A ring-closing metathesis approach to eight-membered benzannelated scaffolds and subsequent internal alkene isomerizations

Article abstract of DOI:10.1016/j.tet.2012.12.043

A set of eight-membered benzannelated heterocycles containing two heteroatoms (O,O, NR,NR and O,NR where R=protecting group) was synthesized by ring-closing metathesis from the corresponding ortho-bis-allyl precursors. In this manner, 7-methoxy-2,5-dihydro-1,6-benzodioxocine, 1,2,5,6-tetrahydro-1,6- benzodiazocines, 5,6-dihydro-2H-1,6-benzoxazocines and 5,6,9,10- tetrahydropyrido[2,3-b][1,4]diazocine were synthesized. A number of these compounds were then treated with the catalyst [RuClH(CO)(PPh₃) ₃] to facilitate isomerization of the alkene into conjugation with the heteroatoms in the eight-membered ring. Quite surprisingly, an equal ratio of regioisomers was obtained, even if the heteroatoms were different.

Full text of DOI:10.1016/j.tet.2012.12.043

Tetrahedron 69 (2013) 2038e2047
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A ring-closing metathesis approach to eight-membered
benzannelated scaffolds and subsequent internal alkene
isomerizations
Abu Taher a, Blessing A. Aderibigbe b, Garreth L. Morgans b, Lee G. Madeley yb,
,
Setshaba D. Khanye b, Leandi van der Westhuizen a, Manuel A. Fernandes b
,
Vincent J. Smith a y, Joseph P. Michael b, Ivan R. Green a, Willem A.L. van Otterlo a
,
,b,
*
a Department of Chemistry and Polymer Science, Stellenbosch University, Stellenbosch, 7602 Western Cape, South Africa
b 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:
A set of eight-membered benzannelated heterocycles containing two heteroatoms (O,O, NR,NR and
O,NR where R¼protecting group) was synthesized by ring-closing metathesis from the corresponding ortho-
bis-allyl precursors. In this manner, 7-methoxy-2,5-dihydro-1,6-benzodioxocine, 1,2,5,6-tetrahydro-1,6-
benzodiazocines, 5,6-dihydro-2H-1,6-benzoxazocines and 5,6,9,10-tetrahydropyrido[2,3-b][1,4]diazocine
were synthesized. A number of these compounds were then treated with the catalyst [RuClH(CO)(PPh3)3] to
facilitate isomerization of the alkene into conjugation with the heteroatoms in the eight-membered ring.
Quite surprisingly, an equal ratio of regioisomers was obtained, even if the heteroatoms were different.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 23 September 2012
Received in revised form 4 December 2012
Accepted 17 December 2012
Available online 29 December 2012
Keywords:
Ring-closing metathesis
Isomerization
Benzodioxocine
Benzodiazocine
Benzoxazocine
Pyridodiazocine
1. Introduction
contain this motif. See, for example, the compound porritoxin 3,10
extracted from Alternaria porri, which inhibits the growth of
Ring-closing metathesis (RCM) has become an established
method to synthesize medium sized ring systems including five-,
six-, seven- and eight-membered hetero- and carbo-cycles.1 Prob-
ably the most significant contributor to the surge in synthetic
strategies delivering useful unsaturated heterocycles has been the
availability and extensive use of the so-called ‘Grubbs catalysts’.2
The ready application of this robust group of catalysts has also
led to the generation of benzo-fused compounds with varying rings
sizes (see, for example, benzo-fused five-,3 six-,4 seven-5 and eight-
membered6 systems) and the synthesis of this class of compounds
using RCM has been a topic of interest in our group.7
The importance of eight-membered benzo-fused compounds,
particularly those with one or more heteroatoms in the heterocyclic
core, has also been increasing. Examples of compounds being
investigated in the medicinal chemistry realm include compounds,
such as 1 (NK1 antagonists)8 and 2 (nefopam, a potent non-sedative
analgesic)9 (Fig. 1). Compounds from the natural product world also
* Corresponding author. E-mail addresses: wvo@sun.ac.za, Willem.vanOtterlo@
wits.ac.za (W.A.L. van Otterlo).
Fig. 1. Representative structures of natural and synthetic compounds containing
a benzo-fused eight-membered ring system with one or more heteroatoms.
y
For X-ray crystallography.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.12.043

A. Taher et al. / Tetrahedron 69 (2013) 2038e2047
2039
seedlings; and heliannuol A 4,11 a member of a well populated sesqui-
terpenoid family with well-documented allelochemical bioactivities.12
An additional point of interest, in terms of eight-membered benzo-
fused rings, is that as the benzannelated ring system increases in size,
so too does the conformational space that can be occupied increase,
particularly when compared to that occupied by similar six- and
seven-membered systems.13 As medicinal chemists have increasingly
started to appreciate that the flexibility of molecules is important in
overcoming resistance from amino acid mutations in and near the
active site, this could make the eight-membered benzo-fused hetero-
cycles worthy of more investigation.14 It can be argued that one of the
reasons for the comparative rarity of medicinal investigations into
eight-membered systems is due to the increased difficulty of their
controlled synthesis. This paper aims to make a contribution in this
regard. It should be noted that in recent years a number of papers
describing the application of RCM to eight-membered ring systems
have beenpublished,15 and we trust our work will add value to this area.
Along with the increase of synthetic applications of RCM have been
the reports of isomerizations associated with the methodology. On the
one hand, these reports could describe this problematic side-reaction
leading to a decrease in yield of the desired compound, on the other
as a useful strategy to move the resulting alkene from the RCM into
a new targeted position. The identification of metathesis products
resulting from ‘pre-’ or ‘post-’metathetic isomerizations has thus seen
much investigation and this work has been summarized in recent
reviews.16 Examples are known where isomerization prior to the RCM
results in cycles containing one less carbon atom than expected, in most
cases an undesired result. In fact, it has been shown that in slow met-
athetic transformations the presence of a ruthenium hydride, originat-
ing from the decomposition of the actual Grubbs catalyst, is responsible
for the isomerization of the terminal alkenes to the more thermody-
namically stable internal regioisomers.17 Other work, focussing on the
isomerization of the alkene functionality after the metathesis event, has
alsoelicited interest.18 Forinstance, seminal workby the research groups
headed by Schmidt,16c,19 Snapper20 and other more recent work,21 have
demonstrated how useful the RCM-isomerization strategy can be.
Of interest to note is that the intentional isomerization of cyclic
alkenes after metathesis has mainly been applied to the smaller
ring systems, with seven-membered rings often being the upper
limit tested. With this particular background in mind we thus
disclose our results concerning the generally facile metathetic
construction of eight-membered benzo-fused heterocyclic systems
containing two heteroatoms with the Grubbs second generation
catalyst 5 (i.e., transformation 8 / 9 in Scheme 1), from ortho-bis-
allyl substrates generated from the commercially available 7. This
would be followed by the intentional post-metathetic isomeriza-
tion of the resultant eight-membered products to afford alkenes
now in conjugation to a heteroatom (i.e., transformation 9 / 10 &
100, Scheme 1). The isomerizations were not performed by an in situ
procedure, as has so successfully been utilized by Schmidt and co-
workers,19 but by a sequential isomerization performed with the
ruthenium hydride 6, previously utilized in our group. The com-
pounds thus formed by this approach were studied by spectro-
scopic methods and in several cases their structures were
confirmed by single crystal X-ray crystallographic studies.
2. Results and discussion
To access the eight-membered benzannelated ring systems 9 it
was initially necessary to synthesize a range of ortho-bis-allyl an-
alogues 8. Scheme 2 illustrates how the benzo- and pyrido-bisallyl
systems 8 were synthesized in general, utilizing a variety of
protection and allylation strategies from the diamino, dihydroxy or
aminohydroxy compounds 7 (see Experimental section for specific
details). To probe the scope of the reactions, 3-methoxycatechol
(O,O-7) and 1,2-diaminobenzene (N,N-7) were initially utilized;
the latter’s amino groups protected as the tert-butyl carbamate 7b,
the phenyl benzamide 7c, the tosyl sulfonamide 7d and as the
acetamide 7e. The ortho-bis-allyl derivatives were then readily
synthesized to afford compounds 8aee in acceptable yields. Next,
the respective pyrido ortho-bis-allyl equivalents were generated
from pyridine-2,3-diamine and 2-chloro-pyridin-3-ol22 to give
in hand compounds 8feg. Finally, 2-aminophenol (N,O-7) was
N-protected with the Boc, benzoyl and tosyl groups and converted
into the ortho-bis-allyl equivalents 8h, 8i and 8j, respectively.
Scheme 2. For information concerning structure (i.e., X, Y and Z) and results of the
RCM reactions (8 / 9), see Table 1. For other conditions see Experimental section.
The first key-step involved exposure of these ortho-bis-allyl
precursors to the Grubbs second generation catalyst 5, surprisingly
with mixed results. In general, the benzene derivatives readily affor-
dedtheirrespectiveeight-memberedsystems9asexpectedandTable
1 (Scheme 2) summarizes these synthetic results. The yields for ring
systems 9aee ranged from moderate(49% for9b)to excellent(97%for
9c). It should be noted that for 9c the best results were obtained when
a catalytic amountof p-toluenesulfonicacidwasadded tothe reaction
mixture. In contrast, the pyrido ortho-bis-allyl derivatives 8f and 8g
gave mixed results when subjected to the ring-closing conditions.
