First synthesis of bi- and tricyclic α,β-unsaturated δ-oxacaprolactams from cyclic imines via ring-closing metathesis

Article abstract of DOI:10.1002/ejoc.200800254

A new class of α,β-unsaturated δ-oxacaprolactams was synthesized from imines as starting material. The synthetic procedure is based on an acyl chloride addition in the first step, followed by a ring-closing metathesis using a ruthenium catalyst. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800254

FULL PAPER
DOI: 10.1002/ejoc.200800254
First Synthesis of Bi- and Tricyclic α,β-Unsaturated δ-Oxacaprolactams from
Cyclic Imines via Ring-Closing Metathesis
Martin Watzke,[a] Knut Schulz,[a] Katharina Johannes,[a] Pasqual Ullrich,[a] and
Jürgen Martens*[a]
Keywords: Heterocyclic imines / Ring-closing metathesis / Unsaturated caprolactams / Acrylamides / Ruthenium catalysis
A new class of α,β-unsaturated δ-oxacaprolactams was syn-
thesized from imines as starting material. The synthetic pro-
cedure is based on an acyl chloride addition in the first step,
followed by a ring-closing metathesis using a ruthenium cat-
alyst.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
α,β-Unsaturated lactams are a very interesting class of
The cyclic amine parts of our lactams resulting from the
organic molecules. A plenty of these lactams show a high imine precursors were selected because of being interesting
bioactivity because of their characteristics as a lactam as building blocks in different applications. 3-Thiazolidine de-
well as a Michael acceptor. A couple of these lactams can rivatives for example can be found in penicillins[7] and Dia-
be isolated from natural products and are known and exam- betes mellitus drugs.[8] Clavulanic acid which is a strong β-
ined for a long time.[1]
lactamase inhibitor contains an 3-oxazolidine structure[7d,9]
Yet unknown were the α,β-unsaturated δ-oxacaprolac- and the 1,4-benzothiazine respectively the 1,4-benzoxazine
tams, so our aim was to design this new substance class. We substructures are potent potassium and calcium channel
chose to start with some heterocyclic imines and wanted to openers,[10] inflammatory inhibitors[11] or antibiotica.[12]
add unsaturated carbonic acyl chlorides followed by treat-
ment with allyl alcohol to prepare the acrylamides.[2] Doing
a ring-closing metathesis (RCM) with these acrylamides the
synthetic protocol products should straightly lead to the bi-
Synthesis of the Heterocyclic Imine Precursors
or tricyclic lactams shown in Figure 1.
The used heterocyclic imines were on the one hand the
monocyclic five-membered 2,5-dihydro-thiazole 1a[13] and
2,5-dihydrooxazole 1b,[14] which were synthesised by a
modified protocol of the Asinger reaction[15] (Scheme 1)
and on the other hand the bicyclic 2H-1,4-benzothiazine 2a
and 2H-1,4-benzoxazine 2b.
Figure 1. Retrosynthetical consideration of the target structure.
Some derivatives of α,β-unsaturated caprolactams show
central nervous system activity and causes the loss of mus-
cle control of mice.[3] Also activity against leucemia, mela-
noma and sarcoma cancer cells was reported.[4] Some satu-
rated caprolactam derivatives are for example known for
their cytotoxicity and the inhibition of proliferation of kera-
tinocytes and fibroblasts[5] or antibacterial and antifungal
effects.[6] Building blocks of the resulting caprolactams pos-
sess a double bond representing a useful handle for further
functionalisation.
Scheme 1. Synthesis of the 2,5-dihydro-thiazole 1a and 2,5-dihy-
drooxazole 1b.
The known 1,4-benzothiazine 2a was synthesized by a
modified protocol.[16] In a one-pot procedure the 2-amino-
thiophenol reacted with sodium hydride in THF. The re-
sulting phenolate reacted with 2-bromo-2-methylpropanal
whereupon the resulting amino aldehyde condensed in situ
to give the cyclic imine (Scheme 2). The use of NaH/THF
increased the yield by more than 20% compared to the de-
scribed old protocol, in which the base sodium ethanolate
was used.
[a] Institut für Reine und Angewandte Chemie, Carl von Ossietzky
Universität Oldenburg,
P. O. Box 2503, 26111 Oldenburg, Germany
E-mail: Juergen.Martens@uni-oldenburg.de
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M. Watzke, K. Schulz, K. Johannes, P. Ullrich, J. Martens
FULL PAPER
droxy or alkoxy group. This type of reaction was extended
to cyclic imines by Schwarze et al.[2b] Thus, acryloyl chlo-
ride and 2-methylarcryloyl chloride, respectively, was added
to the imines 1, 2. Without isolation of the addition product
upon treatment with allyl alcohol the acrylamides 8, 9 were
obtained (Scheme 4).
Scheme 2. Synthesis of the 1,4-benzothiazine 2a.
Attempts to synthesize 2,2-dimethyl-2H-1,4-benzoxazine
(2b) by an analogous procedure using 2-aminophenol in-
stead of 2-aminothiophenol failed. Instead of the benzoxa-
zine compound 2b we could isolate the 3,3-dimethyl-3,4-
dihydro-2H-1,4-benzoxazine-2-ol (3), a stable hemiacetal
(Figure 2).
Scheme 4. Formation of the acrylamides 8 and 9.
After workup by crystallisation or column chromatog-
raphy the unsaturated compounds 8a–d and 9a–d can be
used as reaction partners for ring-closing metathesis
(Table 1).
Figure 2. Hemiacetal 3.
The preparation of compound 2b was realized with a
multistage synthetic route, based on 2-aminophenol
(Scheme 3). In the first step the amino group was protected
as a phthalic imide 4. In the next step the phenolic ether 5
was synthesized by deprotonation with tBuOK/18-crown-6
in acetonitrile and treatment with 2-bromo-2-methylpro-
panal. After protecting the aldehyde with ethylene glycol as
dioxolan 6 the phthalic imide was deprotected with hydra-
zine to get the free aniline derivative 7. The formation of
the 2b was realised by deprotecting the aldehyde followed
by the ring-closing reaction in concentrated hydrochloric
acid and basifying with aqueous ammonia.
