One-pot ring-closing metathesis-alkene cross metathesis reactions of sulfamide-linked enynes

Article abstract of DOI:10.1002/ejoc.200300725

Ring-closing metathesis (RCM) of sulfamide-linked enynes 7, 11 and 12 containing disubstituted alkynes afforded a series of novel 7-membered cyclic sulfamides 13-15 in good yield. Substrates 5, 9 and 10 containing mono-substituted alkynes gave either simple RCM products 18a-c or those arising from combinations of enyne RCM and olefin cross metathesis 16/17a-c depending on the reaction conditions. Notably, in the presence of two equivalents of styrene or ethyl acrylate, substrates 5, 9 and 10 containing terminal alkynes underwent selective enyne-RCM-olefin-cross metathesis to provide cyclic sulfamides 17a-c and 19b,c in yields of 54-83%. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200300725

FULL PAPER
One-Pot Ring-Closing Metathesis-Alkene Cross Metathesis Reactions of
Sulfamide-Linked Enynes
Sofia S. Salim,[a] Richard K. Bellingham,[b] and Richard C. D. Brown*[a]
Keywords: Sulfamides / Enynes / Domino reactions / Dienes / Metathesis
Ring-closing metathesis (RCM) of sulfamide-linked enynes
7, 11 and 12 containing disubstituted alkynes afforded a
series of novel 7-membered cyclic sulfamides 13−15 in good
ably, in the presence of two equivalents of styrene or ethyl
acrylate, substrates 5, 9 and 10 containing terminal alkynes
underwent selective enyne-RCM-olefin-cross metathesis to
yield. Substrates 5, 9 and 10 containing mono-substituted al- provide cyclic sulfamides 17a−c and 19b,c in yields of
kynes gave either simple RCM products 18a−c or those aris- 54−83%.
ing from combinations of enyne RCM and olefin cross meta- ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
thesis 16/17a−c depending on the reaction conditions. Not-
Germany, 2004)
Introduction
of a simple enyne RCM reaction (process B, Figure 2) has
directly undergone selective CM with an olefin other than
ethylene (process D).[10,11] Here we report RCM reactions
of sulfamide-linked enynes to give a series of novel cyclic
sulfamides, which in certain cases undergo selective in situ
CM with olefins to provide enyne RCM-CM products.
Ruthenium-catalysed enyne metathesis reactions are of
considerable current interest,[1Ϫ5] and a growing number of
applications in target synthesis are emerging.[2] The dis-
covery of robust ruthenium carbene complexes such as 1
and 2a/b, with good activities and functional group toler-
ance has played a key role in the recent development of
the reaction.[6Ϫ8]
Figure 1. Ruthenium carbene metathesis pre-catalysts
An attraction of enyne metathesis is the formation of 1,3-
diene products, which are suitable substrates for a variety
of further useful synthetic transformations such as cycload-
dition reactions.[2] A number of different sub-classes of en-
yne metathesis reactions have now been reported, including:
cross-metathesis (CM, process A), ring-closing metathesis
(RCM, process B), and domino sequences involving combi-
nations of ring-opening metathesis (ROM), enyne RCM,
olefin RCM and olefin CM (process C) (Figure 2).[9] Re-
cently the first examples have appeared where the product
Figure 2. Various processes involving enyne metathesis
[a]
Department of Chemistry, University of Southampton
Results and Discussion
Highfield, Southampton SO17 1BJ, UK
Fax: (internat.) ϩ 44-23-80-596805
E-mail: rcb1@soton.ac.uk
As part of our ongoing studies on the synthesis of cyclic
sulfonamides and sulfamides we considered the possibility
of using enyne RCM to produce cyclic 1,3-dienes, which
would be useful intermediates for further elaboration to a
[b]
Chemical Development, GlaxoSmithKline Pharmaceuticals,
Old Powder Mills, Tonbridge, Kent TN11 9AN, UK
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
800
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300725
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Cross Metathesis Reactions of Sulfamide-Linked Enynes
FULL PAPER
variety of interesting and novel heterocyclic scaffolds.[12Ϫ18] N-Boc protected enyne afforded mainly RCM-homo-CM
To investigate the idea, a number of acyclic sulfamide sub- product 16a (Entry 1, Table 1). The reactions of the enynes
strates were prepared from chlorosulfonyl isocyanate (3) 9 and 10 could also be made to favour the formation of
(Scheme 1).[15,19] Treatment of 3 with tert-butanol then RCM-homo-CM products by using increased amounts of
benzylallylamine gave 4, which underwent N-propar- 2a (Entries 4 and 7, Table 1). By-products present in all of
gylation under basic conditions to afford Boc-protected sul- the reactions were the CM adducts 17aϪc that had incor-
famides 5 and 7. Deprotection and N-alkylation then re- porated the benzylidene group from the pre-catalyst 2a.
turned N,NЈ-dialkyl sulfamides 9 Ϫ12 in good to excellent Formation of the CM products 17aϪc was a very efficient
yields.
process based on the amount of 2a.
Scheme 3. Reagents: (a) 2a (6Ϫ20 mol%), CH2Cl2, reflux, 24 h; (b)
2a (6 mol%), CH2Cl2, microwave irradiation (100 °C), 1 h.
Scheme 1. Reagents: (a) tBuOH, CH2Cl2, Et3N, then allylbenzyla-
mine; (b) tBuOK, 18-crown-6, THF, propargyl bromide or 1-
bromo-2-butyne; (c) TFA, CH2Cl2; (d) tBuOK, 18-crown-6, THF,
MeI or BnBr
Table 1. Enyne RCM reactions of substrates 5, 9 and 10 containing
terminal alkynes (see Scheme 3).
With a range of enyne substrates in hand, their metath-
esis reactions were investigated using 3Ϫ20 mol% of the
ruthenium alkylidene complex 2a in CH2Cl2 (Schemes
2Ϫ4). RCM of internal alkyne substrates was found to oc-
cur sluggishly at room temperature, but proceeded rapidly
in a sealed system under microwave irradiation at 100 °C
to give the seven-membered cyclic sulfamides 13Ϫ15 in high
yields (Scheme 2).[20] Similar results could be obtained by
heating the reactants in sealed crimped cap vials immersed
in a pre-heated oil bath at 100 °C.
Entry
Enyne
(R)
2a (mol%)[a]
Conditions
Yields (%)[b]
16aϪc
17aϪc
18aϪc
1
2
3
4
5
6
7
5 (Boc)
9 (Me)
9 (Me)
9 (Me)
10 (Bn)
10 (Bn)
10 (Bn)
(6 mol%), A
(6 mol%), B
(10 mol%), A
(20 mol%), A
(6 mol%), B
(10 mol%), A
(20 mol%), A
61%
10%
12%
66%
8%
21%
80%
6%
6%
7%
18%
4%
8%
16%
8%
60%
49%
2%
63%
56%
0%
[a]
Reactions were conducted on a 20Ϫ100 mg scale at a concen-
tration of 0.05  with respect to the enyne substrate. Conditions
A: Reaction mixtures in CH2Cl2 were heated at reflux with the
specified amount of 2a for 24 h. Conditions B: Reaction mixtures
in CH2Cl2 were heated in sealed tubes using microwave irradiation
at 100 °C for 1 hour with the specified amount of 2a. A SmithSyn-
[b]
thesizerTM was used for these experiments.
purified material.