In our hands, we were unable to cyclize 2,3-bis(allyloxy)pyridine
8f22 using standard metathesis conditions. Believing that perhaps
coordinationwiththepyridonitrogenwaseffectivelyinterruptingthe
10'
Scheme 1. Proposed route for the synthesis of eight-membered pyrido- and benzo-
fused compounds and the subsequent isomerization reactions (X, Y¼NR and/or O,
where R¼Boc, Bz, Ac or Ts; Z¼N or CH2, R¼H or OMe).

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A. Taher et al. / Tetrahedron 69 (2013) 2038e2047
Table 1
Results for RCM reactions
Entry
X
Y
Z
Yield of ring-closed
products 9 (%)
aa
b
c
d
e
f
O
O
CH
CH
CH
CH
CH
N
60
49
97
92
80
d
NBoc
NBz
NTs
NAc
O
NBoc
NBz
NTs
NAc
O
g
h
i
NTs
O
O
NTs
NBoc
NBz
NTs
N
94
58
78
70
CH
CH
CH
j
O
a
Compounds 8/9a also contained an OMe group in position.
metathetic catalytic cycle, itwas decided to complex the basic nitrogen
as done by other researchers; however, additives, such as titanium
isopropoxide,23 p-toluenesulfonic acid24 and hydrochloric acid25 were
unfortunately ineffective in facilitating ring-closure. Of interest was
that the bis-tosyl derivative 8g did however facilely ring close in ex-
cellent yield of 94%. This could mean that the additional steric hin-
drance of the two bulky sulfonamide groups pre-organizes the allyl
groups insuchawayas todiscouragechelationwith thebasic nitrogen
atom of the pyridine ring, thus allowing for RCM to occur. The exact
reason why chelation of this group did not result in the cyclization of
substrate 8f is still a puzzle. Finally, the benzazocine compounds with
the nitrogen atom protected as the Boc 9h, benzoyl 9i or tosyl de-
rivative 9j were all readily prepared in acceptable to good yields.
In addition, as part of our studies into the solid-state structures of
the eight-membered ring systems, crystal structures of compounds
9b and 9c were successfully determineddsee the ORTEP structures
in Fig. 2. It was further decided to reduce the alkene functionality
found in diazocine 9b, to afford the saturated analogue 11, which
was also studied by single crystal X-ray diffraction (Scheme 3 and
Fig. 2). The effective reduction of the alkene was evident in the new
saturated four-carbon bridge in the structure of 11.
With a number of the eight-membered ring-closed products 9
in hand, it was decided to investigate the possibility of controlled
isomerization of the alkene functionality within the heterocyclic
ring (Scheme 4). To the best of our knowledge the isomerization
of alkenes in eight-membered ring systems has seen very little
investigation; Schmidt and co-workers have performed a post-
metathetic isomerization on an eight-membered glycoside
derivative after converting the Grubbs second generation catalyst
into a ruthenium hydride with sodium borohydride,19b while Ste-
vens and co-workers successfully utilized [RuClH(CO)(PPh3)3] 6 on
a number of 1-phosphonylated 2-benzazocine systems.6a
A number of the eight-membered benzannelated ring-systems were
thus subjected to an induced isomerizationprocess byapplication of the
ruthenium hydride [RuClH(CO)(PPh3)3] 6, a catalyst reliably used in our
previous research.26 The first system to be investigated was the sub-
strate, 7-methoxy-2,5-dihydro-1,6-benzodioxocine 9a. Application of
the isomerization catalyst 6 to this compound afforded, after chroma-
tography, a 1:1 mixture of the regioisomers 10a and 100a, which we
were unable to separate from each other. Of interest here is that it ap-
pears that the methoxy group did not in any way seem to bias the
regiochemical outcome of the isomerization.
Fig. 2. ORTEP diagrams of the X-ray crystal structures of compounds a) 9b, b) 9c (two
orientations) and c) 11 (two orientations), with all thermal ellipsoids at 50% probability.
the isomerization process was confirmed by the fact that the two
simple signals due to the symmetrical eTsNCH2CH]CHCH2NTse
system now appeared as four separate peaks representing two
different sets of CH2 and CH] groups, respectively. The loss of
symmetry was also reflected in a more complicated carbon NMR
spectrum. The isomerization of the double bond was finally con-
firmed by the crystal structure in which the alkene was now clearly
in conjugation with the nitrogen atom (Fig. 3a).
Next, the only pyrido-derivative in hand, namely 5,10-bis-tosyl-
5,6,9,10-tetrahydro-pyrido[2,3-b][1,4]diazocine 9g, was investigated
with regard to catalyst 6. The isomerization reaction was complete
after 18 h (TLC) giving two regioisomeric products in a ratio of 45:55
(from 1H NMR spectroscopy), and with an overall yield of 89%.
Careful flash silica gel column chromatography then afforded a clean
sample of the isomerized product with the higher Rf value, on which
Secondly, application of the hydride catalyst 6 to the protected
benzo[b][1,4]diazocine skeletons gave good results. Use of
[RuClH(CO)(PPh3)3] 6 on the Boc-protected diazocine derivative 9b
afforded the isomerized product 10b after 2 h in a good yield of 81%,
the structure of which was confirmed by NMR spectroscopy. In
addition, under similar conditions, 1,6-bis(toluene-4-sulfonyl)-
1,2,5,6-tetrahydro-benzo[b][1,4]diazocine 9d gratifyingly afforded
the isomerized 10d in a reasonable yield of 61% (for an alternative
synthesis of this compound see reference 14c). For this compound,
Scheme 3. Reduction of alkene 9b to afford 11.

A. Taher et al. / Tetrahedron 69 (2013) 2038e2047
2041
3. Conclusion
In this paper it has been demonstrated that i) the RCM meth-
odology is readily applicable for the synthesis of a number of eight-
membered benzannelated bis-heteroatom-containing heterocy-
cles, although a pyridine nitrogen ortho to an O-allyl groups appears
to hinder the ring closure, and that ii) the alkene group in a number
of the compounds synthesized could be isomerized into conjuga-
tion with the heteroatoms by the application of the isomerization
catalyst [RuClH(CO)(PPh3)3] 6. Of interest, was that the ruthenium
hydride did not appear to discriminate in terms of regioselectivity,
as neither bulk of protecting groups nor a difference in heteroatoms
seemed to affect the 1:1 mixture of regioisomers obtained.
Scheme 4. For information concerning structure (i.e., X, Y and Z) and results of the
isomerization reactions, see Table 2. For other conditions see Experimental section.
4. Experimental
4.1. General
a single crystal X-ray analysis was successfully performed (Fig. 3b),
allowing for the rigorous identification of the regioisomer 10g.
When the isomerization conditions were applied to the O,NTs-
system 9j, once again NMR spectroscopic analysis of the product
indicated a mixture of regioisomers, which were assigned as 10j
and 100j, respectively. Unexpectedly, the ratio of these compounds
was again 1:1, in effect indicating that the catalyst was not differ-
entiating between the oxygen atom and the much bulkier N-tosyl
environment. Careful selection of the crystals afforded from a slow
recrystallization, allowed for the single crystal X-ray structural
determination of both regioisomers 10j and 100j (Fig. 3c and d), and
facilitated a comparison of their solid state conformations.
1H NMR and 13C NMR spectra were recorded on Bruker 300,
Bruker DRX 400, Varian Inova 400 or Varian Inova 300 spectrom-
eters at the frequency indicated. Infra-red spectra were recorded on
Bruker IFS 25, Bruker Vector 22 or Thermo Nicolet Nexus 470
Fourier transform spectrometers. Mass spectra were recorded on
a Kratos MS 9/50, VG 70E MS or VG 70 SEQ mass spectrometer or
alternatively a Waters API Q-TOF Ultima, GCT Premier or SYNAPT
G2 mass spectrometer. Macherey-Nagel Kieselgel 60 (particle
size 0.063e0.200 mm) was used for conventional silica gel
Table 2
Results regarding isomerization reactions performed
Entrya
Substrate
X
O
Y
Z
Yield (ratio)
63 (1:1)
Structure of product(s)
ab
9a
O
CH
b
9b
NBoc
NBoc
CH
81
c
9d
9g
NTs
NTs
NTs
NTs
CH
61
d
N
89 (45:55)
e
9j
O
NTs
CH
78 (1:1)
a
Numbering according to Table 1.
Compounds 9a contained an OMe group in position.
b

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A. Taher et al. / Tetrahedron 69 (2013) 2038e2047
4.1.1. 1,2-Bis(allyloxy)-3-methoxybenzene
(8a). 3-Methoxy-1,2-
benzenediol (0.498 g, 3.56 mmol) was dissolved in acetone
(20 mL) and K2CO3 (1.97 g, 14.3 mmol) and allyl bromide (1.72 g,
14.2 mmol) were added. The reaction mixture was then heated at
reflux for 18 h. After cooling, H2O (30 mL) was added and the crude
product was then extracted with EtOAc (3ꢀ100 mL). The combined
filtrate was then dried with MgSO4 to afford the product as an
yellow oil, which was purified by column chromatography (20%
EtOAc/hexane) to afford the desired compound 8a as a light yellow
oil (0.60 g, 76%). Rf (30% EtOAc/hexane) 0.72; IR vmax (film)/cmꢁ1
1647, 1475, 1104; 1H NMR (300 MHz, CDCl3):
d
(ppm)¼3.83 (s, 3H,
OCH3), 4.53 (d, 2H, J 6.0 Hz, OCH2), 4.57 (d, 2H, J 5.2 Hz, OCH2),
5.16e5.44 (m, 4H, 2ꢀ CH]CH2), 5.99e6.18 (m, 2H, 2ꢀ CH2CH]),
6.67 (d, 2H, J 8.6 Hz, 2ꢀ ArH), 6.92e6.98 (m, 1H, ArH); 13C NMR
(75 MHz, CDCl3):
d
(ppm)¼55.9 (OCH3), 69.8 (OCH2), 74.0 (OCH2),
105.4 (CH2), 107.1 (CH2), 117.1 (CH), 117.4 (CH), 123.4 (CH), 133.4
(CH), 134.5 (CH), 137.7 (C), 152.6 (C), 153.8 (C); m/z (EI): 220
(Mþ, 65%), 205 (27), 179 (96), 41 (100); HRMS: Mþ, calcd for
C13H16O3 220.1099, found 220.1098.