Table 1. Acrylamide precursor 8 and 9 for the RCM.
Yield
[%]
Yield
[%]
Imine Amide
X
R
Imine Amide
X
R
1a
1a
1b
1b
8a
8b
8c
8d
S
S
O
O
H
CH3
H
69
83
52
48
2a
2a
2b
2b
9a
9b
9c
9d
S
S
O
O
H
CH3
H
21
29
16
81
CH3
CH3
Addition of Acyl Chlorides to the Imines
The addition of acyl chlorides to an imine was described
first by Böhme and Hartke.[2a] They used some linear im-
ines and added acyl chlorides. The resulting chlorides are
Ring-Closing Metathesis
The synthesis of the novel α,β-unsaturated ε-lactams 10,
not very stable so the chloride was substituted with a hy- 11 was finalised by ring-closing metathesis (RCM). A few
Scheme 3. New multistep synthesis of the 1,4-benzoxazine 2b.
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α,β-Unsaturated δ-Oxacaprolactams
examples of ring-closing metathesis reactions, using acryl- Table 2. α,β-Unsaturated δ-oxacaprolactams 10 and 11.
amides as precursors can be found in the literature.[17] The
catalysts usually used were the commercially available first
or second-generation Grubbs’ ruthenium complexes (Fig-
ure 3).
Yield
[%]
Yield
[%]
Amide Lactam
X
R
H
Amide Lactam
X
R
8a
8b
8c
8d
10a
10b
10c
10d
S
S
O
O
87
9a
9b
9c
9d
11a
11b
11c
11d
S
S
O
O
H
CH3
H
82
31
82
77
CH3 84
64
CH3 84
H
CH3
Figure 3. Used ruthenium catalysts I and II.
We were able to obtain single crystals of compound 11d
and determined the proposed structure by X-ray analysis
(Figure 5).[20]
Inspired by a work of D’Annibale and Bassetti[18] we de-
cided to use the inexpensive complex I in dichloromethane
for our first attempt. Under the chosen conditions the ε-
lactam 10a was obtained with a moderate yield of 37%.
Even after several modifications, for example the addition
of Ti(OiPr)4[19] we were not able to obtain the ε-lactam 11b
based on the benzothiazine precursor 9b. Only a mixture
of isomers of the cross metathesis product 12 was received
(Figure 4).
Figure 4. Cross metathesis product 12.
After this result we decided to change the used ruthe-
nium complex and chose a catalyst of the second generation
II. With this catalyst we optimised the reaction conditions
for the already obtained lactam 10a (Scheme 5). Interesting
was the influence of the reaction temperature as well as the
solvent. We were able to get the desired lactam 10a (catalyst
II: 5 mol-%, acrylamide: 0.03  solution in CH2Cl2, reflux
conditions) with a yield of 62%. The reaction was moni-
tored by TLC and aborted when no more starting material
8a was detected. Using toluene instead of dichloromethane
at approximately 70 °C increased the yield to 87%.
Figure 5. ORTEP representation of caprolactam 11d in the solid
state.[20]
Conclusions
Starting from imines 1, the new class of α,β-unsaturated
δ-oxacaprolactams 10, 11 2 can be obtained by an acyl
chloride addition reaction and subsequent ring-closing me-
tathesis. These new lactams are potentially bioactive be-
cause of their similarity to known and examined lactams
(cyclic amine structures). By using ruthenium catalyst II in
hot toluene overall yields of up to 70% referring to the
starting imine could be reached. Due to the great number
of known aldimines this reaction allows access to a large
Scheme 5. Ring-closing metathesis to form lactams 10 and 11.
With this improved reaction conditions we were able to number of differently substituted lactams. Furthermore, the
obtain the remaining lactams 10, 11 with good yields up to double bond in these lactams offers opportunity for further
87% (Table 2).
functionalisations.
Eur. J. Org. Chem. 2008, 3859–3867
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M. Watzke, K. Schulz, K. Johannes, P. Ullrich, J. Martens
FULL PAPER
90 °C and stirred for 30 min. The solution was poured in aqueous
ammonia (100 mL, 25%). The reaction mixture was extracted with
dichloromethane, the organic phase was washed with water and
dried with magnesium sulfate. The solvent was removed and the
residue was distilled in a kugelrohr apparatus (60 °C, 0.13 mbar).
The product was obtained as a colourless solid (1.95 g, 12.10 mmol,
52%), m.p. 35–36 °C. 1H NMR (500 MHz, CDCl3): δ = 1.44 (s,
6 H, 2ϫCH3), 6.81 (dd, 3J = 7.9, 4J = 1.0 Hz, 1 H, o-CHArO), 6.94
Experimental Section
General Methods: Synthetic procedures, performed under argon at-
mosphere were performed on a vacuum line using standard Schlenk
techniques. All reagents and solvents were commercial grade and
were purified prior to use when necessary. Preparative column
chromatography was carried out using Grace SiO2 (0.035–
0.070 mm, type KG 60). TLC was performed on Merck SiO2 F254
plates on aluminium sheets. 1H and 13C NMR spectra were re-
corded with Bruker Avance DRX 500 and Avance DPX 300 spec-
trometers. Assignments of the signals in the 13C NMR spectrum
were supported by measurements applying DEPT and COSY tech-
niques. EI-MS, CI-MS, and HRMS spectra were obtained with a
Finnigan MAT 95 spectrometer. IR spectra were recorded with a
Bruker Tensor 27 spectrometer equipped with a “GoldenGate”
diamond-ATR unit.
(ddd, J = 7.6, J = 7.4, J = 1.0 Hz, 1 H, p-CHArO), 7.13 (ddd, 3J
= 7.9, 3J = 7.8, 4J = 1.5 Hz, 1 H, p-CHArN), 7.31 (dd, 3J = 7.7,
4J = 1.4 Hz, 1 H, o-CHArN), 7.43 (s, 1 H, NCH) ppm. 13C NMR
(126 MHz, CDCl3): δ = 24.37 (2ϫCH3), 72.55 [C(CH3)2], 116.49
(o-CHArO), 121.60 (p-CHArO), 127.34 (o-CHArN), 129.26 (p-
3
3
4
CHArN), 131.54 (CAr-N), 146.04 (CArO), 161.28 (CN) ppm. IR: ν
˜
= 2977, 2929, 756 cm–1. MS (CI, isobutane): m/z (%) = 162.1 (100)
[MH]+. HRMS (CI, isobutane): calcd. for [C10H12NO]+: 162.0932,
found 162.0919.