Isolated yields of
Scheme 2. Reagents: (a) 2a (3 mol%), CH2Cl2, microwave ir-
radiation (100 °C)
The precise sequence of events taking place along the re-
action pathway remains unclear, although monitoring the
reaction of enyne 5 by TLC and NMR showed initial for-
Metathesis reactions of the terminal alkynes 5, 9 and 10 mation of the simple RCM product 18a and gradual con-
require further discussion as different products predomi- version into the CM product 16a implying enyne RCM fol-
nated depending on the reaction conditions (Scheme 3, lowed by CM as a significant manifold. Alternative se-
Table 1). Heating enynes 5, 9 and 10 in the presence of quences involving initial olefin CM, intermolecular enyne
6Ϫ20 mol% of the ruthenium complex 2a led to the iso- CM followed by RCM, and product equilibration may also
lation of three main components; the expected enyne-RCM be occurring.
products 18aϪc, RCM-CM products 16aϪc and 17aϪc.[21]
Intrigued by the formation of cross-metathesis products
Using lower amounts of pre-catalyst 2a favoured the forma- 17aϪc, the possibility of a one-pot RCM-CM reaction was
tion of the simple enyne-RCM products for the N-alkylated investigated using three terminal alkyne substrates 5, 9 and
enynes 9 and 10 (Entries 2,3,5 and 6, Table 1), whereas the 10 in the presence of 2Ϫ3 equivalents of either styrene or
Eur. J. Org. Chem. 2004, 800Ϫ806
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
801

S. S. Salim, R. K. Bellingham, R. C. D. Brown
FULL PAPER
mixture was stirred at 0 °C for 10 min then Et3N (460 µL,
3.40 mmol) was added followed by N-allyl-N-benzylamine (0.5 g,
3.40 mmol). The mixture was stirred for 12 h at room temp. CH2Cl2
(5 mL) was added and the solution was washed with 1  HCl (3 ϫ
5 mL) and H2O (2 ϫ 5 mL), dried (MgSO4) and the solvent re-
moved in vacuo. The resulting yellow oil was purified by column
chromatography, eluting with Et2O/hexane (1:9) to provide the title
compound 4 as a colourless oil (0.98 g, 3.02 mmol, 89%). 1H NMR
(300 MHz, CDCl3): δ ϭ 1.50 (s, 9 H, CH3), 3.88 (d, J ϭ 6.4 Hz, 2
H, CH2), 4.56 (s, 2 H, PhCH2), 5.21Ϫ5.25 (m, 2 H, ϭCH2), 5.77
(tdd, J ϭ 6.4, 10.1, 16.7 Hz, 1 H, ϭCH), 7.10 (s, 1 H, NH),
7.30Ϫ7.33 (m, 5 H, CH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ
28.6 (CH3), 50.2 (CH2), 51.6 (CH2), 83.7 (C), 119.8 (CH2), 128.0
(CH), 128.5 (CH), 128.8 (CH), 132.0 (CH), 135.9 (C), 150.2 (Cϭ
O) ppm. IR: ν˜max/cmϪ1: 3285 (NH), 2973, 2931, 1734, 1360 (SO2),
1147 (SO2), 925, 821. LRMS (ESϩ, CH3CN): m/z (relative intensity,
%) ϭ 349 [M ϩ Na]ϩ (40), 675 [2M ϩ Na]ϩ(100).
methyl acrylate (Scheme 4). As anticipated, the desired en-
yne RCM-CM products 17aϪc and 19b,c were produced
selectively in good yields with the expected E-isomer pre-
1
dominant (15:1 or greater by H NMR).
Scheme 4. Reagents: (a) 2a (6 mol%), CH2Cl2, microwave ir-
radiation (100 °C)
N-Allyl-N-benzyl-(NЈ-tert-butoxycarbonyl-NЈ-(2-propynyl))-
sulfamide (5): To
a stirring solution of sulfamide 4 (1.0 g,
3.07 mmol) in THF (50 mL) was added tBuOK (364 mg,
3.07 mmol), 18-crown-6 (810 mg, 3.07 mmol), and propargyl bro-
mide (467 µL of an 80% solution in toluene, 3.07 mmol). The mix-
ture was stirred at room temp. for 24 h, then quenched by the ad-
dition of water (50 mL). The product was extracted with Et2O (3
ϫ 30 mL), the combined Et2O layers were washed with brine (2
ϫ 25 mL), dried (MgSO4) and the solvent removed in vacuo. The
resulting colourless oil was purified by column chromatography,
eluting with Et2O/hexane (1:9) to furnish compound 5 as a colour-
Conclusion
In conclusion, enyne RCM reactions of sulfamide-linked
internal and terminal alkynes provided a new route to vari-
ous novel seven-membered cyclic sulfamides. The substrates
bearing terminal alkynes were shown to undergo selective
one-pot RCM-CM reactions with styrene and methyl acry-
late. Future studies will explore the scope of enyne RCM-
1
less oil (0.81 mg, 2.21 mmol, 72%). H NMR (400 MHz, CDCl3):
CM reactions and further elaboration of the resulting 1,3- δ ϭ 1.55 (s, 9 H, CH3), 2.25 (t, J ϭ 2.3 Hz, 1 H, HCϵC), 3.86 (d,
J ϭ 6.5 Hz, 2 H, CH2), 4.47 (d, J ϭ 2.3 Hz, 2 H, CH2), 4.55 (s, 2
H, PhCH2), 5.13 (dd, J ϭ 17.0, 1.0 Hz, 1 H, CH2), 5.20 (dd, J ϭ
10.0, 1.0 Hz, 1 H, CH2), 5.74 (ddt, J ϭ 17.0, 10.0, 6.5 Hz, 1 H,
CH), 7.26Ϫ7.35 (m, 5 H, CH) ppm. 13C NMR (75 MHz, CDCl3):
δ ϭ 28.3 (CH3), 38.2, (CH2), 50.0 (CH2), 51.7 (CH2), 72.0 (CH),
79.3 (C), 84.5 (C), 119.7 (CH2), 127.9 (CH), 128.5 (CH), 128.6
(CH), 132.2 (CH), 136.1(C), 151.0 (CϭO) ppm. IR: ν˜max. ϭ 2983,
2935, 2121, 1734 (CϭO), 1493, 1412, 1455, 1384 (SO2), 1304, 1284,
1265, 1143 (SO2) cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative inten-
sity, %) ϭ 387 (100) [M ϩ Na]ϩ.
diene products.
Experimental Section
General Remarks: H NMR and 13C NMR were recorded with a
300 or 400 MHz spectrometer (300 or 400 MHz, H NMR respec-
1
1
tively and 75 or 100 MHz, 13C NMR respectively) in deuteriochlor-
oform (CDCl3) with chloroform (δ ϭ 7.26 ppm 1H, δ ϭ 77.00 ppm
13C) as the internal standard. Infrared (IR) spectra are reported in
wavenumbers (cmϪ1). Melting points were obtained in open capil-
lary tubes and are uncorrected. All reactions were carried out un-
der an inert atmosphere, in oven-dried glassware. The following
solvents were distilled before use: THF (from Na/benzophenone)
and CH2Cl2 (from CaH2) and where appropriate, other reagents
and solvents were purified by standard techniques. TLC was per-
formed on glass-backed plates coated with silica gel 60 with an
F254 indicator; the chromatograms were visualised under UV light
and/or by staining with KMnO4 (aq.). Flash column chromatogra-
phy was performed with 40Ϫ63 µm silica gel (Merck).
[Dichloro{1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene}-
(phenylmethylene)(tricyclohexylphosphane)ruthenium] (2a) was
purchased from either Strem or Aldrich and used without further
purification. All microwave-assisted reactions were carried out in a
SmithSynthesizerTM. The reactions were carried out in sealed ves-
sels and run at a fixed temperature and time as defined by the user,
the power being adapted by the instrument to reach and maintain
the set temperature. The maximum power for this instrument is
300 W.
N-Allyl-N-benzyl-NЈ-(2-propynyl)sulfamide (6): To a solution of sul-
famide 5 (500 mg, 1.37 mmol) in CH2Cl2 (50 mL) was added TFA
(10 mL). The mixture was stirred for 2 h at room temp., before
being quenched by the addition of a saturated solution of NaHCO3
(aq) (50 mL). The product was extracted with CH2Cl2 (3 ϫ 30 mL),
dried (MgSO4) and the solvent removed in vacuo. The resulting
colourless oil was purified by column chromatography, eluting with
Et2O/hexane (2:8) to furnish compound 6 as a colourless oil
(330 mg, 1.25 mmol, 91%). 1H NMR (400 MHz, CDCl3): δ ϭ 1.45
(t, J ϭ 2.5 Hz, 1 H, CϵH), 3.76 (d, J ϭ 6.6 Hz, 2 H, CH2), 3.84
(dd, J ϭ 6.0, 2.5 Hz, 2 H, CH2), 4.40 (s, 2 H, PhCH2), 4.54 (t, J ϭ
6.0 Hz, 1 H, NH), 5.20 (dd, J ϭ 17.0, 1.5 Hz, 1 H, CH), 5.25 (dd,
J ϭ 10.0, 1.5 Hz, 1 H, CH2), 5.87 (ddt, J ϭ 17.0, 10.0, 6.6 Hz, 1
H, CH), 7.39Ϫ7.36 (m, 5 H, CH) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 33.1 (CH2) 50.0 (CH2), 50.8 (CH2), 73.0 (CH), 79.1
(C), 119.7 (CH2), 128.0 (CH), 128.8 (CH ϫ 2), 132.8 (CH), 136.2
(C) ppm. IR: ν˜max. ϭ 3285 (NH), 3077, 3025, 2921, 2850, 1332
(SO2), 1143 (SO2) cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative inten-
sity, %) ϭ 551 (100) [2M ϩ Na]ϩ.