4.1.2. 7-Methoxy-2,5-dihydro-1,6-benzodioxocine (9a).5b Bis(allyloxy)
benzene 8a (0.140 g, 0.635 mmol) was dissolved in toluene (10 mL),
after which Grubbs second generation catalyst 5 (10 mol %, 0.054 g,
0.063 mmol) was added and the reaction mixture stirred at 60 ꢂC for
a further 18 h. The solvent was removed under a high vacuum
and silica gel column chromatography (10% EtOAc/hexane) was
performed on the crude product to afford the desired cyclized
compound 9a as an yellow oil (0.072 g, 60%). Rf (20% EtOAc/hexane)
0.46; IR: vmax (film)/cmꢁ11585,1474,1314,1270,1245, 1099; 1H NMR
(300 MHz, CDCl3):
d
(ppm)¼3.82e3.85 (br m, 3H, OCH3), 4.87e5.00
(m, 2H, OCH2), 4.96e4.99 (m, 2H, OCH2), 5.88e5.91 (m, 2H, CH]CH),
6.54e6.57 (m, 2H, 2ꢀ ArH), 6.86e6.92 (m, 1H, ArH); 13C NMR
(75 MHz, CDCl3):
d
(ppm)¼55.9 (OCH3), 67.9 (OCH2), 70.8 (OCH2),
105.1 (CH), 113.6 (CH), 123.6 (CH), 126.9 (CH), 132.1 (CH),
136.6 (C), 149.2 (C), 153.5 (C); m/z (EI): 192 (Mþ, 87%), 151 (47), 110
(90), 94 (100); HRMS: Mþ, calcd for C11H12O3 192.0786, found
192.0785.
4.1.3. 10-Methoxy-2,3-dihydro-1,6-benzodioxocine and 7-methoxy-
2,3-dihydro-1,6-benzodioxocine (10a & 100a). Benzodioxocine 9a
(0.0590 g, 0.307 mmol) was dissolved in toluene (4 mL) and
[RuClH(CO)(PPh3)3] 6 (6 mol %, 0.016 g, 0.020 mmol) was added. The
reaction mixture was then heated at reflux for 48 h. The solvent was
removed under high vacuum and silica gel column chromatography
(20% EtOAc/hexane) was performed to afford an inseparable mix-
ture of regioisomers 10a and 100a as an yellow oil (0.037 g, 63%). Rf
(20% EtOAc/hexane) 0.23; IR: vmax (film)/cmꢁ1 1651, 1591, 1472,
1315, 1270, 1247, 1116, 1090; 1H NMR (300 MHz, CDCl3, combined):
d
(ppm)¼2.18e2.29 (m, 4H, 2ꢀ OCH2CH2), 3.77 and 3.78 (s, 6H,
2ꢀ OCH3), 4.04 and 4.18 (t, 4H, J 5.6 Hz, 2ꢀ OCH2), 4.57e4.64 and
4.75e4.81 (m, 2H, 2ꢀ OCH]CH), 6.36 and 6.47 (d, 2H, J 7.1 Hz,
2ꢀ OCH]CH), 6.55e6.61 (m, 4H, 4ꢀ ArH), 6.84e6.93 (m, 2H,
2ꢀ ArH); 13C NMR (75 MHz, CDCl3, combined):
(ppm)¼23.9 (CH2),
d
25.3 (CH2), 56.1 (OCH3), 56.2 (OCH2), 66.0 (CH2), 68.6 (CH2), 103.7
(CH), 106.7 (CH), 107.3 (CH), 107.8 (CH), 113.5 (CH), 114.6 (CH), 123.6
(CH), 124.2 (CH), 126.8 (C), 132.1 (C), 136.7 (C), 145.2 (2ꢀ CH), 149.5
(C), 152.4 (C), 153.8 (C); m/z (EI): 192 (Mþ, 29%), 153 (39), 136 (30),
107 (42), 89 (49), 77 (100), 51 (38); HRMS: Mþ, calcd for C11H12O3
192.0786, found 192.0781.
Fig. 3. ORTEP diagrams of the X-ray crystal structures of compounds a) 10d (two
orientations, note methyl carbon 24 is disordered over two positions at 50:50), b) 10g,
c) 10j and d) 100j (two orientations), with thermal ellipsoids at 50% probability.
chromatography. All solvents used for reactions and chromatog-
raphy were distilled prior to use. Reactions were performed under
a blanket of inert gas (Ar or N2) unless specified. Melting points are
uncorrected.
4.1.4. Di-tert-butyl 1,2-phenylenebis(allylcarbamate) (8b). Di-tert-
butyl 1,2-phenylenedicarbamate27 (0.930 g, 3.01 mmol) was dis-
solved in DMF (20 mL), to which NaH (60% in oil, 0.389 g,
9.73 mmol) and allyl bromide (0.84 mL, 9.7 mmol) were added. The
reaction mixture was then stirred at rt for 18 h. H2O (50 mL) was
then added and the reaction mixture was extracted with EtOAc
2,3-Bis(allyloxy)pyridine 8f was synthesized according to the
procedures described by Jarvis and Anderson.22

A. Taher et al. / Tetrahedron 69 (2013) 2038e2047
2043
(4ꢀ50 mL). The organic fractions were combined, dried (MgSO4)
and reduced in vacuo, after which column chromatography was
performed (20% EtOAc/hexane) to afford the product 8b as an yel-
low oil (0.770 g, 66%). The NMR spectra showed evidence for the
existence of rotamers in solution, by way of peak broadening. Rf
(20% EtOAc/hexane) 0.53; IR: vmax (film)/cmꢁ1 1701, 1599, 1500,
(6), 305 (48), 249 (16); HRMS (MþH)þ: calcd for C20H29N2O4
361.2127, found 361.2117.
4.1.7. Di(tert-butyl) 2,3,4,5-tetrahydro-1,6-benzodiazocine-1,6-
dicarboxylate (11). Hydrogenation was performed by stirring 10%
Pd/C (0.070 g, 0.05 mol) in EtOH (20 mL), followed by the addition
of compound 9b (0.0480 g, 0.133 mmol) under H2 pressure (5 atm)
for 20 h. The crude product was then filtered under vacuum
through a Celite plug using EtOH (50 mL), after which the solvent
was removed under a vacuum. Silica gel column chromatography
was then performed (30% EtOAc/hexane) to afford the product 11 as
a white solid (0.047 g, 97%). The NMR spectra showed evidence for
the existence of rotamers in solution, by way of peak broadening.
Mp: 100e103 ꢂC; Rf (30% EtOAc/hexane) 0.42; IR: vmax (film)/cmꢁ1
1699, 1598, 1502, 1454, 1385, 1280, 1252; 1H NMR (300 MHz,
1454, 1388, 1307, 1251, 1149; 1H NMR (300 MHz, CDCl3):
d
(ppm)¼
1.25 and 1.36 (2ꢀ br s, 18H, 6ꢀ CH3), 3.63 (br s, 2H, NCH2), 4.47 (br s,
2H, NCH2), 5.08e5.11 (br m, 4H, 2ꢀ CH]CH2), 5.89e5.91 (br m, 2H,
2ꢀ CH2CH]), 7.06e7.09 (m, 2H, 2ꢀ ArH), 7.22 (br s, 2H, 2ꢀ ArH);
13C NMR (75 MHz, CDCl3, quaternary C not observed in spectrum):
d
(ppm)¼28.2 (6ꢀ CH3), 51.3 and 52.8 (br, 2ꢀ CH2), 80.2 (br, 2ꢀ
CeO), 117.4 (br, 2ꢀ CH2), 127.7 (br, 2ꢀ CH), 131.0 (br, 2ꢀ CH), 133.5
(br, 2ꢀ CH),154.3 (br, 2ꢀ C]O); m/z (EI): 388 (Mþ, 5%), 276 (21),187
(30), 159 (33), 57 (100); HRMS: Mþ, calcd for C22H32N2O4 388.2362,
found 388.2371.
CDCl3):
d
(ppm)¼1.44 (br s, 18H, 6ꢀ CH3), 1.67 (br s, 4H, 2ꢀ
CH2CH2), 3.65 (br s, 4H, 2ꢀ NCH2), 7.23 (br s, 2H, 2ꢀ ArH), 7.33e7.39
4.1.5. Di(tert-butyl)-2,5-dihydro-1,6-benzodiazocine-1,6-dicarboxylate
(9b). Bis(allylcarbamate) 8b (0.120 g, 0.309 mmol) was dissolved in
toluene (5 mL) and Grubbs second generation catalyst 5 (10 mol %,
0.026 g, 0.031 mmol) was added, after which the reaction mixture
was stirred for 18 h at 60 ꢂC. The solvent was removed on the high
vacuum and silica gel column chromatography was then performed
(20% EtOAc/hexane) to afford the cyclized compound 9b as a white
solid (0.055 g, 49%). The NMR spectra showed evidence for the ex-
istence of rotamers in solution, by way of peak broadening. Mp:
113e116 ꢂC; Rf (20% EtOAc/hexane) 0.47; IR: vmax (film)/cmꢁ1 1701,
(m, 2H, 2ꢀ ArH); 13C NMR (75 MHz, CDCl3):
(ppm)¼26.5 (2ꢀ CH2),
d
28.2 (6ꢀ CH3), 50.9 (br s, 2ꢀ NCH2), 79.7 (2ꢀ CeO), 128.0 (2ꢀ CH),
129.3 (2ꢀ CH), 140.4 (2ꢀ C), 154.8 (2ꢀ C]O); m/z (EI): 362 (Mþ,
27%), 206 (71), 162 (26), 57 (100); HRMS: Mþ, calcd for C20H30N2O4
362.2206, found 362.2203.
