
for 16 h. A further portion of catalyst 26 (0.030 g, 0.03 mmol,
10 mol %) was added and the NMR tube was heated for an addi-
tional 16 h. Silica gel column chromatography (20% EtOAc/hexane)
then afforded the product 36 (0.094 g, 84%) as a brown solid. The
NMR spectra of compound 36 were very complex because of the
mixtures of E and Z isomers so the product was utilized in the next
reaction without further characterization.
CDCl3)
d (ppm) 1.63 and 1.69 (3H, dd and dd, J 6.9, 1.5 Hz, and J 6.9,
1.6 Hz, OCHCHCH3), 4.20e4.60 (2H, br m, NCH2CHCH2), 4.84e4.94
and 5.29e5.41 (1H, 2ꢁ m, OCHCHCH3), 5.09e5.15 (2H, m,
NCH2CHCH2), 5.86e6.12 (2H, m, 2ꢁ CH2CHCH2), 6.80e6.92 (2H, m,
2ꢁ ArH), 7.03e7.23 (5H, m, 5ꢁ ArH), 7.32e7.36 (2H, m, 2ꢁ ArH); 13C
NMR (75 MHz; CDCl3):
d (ppm) 9.4 and 12.1 (CH3), 52.3 and 52.2
(NCH2), 108.6 and 109.8 (CH), 115.5 and 115.6 (CH), 117.7 and 117.6
(CH), 122.4 and 122.3 (CH), 127.3 (CH), 128.1 (CH), 128.6 and 128.5
(CH), 129.4 (CH), 130.0 and 129.9 (CH), 132.4 and 132.3 (C), 133.2 and
133.3 (CH), 136.1 and 136.2 (C), 140.0 and 140.9 (CH), 152.6 (C), 171.0
(C]O); m/z (EI): 293 (Mþ, 28%), 236 (38), 188 (5), 160 (28), 105 (100),
77 (44), 51 (6); HRMS, required for C19H19NO2 293.1416, found
293.1424.
4.1.9. 5-[(4-Methylphenyl)sulfonyl]-2,5-dihydro-1,5-benzothiazepine
1,1-dioxide 37. Sulfone 36 (0.065 g, 0.17 mmol) was dissolved in
toluene (10 mL) and Grubbs second generation catalyst 25 (5 mol %,
0.007 g, 0.008 mmol) was added under Ar. The reaction was then
stirred at 50 ꢀC for 24 h after which an additional amount of Grubbs
second generation catalyst 25 (5 mol %, 0.007 g, 0.008 mmol) was
added. The reaction was then stirred at 80 ꢀC under Ar for an ad-
ditional 24 h after which it was stirred under air at rt for 16 h. The
solvent was removed under vacuum and column chromatography
(20% EtOAc/hexane) was performed on the crude residue to afford
4.1.6. 5-Benzoyl-4,5-dihydro-1,5-benzoxazepine
32b. Benzamide
31b (0.301 g, 1.03 mmol) and Grubbs second generation catalyst 25
(5 mol %, 0.0436 g, 0.0513 mmol) were dissolved in distilled,
degassed toluene (15 mL). The reaction mixture was then stirred at

2996
D.B. Yadav et al. / Tetrahedron 67 (2011) 2991e2997
the cyclized compound 37 as a white solid (0.026 g, 41%) and
starting material (0.0392 g, 59%). Rf (40% EtOAc/hexanes) 0.41; IR:
vmax (film)/cmꢂ1 1794, 1713, 1663, 1598, 1474, 1361, 1328, 1292,
1170; Mp: 191e192 ꢀC with decomposition; 1H NMR (300 MHz,
4.2.1. 5-[(4-methylphenyl)sulfonyl]-4,5-dihydro-1,5-benzothiazepine
1,1-dioxide 41. According to the general procedure described above
the Grubbs second generation catalyst 25 (20 mol %, 0.043 g) was
added to the sulfone 40 (0.10 g, 0.26 mmol) dissolved in dry toluene
(5 mL). The irradiation was then performed for a period of 10 min
at conditions of 145 ꢀC and 80 W. The desired cyclised compound
41 was then obtained after silica gel column chromatography
(30% EtOAc/hexane) as an off-white solid (0.060 g, 67%). Mp:
203e206 ꢀC; Rf (30% EtOAc/hexanes) 0.21; IR: vmax (film)/cmꢂ1
1734, 1656, 1597, 1493, 1446, 1391, 1295, 1209, 1157, 1124; 1H NMR
CDCl3):
d (ppm) 2.41 (3H, s, CH3), 3.70 (2H, dd, J 4.7, 1.4 Hz, CH2S),
4.97e5.03 (1H, m, NHCCHCH2), 6.95 (1H, d, J 9.8 Hz, NHCCH), 7.26
(2H, d, J 8.2 Hz, 2ꢁ ArH), 7.51e7.56 (1H, m, ArH), 7.64 (2H, d, J 8.2 Hz,
2ꢁ ArH), 7.70e7.75 (1H, m, ArH), 7.86 (1H, d, J 8.0 Hz, ArH), 8.01
(1H, d, J 7.8 Hz, ArH); 13C NMR (75 MHz, CDCl3):
d (ppm) 21.7
(ArCH3), 53.6 (CH2), 104.1 (CH), 127.8 (CH), 128.5 (4ꢁ CH), 129.3 (2ꢁ
CH), 131.3 (CH), 134.4 (CH), 134.8 (C), 135.5 (C), 136.5 (C), 144.7 (C);
m/z (EI): 349 (Mþ, 6%), 285 (38), 221 (23), 194 (18), 155 (5), 130
(100), 91 (30), 65 (11), 39 (8); HRMS, required for C16H15NO4S2
349.0443, found 349.0446.