N-Allyl-N-benzyl-(NЈ-tert-butoxycarbonyl)sulfamide (4): To a stir-
N-Allyl-N-benzyl-(NЈ-tert-butoxycarbonyl-NЈ-(2-butynyl))sulfamide
ring solution of chlorosulfonylisocyanate (290 µL, 3.40 mmol) in (7): To a stirring solution of sulfamide 4 (2.0 g, 6.12 mmol) in THF
CH2Cl2 (8 mL) at 0 °C was added tBuOH (0.25 g, 3.40 mmol). The (70 mL) was added tBuOK (685 mg, 6.12 mmol), 18-crown-6
802
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Eur. J. Org. Chem. 2004, 800Ϫ806

Cross Metathesis Reactions of Sulfamide-Linked Enynes
FULL PAPER
(1.61 g, 6.12 mmol) and 1-bromo-2-butyne (531 µL, 6.12 mmol).
The mixture was stirred for 12 h, then quenched with H2O (50 mL)
and extracted with Et2O (3 ϫ 50 mL). The combined Et2O layers
were washed with brine (2 ϫ 50 mL), dried (Na2SO4) and concen-
trated under reduced pressure. The resulting colourless oil was puri-
fied by column chromatography, eluting with Et2O/hexane (4:2) to
0.380 mmol), and benzyl bromide (44.5 µL, 0.380 mmol). The mix-
ture was stirred for 12 h at room temp., then quenched by the ad-
dition of water (5 mL). The product was extracted with Et2O (3 ϫ
10 mL), the combined Et2O layers were washed with brine (10 mL),
dried (MgSO4) and the solvent removed in vacuo. The resulting
colourless oil was purified by column chromatography, eluting with
Et2O/hexane (2:8) to furnish compound 10 as a colourless oil
provide the title compound 7 as a colourless oil (2.25 g, 6.0 mmol,
1
98%). H NMR (400 MHz, CDCl3): δ ϭ 1.51 (s, 9 H, CH3), 1.70 (103 mg, 0.292 mmol, 77%). 1H NMR (400 MHz, CDCl3): δ ϭ 2.39
(s, 3 H, CH3), 3.80 (d, J ϭ 6.5 Hz, 2 H, CH2), 4.39 (q, J ϭ 2.3 Hz, (t, J ϭ 2.5 Hz, 1 H, HCϵC), 3.80 (d, J ϭ 6.5 Hz, 2 H, CH2), 3.90
2 H, CH2), 4.52 (s, 2 H, PhCH2), 5.09 (tdd, J ϭ 1.2, 1.4, 17.0 Hz, (d, J ϭ 2.5 Hz, 2 H, CH2), 4.46 (s, 2 H, PhCH2), 4.53 (s, 2 H,
1 H, CH2), 5.13 (tdd, J ϭ 1.2, 1.4, 10.3 Hz, 1 H, CH2), 5.71 (ddt,
J ϭ 17.0, 10.3, 6.5 Hz,, 1 H, CH), 7.23Ϫ7.32 (m, 5 H, CH) ppm.
PhCH2), 5.17 (dd, J ϭ 17.0, 1.5 Hz, 1 H, CH2), 5.25 (dd, J ϭ 10.0,
1.5 Hz, 1 H, CH2), 5.90 (ddt, J ϭ 17.0, 10.3, 6.5 Hz, 1 H, CH),
13C NMR (100 MHz, CDCl3): δ ϭ 4.0 (CH3), 29.0 (CH3), 39.2 7.31Ϫ7.41 (m, 10 H, CH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ
(CH2), 50.2 (CH2), 52.0 (CH2), 75.3 (C), 80.4 (C), 84.7 (C), 120.0
(CH2), 128.4 (CH), 129.0 (CH), 129.2 (CH), 132.8 (CH), 136.7 (C), (C), 119.7 (CH2), 127.9 (CH), 128.2 (CH), 128.7 (CH), 128.8 (CH),
151.7 (CϭO) ppm. IR: ν˜max. ϭ 2801, 1724 (CϭO), 1365 (SO2), 128.9 (CH ϫ 2), 132.7 (CH), 135.5 (C) 136.3 (C) ppm. IR: ν˜max. ϭ
36.2 (CH2), 50.0 (CH2), 50.6 (CH2), 50.8 (CH2), 74.0 (CH), 78.1
1128 (SO2) cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative intensity, 3054, 3025, 2921, 2855, 1318 (SO2), 1143 (SO2) cmϪ1. LRMS
%) ϭ 401 (50) [M ϩ Na]ϩ, 779 (100) [2M ϩ Na]ϩ . HRMS (ESϩ):
Calcd. for C19H26N2O4SNa: 401.1505, found 401.1504.
(ESϩ, CH3CN): m/z (relative intensity, %) ϭ 355 (50) [M ϩ H]ϩ,
731 (100) [2M ϩ Na]ϩ. HRMS (ESϩ): Calcd. for C20H22N2O2SNa:
377.1294, found 377.1291.
N-Allyl-N-benzyl-(NЈ-(2-butynyl))sulfamide (8): To a solution of
sulfamide 7 (1.0 g, 2.64 mmol) in CH2Cl2 (50 mL) was added TFA
(10 mL). The mixture was stirred for 2 h at room temp., then
quenched by the addition of a saturated solution of NaHCO3 (aq)
(50 mL). The product was extracted with CH2Cl2 (3 ϫ 30 mL),
dried (MgSO4) and the solvent removed in vacuo. The resulting
colourless oil was purified by column chromatography, eluting with
Et2O/hexane (2:8) to furnish compound 8 as a colourless oil
(609 mg, 2.19 mmol, 83%). 1H NMR (400 MHz, CDCl3): δ ϭ 1.45
(t, J ϭ 2.5 Hz, 1 H, CH3), 3.75 (d, J ϭ 6.8 Hz, 2 H, CH2), 3.79
(dq, J ϭ 6.0, 2.5 Hz, 2 H, CH2), 4.39 (s, 2 H, PhCH2), 4.49 (br. s,
1 H, NH), 5.17 (dd, J ϭ 17.0, 1.0 Hz, 1 H, CH), 5.23 (dd, J ϭ
10.1, 1.0 Hz, 1 H, CH2), 5.89 (1 H, ddt, J ϭ 17.0, 10.1, 6.8 Hz,
CH), 7.26Ϫ7.36 (m, 5 H, CH) ppm. 13C NMR (75 MHz, CDCl3):
δ ϭ 3.6 (CH3), 33.5 (CH2), 50.0 (CH2), 50.8 (CH2), 74.3 (C), 80.9
(C), 119.6 (CH2), 127.9 (CH), 128.7 (CH ϫ 2), 132.9 (CH), 136.3
(C) ppm. IR: ν˜max. ϭ 3295 (NH), 3077, 3025, 2916, 2855, 1341
(SO2), 1151 (SO2) cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative
intensity, %) ϭ 579 (100) [2M ϩ Na]. HRMS (ESϩ): Calcd. for
C28H36N4O4S2Na: 579.2070, found 579.2070.