X-ray crystal structure details of compound 11: crystallized from
30% EtOAc/hexane, formula: C20H30N2O4, M¼362.46, colour of
crystal: colourless, needle, crystal size 0.34ꢀ0.25ꢀ0.24 mm,
ꢀ
ꢀ
ꢀ
b
a¼9.1809(14) A, b¼23.088(4) A, c¼9.9199(16) A,
¼91.996(10)ꢂ,
3
V¼2101.5(6) A , rcalcd¼1.146 Mg/m3,
m
¼0.080 mmꢁ1, F(000)¼784,
ꢀ
1499, 1454, 1368, 1246, 1165; 1H NMR (300 MHz, CDCl3):
d
(ppm)¼
Z¼4, monoclinic, space group P2(1)/n, T¼173(2) K, 21,655
reflections collected, 5072 independent reflections, qmax 28.00ꢂ,
236 refined parameters, maximum residual electron density 0.209
1.43 (br s,18H, 6ꢀ CH3), 4.08 (br s, 4H, 2ꢀ NCH2), 5.86 (br s, 2H, CH]
CH), 7.12e7.14 (br m, 2H, 2ꢀ ArH), 7.15e7.30 (br m, 2H, 2ꢀ ArH); 13C
ꢀꢁ3
NMR (75 MHz, CDCl3):
d
(ppm)¼28.2 (6ꢀ CH3), 45.7 (2ꢀ CH2), 80.6
and ꢁ0.210 e A . R1¼0.0456, wR2¼0.1005. Crystallographic data
(2ꢀ CeO), 125.3 (2ꢀ C), 128.5 (2ꢀ CH), 129.2 (2ꢀ CH), 136.5 (2ꢀ CH),
154.6 (br, 2ꢀ C]O); m/z (EI): 360 (Mþ, 6%), 248 (29), 204 (48), 159
(33), 57 (100); HRMS: Mþ, calcd for C20H28N2O4 360.2049, found
360.2069.
for the structure have been deposited with the Cambridge Crys-
tallographic Data Centre as deposition No. CCDC-901916.
4.1.8. N-Allyl-N-{2-[allyl(benzoyl)amino]phenyl}benzamide (8c). To
a solution of N-[2-(benzoylamino)phenyl]benzamide28 (1.00 g,
3.16 mmol) in DMSO (20 mL) was added NaH (60% in oil, 0.520 g,
13.0 mmol), followed by allyl bromide (1.09 mL, 12.4 mmol) 5 min
later. The reaction mixture was then stirred at rt for 20 h under N2,
after which H2O (10 mL) was added. The mixture was then
extracted using EtOAc (3ꢀ100 mL) and the combined fractions
were dried (MgSO4). Silica gel column chromatography was next
performed (20% EtOAc/hexane) to afford the product 8c as a white
solid (1.01 g, 81%). The NMR spectra showed evidence for the
existence of rotamers in solution, by way of significant peak
broadening. Mp: 132e135 ꢂC; Rf (20% EtOAc/hexane) 0.33; IR: vmax
(film)/cmꢁ1 1651, 1596, 1577, 1494, 1448, 1426, 1373, 1308, 1217; 1H
X-ray crystal structure details of compound 9b: crystallized
from 20% EtOAc/hexane, formula: C20H28N2O4, M¼360.44, colour of
crystal: colourless, needle, crystal size 0.22ꢀ0.15ꢀ0.07 mm,
ꢀ
ꢀ
ꢀ
a¼5.966(5) A, b¼11.293(5) A, c¼14.888(5) A,
a
¼86.038(5)ꢂ,
3
ꢀ
b
m
¼88.040(5)ꢂ,
g
¼88.792(5) , V¼999.9(10) A , rcalcd¼1.197 Mg/m3,
ꢂ
¼0.083 mmꢁ1, F(000)¼388, Z¼2, triclinic, space group Pe1,
T¼173(2) K, 12,980 reflections collected, 4908 independent re-
flections, qmax 28.28ꢂ, 235 refined parameters, maximum residual
ꢀꢁ3
electron density 0.259 and ꢁ0.279 e A . R1¼0.0492, wR2¼0.1146.
Crystallographic data for the structure have been deposited with
the Cambridge Crystallographic Data Centre as deposition No.
CCDC-901912.
NMR (300 MHz, CDCl3):
d
(ppm)¼3.90e4.20 [br m, 2H, 2ꢀ NC(H)H],
4.1.6. Di(tert-butyl) 2,3-dihydro-1,6-benzodiazocine-1,6-dicarboxylate
(10b). 1,6-Benzodiazocine 9b (0.080 g, 0.222 mmol) was dissolved
in d8-toluene and ruthenium isomerization catalyst 6 (0.011 g,
5 mol %, 0.011 mmol) was added. The reaction mixture was then
heated at 95 ꢂC for 2 h at which point 1H NMR spectroscopy con-
firmed that the reaction was complete. The solvent was sub-
sequently removed under high vacuum and silica gel column
chromatography was performed (30% EtOAc/hexane) to afford the
desired compound 10b as a white crystalline solid (0.065 g, 81%).
Mp: 78e80 ꢂC; Rf (20% EtOAc/hexane) 0.50; IR: vmax (film)/cmꢁ1
2973, 1700, 1390, 1297, 1155, 1069; 1H NMR (300 MHz, CDCl3):
4.37 [br s, 2H, 2ꢀ NC(H)H], 5.11 (br s, 4H, 2ꢀ CH]CH2), 5.86 (br s,
2H, 2ꢀ CH2CH]), 7.26e7.40 (m, 14H, 14ꢀ ArH); 13C NMR (75 MHz,
CDCl3):
d
(ppm)¼52.1 (br, 2ꢀ CH2), 116.3 (br, 2ꢀ CH2), 126.8 (CH),
126.9 (CH), 127.8 (br, 2ꢀ CH), 129.4 (br, 2ꢀ CH), 130.6 (CH) 134.2
(2ꢀ CH), 136.0 (br, 2ꢀ C), 140.2 (2ꢀ C), 168.3 (br, 2ꢀ C]O); m/z (EI):
396 (Mþ, 7%), 291 (45), 275 (98), 105 (100), 77 (57); HRMS: Mþ,
calcd for C26H24N2O2 396.1837, found 396.1842.
4.1.9. 1,6-Dibenzoyl-1,2,5,6-tetrahydro-1,6-benzodiazocine (9c). Dibe-
nzamide 8c (0.190 g, 0.479 mmol) was dissolved in toluene (20 mL)
and p-toluenesulfonic acid (0.009 g, 0.052 mmol) was added,
followed by Grubbs second generation catalyst 5 (10 mol %, 0.017 g,
0.020 mmol). The reaction mixture was then stirred for 23 h at rt,
after which the solvent was removed under vacuum. Silica gel
column chromatography was performed on the crude material (30%
EtOAc/hexane) to give the cyclized product 9c as a white solid
(0.170 g, 97%). Mp: 195e198 ꢂC; Rf (30% EtOAc/hexane) 0.12; IR:
vmax (film)/cmꢁ1 1731, 1642, 1575, 1493, 1474, 1363, 1294, 1261, 1096;
d
(ppm)¼1.47 (br s, 18H, 6ꢀ CH3), 1.74e1.83 (m, 2H, CH2), 3.53 (br s,
2H, NCH2), 4.66e4.63 (m, 1H, CH]CHCH2), 6.93 (d, 1H, J 12.0 Hz,
NCH]CH), 7.08e7.11 (br m,1H, ArH), 7.24e7.35 (m, 3H, 3ꢀ ArH); 13C
NMR (75 MHz, CDCl3):
d
(ppm)¼22.0 (CH2), 27.9 (3ꢀ CH3), 28.2 (3ꢀ
CH3), 45.9 (CH2), 79.8 (CeO), 81.8 (CeO),104.1 (CH),127.3 (CH),128.4
(CH), 128.5 (CH), 128.9 (CH), 130.0 (CH), 136.1 (C), 137.4 (C), 152.7
(C]O), 154.6 (C]O); m/z (EI): 383 (MþþNa, 100%), 360 (Mþ, 9), 327

2044
A. Taher et al. / Tetrahedron 69 (2013) 2038e2047
1H NMR (300 MHz, CDCl3):
d
(ppm)¼4.74 (br s, 4H, 2ꢀ NCH2),
(100), 131 (21), 91 (41); HRMS: Mþ, calcd for C24H24N2O4S2
468.1178, found 468.1172.
5.79 (br s, 2H, CH]CH), 6.89e7.00 (m, 6H, 6ꢀ ArH), 7.08e7.13
(m, 4H, 4ꢀ ArH), 7.22e7.27 (m, 4H, 4ꢀ ArH); 13C NMR (75 MHz,
X-ray crystal structure details of compound 10d: crystallized
from EtOAc/hexane, formula: C24H24N2O4S2, M¼468.57, colour of
crystal: colourless, needle, crystal size 0.18ꢀ0.08ꢀ0.08 mm,
CDCl3):
d
(ppm)¼45.4 (2ꢀ CH2), 126.9 (2ꢀ CH), 127.9 (4ꢀ CH), 128.7
(4ꢀ CH), 129.0 (2ꢀ CH), 129.8 (2ꢀ CH), 130.0 (2ꢀ CH), 135.5 (2ꢀ C),
137.4 (2ꢀ C), 169.6 (2ꢀ C]O); m/z (EI): 368 (Mþ, 10%), 247 (45), 105
(100), 77 (49); HRMS: Mþ, calcd for C24H20N2O2 368.1524, found
368.1539.