(300 MHz, CDCl3):
d (ppm) 2.41 (3H, s, ArCH3), 3.69 (2H, dd, J 4.8,
1.5 Hz, NCH2), 4.97e5.03 (1H, m, CHCH2), 6.94 (1H, d, J 9.6 Hz, SCH),
7.19e7.26 (2H, m, 2ꢁ ArH), 7.51e7.56 (1H, m, ArH), 7.64 (2H, d, J
8.1 Hz, 2ꢁ ArH), 7.69e7.75 (1H, m, ArH), 7.86 (1H, d, J 8.1 Hz, ArH),
X-ray crystal structure details of compound 37: crystallized from
EtOAc/hexane, formula: C16H15NO4S2, M¼349.41, colour of crystal:
8.00 (1H, dd, J 7.8, 1.2 Hz, ArH); 13C NMR (75 MHz, CDCl3):
d (ppm)
21.7 (ArCH3), 53.6 (CH2), 104.1 (CH), 127.8 (CH), 128.5 (4ꢁ CH), 129.4
(2ꢁ CH), 131.3 (CH), 134.4 (CH), 134.8 (C), 135.5 (C), 136.5 (C), 144.7
(C); m/z (EI): 350 (MþþH, 55%), 294 (5), 155 (5); HRMS, required for
C16H16NO4S2 (MþþH) 350.0521, found 350.0526.
ꢁ
colourless, needle, crystal size 0.38ꢁ0.36ꢁ0.32 mm, a¼7.8710(4) A,
3
ꢀ
ꢁ
ꢁ
ꢁ
b¼14.5770(7) A, c¼13.7102(6) A,
b
¼96.093(3) , V¼1564.16(13) A ,
rcalcd¼1.484 Mg/m3,
m
¼0.360 mmꢂ1, F(000)¼728, Z¼4, monoclinic,
space group P2(1)/n, T¼173(2) K, 10,989 reflections collected, 3783
independent reflections, qmax 28.00ꢀ, 209 refined parameters,
4.2.2. 5-[(4-Methylphenyl)sulfonyl]-4,5-dihydro-1,5-benzothiazepine
42. According to the general procedure described above the Grubbs
second generation catalyst 25 (20 mol %, 0.037 g) was added to the
sulfone 39 (0.080 g, 0.22 mmol) dissolved in dry toluene (4 mL). The
irradiation was then performed for a period of 10 min at conditions
of 145 ꢀC and 80 W. The desired cyclized compound 42 was then
obtained after silica gel column chromatography (30% EtOAc/hex-
ane) as an off-white solid (0.065 g, 92%). Mp: 105e108 ꢀC; Rf (30%
EtOAc/hexanes) 0.53; IR: vmax (film)/cmꢂ1 1732, 1625, 1597, 1492,
1469, 1438, 1396, 1313, 1230, 1184, 1127, 1070; 1H NMR (300 MHz,
ꢁꢂ3
maximum residual electron density 0.435 and ꢂ0.375 e A
.
R1¼0.0319, wR2¼0.0876. Crystallographic data for the structure
have been deposited with the Cambridge Crystallographic Data
Centre as deposition No. CCDC-791247.