N-Allyl-N-benzyl-NЈ-(2-butynyl)-NЈ-methylsulfamide (11): To a stir-
ring solution of sulfamide 8 (250 mg, 0.90 mmol) in THF (10 mL)
was added tBuOK (153 mg, 0.90 mmol), 18-crown-6 (237 mg,
0.90 mmol), and MeI (56 µL, 0.90 mmol). The mixture was stirred
at room temp. for 12 h, then quenched by the addition of water
(10 mL). The product was extracted with Et2O (3 ϫ 10 mL), the
combined Et2O layers were washed with brine (10 mL), dried
(MgSO4) and the solvent removed in vacuo. The resulting yellow
oil was purified by column chromatography, eluting with Et2O/hex-
ane (1:9) to furnish compound 11 as a colourless oil (181 mg,
0.62 mmol, 69%). 1H NMR (400 MHz, CDCl3): δ ϭ 1.8 (t, J ϭ
2.2 Hz, 3 H, CH3), 2.80 (s, 3 H, CH3), 3.70 (d, J ϭ 6.6 Hz, 2 H,
CH2), 3.95 (q, J ϭ 2.2 Hz, 2 H, CH2), 4.37 (s, 2 H, PhCH2), 5.13
(dd, J ϭ 17.0, 1.5 Hz, 1 H, CH), 5.23 (dd, J ϭ 10.2, 1.5 Hz, 1 H,
CH2), 5.83 (ddt, J ϭ 17.0, 10.2, 6.6 Hz, 1 H, CH), 7.29Ϫ7.35 (m,
5 H, CH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 4.1 (CH3), 35.2
(CH3), 41.2 (CH2), 50.2 (CH2), 51.1 (CH2), 73.8 (C), 82.1 (C), 120.1
(CH2), 128.4 (CH), 129.2 (CH), 129.3 (CH), 133.5 (CH), 136.9 (C)
ppm. IR: ν˜max. ϭ 2922, 1454, 1326 (SO2), 1143 (SO2) cmϪ1. LRMS
(ESϩ, CH3CN): m/z (relative intensity, %) ϭ 315 (10) [M ϩ Na]ϩ,
603 (100) [2M ϩ Na]ϩ.
N-Allyl-N-benzyl-(NЈ-(2-propynyl))sulfamide (9): To a stirring solu-
tion of sulfamide 6 (100 mg, 0.380 mmol) in THF (5 mL) was ad-
ded tBuOK (43 mg, 0.380 mmol), 18-crown-6 (100 mg,
0.380 mmol), and MeI (23 µL, 0.380 mmol). The mixture was
stirred for 12 h at room temp., then quenched by the addition of
water (5 mL). The product was extracted with Et2O (3 ϫ 5 mL),
the combined Et2O layers were washed with brine (10 mL), dried
(MgSO4) and the solvent removed in vacuo. The resulting yellow
oil was purified by column chromatography, eluting with Et2O/hex-
ane (1:3) to furnish compound 9 as a colourless oil (91 mg,
N-Allyl-N,NЈ-dibenzyl-NЈ-(2-butynyl)sulfamide (12): To a stirring
solution of sulfamide 8 (250 mg, 0.90 mmol) in THF (10 mL) was
added tBuOK (153 mg, 0.90 mmol), 18-crown-6 (237 mg,
0.90 mmol), and benzyl bromide (106 mg, 0.90 mmol). The mixture
was stirred for 12 h at room temp., then quenched by the addition
of water (10 mL). The product was extracted with Et2O (3 ϫ
10 mL), the combined Et2O layers were washed with brine (10 mL),
dried (MgSO4) and the solvent removed in vacuo. The resulting
yellow oil was purified by column chromatography, eluting with
Et2O/hexane (1:9) to furnish compound 12 as a colourless oil
(251 mg, 0.68 mmol, 76%). 1H NMR (400 MHz, CDCl3): δ ϭ 1.71
(t, J ϭ 2.0 Hz, 3 H, CH3), 3.66 (t, J ϭ 6.8 Hz, 2 H, CH2), 3.74 (q,
J ϭ 2.0 Hz, 2 H, CH2), 4.33 (s, 2 H, PhCH2), 4.40 (s, 2 H, PhCH2),
5.05 (dd, J ϭ 17.0, 1.5 Hz, 1 H, CH2), 5.12 (dd, J ϭ 10.3, 1.5 Hz,
1 H, CH2), 5.77 (ddt, J ϭ 17.0, 10.3, 6.8 Hz, 1 H, CH), 7.18Ϫ7.30
(m, 10 H, CH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 3.9 (CH3),
37.1 (CH2), 50.2 (CH2), 51.0 (CH2), 51.2 (CH2), 73.7 (C), 82.1 (C),
119.8 (CH), 128.8 (CH), 129.0 (CH), 129.1 (CH), 129.2 (CH), 129.4
(CH), 129.7 (CH), 133.4 (CH), 136.7 (C), 138.2 (C) ppm. IR:
1
0.326 mmol, 86%). H NMR (400 MHz, CDCl3): δ ϭ 2.26 (t, J ϭ
2.5 Hz, 1 H, HCϵC), 2.72 (s, 3 H, CH3), 3.68 (d, J ϭ 6.5 Hz, 2 H,
CH2), 3.90 (d, J ϭ 2.5 Hz, 2 H, CH2), 4.29 (s, 2 H, PhCH2), 5.06
(d, J ϭ 17.1 Hz, 1 H, CH2), 5.14 (d, J ϭ 10.3 Hz, 1 H, CH2), 5.74
(ddt, J ϭ 17.1, 10.3, 6.5 Hz, 1 H, CH), 7.18Ϫ7.28 (m, 5 H, CH)
ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 35.1 (CH3), 40.6 (CH2),
50.1 (CH2), 51.0 (CH2), 74.1 (CH), 78.3 (C), 119.9 (CH2), 128.6
(CH), 129.1 (CH ϫ 2), 133.1 (CH), 136.5 (C) ppm. IR: ν˜max.
ϭ
3271, 3077, 2916, 1322 (SO2), 1143 (SO2) cmϪ1. LRMS (ESϩ,
CH3CN): m/z (relative intensity, %) ϭ 279 (100) [M ϩ H]ϩ.
N-Allyl-N,NЈ-dibenzyl-NЈ-(2-propynyl)sulfamide (10): To a stirring
solution of sulfamide 6 (100 mg, 0.380 mmol) in THF (5 mL) was ν˜max. ϭ 3068, 3039, 2992, 2912, 1502, 1445, 1360, 1332 (SO2), 1152
added tBuOK (43 mg, 0.380 mmol), 18-crown-6 (100 mg,
(SO2) cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative intensity, %) ϭ
Eur. J. Org. Chem. 2004, 800Ϫ806
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
803

S. S. Salim, R. K. Bellingham, R. C. D. Brown
369 (40) [M ϩ H]ϩ, 759 (100) [2M ϩ Na]ϩ. HRMS (ESϩ): Calcd. tert-Butyl 7-Benzyl-4-{(E)-2-[7-benzyl-2-(tert-butoxycarbonyl)-1,1-
FULL PAPER
for C21H24N2O2SNa: 391.1450, found 391.1450.
dioxo-2,3,6,7-tetrahydro-1H-1λ6,2,7-thiadiazepin-4-yl]-1-ethenyl}-
1,1-dioxo-2,3,6,7-tetrahydro-1H-1λ6,2,7-thiadiazepine-2-carboxylate
(16a): To a solution of sulfamide 5 (100 mg, 0.27 mmol) in CH2Cl2
(7.5 mL) was added ruthenium complex 2a (13.8 mg, 16.3 µmol).