2,2,5,5-Tetramethyl-2,5-dihydrothiazole (1a):[13] To a suspension of
sodium hydrogen sulfide hydrate (11.58 g, 0.21 mol) in dry dichlo-
romethane a solution of acetone (32.71 g, 0.56 mol) and 2-chloro-
2-methylpropanal (20.00 g, 0.19 mol) was added under argon atmo-
sphere. The suspension was cooled to –15 °C and gaseous ammonia
was lead in for 15 min. The suspension was warmed up to room
temperature and stirred for 12 h. Water (100 mL) was added and
the aqueous layer was extracted with three portions of dichloro-
methane. The combined organic layers were dried with magnesium
sulfate and the solvent was removed at the rotary evaporator. The
residue was recrystallized from petroleum ether ether 40/60 and
gave a colourless solid (24.74 g, 0.17 mol, 92%), m.p. 53 °C (50–
52 °C).[13]
3,3-Dimethyl-3,4-dihydro-2H-1,4-benzoxazine-2-ol (3): Under argon
atmosphere, to
a suspension of sodium hydride (2.00 g,
50.00 mmol, 60% in oil) in anhydrous THF (70 mL) a solution of
2-aminophenol (5.24 g, 48.00 mmol) in anhydrous THF (20 mL)
was added via a syringe at 0 °C. The resulted violet coloured reac-
tion mixture was stirred for 18 h at room temperature. The 2-
bromo-2-methylpropanal (7.62 g, 50.50 mmol), solved in anhy-
drous THF (15 mL) was added dropwise. After the addition has
been finished, molecular sieves was added and the reaction mixture
was stirred overnight. The mixture was filtered through celite and
the solvent was removed on a rotary evaporator. The crude product
was purified by column chromatography on silica gel (solvent: n-
hexane/ethyl acetate, 3:1, Rf = 0.23). The product was obtained as a
colourless solid (1.79 g, 10.0 mmol, 21%), m.p. 82–83 °C. 1H NMR
(500 MHz, CDCl3): δ = 1.18 (s, 3 H, CH3), 1.26 (s, 3 H, CH3), 3.38
2,2,5,5-Tetramethyl-2,5-dihydrooxazole (1b):[14] To a solution of
water (21.6 mL, 1.2 mol), 25% aqueous ammonia solution
(90.8 mL, 1.2 mol) and acetone (88.1 mL, 1.2 mol) at 0 °C 2-
chloro-2-methylpropanal (31.97 g, 0.3 mol) dissolved in dichloro-
methane (20 mL) was added dropwise while the temperature was
not allowed to increase about 5 °C. After finished addition the
solution was stirred one hour at 5 °C and overnight at room tem-
perature.
3
(br. s, 2 H, NH, OH), 5.05 (s, 1 H, CH), 6.63 (dd, J = 7.5, 4J =
3
3
4
1.7 Hz, 1 H, o-CHArO), 6.75 (ddd, J = 7.5, J = 7.5, J = 1.8 Hz,
1 H, p-CHArN), 6.81 (dd, 3J = 7.5, 4J = 1.8 Hz, 1 H, o-CHArN),
6.85 (ddd, 3J = 7.5, 3J = 7.5, 4J = 1.8 Hz, 1 H, p-CHArO) ppm.
13C NMR (126 MHz, CDCl3): δ = 24.04 (CH3), 24.53 (CH3), 51.20
[C(CH3)2], 95.11 (COH), 115.81, 117.37, 120.09, 121.81, 131.05,
The phases were separated and the aqueous phase was extracted
with dichloromethane (3ϫ30 mL). The recombined organic phases
were dried with magnesium sulfate. After removal the solvent under
reduced pressure, the crude product was purified by fractioning
distillation (46–52 °C, 110 mbar) (117 °C, 760 Torr)[14] and ob-
tained as colourless oil (17.17 g, 0.14 mol, 45%).
140.29 (CAr) ppm. IR: ν = 3415, 3325, 3273, 2983, 1254, 741 cm–1.
˜
MS (CI, isobutane): m/z (%) = 180.0 (100) [MH]+. HRMS (EI):
calcd. for C10H13NO2: 179.0946, found 179.0945.
2-(2-Hydroxyphenyl)isoindole-1,3-dione (4):[21] A mixture of 2-ami-
nophenol (4.80 g, 44.00 mmol) and phthalic anhydride (6.52 g,
44.00 mmol) in acetic acid (100 mL) was refluxed for two hours
and put in cooled water. The suspension was filtered and the aque-
ous filtrate was extracted with chloroform. The organic phase was
dried with magnesium sulfate and the solvent was removed. The
residue and the solid, achieved by filtration, was used in further
steps without further purification (7.80 g, 33.00 mmol, 74%), m.p.
187–230 °C (238–240 °C).[21]
2,2-Dimethyl-2H-1,4-benzothiazine (2a):[16] Under argon atmo-
sphere, to a suspension of sodium hydride (2.00 g, 50.00 mmol,
60% in oil) in anhydrous THF (70 mL) a solution of 2-aminothi-
ophenol (6.00 g, 48.00 mmol) in anhydrous THF (20 mL) was
added via a syringe at 0 °C. The resulted foamy white/violet col-
oured reaction mixture (a very effective stirrer bar was needed!)
was stirred for 2 h at room temperature. The 2-bromo-2-methylpro-
panal (7.62 g, 50.50 mmol), solved in anhydrous THF (15 mL) was
added dropwise. After the addition has been finished, molecular
sieves was added and the reaction mixture was stirred overnight.