4.1.10. N-Allyl-4-methyl-N-[2-(1-propenylsulfonyl)-phenyl]benzene-
sulfonamide 40. The diene 3915a (0.799 g, 2.22 mmol) was dissolved
in dry CH2Cl2 (20 mL) and cooled to 0 ꢀC under N2. mCPBA (70%,
1.15 g, 4.66 mmol) was added in portion-wise and stirring was
continued for 4 h during which the reaction warmed to rt. CH2Cl2
(50 mL) was added and the organic phase was washed with H2O
(50 mL) and saturated NaHCO3 (50 mL). The organic extracts were
dried over Na2SO4, filtered and evaporated to afford a thick yellow
oil. Flash column chromatography (20% EtOAc/hexane) sub-
sequently afforded the desired product 40 (0.729 g, 84% yield) as
a white solid. Mp: 116e119 ꢀC; 1H NMR spectroscopy showed that
compound 40 consisted of a 1:1 mixture of E/Z isomers. Rf (30%
EtOAc/hexanes) 0.26; IR: vmax (film)/cmꢂ1 1733, 1642, 1594, 1493,
1473, 1348, 1335, 1318, 1220, 1180, 1145, 1123, 1018; 1H NMR
CDCl3): d (ppm) 2.40 (3H, s, ArCH3), 4.44 (2H, d, J 1.8 Hz, NCH2), 5.71
(1H, dt, J 10.8, 3.6 Hz, CHCH2), 5.82 (1H, dt, J 10.8, 1.5 Hz, SCH),
7.18e7.31 (5H, m, 5ꢁ ArH), 7.34e7.47 (1H, m, ArH), 7.65 (2H, d, J
8.1 Hz, 2ꢁ ArH); 13C NMR (75 MHz, CDCl3):
d (ppm) 21.6 (ArCH3),
49.5 (CH2), 119.9 (CH), 122.9 (CH), 127.7 (2ꢁ CH), 128.4 (CH), 128.7
(CH), 129.2 (2ꢁ CH), 130.3 (CH), 131.6 (CH), 135.8 (C), 137.6 (C), 141.0
(C),143.3 (C); m/z (EI): 318 (MþþH, 60%), 272 (2),163 (30),162 (100);
HRMS, required for C16H16NO2S2 (MþþH) 318.0622, found 318.0638.
4.2.3. 1-(Allyloxy)-2-(1-propenylsulfonyl)benzene 45. The bis-al-
kene 4415a (0.50 g, 2.4 mmol) was dissolved in dry CH2Cl2 (20 mL)
and cooled to ꢂ5 ꢀC under N2. mCPBA (0.92 g, 5.3 mmol) was added
in one portion and stirring was continued for 24 h at 0 ꢀC. The re-
action mixture was then poured into a saturated solution of NaHCO3
(25 mL) and extracted with additional CH2Cl2 (25 mL). The organic
extracts were washed with brine (20 mL), dried over Na2SO4, filtered,
and evaporated to afford a thick yellow oil. Column chromatography
(30% EtOAc/hexane) subsequently afforded the desired product 45
(0.41 g, 70%) as an colorless thick liquid. 1H NMR spectroscopy
showed that compound 45 consisted of a 1:1 mixture of E/Z isomers.
Rf (30% EtOAc/hexanes) 0.34; IR: vmax (film)/cmꢂ1 1729, 1629, 1445,
1424, 1347, 1304, 1279, 1228, 1129, 1099, 1043; 1H NMR (300 MHz,
(300 MHz, CDCl3)
d
2.02 and 2.17 (3H, 2ꢁ dd, J 6.9, 1.6, and 7.4,
1.6 Hz, CH3), 2.48 (3H, s, CH3), 4.27e4.45 (2H, m, CH2), 4.92e4.99
(2H, m, CHCH2), 5.57e5.72 (1H, m, CHCH2), 6.46e6.57 (0.5H, m,
CH), 6.74e6.83 (1.5H, m, ArH and CH), 6.87e6.99 (0.5H, m, CH),
7.06e7.18 (0.5H, m, CH), 7.38 (2H, br d, J 8.3, 2ꢁ ArH), 7.42e7.63 (2H,
m, 2ꢁ ArH), 7.66e7.83 (2H, m, 2ꢁ ArH), 8.11e8.32 (1H, m, ArH); 13C
NMR (75 MHz, CDCl3)
d 14.4 and 17.5 (CHCH3), 21.6 (ArCH3), 55.4
and 55.5 (CH2), 120.3 and 120.4 (CH), 128.3 and 128.4 (2ꢁ CH2),
129.1 and 129.2 (CH), 129.8 (2ꢁ CH2), 130.5 (CH), 130.9 and 131.0
(CH), 131.2 (CH), 131.4 and 131.5 (CH), 133.4 and 133.5 (CH), 136.9
and 137.0 (C), 138.1 and 138.2 (C), 141.5 (C), 142.5 (C), 143.2 (CH),
144.1 and 144.2 (CH), 144.6 (CH); m/z (EI): 414 (MþþNa, 100%), 287
(25), 236 (74), 130 (10); HRMS, required for C19H22NO4S2 (MþþH)
392.0972, found 392.0984.