ꢀ
ꢀ
ꢀ
b
a¼16.2510(15) A, b¼8.8288(8) A, c¼17.4649(17) A,
¼115.060(6)ꢂ,
3
V¼2269.9(4) A , rcalcd¼1.371 Mg/m3,
m
¼0.269 mmꢁ1, F(000)¼984,
ꢀ
Z¼4, monoclinic, space group P2(1)/c, T¼173(2) K, 15,943
reflections collected, 4955 independent reflections, qmax 27.00ꢂ,
290 refined parameters, maximum residual electron density 0.282
X-ray crystal structure details of compound 9c: crystallized from
30% EtOAc/hexane, formula: C24H20N2O2, M¼368.42, colour of
crystal: colourless, needle, crystal size 0.36ꢀ0.18ꢀ0.15 mm,
ꢀꢁ3
and ꢁ0.401 e A . R1¼0.0447, wR2¼0.0999. Crystallographic data
a¼15.201(5) A, b¼8.703(5) A, c¼15.347(5) A,
¼112.263(5)ꢂ,
for the structure have been deposited with the Cambridge Crys-
tallographic Data Centre as deposition No. CCDC-902341.
ꢀ
ꢀ
ꢀ
b
3
V¼1879.0(14) A , rcalcd¼1.302 Mg/m3,
m
¼0.08 mmꢁ1, F(000)¼776,
ꢀ
Z¼4, monoclinic, space group P2(1)/c, T¼173(2) K, 11,690 re-
flections collected, 4662 independent reflections, qmax 28.30ꢂ, 253
refined parameters, maximum residual electron density 0.22 and
4.1.13. N-{2-[Acetyl(allyl)amino]phenyl}-N-allylacetamide (8e). N-[2-
(Acetylamino)phenyl]acetamide 7e32 (0.478 g, 2.49 mmol) was dis-
solved in dry acetone (15 mL) and the temperature of the mixture
was lowered to ꢁ14 ꢂC (ice and salt slurry bath), followed by the
sequential addition of NaH (60% in oil, 0.191 g, 4.97 mmol) and allyl
bromide (0.66 g, 0.47 mL, 5.5 mmol). The reaction mixture was then
stirred at rt for 24 h under N2. The reaction mixture was then
quenched with H2O (100 mL) and extracted with EtOAc (3ꢀ50 mL),
after which the combined fractions were dried (MgSO4). After
filtration, the solvent was then removed under reduced pressure and
the resulting crude residue purified through a silica gel column
(EtOAc) to afford the desired product 8e as a white, low melting point
solid (0.626 g, 92%). Mp: 25e26 ꢂC; Rf (100% EtOAc) 0.27; IR: vmax
(ATR)/cmꢁ1: 2916, 1645, 1594, 1499, 1441, 1378, 1333, 1298, 1281,
ꢀꢁ3
ꢁ0.27 e A . R1¼0.0487, wR2¼0.1049. Crystallographic data for the
structure have been deposited with the Cambridge Crystallographic
Data Centre as deposition No. CCDC-901913.
4.1.10. N-Allyl-N-(2-{allyl[(4-methylphenyl)sulfonyl]amino}phenyl)-4-
methylbenzenesulfonamide (8d). 4-Methyl-N-(2-{[(4-methylphenyl)
sulfonyl]amino}phenyl)benzenesulfonamide29 (1.00 g, 2.40 mmol)
was dissolved in acetone (20 mL) and treated with allyl bromide
(1.00 mL, 9.60 mmol) and K2CO3 (1.33 g, 9.60 mmol). The reaction
mixture was stirred at reflux for 18 h, after which the reaction
was filtered (cotton wool plug) and the filtrate concentrated under
reduced pressure. The resultant residue was purified by silica gel
column chromatography (10e30% EtOAc/hexane) to afford diallyl 8d
(1.10 g, 92%) as light brown crystals. Mp: 141e143 ꢂC; Rf (30% EtOAc/
1250, 1228; 1H NMR (300 MHz, CDCl3):
d
(ppm)¼2.04 (s, 6H,
2ꢀ CH3), 3.78 [br m, 2H, CH]CH(H)], 5.20 [br m, 2H, CH]CH(H)],
5.26e5.44 (m, 4H, NCH2CH]CH2), 6.02e6.23 (m, 2H, CH]CH2), 7.47
(m, 2H, 2ꢀ ArH), 7.71 (m, 2H, 2ꢀ ArH); 13C NMR (75 MHz, CDCl3):
hexane) 0.50; 1H NMR (300 MHz, CDCl3):
d
(ppm)¼2.47 (s, 6H,
ArCH3), 4.40 (br d, 4H, J 5.5 Hz, 2ꢀ CH2CH]), 4.99e5.09 (m, 4H,
2ꢀ CH]CH2), 5.71e5.84 (m, 2H, 2ꢀ CH]CH), 6.97e7.00 (m, 2H,
2ꢀ ArH), 7.23e7.26 (m, 2H, 2ꢀ ArH), 7.35 (d, 4H, J 8.1 Hz, 2ꢀ ArH),
d
(ppm)¼22.7 (2ꢀ CH3), 49.9 (2ꢀ CH2), 118.1 (2ꢀ CH), 129.0 (2ꢀ CH),
131.9 (2ꢀ CH), 132.5 (2ꢀ CH),138.7 (2ꢀ C), 169.8 (2ꢀ C]O); m/z (EI):
272 (Mþ, 2%), 230 (22), 213 (100), 187 (46), 172 (20), 159 (48), 145
(32), 119 (34), 92 (8), 77 (9); HRMS: Mþ, calcd for C16H20N2O2
272.1525, found: 272.1526.
7.81 (d, 4H, J 8.1 Hz, 2ꢀ ArH); 13C NMR (75 MHz, CDCl3):
d
(ppm)¼
21.6 (2ꢀ CH3), 54.6 (2ꢀ CH2), 119.5 (2ꢀ CH), 128.3 (2ꢀ CH), 128.6
(2ꢀ CH), 129.6 (2ꢀ CH), 131.3 (2ꢀ CH), 132.7 (2ꢀ C), 137.4 (2ꢀ C),
139.3 (2ꢀ CH), 143.7 (2ꢀ C); m/z (EI): 496 (Mþ, 1%), 285 (46), 264
(23), 219 (81), 185 (27), 171 (51), 155 (32), 131 (51), 91 (35), 69 (100).
4.1.14. 1,6-Diacetyl-1,2,5,6-tetrahydro-1,6-benzodiazocine (9e). Bis-
acetamide 8e (0.141 g, 0.518 mmol) and Grubbs second generation
catalyst 5 (0.0352 g, 0.0414 mmol, 8 mol %) were dissolved in dis-
tilled, degassed toluene (15 mL). The reaction mixture was then
stirred at 90 ꢂC for 18 h under Ar. The reaction mixture was then
evaporated under reduced pressure and the resultant crude prod-
uct was purified by silica gel column chromatography (10% EtOAc/
hexanee100% EtOAc) to afford the cyclized 9e as a dark oil (0.101 g,
80%). Note that the NMR spectra showed evidence for the existence
4.1.11. 1,6-Bis[(4-methylphenyl)sulfonyl]-1,2,5,6-tetrahydro-1,6-
benzodiazocine (9d). The benzenesulfonamide 8d (0.104 g,
0.202 mmol) was reacted with Grubbs second generation catalyst
5 (0.0086 g, 0.010 mmol, 5 mol %) in toluene (10 mL). The reaction
mixture was then carried out at rt for 5 h under N2. The solvent
was removed to give 9d (0.090 g, 92%) as white-coloured crystals
after column chromatography (10e30% EtOAc/hexane). Mp:
203e205 ꢂC. See reference 31 for a reported crystal structure. The
reaction was also performed on a bigger scale (0.80 mmol) to af-
ford the cyclized product in a yield of 96%. 13C NMR (75 MHz,
of rotamers in solution. Rf (100% EtOAc) 0.28; IR: vmax (ATR)/cmꢁ1
2931, 1712, 1662, 1599, 1500, 1362, 1304, 1283, 1223; 1H NMR
(300 MHz, CDCl3):
(ppm)¼1.82e2.00 (m, 6H, 2ꢀ CH3), 3.47e5.19
:
d
CDCl3):
d
(ppm)¼21.6 (CH3), 47.7 (CH2), 127.8 (CH), 128.2 (CH),
(br m, 4H, 2ꢀ NCH2), 5.82e6.11 (m, 2H, CH]CH), 7.24e7.50 (br m,
128.7 (CH), 128.9 (CH), 129.2 (CH), 136.2 (C), 136.5 (C), 144.9 (C).
The rest of the spectra compared well with that available in the
literature.14a,30
4H, 4ꢀ ArH); 13C NMR (75 MHz, CDCl3):
d
(ppm)¼22.4 (2ꢀ CH3),
45.2 (2ꢀ CH2), 128.7 (2ꢀ CH), 129.1 (br, 2ꢀ CH), 130.1 (br, 2ꢀ CH2),
139.1 (br, 2ꢀ C), 169.2 (2ꢀ C]O). m/z (EI): 244 (Mþ, 34%), 230 (8),
202 (100), 184 (82), 159 (93), 143 (64), 119 (84), 93 (6), 92 (16), 77
(18), 65 (9); HRMS: Mþ, calcd for C14H16N2O2 244.1212, found:
244.1212.