2-[2-(1,3-Dioxo-1,3-dihydroisoindole-2-yl)phenoxy]-2-methylpropion-
aldehyde (5): A solution of dione 4 (1.19 g, 5.00 mmol) in anhy-
drous acetonitrile (50 mL) was cooled to 0 °C. tBuOK (0.62 g,
5.55 mmol) was added in small amounts and stirred, while the reac-
tion mixture was warmed up to room temperature. 18-crown-6
(1.32 g, 5.00 mmol) was added. The reaction mixture was allowed
to stir for 15 min at room temperature and was then promptly
taken to 0 °C. Freshly prepared solution of 2-bromo-2-methylpro-
panal (1.15 g, 7.60 mmol) in acetonitrile (20 mL) was added drop-
wise. The reaction was then brought to room temperature and sub-
sequently heated to 60 °C for 1 h. The reaction mixture was cooled
down to room temperature and then diluted in 300 mL diethyl
The mixture was filtered through celite and the solvent was re-
moved on a rotary evaporator. The crude product was distilled with
a kugelrohr distillation apparatus. The product was obtained at
140 °C (0.14 mbar) (63–65 °C, 0.01 mbar).[16] For further cleaning
the benzothiazine 2a was crystallized from petroleum ether/diethyl
ether 40/60 (5.69 g, 32.10 mmol, 67%), m.p. 57–59 °C.
2,2-Dimethyl-2H-1,4-benzoxazine (2b): To phenylamine 7 (5.22 g,
23.40 mmol) was added concentrated HCl (30 mL) and heated to
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α,β-Unsaturated δ-Oxacaprolactams
ether. The organic phase was washed with water and brine. The
ether layer was dried with magnesium sulfate, filtered, and concen-
trated in vacuo. The crude product was purified by column
chromatography on silica gel (solvent: n-hexane/ethyl acetate, 1:1,
Rf = 0.60) and obtained as colourless crystals (0.30 g, 1.00 mmol,
19%). 1H NMR (500 MHz, CDCl3): δ = 1.33 (s, 6 H, 2ϫCH3),
and the aqueous phase was extracted with dichloromethane three
times. The recombined organic phases were washed with saturated
sodium hydrogen carbonate solution once, with water twice and
dried with magnesium sulfate. The solvent was removed under re-
duced pressure. The purification of the crude product is described
in the experiments.
3
4
3
3
6.82 (dd, J = 8.2, J = 0.8 Hz, 1 H, HAr), 7.10 (ddd, J = 8.0, J
1-(4-Allyloxy-2,2,5,5-tetramethylthiazolidin-3-yl)propenone (8a):
Following GP A, dihydro-thiazole 1a (3.50 g, 24.40 mmol), acryloyl
chloride (2.21 g, 24.40 mmol), allyl alcohol (5.31 g, 91.50 mmol)
and triethylamine (4.32 g, 42.70 mmol) were used. The crude prod-
uct was dissolved in a small portion of dichloromethane and n-
hexane was added dropwise until a stable clouding remained. At
–30 °C the product was received as a colourless solid (4.30 g,
16.80 mmol, 69%), m.p. 185–210 °C. 1H NMR (500 MHz, CDCl3):
δ = 1.39 [s, 3 H, SC(CH3)2CH], 1.47 [s, 3 H, SC(CH3)2CH], 1.82 [s,
4
= 7.8, J = 1.2 Hz, 1 H, HAr), 7.21–7.34 (m, 2 H, HAr), 7.72–7.78
(m, 2 H, HPhth), 7.88–7.94 (m, 2 H, HPhth), 9.71 (s, 1 H, COH) ppm.
13C NMR (126 MHz, CDCl3): δ = 21.69 (2 ϫ CH3), 84.06
[C(CH3)2], 117.57, 122.58, 123.15, 123.65, 130.08, 130.47, 132.09,
134.26, 151.50 (CAr), 167.16 (CO), 202.79 (COH) ppm. IR: ν =
˜
2926, 2834, 1737, 1734, 1714, 1497 cm–1. MS (CI, isobutane): m/z
(%) = 310.1 (100) [MH]+. HRMS (CI, isobutane): calcd. for
[C18H16NO4]+: 310.1074, found 310.1081.
2-[2-(1-(1,3-Dioxolan-2-yl)-1-methylethoxy)phenyl]isoindole-1,3-di- 3 H, SC(CH3)2N], 1.93 [s, 3 H, SC(CH3)2N], 3.90 (dd, 2J = 12.5,
one (6): A solution of aldehyde 5 (260 mg, 0.840 mmol), ethylene
glycol (57 mg, 0.930 mmol) and a catalytic amount of p-toluenesul-
fonic acid in dichloromethane was refluxed for 2.5 h in a Dean trap.
The reaction mixture was cooled down to room temperature and
washed with a saturated solution of sodium hydrogen carbonate,
saturated sodium hydrogen sulfite and water. The organic layer was
dried with magnesium sulfate and the solvent was removed. The
obtained product was obtained as colourless crystals without fur-
ther purification (280 mg, 0.790 mmol, 94 %), m.p. 133–151 °C.
1H NMR (500 MHz, CDCl3): δ = 1.17 (s, 6 H, 2ϫCH3), 3.48–3.64
(m, 4 H, O-CH2-CH2-O), 4.66 (s, 1 H, CH), 7.15–7.42 (m, 4 H,
3J = 3.7 Hz, 1 H, OCH2CH=CH2), 4.07 (dd, 2J = 12.5, 3J = 3.3 Hz,
2
1 H, OCH2CH=CH2), 5.11 (br. s, 1 H, NCH), 5.15 (dd, J = n.a.,
3J = 10.5 Hz, 1 H, OCH2CH=CH2), 5.26 (dd, 2J = n.a., 3J =
2
3
17.2 Hz, 1 H, OCH2CH=CH2), 5.69 (dd, J = n.a., J = 10.4 Hz,
1 H, COCH=CH2), 5.78–5.87 (m, 1 H, OCH2CH=CH2), 6.32 (dd,
3
3
3
2J = n.a., J = 16.6 Hz, 1 H, COCH=CH2), 6.52 (dd, J = 10.4, J
= 16.6 Hz, 1 H, COCH=CH2) ppm. 13C NMR (126 MHz, CDCl3):
δ = 23.22 [SC(CH3)2CH], 30.97 [SC(CH3)2N], 52.52 [SC(CH3)
2CH], 67.61 (OCH2CH=CH2), 72.35 [SC(CH3)2N], 96.68 (NCH),
117.04 (OCH2 CH=CH2 ), 128.37 (COCH=CH2 ), 130.24
(COCH=CH ), 133.66 (OCH CH=CH ), 165.46 (CO) ppm. IR: ν
˜
2
2
2
HAr), 7.72–7.79 (m, 2 H, HPhth), 7.90–7.97 (m, 2 H, Phth) . = 2961, 2923, 2854, 1651, 1447, 1377, 1061 cm–1. MS (CI, isobut-
13C NMR (126 MHz, CDCl3): δ = 21.56 (2 ϫ CH3), 65.17 ane): m/z (%) = 256.0 (100) [MH]+. HRMS (CI, isobutane): m/z
(2ϫCH2), 82.66 [C(CH3)2], 106.60 (CH), 123.30, 123.82, 124.24, calcd. for [C13H22NO2S]+: 256.1371, found 256.1372.