The mixture was stirred at reflux for 24 h. The solvent was removed
in vacuo and the resulting brown oil was purified by column chro-
matography, eluting with Et2O/hexane (1:9) to give 16a as a white
solid (59.1 mg, 0.084 mmol, 61%), 17a as a white solid (7 mg,
0.016 mmol, 6%), and 18a as a colourless oil (8.1 mg, 0.022 mmol,
8%). Data for 16a: M.p. 158Ϫ160 °C (EtOAc/hexane). 1H NMR
(400 MHz, CDCl3): δ ϭ 1.5 (s, 18 H, CH3), 4.0 (d, J ϭ 4.2 Hz, 4
H, CH2), 4.48 (s, 4 H, CH2), 4.51 (s, 4 H, CH2), 5.75 (t, J ϭ 4.2 Hz,
2 H, CH), 6.50 (s, 2 H, CH), 7.38Ϫ7.43 (m, 10 H, CH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 28.3 (CH3), 42.5 (CH2), 45.1 (CH2),
52.8 (CH2), 84.5 (C), 127.4 (CH), 128.4 (CH), 128.5 (CH), 129.1
(CH), 129.4 (CH), 135.4 (C), 138.5 (C), 151.8 (CϭO) ppm. IR:
ν˜max. ϭ 2968, 2926, 1734 (CϭO), 1327 (SO2), 1174 (SO2), 1138
cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative intensity, %) ϭ 723.4
(100) [M ϩ Na]ϩ, 1423 (10) [2M ϩ Na]ϩ. The structure of 16a was
unambiguously established by X-ray crystallography.
7-Benzyl-2-tert-butoxycarbonyl-1,1-dioxo-4-[(E)-2-phenyl-1-eth-
enyl]-2,3,6,7-tetrahydro-1H-1λ6,2,7-thiadiazepine (17a): M.p.
155Ϫ156 °C (EtOAc/hexane). 1H NMR (400 MHz, CDCl3): δ ϭ
1.5 (s, 9 H, CH3), 3.98 (d, J ϭ 4.7 Hz, 2 H, CH2), 4.52 (s, 2 H,
CH2), 4.62 (s, 2 H, CH2), 5.73 (t, J ϭ 4.7 Hz, 1 H, CH), 6.78 (s, 2
H, CH), 7.30Ϫ7.47 (m, 10 H, CH) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 26.5 (CH3), 41.1 (CH2), 43.2 (CH2), 50.9 (CH2), 82.5
(C), 124.4 (CH), 125.0 (CH), 126.4 (CH), 126.6 (CH), 126.7 (CH),
127.1 (CH), 127.2 (CH), 127.7 (CH), 133.7 (C), 135.1 (C), 137.3
(C), 149.9 (CϭO) ppm. IR: ν˜max. ϭ 3054, 2997, 2926, 1717 (Cϭ
O), 1368 (SO2), 1272, 1173 (SO2) cmϪ1. LRMS (ESϩ, CH3CN):
m/z (relative intensity, %) ϭ 441 (20) [M ϩ H]ϩ, 441 (50) [M ϩ
Na]ϩ, 903 (100) [2M ϩ Na]ϩ.
Enyne-RCM Procedures
7-Benzyl-2-tert-butoxycarbonyl-4-isopropenyl-1,1-dioxo-2,3,6,7-
tetrahydro-1H-1λ6,2,7-thiadiazepine (13): To a solution of sulfamide
7 (60 mg, 0.16 mmol) in CH2Cl2 (5 mL) was added ruthenium com-
plex 2a (4.0 mg, 4.8 µmol), the mixture was sealed in a crimped-
cap vessel under an atmosphere of argon and heated with micro-
waves at 100 °C for 30 minutes. The solvent removed in vacuo and
the resulting brown oil was purified by column chromatography,
eluting with Et2O/hexane (1:2) to furnish compound 13 as a colour-
less oil (49 mg, 0.13 mmol, 81%). 1H NMR (400 MHz, CDCl3):
δ ϭ 1.54 (s, 9 H, CH3), 1.95 (s, 3 H, CH3), 3.96 (d, J ϭ 5.0 Hz, 2H
CH2), 4.50 (s, 2 H, CH2), 4.52 (s, 2 H, CH2), 5.10 (s, 1 H, CH2),
5.27 (s, 1 H, CH2), 5.62 (t, J ϭ 5.0 Hz, 1 H, CH), 7.30Ϫ7.35 (m,
5 H, CH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 21.7 (CH3), 28.4
(CH3), 43.7 (CH2), 45.0 (CH2), 52.8 (CH2), 84.2 (C), 113.9 (CH2),
121.8 (CH), 128.5 (CH), 128.9 (CH ϫ 2), 135.6 (C), 140.5 (C),
142.0 (C), 151.7 (CϭO) ppm. IR: ν˜max. ϭ 3025, 2983, 2916, 1725
(CϭO), 1322 (SO2), 1176, 1147 (SO2) cmϪ1
.
LRMS (ESϩ,
CH3CN): m/z (relative intensity, %) ϭ 401 (25) [M ϩ Na]ϩ,
779(100) [2M ϩ Na]ϩ. HRMS (ESϩ): Calcd. for C38H52N4O8S2Na:
779.3118, found 779.3102.
7-Benzyl-4-isopropenyl-2-methyl-2,3,6,7-tetrahydro-1H-1λ6,2,7-thia-
diazepine-1,1-dione (14): To a solution of sulfamide 11 (60 mg,
0.21 mmol) in CH2Cl2 (5 mL) was added ruthenium complex 2a
(5.3 mg, 6.3µmol). The mixture was sealed in a crimped-cap vessel
under argon and heated with microwaves at 100 °C for 30 minutes.
The solvent removed in vacuo and the resulting brown oil was puri-
fied by column chromatography, eluting with Et2O/hexane (1:2) to
furnish compound 14 as a colourless oil (44 mg, 0.15 mmol, 72%).
1H NMR (400 MHz, CDCl3): δ ϭ 1.95 (s, 3 H, CH3), 2.93 (s, 3 H,
CH3) 3.73 (d, J ϭ 6.0 Hz, 2 H, CH2), 4.17 (s, 2 H, CH2), 4.40 (s,
2 H, PhCH2), 5.10 (s, 1 H, CH2), 5.13 (s, 1 H, CH2), 5.92 (t, J ϭ
6.0 Hz, 1 H, CH), 7.29Ϫ7.38 (m, 5 H, CH) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 21.5 (CH3), 36.2 (CH3), 43.4 (CH2), 48.0
(CH2), 52.5 (CH2), 113.9 (CH2), 124.6 (CH), 128.0 (CH), 128.4
(CH), 128.8 (CH), 136.4 (C), 142.4 (C), 142.9 (C) ppm. IR: ν˜max. ϭ
3082, 3063, 3016, 2945, 1583, 1497, 1441, 1360 (SO2), 1332, 1157
(SO2) cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative intensity, %) ϭ
293 (40) [M ϩ H]ϩ, 585 (100) [2M ϩ Na]. HRMS (ESϩ): Calcd.
for C30H40N4O4S2Na: 607.2382, found 607.2388.
2-tert-Butoxycarbonyl-7-benzyl-1,1-dioxo-4-vinyl-2,3,6,7-tetrahydro-
1
1H-1λ6,2,7-thiadiazepine (18a): H NMR (400 MHz, CDCl3): δ ϭ
1.54 (s, 9 H, CH3), 3.92 (d, J ϭ 4.3 Hz, 2 H, CH2), 4.47 (s, 4 H,
CH2), 5.18 (d, J ϭ 11.0 Hz, 1 H, CH2), 5.43 (d, J ϭ 17.6 Hz, 1 H,
CH2), 5.58 (t, J ϭ 4.3 Hz, 1 H, CH), 6.34 (dd, J ϭ 11.0, 17.6 Hz,
1 H, CH), 7.32Ϫ7.38 (m, 5 H, CH) ppm 13C NMR (75 MHz,
CDCl3): δ ϭ 26.9 (CH3), 40.7 (CH2), 43.6 (CH2), 51.5 (CH2), 83.0
(C), 112.8 (CH2), 124.9 (CH), 127.1 (CH ϫ 2), 127.7 (CH), 134.2
(C), 136.2 (C), 137.6 (C), 150.4 (CϭO) ppm. IR: ν˜max. ϭ 2992,
2940, 1720 (CϭO), 1587, 1367 (SO2), 1328, 1258, 1176 (SO2), 1146
cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative intensity, %) ϭ 403 (50)
[M ϩ K]ϩ, 751 (100) [2M ϩ Na]ϩ. HRMS (ESϩ): Calcd. for
C18H24N2O4S1Na: 387.1349, found 384.1359.