4.1.12. 1,6-Bis[(4-methylphenyl)sulfonyl]-1,2,3,6-tetrahydro-1,6-
benzodiazocine (10d). Benzodiazocine 9d (0.280 g, 0.597 mmol)
was dissolved in toluene (5 mL) at rt and [RuClH(CO)(PPh3)3] 6
(0.022 g, 0.024 mmol, 4 mol %) was added. The reaction mixture
was then stirred for a further 20 h at 100 ꢂC. The solvent was
removed under vacuum and silica gel column chromatography was
performed (30% EtOAc/hexane) to afford the desired compound
10d as a light brown-coloured solid (0.170 g, 61%). Mp: 134e138 ꢂC;
Rf (40% EtOAc/hexane) 0.42; IR: vmax (film)/cmꢁ1 1654, 1493, 1449,
1351, 1163, 1084; The rest of the spectra compared well with that
available in the literature.14c; m/z (EI): 468 (Mþ, 12%), 313 (38), 159
4.1.15. N-Allyl-N-(3-{allyl[(4-methylphenyl)sulfonyl]amino}-2-
pyridinyl)-4-methylbenzenesulfonamide (8g). 2,3-Diaminopyridine
7g (1.00 g, 9.16 mmol) was dissolved in pyridine (15 mL), after
which p-toluenesulfonyl chloride (5.24 g, 27.5 mmol) was added.
The reaction mixture was then stirred at 60 ꢂC for 23 h under N2.
After completion of the reaction the reaction mixture was poured
into ice-cold H2O (100 mL), after which the resultant brown
precipitate was collected by filtration. The filter cake was washed

A. Taher et al. / Tetrahedron 69 (2013) 2038e2047
2045
with copious amounts of H2O, after which it was dried and purified
by way of recrystallization (95% ethanol). The material obtained
(1.91 g, 50%) was used directly in the next reaction as NMR
spectroscopy revealed that the product 4-methyl-N-(2-{[(4-
methylphenyl)sulfonyl]amino}-3-pyridinyl)benzenesulfonamide
was not entirely pure. This compound (0.500 g, 1.19 mmol) was
dissolved in acetone (30 mL), after which K2CO3 (1.32 g, 9.58 mmol,
in two equal portions, the second after 10 h) and allyl bromide
(0.434 g, 3.59 mmol, in two equal portions, the second after 10 h)
were added. The reaction mixture was then heated at reflux for
24 h. After completion of the reaction, as monitored by TLC, the
K2CO3 was removed by filtration and the solvent was removed
under reduced pressure to afford a residue. This was purified by
column chromatography (15% EtOAc/hexane) to give the desired
product 8g as white solid (0.260 g, 44%). Mp: 144e145 ꢂC; Rf (30%
EtOAc/hexane) 0.55; IR: vmax (ATR)/cmꢁ1 2988, 1452, 1339, 1157,
(CH), 136.2 (C), 139.1 (CH), 139.2 (C), 139.6 (C), 140.1 (CH), 143.0 (C),
143.9 (C), 144.5 (CH), 146.7 (C); m/z (EI): 470 (MþHþ, 100%); HRMS:
m/z calcd for C23H23N3O4S2 [MþH]þ 470.1208, found 470.1210.
X-ray crystal structure details of compound 10g: crystallized from
EtOAc/MeCN/hexane, formula: C23H23N3O4S2, M¼469.56, colour of
crystal: colourless, needle, crystal size 0.25ꢀ0.25ꢀ0.06 mm,
¼114.496(2)ꢂ,
ꢀ
ꢀ
ꢀ
a¼16.695(2) A, b¼8.5195(10) A, c¼17.160(2) A,
b
3
V¼2220.9(5) A , rcalcd¼1.404 Mg/m3,
m
¼0.276 mmꢁ1, F(000)¼984,
ꢀ
Z¼4, monoclinic, space group P2(1)/c, T¼100(2) K, 13,901 reflections
collected, 5268 independent reflections, qmax 28.7ꢂ, 291 refined
parameters, maximum residual electron density 0.96 and
ꢀꢁ3
ꢁ0.64 e A . R1¼0.046, wR2¼0.123. Crystallographic data for the
structure have been deposited with the Cambridge Crystallographic
Data Centre as deposition No. CCDC-901932.
4.1.18. tert-Butyl-2,5-dihydro-6H-1,6-benzoxazocine-6-carboxylate
(9h). tert-Butyl allyl[2-(allyloxy)phenyl]carbamate 8h7b (0.080 g,
0.276 mmol) was dissolved in toluene (3 mL) and Grubbs second
generation catalyst 5 (10 mol %, 0.023 g, 0.027 mmol) was added.
The reaction mixture was then stirred for a further 18 h at rt. The
crude product was then passed through a silica gel column (10%
EtOAc/hexane) to afford the cyclized product as a brown solid
(0.042 g, 58%). Note that the NMR spectra showed evidence for the
existence of rotamers in solution. Mp: 65e68 ꢂC; Rf (20% EtOAc/
hexane) 0.56; IR: vmax (film)/cmꢁ1 1700, 1496, 1451, 1388, 1315,
1059, 879; 1H NMR (CDCl3, 400 MHz)
d (ppm): 2.44 (s, 3H, CH3),
2.45 (s, 3H, CH3), 4.25 (d, 2H, J 8.0 Hz, CH2), 4.40 (d, 2H, J 8.0 Hz,
CH2), 4.90e5.10 (m, 4H, 2ꢀ CH]CH2), 5.67e5.83 (m, 2H, 2ꢀ CH]
CH2), 7.22e7.35 (m, 5H, 5ꢀ ArH), 7.47e7.50 (m, 1H, ArH), 7.85
(d, 4H, J 8.0 Hz, 4ꢀ ArH), 8.38 (d, 1H, J 4.0 Hz, ArH); 13C NMR
(100 MHz, CDCl3):
d
(ppm)¼21.8 (CH3), 21.9 (CH3), 53.7 (CH2), 54.1
(CH2), 118.7 (CH), 120.6 (CH), 123.5 (CH), 128.4 (2ꢀ CH), 129.3
(2ꢀ CH), 129.4 (2ꢀ CH), 130.0 (2ꢀ CH), 132.4 (CH), 132.8 (CH), 135.2
(C), 136.7 (C), 137.2 (C), 140.3 (CH), 143.9 (C), 144.3 (C), 148.0 (CH),
153.0 (C); m/z (EI): 498 (MþHþ,100%), 483 (3); HRMS (MþH)þ calcd
for C25H27N3O4S2 498.1521, found 498.1520.
1239, 1166; 1H NMR (300 MHz, CDCl3):
d
(ppm)¼1.41 (br s, 9H,
3ꢀ CH3), 4.34 (br s, 2H, NCH2), 4.71 (d, 2H, J 6.6 Hz, OCH2),
5.78e5.92 (m, 2H, CH]CH), 6.92e6.97 (m, 2H, 2ꢀ ArH), 7.11e7.17
4.1.16. 5,10-Bis-[(4-methylphenyl)sulfonyl]-5,6,9,10-tetrahydropyrido
[2,3-b][1,4]diazocine (9g). The ortho-bis-allyl compound 8g
(0.100 g, 0.201 mmol) was dissolved in toluene (5 mL) and Grubbs
second generation catalyst 5 (0.009 g, 0.010 mmol, 5 mol %) was
added. The reaction mixture was then stirred at rt for 5 h under N2.
After completion of the reaction, confirmed by TLC, the solvent was
removed on the high vacuum and column chromatography was
performed on the residue (20% EtOAc/hexane) to afford the cyclized
compound 9g as a white solid (0.089 g, 94%). Spectroscopic data for
this compound corresponded well with that in the literature.30
(m, 2H, 2ꢀ ArH); 13C NMR (75 MHz, CDCl3)
(ppm)¼28.2 (3ꢀ CH3),
d
48.9 (CH2), 65.1 (br, CH2), 80.5 [C(CH3)3], 120.8 (CH), 121.8 (CH),
125.5 (C), 127.9 (CH), 129.8 (2ꢀ CH), 132.6 (CH), 136.6 (C), 154.7 (C]
O); m/z (EI): 261 (Mþ, 41%), 218 (3), 148 (48), 117 (100), 68 (56), 57
(62); HRMS: Mþ, calcd for C15H19NO3 261.1322, found 261.1321.
4.1.19. 6-Benzoyl-5,6-dihydro-2H-1,6-benzoxazocine (9i). N-Allyl-
N-[2-(allyloxy)phenyl]benzamide 8i7b (0.201 g, 0.685 mmol) and
Grubbs second generation catalyst 5 (0.029 g, 0.034 mmol, 5 mol %)
were dissolved in distilled, degassed toluene (15 mL). The reaction
mixture was then stirred at 90 ꢂC for 18 h under Ar. After cooling,
the reaction mixture was diluted with a 10% EtOAc/hexane mixture
and filtered through a compacted Celite plug (washed 3ꢀ20 mL,
10% EtOAc/hexane) to remove the catalyst. The solvent was then
removed under reduced pressure and the resulting crude residue
purified through a silica gel column (15% EtOAc/hexane) to afford
the cyclized product 9i as a low melting point solid (0.142 g, 78%).