126.26, 129.70, 129.81, 132.65, 133.75, 151.80 (CAr), 167.29 (CO)
1-(4-Allyloxy-2,2,5,5-tetramethylthiazolidin-3-yl)-2-methylpropen-
one (8b): Following GP A, dihydro-thiazole 1a (1.00 g, 7.00 mmol),
ppm. IR: ν = 1734, 1713, 1500, 1463, 764, 749 cm–1. MS (CI, isobu-
˜
tane): m/z (%) = 354.2 (100) [MH]+. HRMS (EI): calcd. for
2-methylacryloyl chloride (0.73 g, 7.00 mmol), allyl alcohol (1.52 g,
C20H19NO5: 353.1263, found 353.1263.
26.20 mmol) and triethylamine (1.24 g, 12.20 mmol) were used. The
2-[1-(1,3-Dioxolan-2-yl)-1-methylethoxy]phenylamine (7): A solu-
tion of dioxolan 6 (110 mg, 0.310 mmol) and hydrazine hydrate
(20 mg, 0.310 mmol, 80%) in ethanol (20 mL) was refluxed for 2 h.
The reaction mixture was cooled down to room temperature and
the mixture was filtered through celite. The solvent was removed
and the crude product was purified by column chromatography on
silica gel (solvent: n-hexane/ethyl acetate, 7:3, Rf = 0.27) and ob-
tained as a red oil (62 mg, 0.280 mmol, 91%).1H NMR (500 MHz,
CDCl3): δ = 1.30 (s, 6 H, 2ϫCH3), 3.95–4.09 (m, 6 H, 2ϫCH2,
NH2), 4.95 (s, 1 H, CHO2), 6.62 (ddd, 3J = 7.6, 3J = 7.6, 4J =
1.3 Hz, 1 H, p-CHArO), 6.71 (dd, 3J = 7.9, 4J = 1.3 Hz, 1 H, o-
CHArO), 6.89 (ddd, 3J = 7.7, 3J = 7.5, 4J = 1.3 Hz, 1 H, p-
CHArNH2), 6.96 (dd, 3J = 7.9, 4J = 1.0 Hz, 1 H, o-CHArNH2) ppm.
crude product was crystallized from methanol at –30 °C and gave
a light yellow solid (1.57 g, 5.80 mmol, 83%) which melted during
1
warming up to room temperature. H NMR (500 MHz, CDCl3): δ
= 1.35 [s, 3 H, SC(CH3)2CH], 1.50 [s, 3 H, SC(CH3)2CH], 1.80 [s,
3 H, SC(CH3)2N], 1.87 [s, 3 H, SC(CH3)2N], 1.95 [s, 3 H,
COC(CH3)=CH2], 3.80 (dd, 2J = 12.5, 3J = 4.9 Hz, 1 H,
OCH2 CH=CH2 ), 3.99 (dd, 2 J = 12.5, 3 J = 4.1 Hz, 1 H,
OC H2 CH=CH 2 ) , 5 . 1 0– 5 . 1 3 [ m , 2 H , O CH2 CH=CH2 ,
COC(CH3)=CH2], 5.22–5.26 [m, 3 H, NCH, OCH2CH=CH2,
COC(CH3)=CH2], 5.77–5.85 (m, 1 H, OCH2CH=CH2) ppm.
13C NMR (126 MHz, CDCl3): δ = 20.45 [COC(CH3)=CH2], 23.19
[SC(CH3)2CH], 30.86 [SC(CH3)2CH], 31.32 [SC(CH3)2N], 31.45
[SC(CH3)2N], 52.71 [SC(CH3)2CH], 68.13 (OCH2CH=CH2), 71.75
13C NMR (126 MHz, CDCl3): δ = 21.36 (2 ϫ CH3), 65.65 [SC(CH3)2N], 98.56 (NCH), 116.69, 117.74 [OCH2CH=CH2,
(2 ϫ CH2), 81.92 [C(CH3)2], 107.35 (CH), 115.76 (o-CHArO), C O C ( C H 3 ) = C H 2 ] , 1 3 3 . 3 9 ( O C H 2 C H = C H 2 ) , 1 4 1 . 8 5
117.74 (p-CHArO), 123.75 (o-CHArNH2), 124.39 (p-CHArNH2), [COC(CH )=CH ], 171.16 (CO) ppm. IR: ν = 3085, 2978, 2930,
˜
3
2
141.75 (CArO) ppm. IR: ν = 3466, 3367, 2981, 2884, 1113, 733
2964, 1650, 1628, 1385, 1375, 1356, 1062 cm–1. MS (CI, isobutane):
m/z (%) = 269.9 (100) [MH]+. HRMS (CI, isobutane): m/z calcd.
for [C14H24NO2S]+: 270.1528, found 270.1530.
˜
cm–1. MS (CI, isobutane): m/z (%) = 224.2 (100) [MH]+. HRMS
(CI, isobutane): calcd. for [C12H18NO3]+: 224.1281, found
224.1285.
1-(4-Allyloxy-2,2,5,5-tetramethyloxazolidin-3-yl)propenone (8c):
Following GP A, dihydrooxazole 1b (636 mg, 5.000 mmol), acryloyl
chloride (498 mg, 5.500 mmol), allyl alcohol (1.074 mg,
18.500 mmol) und triethylamine (885 mg, 8.750 mmol) were used.