2,7-Dibenzyl-4-isopropenyl-2,3,6,7-tetrahydro-1H-1λ6,2,7-thiadia-
zepine-1,1-dione (15): To a solution of sulfamide 12 (60 mg,
0.16 mmol) in CH2Cl2 (5 mL) was added the ruthenium complex
2a (4.1 mg, 4.8 µmol). The mixture was sealed in a crimped-cap
vessel under argon and irradiated with microwaves at 100 °C for
50 minutes. The solvent was removed in vacuo and the resulting
brown oil was purified by column chromatography, eluting with
7-Benzyl-2-methyl-1,1-dioxo-4-vinyl-2,3,6,7-tetrahydro-1H-1λ6,2,7-
thiadiazepine (18b): To a solution of the sulfamide 9 (74 mg,
0.27 mmol) in CH2Cl2 (5 mL) was added ruthenium complex 2a
(13.8 mg, 16.2 µmol). The mixture was sealed in a crimped-cap ves-
Et2O/hexane (1:2) to furnish compound 15 as a white solid (40 mg, sel under argon and heated with microwaves at 100 °C for 60 mi-
0.11 mmol, 68%). M.p. 95Ϫ97 °C (EtOAc/hexane). 1H NMR nutes. The solvent removed in vacuo and the resulting brown oil
(400 MHz, CDCl3): δ ϭ 1.90 (s, 3 H, CH3), 3.80 (d, J ϭ 5.5 Hz, 2
was purified by column chromatography, eluting with Et2O/hexane
H, CH2), 4.02 (s, 2 H, CH2), 4.42 (s, 2 H, PhCH2), 4.45 (s, 2 H, (1:9) to furnish 18b as a colourless oil (45 mg, 0.16 mmol, 60%),
PhCH2), 4.77 (s, 1 H, CH2), 4.69 (s, 1 H, CH2), 5.84 (t, J ϭ 5.5 Hz, 16b as a white solid (14 mg, 0.027 mmol, 10%), and 17b as a white
1 H, CH), 7.36Ϫ7.39 (m, 5 H, CH) ppm. 13C NMR (75 MHz, solid (5.5 mg, 0.015 mmol, 6%). Data for 18b: 1H NMR (400 MHz,
CDCl3): δ ϭ 21.5 (CH3), 43.7 (CH2), 44.4 (CH2), 52.2 (CH2 ϫ 2), CDCl3): δ ϭ 2.90 (s, 3 H, CH3), 3.70 (d, J ϭ 5.5 Hz, 2 H, CH2),
114.0 (CH2), 124.2 (CH), 128.0 (CH), 128.1 (CH), 128.3 (CH), 4.10 (s, 2 H, CH2), 4.40 (s, 2 H, PhCH2), 5.16 (d, J ϭ 10.6 Hz, 1
128.5 (CH), 128.7 (CH), 128.8 (CH), 136.2 (C), 136.7 (C), 142.0
H, CH2), 5.29 (d, J ϭ 17.6 Hz, 1 H, CH2), 5.86 (t, J ϭ 5.5 Hz, 1
(C), 142.5 (C) ppm. IR: ν˜max. ϭ 3062, 3031, 2952, 2928, 1337 (SO2), H, CH), 6.41 (dd, J ϭ 10.6, 17.6 Hz, 1 H, CH), 7.26Ϫ7.35 (m, 5
1156 (SO2), 1122 cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative inten-
sity, %) ϭ 407 (15) [M ϩ K]ϩ, 759 (100) [2M ϩ Na]ϩ.
H, CH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 36.6 (CH3), 43.6
(CH2), 46.6 (CH2), 53.0 (CH2), 114.4 (CH2), 128.4 (CH), 128.8
804
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 800Ϫ806

Cross Metathesis Reactions of Sulfamide-Linked Enynes
FULL PAPER
(CH), 129.1 (CH), 129.2 (CH), 129.4 (CH), 136.7 (C), 138.9 (C), 2,7-Dibenzyl-4-[(E)-2-phenyl-1-ethenyl]-2,3,6,7-tetrahydro-1H-
140.9 (C) ppm. IR: ν˜max. ϭ 2921, 2897, 1359 (SO2), 1331, 1158
(SO2) cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative intensity, %) ϭ
301 (100) [M ϩ Na]ϩ, 579 (50) [2M ϩ Na]ϩ.
1λ6,2,7-thiadiazepine-1,1-dione (17c): M.p. 110Ϫ112 °C (EtOAc/
hexane). H NMR (400 MHz, CDCl3): δ ϭ 3.84 (d, J ϭ 6.1 Hz, 2
1
H, CH2) 4.10 (s, 2 H, CH2), 4.46 (s, 2 H, CH2), 4.48 (s, 2 H, CH2),
6.01 (t, J ϭ 6.1 Hz, 1 H, CH), 6.16 (d, J ϭ 16.5 Hz, 1 H, CH),
6.80 (d, J ϭ 16.5 Hz, 1 H, CH), 7.29Ϫ7.38 (m, 15 H, CH) ppm.
13C NMR (90 MHz, CDCl3): δ ϭ 42.9 (CH2), 43.7(CH2), 52.0
(CH2), 52.1 (CH2), 126.7 (CH), 128.2 (CH), 128.3 (CH), 128.6
(CH), 128.7 (CH), 128.8 (CH), 128.9 (CH ϫ 2), 129.1 (CH), 129.2
7-Benzyl-4-[(E)-2-(7-benzyl-2-methyl-1,1-dioxo-2,3,6,7-tetrahydro-
1H-1λ6,2,7-thiadiazepin-4-yl)-1-ethenyl]-2-methyl-2,3,6,7-
t e t r a h y d r o - 1 H - 1 λ 6 , 2 , 7 - t h i a d i a z e p i n e - 1 , 1 - d i o n e
(16b): M.p. 170Ϫ172 °C (EtOAc/hexane). 1H NMR (400 MHz,
CDCl3): δ ϭ 2.9 (s, 3 H, CH3), 3.74 (d, J ϭ 6.0 Hz, 4 H, CH2),
4.13 (s, 4 H, CH2), 4.41 (s, 4 H, CH2), 5.95 (t, J ϭ 5.8 Hz, 2 H,
CH), 6.31 (s, 2 H, CH), 7.30Ϫ7.36 (m, 5 H, CH) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 36.7 (CH3), 43.8 (CH2), 47.2 (CH2), 53.0
(CH2), 128.5 (CH), 128.7 (CH), 129.2 (CH), 130.6 (CH), 130.5
(CH), 136.5 (C), 140.0 (C) ppm. IR: ν˜max. ϭ 1354 (SO2), 1357, 1153
(SO2), 1110 cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative intensity,
%) ϭ 1095 (100) [2M ϩ K]ϩ.
(CH), 130.0 (C), 136.5 (C), 136.6 (C), 141.3 (C) ppm. IR: ν˜max.
ϭ
3063, 3030, 2916, 2860, 1351 (SO2), 1318, 1152 (SO2), 1114 cmϪ1
.
LRMS (ESϩ, CH3CN): m/z (relative intensity, %) 431 (10) [M ϩ
H]ϩ, 883 (100) [2M ϩ Na]ϩ. The structure of 17c was unambigu-
ously established by X-ray crystallography.