4.1.17. 5,10-Bis[(4-methylphenyl)sulfonyl]-5,8,9,10-tetrahydropyrido
[2,3-b][1,4]diazocine (10g) and 5,10-bis[(4-methylphenyl)sulfonyl]-
5,6,7,10-tetrahydropyrido[2,3-b][1,4]diazocine (100g). The diazocine
9g (0.0840 g, 0.179 mmol) was dissolved in toluene (5 mL) and the
solution was degassed with N2. [RuClH(CO)(PPh3)3] 2 (0.0085 g,
0.0090 mmol, 5 mol %) was added and the reaction mixture was
stirred at 90 ꢂC for 18 h. After completion of the reaction, as
monitored by TLC, the solvent was removed under vacuum and
column chromatography was performed (15% EtOAc/hexane) to
afford the desired product as an inseparable mixture of
regioisomers 10g and 100g (45:55) and as a white solid (0.075 g,
89%). Mp: 182e184 ꢂC; Rf (40% EtOAc/hexane) 0.45; IR: vmax (ATR)/
cmꢁ1 2928, 1655, 1439, 1337, 1156; 1H NMR (CDCl3, 400 MHz,
Mp: 29e30 ꢂC; Rf (20% EtOAc/hexane) 0.13; IR: vmax (ATR)/cmꢁ1
1645, 1497, 1360, 1325, 1274, 1249; 1H NMR (300 MHz, CDCl3):
:
d
(ppm)¼4.20e5.48 (br m, 4H, NCH2 and OCH2), 5.68e5.77 (m, 1H,
OCH2CH), 5.85e5.91 (m, 1H, NCH2CH), 6.70e6.75 (m, 2H, 2ꢀ ArH),
6.89 (br dd, 1H, J 8.2, 0.6 Hz, ArH), 7.06e7.14 (m, 1H, ArH), 7.14e7.27
(m, 3H, 3ꢀ ArH), 7.38 (br d, 2H, J 7.6 Hz, 2ꢀ ArH); 13C NMR (75 MHz,
CDCl3):
d
(ppm)¼49.1 (br, NCH2), 65.2 (OCH2), 121.3 (br, CH), 122.3
combined assignments)
d
1.73 (dd, 2H, J 13.6, 5.7 Hz, CH2), 1.87
(br, CH), 124.7 (CH), 127.4 (br, CH), 127.6 (br, CH), 128.1 (br, 2ꢀ CH),
129.4 (br, 2ꢀ CH), 130.1 (br, CH), 131.4 (CH), 132.8 (C), 135.6 (C),
153.1 (C), 171.2 (C]O). m/z (EI): 265 (Mþ, 4%), 251 (30), 234 (5), 146
(6), 131 (24), 105 (100), 77 (42), 51 (9); HRMS: Mþ, calcd for
C17H15NO2 265.1103, found: 265.1117.
(dd, 2H, J 13.8, 5.7 Hz, CH2), 2.41 (s, 3H, CH3), 2.42 (s, 3H, CH3), 2.42
(s, 3H, CH3), 2.43 (3H, CH3), 3.10 (t, 2H, J 5.9 Hz, NCH2), 3.47 (t, 2H, J
5.9 Hz, NCH2), 4.71 (dd, 1H, J 18.1, 8.2 Hz, NCH]CH), 4.83 (dd, 1H, J
18.0, 8.1 Hz, NCH]CH), 6.56 (d,1H, J 9.9 Hz, NCH]CH), 6.72 (d, 1H, J
10.0 Hz, NCH]CH), 7.27e7.33 (m, 10H, Ar), 7.76 (d, 1H, J 1.8 Hz, Ar),
7.79 (d, 2H, J 6.7 Hz, Ar), 7.82 (d, 2H, J 8.3 Hz, Ar), 7.86 (d, 2H, J 8.3 Hz,
Ar), 7.93 (d, 2H, J 8.3 Hz, Ar), 8.01 (dd, 1H, J 8.0, 1.8 Hz, Ar), 8.32
(dd, 1H, J 4.7, 1.8 Hz, Ar), 8.45 (dd, 1H, J 4.7, 1.8 Hz, Ar). 13C NMR
4.1.20. 6-[(4-Methylphenyl)sulfonyl]-5,6-dihydro-2H-1,6-benzoxazocine
(9j). N-Allyl-N-(2-(allyloxy)phenyl)-4-methylbenzenesulfonamide
8j7b (0.150 g, 0.437 mmol) was reacted with 5 mol % of Grubbs second
generation catalyst 5 (0.013 g, 0.022 mmol) in toluene (10 mL). The
reaction mixture was then stirred at rt for 5 h under N2. The solvent
was removed to give 9j (0.096 g, 70%) as white crystals after column
chromatography (5% EtOAc/hexane). Mp: 103e105 ꢂC; IR: vmax (film)/
(CDCl3, 100 MHz): d 17.1 (CH2), 17.1 (CH2), 17.1 (CH3), 17.2 (CH3), 17.8
(CH3), 18.2 (CH3), 42.5 (CH2), 42.7 (CH2), 101.8 (CH), 102.1 (C), 118.9
(CH), 119.0 (C), 123.4 (CH), 123.5 (C), 123.6 (CH), 123.9 (CH), 123.9
(CH), 124.6 (CH), 124.7 (C), 124.7 (CH), 124.8 (CH), 125.3 (CH), 125.4
(CH), 128.1 (CH), 130.9 (CH), 131.3 (CH), 131.6 (C), 133.4 (C), 135.9
cmꢁ1 1595, 1150; 1H NMR (300 MHz, CDCl3):
d
(ppm)¼2.42 (s, 3H,

2046
A. Taher et al. / Tetrahedron 69 (2013) 2038e2047
ArCH3), 4.38 (d, 2H, J 6.1 Hz, CH2), 4.76 (d, 2H, J 4.8 Hz, CH2), 5.63e5.70,
(m, 1H, HC]CH), 5.76e5.81 (m, 1H, HC]CH), 6.90 (d, 1H, J 8.2 Hz,
ArH), 6.91e7.02 (m, 1H, ArH), 7.16e7.26 (m, 4H, 4ꢀ ArH), 7.51 (d, 2H, J
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
Max Planck Institute for Molecular Physiology, Dortmund, Germany)
and Mr. B. Moolman, Mr. F. Hiten and Dr. M. Stander (Stellenbosch
University) are gratefully acknowledged for providing MS spec-
troscopy services. Dr. D.A. Haynes (Stellenbosch) is also gratefully
appreciated for help with the submission of the cif files.
8.1 Hz, 2ꢀ ArH); 13C NMR (75 MHz, CDCl3)
d
(ppm)¼21.6 (CH3), 49.4
(CH2), 68.5 (CH2), 122.0 (CH), 123.3 (CH), 127.6 (CH), 128.7 (CH), 129.1
(C), 129.3 (CH), 129.4 (CH), 129.7 (CH), 130.4 (C), 135.5 (CH), 143.5 (C),
154.1 (CeO); m/z (EI): 315 (Mþ, 41%), 160 (100), 120 (12), 91 (15), 41
(24); HRMS: Mþ, calcd for C17H17NO3S 315.0929, found 315.0939.
4.1.21. 6-[(4-Methylphenyl)sulfonyl]-3,6-dihydro-2H-1,6-benzoxazo-
cine and 6-[(4-methylphenyl)sulfonyl]-5,6-dihydro-4H-1,6-
benzoxazocine (10j & 100j). Benzoxazocine 9j (0.037 g, 0.12 mmol)
was dissolved in d8-toluene at rt and [RuClH(CO)(PPh3)3] 6 (0.001 g,
0.011 mmol) was added. The reaction mixture was then heated at
60e70 ꢂC in an oil bath for a further 18 h after which the solvent
was removed under high vacuum. Silica gel column chromatogra-
phy (5% EtOAc/hexane) was then performed to afford the desired
product as an equimolar mixture of regioisomers 10j and 100j as
a white solid (0.029 g, 78%). Mp: 101e104 ꢂC; Rf (10% EtOAc/hexane)
0.35; IR: vmax (film)/cmꢁ1 1649, 1597, 1492, 1350, 1305, 1254, 1165,
References and notes
1. (a) Lozano-Vila, A. M.; Monsaert, S.; Bajek, A.; Verpoort, F. Chem. Rev. 2010, 110,
4865e4909; (b) Majumdar, K. C.; Chattopadhyay, B.; Ray, K. Curr. Org. Synth.
2010, 7, 153e176; (c) Merino, P.; Tejero, T.; Greco, G.; Marca, E.; Delso, I.;
ꢁ
Gomez-SanJuan, A.; Matute, R. Heterocycles 2012, 84, 75e100; (d) van Otterlo,
W. A. L.; de Koning, C. B. Chem. Rev. 2009, 109, 3743e3782.
2. Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18e29.
3. See, for example: (a) Kasaya, Y.; Hoshi, K.; Terada, Y.; Nishida, A.; Shuto, S.;
Arisawa, M. Eur. J. Org. Chem. 2009, 4606e4613; (b) Terada, Y.; Arisawa, M.;
Nishida, A. Angew. Chem., Int. Ed. 2004, 43, 4063e4067.
4. See, for example: (a) van den Hoogenband, A.; den Hartog, J. A. J.; Faber-Hilhorst,
N.; Lange, J. H. M.; Terpstra, J. W. Tetrahedron Lett. 2009, 50, 5040e5043; (b)
Bennasar, M.-L.; Roca, T.; Monerris, M.; García-Díaz, D. J. Org. Chem. 2006, 71,
7028e7034.