General Procedure (GP A): Under argon atmosphere one equiva-
lent of the respective imine dissolved in anhydrous dichlorometh-
ane was cooled down to 0–5 °C before 1.1 equiv. of the acyl chlo-
ride was added dropwise. After stirring for three hours at room The crude product was purified by column chromatography on sil-
temperature 3.7 equiv. of the respective alcohol and 1.75 equiv. an-
hydrous triethylamine in anhydrous dichloromethane were added
dropwise at 0–5 °C. After stirring one hour at room temperature,
the solution was poured in ice-water. The phases were separated
ica gel (solvent: n-hexane/ethyl acetate, 7:3, Rf = 0.56) and obtained
as colourless oil (620 mg, 2.591 mmol, 52%). H NMR (500 MHz,
CDCl3): δ = 1.29 [s, 3 H, OC(CH3)2CH], 1.36 [s, 3 H, OC(CH3)2-
CH], 1.61 [s, 3 H, OC(CH3)2N], 1.67 [s, 3 H, OC(CH3)2N], 4.01 (br.
1
Eur. J. Org. Chem. 2008, 3859–3867
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3863

M. Watzke, K. Schulz, K. Johannes, P. Ullrich, J. Martens
FULL PAPER
s, 2 H, OCH2CH=CH2), 4.92 (s, 1 H, NCH), 5.16 (d, 3J = 10.3 Hz, 2.820 mmol), 2-methylacryloyl chloride (320 mg, 3.100 mmol), allyl
1 H, OCH2CH=CH2), 5.27 (dd, 2J = 1.6, 3J = 17.1 Hz, 1 H, alcohol (610 mg, 10.440 mmol) and triethylamine (500 mg,
OCH2 CH=CH2 ), 5.72 (dd, 2 J = 2.0, 3 J = 10.0 Hz, 1 H,
4.900 mmol) were used. The crude product was purified by column
chromatography on silica gel (solvent: n-hexane/ethyl acetate, 7:3,
Rf = 0.57) and obtained as a colourless solid (250 mg, 0.820 mmol,
2
COCH=CH2), 5.81–5.90 (m, 1 H, OCH2CH=CH2), 6.41 (dd, J =
2.0, 3J = 16.8 Hz, 1 H, COCH=CH2), 6.48 (dd, 3J = 10.0, 3J =
16.8 Hz, 1 H, COCH=CH2) ppm. 13C NMR (126 MHz, CDCl3): δ
29%), m.p. 98 °C. H NMR (500 MHz, CDCl3): δ = 1.47 (s, 3 H,
1
= 22.94 (CH3) 27.48 (CH3), 27.62 (CH3), 27.83 (CH3), 68.88 CH3), 1.49 (s, 3 H, CH3), 1.86–1.87 [m, 3 H, COC(CH3)=CH2],
(OCH2CH=CH2), 81.74 [OC(CH3)2CH], 91.43 (NCH), 95.48 3.88–3.89 (m, 2 H, OCH2 CH=CH2 ), 5.09–5.13 (m, 1 H,
[OC(CH3)2N], 116.86 (OCH2CH=CH2), 128.53 (COCH=CH2),
129.12 (COCH=CH2), 133.56 (OCH2CH=CH2), 164.02 (CO) ppm.
OCH2CH=CH2), 5.18–5.23 (m, 1 H, OCH2CH=CH2), 5.25–5.27
[m, 1 H, COC(CH3)=CH2], 5.28–5.29 [m, 1 H, COC(CH3)=CH2],
5.71–5.80 (m, 1 H, OCH2CH=CH2), 5.87 (s, 1 H, NCH), 6.91 (m,
IR: ν = 2983, 2937, 1659, 1416, 1068 cm–1. MS (CI, isobutane):
˜
m/z (%) = 240.1 (79) [MH]+, 182.1 (100) [M – OCH2CHCH2]+. 2 H, CHAr), 6.99–7.04 (m, 1 H, CHAr), 7.08–7.11 (m, 1 H, CHAr
)
HRMS (CI, isobutane): m/z calcd. for [C13H22NO3]+: 240.1600,
ppm. 13C NMR (126 MHz, CDCl3): δ = 19.53 [COC(CH3)=CH2],
found 240.1601.
2 6 . 4 2 ( C H 3 ) , 3 0 . 9 8 ( C H 3 ) , 4 8 . 7 5 [ C ( C H 3 ) 2 ] , 6 8 . 7 0
(OCH2CH=CH2), 82.52 (NCH), 117.79 (OCH2CH=CH2), 121.80
[COC(CH3)=CH2], 123.53, 125.31, 125.82, 125.83 (CHAr), 128.26
(CArS), 132.40 (CArN), 133.44 (OCH2CH=CH2), 140.33
1-(4-Allyloxy-2,2,5,5-tetramethyloxazolidin-3-yl)-2-methylpropen-
one (8d): Following GP A, dihydrooxazole 1b (636 mg,
5.000 mmol), 2-methylacryloyl chloride (575 mg, 5.500 mmol), allyl
alcohol (1.074 mg, 18.500 mmol) und triethylamine (885 mg,
8.750 mmol) were used. The crude product was purified by column
chromatography on silica gel (solvent: n-hexane/ethyl acetate, 7:3,
Rf = 0.67) and obtained as colourless solid (610 mg, 2.408 mmol,
48%), m.p. 45–47 °C. 1H NMR (500 MHz, CDCl3): δ = 1.31 [s,
3 H, OC(CH3)2CH], 1.33 [s, 3 H, OC(CH3)2CH], 1.61 [s, 3 H,
OC(CH3 )2 N], 1. 64 [s, 3 H, OC(CH3 )2 N], 1.98 [s, 3 H,
C( CH3 )=CH 2 ] , 3 . 89 (dd, 2 J = 12. 2, 3 J = 5.0 Hz, 1 H,
OCH2 CH=CH2 ), 3.95 (dd, 2 J = 12.2, 3 J = 4.2 Hz, 1 H,
OCH2CH=CH2), 5.05 (br. s, 1 H, NCH), 5.13–5.14 [m, 2 H,
OCH2 CH=CH2 , COC(CH3 )=CH2 ], 5.24–5.27 [m, 2 H,
OCH2 CH=CH2 , COC(CH3 )=CH2 ], 5.80–5.88 (m, 1 H,
OCH2CH=CH2) ppm. 13C NMR (126 MHz, CDCl3): δ = 20.29
[C(CH3)CH2], 22.80 (CH3), 27.48 (CH3), 69.38 (OCH2CH=CH2),
81.39 [OC(CH3)2CH], 93.17 (NCH), 95.01 [OC(CH3)2N], 116.55
[OCH2CH=CH2, COC(CH3)=CH2], 133.63 (OCH2CH=CH2),
[COC(CH )=CH ], 171.39 (CO) ppm. IR: ν = 3072, 2964, 2920,
˜
3
2
1649, 1477, 1260, 756 cm–1. MS (CI, isobutane): m/z (%) = 303.1
(10) [MH]+, 246.0 (100) [M – OCH3]+. HRMS (EI): calcd. for
C17H21NO2S: 303.1293, found 303.1294.