Enyne RCM؊CM Procedures
7-Benzyl-2-tert-butoxycarbonyl-1,1-dioxo-4-[(E)-2-phenyl-1-
ethenyl]-2,3,6,7-tetrahydro-1H-1λ6,2,7-thiadiazepine (17a): To
a
7-Benzyl-2-methyl-4-[(E)-2-phenyl-1-ethenyl]-2,3,6,7-tetrahydro-1H-
1λ6,2,7-thiadiazepine-1,1-dione (17b): M.p. 153Ϫ155 °C (EtOAc/
hexane). 1H NMR (400 MHz, CDCl3): δ ϭ 2.97 (s, 3 H, CH3), 3.76
(d, J ϭ 6.0 Hz, 2 H, CH2), 4.26 (s, 2 H, CH2), 4.45 (s, 2 H, CH2),
6.01 (t, J ϭ 6.0 Hz, 1 H, CH), 6.65 (d, J ϭ 16.5 Hz 1 H, CH), 6.85
(d, J ϭ 16.5 Hz, 1 H, CH), 7.30Ϫ7.47 (m, 10 H, CH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 36.1 (CH3), 43.2 (CH2), 46.7 (CH2),
52.3 (CH2), 126.6 (CH), 127.9 (CH), 128.2 (CH), 128.3 (CH), 128.6
(CH), 128.7 (CH), 128.8 (CH), 128.9 (CH), 130.4 (CH), 136.1 (C),
136.5 (C), 140.5 (C) ppm. IR: ν˜max. ϭ 3625, 1494, 1450, 1360 (SO2),
1332, 1157 (SO2) cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative inten-
sity, %) ϭ 355 (60) [M ϩ H]ϩ, 394 (85) [M ϩ CH3CN]ϩ, 730 (100)
[2M ϩ Na]ϩ.
solution of sulfamide 5 (100 mg, 0.27 mmol) in CH2Cl2 (5 mL) was
added ruthenium complex 2a (13.8 mg, 16.3 µmol) and styrene (62
µL, 0.54 mmol). The mixture was sealed in a crimped-cap vessel
under an atmosphere of argon and heated with microwaves at 100
°C for 2 h. The solvent removed in vacuo and the resulting brown
oil was purified by column chromatography, eluting with Et2O/hex-
ane (2:3) to furnish compound 17a as a white solid (54 mg,
0.15 mmol, 55%). Analytical data were identical to those reported
above.
7-Benzyl-2-methyl-4-[(E)-2-phenyl-1-ethenyl]-2,3,6,7-tetrahydro-1H-
1λ6,2,7-thiadiazepine-1,1-dione (17b): To a solution of sulfamide 9
(100 mg, 0.36 mmol) in CH2Cl2 (5 mL) was added ruthenium com-
plex 2a (18.3 mg, 21.6 µmol) and styrene (82.5 µL, 0.72 mmol). The
mixture was sealed in a crimped-cap vessel under argon and heated
with microwaves at 100 °C for 2 h. The solvent removed in vacuo
and the resulting brown oil was purified by column chromatogra-
phy, eluting with Et2O/hexane (1:4) to furnish compound 17b as a
white solid (79 mg, 0.22 mmol, 62%). Analytical data were identical
to those reported above.
2,7-Dibenzyl-1,1-dioxo-4-vinyl-2,3,6,7-tetrahydro-1H-1λ6,2,7-thia-
diazepine (18c): To a solution of sulfamide 10 (95 mg, 0.27 mmol)
in CH2Cl2 (5 mL) was added ruthenium complex 2a (13.8 mg, 16
µmol). The mixture was sealed in a crimped-cap vessel under argon
and heated with microwaves at 100 °C for 60 minutes. The solvent
removed in vacuo and the resulting brown oil was purified by col-
umn chromatography, eluting with Et2O/hexane (1:9) to furnish 18c
as a colourless oil (60 mg, 0.17 mmol, 63%), 16c as a white solid
(15 mg, 0.022 mmol, 8%) and 17c as a white solid (4.5 mg,
2,7-Dibenzyl-4-[(E)-2-phenyl-1-ethenyl]-2,3,6,7-tetrahydro-1H-
1λ6,2,7-thiadiazepine-1,1-dione(17c): To a solution of sulfamide 10
(150 mg, 0.42 mmol) in CH2Cl2 (5 mL) was added ruthenium com-
plex 2a (21.6 mg, 25 µmol) and styrene (96 µL, 0.84 mmol). The
mixture was sealed in a crimped-cap vessel under an atmosphere
of argon and heated with microwaves at 100 °C for 2 h. The solvent
removed in vacuo and the resulting brown oil was purified by col-
umn chromatography, eluting with Et2O/hexane (1:9) to furnish
compound 17c as a white solid (142 mg, 0.33 mmol, 79%). Analyti-
cal data were identical to those reported above.
1
0.010 mmol, 4%). Data for 18c: H NMR (400 MHz, CDCl3): δ ϭ
3.76 (d, J ϭ 5.7 Hz, 2 H, CH2), 3.92 (s, 2 H, CH2), 4.44 (s, 4 H,
PhCH2), 4.88 (d, J ϭ 17.5 Hz, 1 H, CH2), 5.03 (d, J ϭ 11.1 Hz, 1
H, CH2), 5.82 (t, J ϭ 5.7 Hz, 1 H, CH), 6.34 (dd, J ϭ 17.5, 11.1 Hz,
1 H, CH), 7.33Ϫ7.37 (m, 10 H, CH) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 42.7 (CH2), 43.8 (CH2), 52.5 (CH2), 52.6 (CH2), 114.6
(CH2), 128.8 (CH), 128.9 (CH), 129.1 (CH), 129.2 (CH), 136.5
(CH), 136.9 (C), 138.5 (C), 140.9 (C) ppm. IR: ν˜max. ϭ 3087, 3030,
1360 (SO2), 1332, 1158 (SO2) cmϪ1. LRMS (ESϩ, CH3CN): m/z
(relative intensity, %) ϭ 731 (100) [2M ϩ Na]ϩ. HRMS (ESϩ):
Calcd. for C20H22N2O2SNa: 377.1294, found 377.1293.
Methyl (E)-3-(7-Benzyl-2-methyl-1,1-dioxo-2,3,6,7-tetrahydro-1H-
1λ6,2,7-thiadiazepin-4-yl)-2-propenoate (19b): To a solution of sul-
famide 9 (100 mg, 0.36 mmol) in CH2Cl2 (5 mL) was added ru-
2,7-Dibenzyl-4-[(E)-2-(2,7-dibenzyl-1,1-dioxo-2,3,6,7-tetrahydro- thenium complex 2a (18.3 mg, 21.6 µmol) and methyl acrylate (64
1H-1λ6,2,7-thiadiazepin-4-yl)-1-ethenyl]-2,3,6,7-tetrahydro-1H- µL, 0.72 mmol). The mixture was stirred for 1 h at 100 °C in the
1λ6,2,7-thiadiazepine-1,1-dione (16 c): M.p. 180Ϫ182 °C (EtOAc/
microwave, the solvent removed in vacuo and the resulting brown
hexane). 1H NMR (400 MHz, CDCl3): δ ϭ 2.92 (s, 4 H, CH2), 3.74 oil was purified by column chromatography, eluting with Et2O/hex-
(d, J ϭ 5.8 Hz, 4 H, CH2), 4.14 (s, 4 H, CH2), 4.41 (s, 4 H, CH2),
ane (1:1) to furnish compound 19b as a white solid (100 mg,
5.95 (t, J ϭ 5.8 Hz, 2 H, CH), 6.34 (s, 2 H, CH), 7.33Ϫ7.38 (m, 10 0.30 mmol, 83%). M.p. 114Ϫ115 °C (EtOAc/hexane). 1H NMR
H, CH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 43.3 (CH2), 44.2 (400 MHz, CDCl3): δ ϭ 2.80 (s, 3 H, CH3), 3.75 (d, J ϭ 4.1 Hz, 2
(CH2), 52.5 (CH2), 52.8 (CH2), 128.7 (CH), 128.9 (CH), 129.0 H, CH2), 3.77 (s, 3 H, CH3), 4.10 (s, 2 H, CH2), 4.39 (s, 2 H,
(CH), 129.1 (CH), 129.4 (CH), 129.6 (CH), 130.7 (CH), 130.9
PhCH2), 5.93 (d, J ϭ 11.0 Hz, 1 H, CH), 6.20 (t, J ϭ 4.1 Hz, 1 H,
(CH), 136.5 (C), 137.0 (C), 140.9 (C) ppm. ν˜max. ϭ 3030, 1359 CH), 7.35Ϫ7.28 (m, 6 H, CH) ppm. 13C NMR (90 MHz, CDCl3):
(SO2), 1333, 1120 (SO2) cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative
intensity, %) ϭ 1384 (100) [2M ϩ Na]ϩ.