CDCl3):
d
(ppm) 1.99 and 2.07 (3H, 2ꢁ dd, J 6.9, 1.5 Hz and 7.2, 1.5 Hz,
CH3), 4.67e4.70 (2H, m, OCH2), 5.29e5.52 (2H, m, CHCH2), 5.99e6.14
(1H, m, OCH2CHCH2), 6.32e6.38 (0.5H, m, SCHCHCH3), 6.49e6.64
(1H, m, SCH), 6.97e7.11 (2.5H, m, 2ꢁ ArH and SCHCHCH3), 7.50e7.56
(1H, m, ArH), 7.94e8.02 (1H, m, ArH); 13C NMR (75 MHz, CDCl3):
4.2. General procedure for RCM reactions performed
in the CEM discover microwave
d
(ppm) 14.1 and 17.3 (CH3), 58.8 (OCH2), 113.4 and 113.5 (CH), 118.3
and 118.5 (CH2), 120.6 and 120.7 (CH), 129.41 and 129.45 (C), 131.1
and 131.4 (CH), 132.0 (CH), 135.1 (CH), 141.6 (CH), 143.3 (CH), 156.2
and 156.3 (C); m/z (EI): 239 (MþþH, 100%), 197 (4); HRMS, required
for C12H15O3S (MþþH) 239.0742, found 239.0742.
To a flame dried 10 mL microwave vial, equipped with a stirring
bar, were added the diene and anhydrous toluene, all under Ar gas.
The Grubbs second generation catalyst 25 was subsequently added
under Ar to the vial after which it was sealed. The vial was then
irradiated in a microwave reactor for the recorded period and re-
action conditions. After cooling the crude product was purified by
column chromatography on silica gel.
4.2.4. 2H-1,5-benzoxathiepine 47. According to the general pro-
cedure described above the Grubbs second generation catalyst 25
(20 mol %, 0.041 g) was added to the sulfone 44 (0.050 g,

D.B. Yadav et al. / Tetrahedron 67 (2011) 2991e2997
2997
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0.24 mmol) dissolved in dry toluene (3 mL). The irradiation was
then performed for a period of 10 min at conditions of 150 ꢀC and
100 W. After cooling the reaction mass, a further portion of Grubbs
second generation catalyst (20 mol %, 0.041 g) was loaded and the
sample was irradiated for a further 10 min (150 ꢀC and 100W). The
desired cyclised compound 47 was then obtained after silica gel
column chromatography (5% EtOAc/hexane) as a pale yellow oil
(0.025 g, 62%). Rf (5% EtOAc/hexanes) 0.50; IR: vmax (film)/cmꢂ1
1725, 1623, 1572, 1439, 1469, 1375, 1345, 1232, 1154, 1121, 1070,
€
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d (ppm) 4.72 (2H, dd, J 3.6, 1.8 Hz,
12. Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18e29.
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691, 5222e5239; (d) Pelly, S. C.; Parkinson, C. J.; van Otterlo, W. A. L.; de Koning,
C. B. J. Org. Chem. 2005, 70, 10474e10481; (e) van Otterlo, W. A. L.; Morgans, G.
L.; Khanye, S. D.; Aderibigbe, B. A. A.; Michael, J. P.; Billing, D. G. Tetrahedron Lett.
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OCH2), 5.85 (1H, dt, J 11.0, 3.6 Hz, CHCH2), 6.13 (1H, dt, J 11.0, 1.8 Hz,
SCH), 7.02e7.08 (2H, m, 2ꢁ ArH), 7.20e7.25 (1H, m, ArH), 7.32 (1H,
dd, J 7.5, 1.5 Hz, ArH); 13C NMR (75 MHz, CDCl3):
d (ppm) 72.0 (CH2),
120.2 (CH), 122.8 (CH), 124.4 (CH), 125.8 (CH), 128.9 (CH), 130.0
(CH), 130.1 (C), 160.1 (C); m/z (EI LCMS): 164 (Mþ, 100%), 163 (80),
137 (85); HRMS, required for C9H8OS 164.0296, found 164.0299.
Acknowledgements
14. For reviews see the following references: (a) Schmidt, B. Eur. J. Org. Chem. 2004,
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5129e5147.
This work was supported by the National Research Foundation
(NRF), Pretoria, and the University of the Witwatersrand (Univer-
sity and Science Faculty Research Councils). DBY thanks the Uni-
versity of the Witwatersrand Research Office for a postdoctoral
fellowship. We also gratefully acknowledge Mr. R. Mampa for the
NMR spectroscopy service. Finally, Mr. T. van der Merwe (University
of the Witwatersrand), Dr. A. Dinsmore and Mrs. M. Ferreira
(University of the Witwatersrand, LRMS), Ms J. Schneider and Ms M.
Ismail (Mass Spectroscopy Service), University of Dortmund and
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Supplementary data
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Chem. 2005, 690, 5398e5406; (g) Jimenez-Gonzalez, L.; Alvarez-Corral, M.;
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