1-(3-Allyloxy-2,2-dimethyl-2,3-dihydro-1,4-benzoxazine-4-yl)pro-
penone (9c): Following GP A, benzoxazine 2b (117 mg,
0.727 mmol), acryloyl chloride (72 mg, 0.799 mmol), allyl alcohol
(156 mg, 2.690 mmol) and triethylamine (129 mg, 1.270 mmol)
were used. The crude product was purified by column chromatog-
raphy on silica gel (solvent: dichloromethane, Rf = 0.52) and ob-
tained as a colourless oil (31 mg, 0.114 mmol, 16 %). 1H NMR
(500 MHz, CDCl3): δ = 1.18 (s, 3 H, CH3), 1.52 (s, 3 H, CH3),
4.03–4.12 (m, 2 H, OCH2 CH=CH2 ), 5.11–5.14 (m, 1 H,
OCH2CH=CH2), 5.21–5.26 (m, 1 H, OCH2CH=CH2), 5.67 (br. s,
1 H, NCH), 5.76–5.84 (m, 1 H, OCH2CH=CH2), 5.83 (dd, 2J =
1.8, 3J = 10.3 Hz, 1 H, COCH=CH2), 6.54 (dd, 2J = 1.8, 3J =
16.8 Hz, 1 H, COCH=CH2), 6.69 (dd, 3J = 10.3, 3J = 16.8 Hz, 1 H,
141.76 [COC(CH )=CH ], 170.61 (CO) ppm. IR: ν = 2989, 2941,
˜
3
2
4
COCH=CH2), 6.85–6.89 (m, 1 H, p-CHArO), 6.91 (dd, 3J = 8.2, J
1646, 1619, 1367, 1063 cm–1. MS (CI, isobutane): m/z (%) = 254.1
(100) [MH]+, 196.1 (59) [M – OCH2CHCH2]+. HRMS (CI, isobut-
ane): m/z calcd. for [C14H24NO3]+: 254.1756, found 254.1757.
= 1.2 Hz, 1 H, o-CHArO), 6.99–7.06 (m, 1 H, p-CHArN), 7.07–7.11
(m, 1 H, o-CHArN) ppm. 13C NMR (126 MHz, CDCl3): δ = 24.17
(CH3), 24.43 (CH3), 68.23 (OCH2CH=CH2), 77.17 [C(CH3)2],
80.56 (NCH), 117.44 (o-CHArO), 117.59 (OCH2CH=CH2), 119.77
(p-CHArO), 121.24 (CArN), 124.46 (o-CHArN), 126.32 (p-CHArN),
1 2 8 . 9 9 ( COCH=CH 2 ) , 1 2 9 . 8 8 ( CO C H =CH2 ), 133. 77
1-(3-Allyloxy-2,2-dimethyl-2,3-dihydro-1,4-benzothiazine-4-yl)pro-
penone (9a): Following GP A, benzothiazine 2a (500 mg,
2.820 mmol), acryloyl chloride (280 mg, 3.100 mmol), allyl alcohol
(610 mg, 10.440 mmol) and triethylamine (500 mg, 4.900 mmol)
were used. The crude product was purified by column chromatog-
raphy on silica gel (solvent: dichloromethane, Rf = 0.58) and ob-
tained as a colourless solid (170 mg, 0.590 mmol, 21%), m.p. 56 °C.
1H NMR (500 MHz, CDCl3): δ = 1.37 (s, 3 H, CH3), 1.47 (s, 3 H,
CH3), 3.95–4.01 (m, 2 H, OCH2CH=CH2), 5.12 (dd, 2J = 10.4, 3J =
1.1 Hz, 1 H, OCH2CH=CH2), 5.22–5.28 (m, 1 H, OCH2CH=CH2),
5.72–5.80 (m, 2 H, COCH=CH2, OCH2CH=CH2), 5.73 (s, 1 H,
NCH), 6.41–6.53 (m, 2 H, COCH=CH2), 6.94–6.97 (m, 1 H, o-
CHArN), 6.99 (ddd, 3J = 7.5, 3J = 7.1, 4J = 1.4 Hz, 1 H, p-CHArS),
7.00 (ddd, 3J = 7.6, 3J = 7.9, 4J = 1.5 Hz, 1 H, p-CHArN), 7.07 (dd,
(OCH2CH=CH2), 146.04 (CArO), 165.32 (CO) ppm. IR: ν = 3063,
˜
2979, 2935, 1658, 1493, 1261, 749 cm–1. MS (CI, isobutane): m/z
(%) = 274.1 (100) [MH]+. HRMS (EI): calcd. for [C16H19NO3]:
273.1365, found 273.1366.