δ ϭ 36.7 (CH3), 43.8 (CH2), 47.1 (CH2), 52.3 (CH2), 53.2 (CH3),
118.4 (CH), 128.5 (CH), 128.7 (CH), 129.2 (CH), 136.2 (C), 137.3
Eur. J. Org. Chem. 2004, 800Ϫ806
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
805

S. S. Salim, R. K. Bellingham, R. C. D. Brown
FULL PAPER
M. Mori, in Alkene Metathesis in Organic Synthesis (Ed.: A.
Fürstner), Springer-Verlag, Berlin, 1998, pp. 133Ϫ154.
C. S. Poulsen, R. Madsen, Synthesis 2003, 1Ϫ18.
For early examples of enyne RCM using ruthenium alkylidene
pre-catalysts see ref.[4] and: A. Kinoshita, M. Mori, Synlett
1994, 1020Ϫ1022.
(CH), 138.8 (C), 146.1 (CH), 167.3 (CϭO) ppm. IR: ν˜max. ϭ 3063,
3030, 2945, 2860, 1706 (CϭO), 1620, 1356, 1313, 1147 cmϪ1
.
[2]
[3]
LRMS (ESϩ, CH3CN): m/z (relative intensity, %) ϭ 711 (100) [2M
ϩ K]ϩ. The structure of 19b was unambiguously established by X-
ray crystallography.
[4]
[5]
S.-H. Kim, N. Bowden, R. H. Grubbs, J. Am. Chem. Soc. 1994,
Methyl
(E)-3-(2,7-Dibenzyl-1,1-dioxo-2,3,6,7-tetrahydro-1H-
116, 10801Ϫ10802.
1λ6,2,7-thiadiazepin-4-yl)-2-propenoate (19c): To a solution of sulfa-
mide 10 (100 mg, 0.28 mmol) in CH2Cl2 (5 mL) was added ru-
thenium complex 2a (14.2 mg, 16.8 µmol) and methyl acrylate (50
µL, 0.56 mmol). The mixture was stirred for 1 h at 100 °C in the
microwave, the solvent removed in vacuo and the resulting brown
oil was purified by column chromatography, eluting with Et2O/hex-
ane (1:2) to furnish compound 19c as a white solid (62 mg,
0.15 mmol, 54%). M.p. 120Ϫ122 °C (EtOAc/hexane). 1H NMR
(400 MHz, CDCl3): δ ϭ 3.70 (s, 3 H, CH3), 3.83 (d, J ϭ 5.5 Hz, 2
H, CH2), 3.93 (s, 2 H, CH2), 4.41 (s, 2 H, PhCH2), 4.42 (s, 2 H,
CH2), 5.52 (d, J ϭ 16.1 Hz, 1 H, CH), 6.12 (t, J ϭ 5.5 Hz, 1 H,
CH), 7.22Ϫ7.36 (m, 11 H, CH) ppm. 13C NMR (90 MHz, CDCl3):
δ ϭ 43.3 (CH2), 44.2 (CH2), 52.4 (CH2), 52.9 (CH2), 53.1 (CH3),
118.5 (CH), 128.6 (CH), 128.7 (CH), 128.9 (CH), 129.3 (CH ϫ 2),
129.4 (CH), 136.3 (C), 136.4 (C), 138.7 (C), 145.7 (CH), 167.5 (Cϭ
O) ppm. IR: ν˜max. ϭ 3052, 3030, 2948, 1718 (CϭO), 1625, 1585,
1495, 1361, 1285, 1149 cmϪ1. LRMS (ESϩ, CH3CN): m/z (relative
intensity, %) ϭ 435 (100) [M ϩ Na]ϩ.
For a recent, more general review of the mechanistic aspects of
metal catalysed 1,6-enyne isomerisations: G. C. Lloyd-Jones,
Org. Biomol. Chem. 2003, 1, 215Ϫ236.
T. L. Choi, R. H. Grubbs, Chem. Commun. 2001, 2648Ϫ2649.
W. J. Zuercher, M. Scholl, R. H. Grubbs, J. Org. Chem. 1998,
63, 4291Ϫ4298.
[6]
[7]
[8]
[9]
S. Randl, N. Lucas, S. J. Connon, S. Blechert, Adv. Synth. Ca-
tal. 2002, 344, 631Ϫ633.
For an excellent overview of ruthenium carbene-mediated dom-
ino metathesis reactions see ref.[2] For polycyclisations involv-
ing domino enyne RCM-olefin RCM see refs.[2,3] and: M. S.
M. Timmer, H. Ovaa, D. V. Filippov, G. A. van der Marel, J.
H. van Boom, Tetrahedron Lett. 2001, 42, 8231Ϫ8233.
F. Royer, C. Vilain, L. Elka¨ım, L. Grimaud, Org. Lett. 2003,
5, 2007Ϫ2009.
H.-Y. Lee, H. Y. Kim, H. Tae, B. G. Kim, J. Lee, Org. Lett.
2003, 5, 3439Ϫ3442.
For olefin RCM approaches to cyclic sulfonamides see
refs.[13,14] and: P. R. Hanson, D. A. Probst, R. E. Robinson,
M. Yau, Tetrahedron Lett. 1999, 40, 4761Ϫ4764.
R. C. D. Brown, J. L. Castro, J. D. Moriggi, Tetrahedron Lett.
2000, 41, 3681Ϫ3685.
[10]
[11]
[12]
[13]
[14]
[15]
CCDC-222239 (16a), -222240 (17c), -222241 (19b) contain the sup-
plementary crystallographic data for this paper. These data can be
obtained free of charge at www.ccdc.cam.ac.uk/conts/retriev-
ing.html [or from the Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge CB2 1EZ, UK; Fax: (internat.)
ϩ 44-1223-336-033; E-mail: deposit@ccdc.cam.ac.uk].
D. D. Long, A. P. Termin, Tetrahedron Lett. 2000, 41,
6743Ϫ6747.
For olefin RCM approaches to sulfamides see refs.[16, 17] and:
J. M. Dougherty, D. A. Probst, R. E. Robinson, J. D. Moore,
T. A. Klein, K. A. Snelgrove, P. R. Hanson, Tetrahedron 2000,
56, 9781Ϫ9790.
[16]
[17]
[18]
[19]
[20]
[21]
A. M. Harned, S. Mukherjee, D. L. Flynn, P. R. Hanson, Org.
Lett. 2003, 5, 15Ϫ18.
Acknowledgments
´
J. H. Jun, J. M. Dougherty, M. del Sol Jimenez, P. R. Hanson,
We acknowledge EPSRC and GlaxoSmithKline for a CASE award
(S. S. S.), the Royal Society for a University Research Fellowship
(R. C. D. B.), and Merck Sharp & Dohme, Syngenta, AstraZeneca
and Pfizer for unrestricted grants. Personal Chemistry are thanked
for the donation of the SmithSynthesizerTM used in this work. We
are also grateful to Dr. P. N. Horton, and Professor M. B. Hurst-
house for providing X-ray structural determination.
Tetrahedron 2003, 59, 8901Ϫ8912.
For olefin RCM approaches to sultones: S. Karsch, P. Schwab,
P. Metz, Synlett 2002, 2019Ϫ2022.
G. Dewynter, N. Aouf, M. Criton, J. L. Montero, Tetrahedron
1993, 49, 65Ϫ76.
Personal Chemistry are thanked for the donation of the
SmithSynthesizerTM used in this work.
The structures of compounds 16a, 17c and 19b were confirmed
by X-ray crystallography.
[1]
For recent reviews dealing with enyne metathesis see ref.[2] and:
Received November 14, 2003
806
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 800Ϫ806