1086; 1H NMR (300 MHz, CDCl3, combined compounds):
d
(ppm)¼
1.89e1.97 and 1.99e2.03 (2ꢀ m, 2ꢀ 2H, 2ꢀ CH2). 2.41 and 2.43 (2ꢀ
s, 2ꢀ 3H, 2ꢀ CH3), 3.42 (t, 2H, J 5.8 Hz, OCH2), 3.73 (t, 2H, J
5.5 Hz, NCH2), 4.44e4.48 (m, 1H, NCH]CH), 4.81e4.87 (m, 1H,
OCH]CH)], 6.14 (d, 1H, J 7.5 Hz, NCH]), 6.86e7.27 (m, 12H, 11ꢀ
ArH and OCH]), 7.47e7.54 (m, 3H, 3ꢀ ArH), 7.67e7.70 (m, 2H, 2ꢀ
ArH); 13C NMR (75 MHz, CDCl3, 3 signals not observed in aromatic
region): 21.5 and 21.6 (CH3), 22.1 and 22.7 (CH2), 45.7 (NCH2), 71.2
(OCH2), 100.9 (CH), 106.7 (CH), 121.4 (CH), 123.4 (CH), 124.6
and 124.9 (CH), 127.5 and 127.6 (CH), 129.1 (CH), 129.3 (CH), 129.9
(CH), 130.0 (CH), 130.8 (CH), 131.6 (CH), 132.1 (CH), 135.8 (C), 137.9
(C), 143.2 (C), 143.6 (C), 144.0 (C), 154.3 (C); m/z (EI): 315 (Mþ, 36%),
160 (100); HRMS: Mþ, calcd for C17H17NO3S 315.0929, found
315.0914.
5. See, for example: (a) Ye, K.-Y.; Dai, L.-X.; You, S.-L. Org. Biomol. Chem. 2012, 10,
5932e5939; (b) Mamouni, R.; Soukri, M.; Lazar, S.; Akssira, M.; Guillaumet, G.
Tetrahedron Lett. 2004, 45, 2631e2633; (c) Pain, C.; Celanire, S.; Guillaumet, G.;
ꢁ
Joseph, B. Synlett 2003, 2089e2091.
6. See, for example: (a) Dieltiens, N.; Stevens, C. V.; Masschelein, K.; Hennebel, G.;
Van der Jeught, S. Tetrahedron 2008, 64, 4295e4303; (b) Brahma, S.; Maity, S.;
Ray, J. K. J. Heterocycl. Chem. 2007, 44, 29e34; (c) Chattopadhyay, S. K.; Biswas,
T.; Maity, S. Synlett 2006, 2211e2214; (d) Nguyen, V. T. H.; Bellur, E.; Langer, P.
Tetrahedron Lett. 2006, 47, 113e116; (e) Mori, M.; Kitamura, T.; Sato, Y. Synthesis
2001, 654e664.
7. (a) Yadav, D. B.; Morgans, G. L.; Aderibigbe, B. A.; Madeley, L. G.; Fernandes, M.
A.; Michael, J. P.; de Koning, C. B.; van Otterlo, W. A. L. Tetrahedron Lett. 2011, 67,
2991e2997; (b) Morgans, G. L.; Ngidi, E. L.; Madeley, L. G.; Khanye, S. D.;
Michael, J. P.; de Koning, C. B.; van Otterlo, W. A. L. Tetrahedron 2009, 65,
10650e10659; (c) Scalzullo, S. M.; Ul Islam, R.; Morgans, G. L.; Michael, J. P.; van
Otterlo, W. A. L. Tetrahedron Lett. 2008, 49, 7403e7405; (d) Panayides, J.-L.;
Pathak, R.; Panagiotopoulos, H.; Davids, H.; Fernandes, M. A.; de Koning, C. B.;
van Otterlo, W. A. L. Tetrahedron 2007, 63, 4737e4747; (e) Panayides, J.-L.;
Pathak, R.; de Koning, C. B.; van Otterlo, W. A. L. Eur. J. Org. Chem. 2007,
4953e4961; (f) van Otterlo, W. A. L.; Coyanis, E. M.; Panayides, J.-L.; de Koning,
C. B.; Fernandes, M. A. Synlett 2005, 501e505 For the non-metathetic syntheses
of 6-membered benzannelated compounds involving isomerization, see the
next two references; (g) Pathak, R.; Naiker, P.; Thompson, W. A.; Fernandes, M.
A.; de Koning, C. B.; van Otterlo, W. A. L. Eur. J. Org. Chem. 2007, 5337e5345; (h)
van Otterlo, W. A. L.; Pathak, R.; de Koning, C. B.; Fernandes, M. A. Tetrahedron
Lett. 2004, 45, 9561e9563.
8. (a) Seto, S.; Tanioka, A.; Ikeda, M.; Izawa, S. Bioorg. Med. Chem. 2005, 13,
5717e5732; (b) Seto, S.; Tanioka, A.; Ikeda, M.; Izawa, S. Bioorg. Med. Chem. Lett.
2005, 15, 1479e1484; (c) Seto, S.; Tanioka, A.; Ikeda, M.; Izawa, S. Bioorg. Med.
Chem. Lett. 2005, 15, 1485e1488.
9. Novelli, A.; Díaz-Trelles, R.; Groppetti, A.; Fernandez-Sanchez, M. T. Amino Acids
2005, 28, 183e191.
10. Suemitsu, R.; Ohnishi, K.; Horiuchi, M.; Kitaguchi, A.; Odamura, K. Phyto-
chemistry 1992, 31, 2325e2326.
11. (a) Macías, F. A.; Torres, A.; Galindo, J. L. G.; Varela, R. M.; Alvarez, J. A.; Molinillo,
J. M. G. Phytochemistry 2002, 61, 687e692; (b) Macías, F. A.; Varela, R. M.; Torres,
A.; Molinillo, J. M. G.; Fronczek, F. R. Tetrahedron Lett. 1993, 34, 1999e2002.
12. Vyvyan, J. R. Tetrahedron 2002, 58, 1631e1646.
13. (a) Qadir, M.; Cobb, J.; Sheldrake, P. W.; Whittall, N.; White, A. J. P.; Hii, K. K.;
Horton, P. N.; Hursthouse, M. B. J. Org. Chem. 2005, 70, 1545e1551; (b) Qadir, M.;
Cobb, J.; Sheldrake, P. W.; Whittall, N.; White, A. J. P.; Hii, K. K.; Horton, P. N.;
Hursthouse, M. B. J. Org. Chem. 2005, 70, 1552e1557.
X-ray crystal structure details of compound 10j: crystallized
from MeOH, formula: C17H17NO3S, M¼315.38, colour of crystal:
ꢀ
colourless, needle, crystal size 0.35ꢀ0.18ꢀ0.14 mm, a¼10.167(5) A,
3
ꢂ
ꢀ
ꢀ
ꢀ
b¼9.085(5) A, c¼17.170(5) A,
b
¼104.047(5) , V¼1538.5(12) A ,
rcalcd¼1.362 Mg/m3,
m
¼0.222 mmꢁ1, F(000)¼664, Z¼4, monoclinic,
space group P2(1)/n, T¼173(2) K, 10,102 reflections collected, 3796
independent reflections, qmax 28.28ꢂ, 199 refined parameters,
ꢀꢁ3
maximum residual electron density 0.365 and ꢁ0.322 e A
.
R1¼0.0459, wR2¼0.1057. Crystallographic data for the structure
have been deposited with the Cambridge Crystallographic Data
Centre as deposition No. CCDC-901914.
X-ray crystal structure details of compound 100j: crystallized
from MeOH, formula: C17H17NO3S, M¼315.38, colour of crystal:
ꢁ
ꢁ
ꢀ
3
ꢀ
colourless, needle, crystal size 0.22ꢀ0.12ꢀ0.08 mꢂm, a¼7.8540(11) A,
ꢀ
ꢀ
b¼16.538(3) A, c¼12.3164(18) A, ¼103.092(8) , V¼1558.2(4) A ,
b
ꢁ
rcalcd¼1.344 Mg/m3,
m
¼0.220 mmꢁ1, F(000)¼664, Z¼4, monoclinic,
space group P2(1)/n, T¼173(2) K, 9372 reflections collected, 3402
independent reflections, qmax 27.00ꢂ, 200 refined parameters,
ꢀꢁ3
maximum residual electron density 0.285 and ꢁ0.375 e A
.
R1¼0.0494, wR2¼0.0965. Crystallographic data for the structure
have been deposited with the Cambridge Crystallographic Data
Centre as deposition No. CCDC-901915.
14. (a) Proust, N.; Gallucci, J. C.; Paquette, L. A. J. Org. Chem. 2008, 73, 6279e6282;
(b) Proust, N.; Gallucci, J. C.; Paquette, L. A. J. Org. Chem. 2009, 74, 2897e2900;
(c) Proust, N.; Preston, A. J.; Paquette, L. A. Heterocycles 2009, 77, 163e166; (d)
ꢂ
ꢂ
ꢁ
€
Fisera, L.; Jaroskova, L.; Schroth, W.; Gabler, M.; Oravec, P. Collect. Czech. Chem.
Commun. 1988, 53, 1060e1067.
Acknowledgements
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Nakashima, K.; Saito, Y.; Sono, M.; Tori, M. Tetrahedron Lett. 2009, 50,
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This work was supported by the National Research Foundation
(NRF), Pretoria, the University of the Witwatersrand (University
and Science Faculty Research Councils) and Stellenbosch University
(Faculty and Departmental funding). A.T. thanks the NRF for an
Innovation Postdoctoral Fellowship. We also gratefully acknowl-
edge Mr. R. Mampa (University of the Witwatersrand) and Dr. J.
Brand and Ms. E. Malherbe (Stellenbosch University) for the NMR
€
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