1-(3-Allyloxy-2,2-dimethyl-2,3-dihydro-1,4-benzoxazine-4-yl)-2-meth-
ylpropenone (9d): Following GP A, benzoxazine 2b (94 mg,
0.584 mmol), 2-methylacryloyl chloride (67 mg, 0.642 mmol), allyl
alcohol (126 mg, 2.160 mmol) and triethylamine (103 mg,
1.020 mmol) were used. The crude product was purified by column
chromatography on silica gel (solvent: n-hexane/ethyl acetate, 7:3,
Rf = 0.55) and obtained as a colourless oil (135 mg, 0.470 mmol,
81%). 1H NMR (500 MHz, CDCl3): δ = 1.27 (s, 3 H, CH3), 1.52
(s, 3 H, CH3), 1.96 [s, 3 H, COC(CH3)=CH2], 4.04–4.14 (m, 2 H,
OCH2CH=CH2), 5.09–5.13 (m, 1 H, OCH2CH=CH2), 5.20–5.25
(m, 1 H, OCH2CH=CH2), 5.32–5.34 [m, 1 H, COC(CH3)=CH2],
5.37–5.38 [m, 1 H, COC(CH3)=CH2], 5.62 (s, 1 H, NCH), 5.75–
4
3J = 7.9, J = 1.1 Hz, 1 H, o-CHArS) ppm. 13C NMR (126 MHz,
CDCl3): δ = 25.94 (CH3), 30.41 (CH3), 47.71 [C(CH3)2], 68.72
(OCH2CH=CH2), 82.35 (NCH), 117.98 (OCH2CH=CH2), 123.59
(p-CArN), 125.66 (p-CArS), 126.13 (o-CArS), 126.65 (o-CArN),
128.80 (CArS), 129.27 (COCH=CH2), 129.54 (COCH=CH2),
130.82 (CArN), 133.42 (OCH CH=CH ), 166.17 (CO) ppm. IR: ν
˜
2
2
3
3
4
5.84 (m, 1 H, OCH2CH=CH2), 6.79 (ddd, J = 7.8, J = 7.4, J =
1.3 Hz, 1 H, p-CHArO), 6.88 (dd, 3J = 8.2, 4J = 1.3 Hz, 1 H, o-
CHArO), 7.04 (ddd, 3J = 7.1, 3J = 8.1, 4J = 1.6 Hz, 1 H, p-CHArN),
7.12 (d, 3J = 7.9 Hz, 1 H, o-CHArN) ppm. 13C NMR (126 MHz,
= 3071, 2967, 2932, 2867, 1651, 1475, 1233, 731 cm–1. MS (CI,
isobutane): m/z (%) = 290.1 (10) [MH]+, 232.0 (100) [M – OCH3]
+. HRMS (EI): calcd. for C16H19NO2S: 289.1136, found 289.1137.
1-(3-Allyloxy-2,2-dimethyl-2,3-dihydro-1,4-benzothiazine-4-yl)-2- CDCl3): δ = 19.82 [COC(CH3)=CH2], 24.53 (CH3), 24.92 (CH3),
methylpropenone (9b): Following GP A, benzothiazine 2a (500 mg, 68.80 (OCH2CH=CH2), 77.41 [C(CH3)2], 80.37 (NCH), 117.29 (o-
3864
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3859–3867

α,β-Unsaturated δ-Oxacaprolactams
CHArO), 117.31 (OCH2CH=CH2), 119.61 (p-CHArO), 120.91
[COC(CH3)=CH2], 121.95 (CArN), 123.50 (o-CHArN), 125.86 (p-
isobutane): m/z (%) = 483.1 (55) [M2H]+, 242.0 (100) [MH]+.
HRMS (CI, isobutane): m/z calcd. for [C12H20NO2S]+: 242.1215,
CHArN), 133.92 (OCH2CH=CH2), 140.51 [COC(CH3)=CH2], found 242.1215.
145.34 (CArO), 170.21 (CO) ppm. IR: ν = 3065, 2981, 1651, 1494,
˜
7,7,9,9-Tetramethyl-9,9a-dihydro[1,3]oxazolo[4,3-b][1,3]oxazepin-
5(2H)-one (10c): Following GP B, acrylamide 8c (32 mg,
0.134 mmol) and ruthenium catalyst II (6.3 mg, 6.7 µmol) were
used. The crude product was purified by column chromatography
on silica gel (solvent: n-hexane/ethyl acetate, 1:1, Rf = 0.36) and
obtained as colourless solid (18 mg, 0.085 mmol, 64%), m.p. 65–
1259, 738 cm–1. MS (CI, isobutane): m/z (%) = 288.1 (100) [MH]+.
HRMS (CI, isobutane): calcd. for [C17H21NO3]+: 287.1521, found
287.1520.
General Procedure (GP B): One equivalent of the acrylamides syn-
thesized according to GP A and 0.05 equiv. of the ruthenium cata-
lyst II in toluene (10 mL) were slowly heated to 70 °C until the
reaction is finished controlled by thin layer chromatography. The
solvent was removed under reduced pressure. The purification of
the crude product is described in the experiments.
1
66 °C. H NMR (500 MHz, CDCl3): δ = 1.31 [s, 3 H, OC(CH3)2-
CH], 1.35 [s, 3 H, OC(CH3)2CH], 1.61 [s, 3 H, OC(CH3)2N], 1.64
2
3
4
[s, 3 H, OC(CH3)2N], 4.39 (ddd, J = 19.3, J = 2.5, J = 2.5 Hz,
2
3
4
1 H, CH2), 4.53 (ddd, J = 19.3, J = 2.5, J = 2.5 Hz, 1 H, CH2),
4.84 (s, 1 H, NCH), 5.97 (ddd, 3J = 12.7, 4J = 2.5, 4J = 2.5 Hz,
1 H, COCH=CH), 6.15 (ddd, 3J = 12.7, 3J = 2.5, 3J = 2.5 Hz, 1 H,
COCH=CH) ppm. 13C NMR (126 MHz, CDCl3): δ = 23.79 (CH3),
27.39 (CH3), 27.96 (CH3), 28.86 (CH3), 70.28 (CH2), 80.73
[OC(CH3)2CH], 92.13 (NCH), 95.47 [OC(CH3)2N], 126.91
7,7,9,9-Tetramethyl-9,9a-dihydro[1,3]thiazolo[4,3-b][1,3]oxazepin-
5(2H)-one (10a): (a) Under argon atmosphere acrylamide 8a
(200 mg, 0.783 mmol) was dissolved in dry dichloromethane
(30 mL) and 5 mol-% of the ruthenium catalyst I (32 mg,
0.039 mol) were added. After stirring 15 h at room temperature
DMSO (0.1 mL, 1.57 mmol) was added and the solution was
stirred for another 24 h at room temperature. The solution was
washed three times with water. The organic layer was dried with
magnesium sulfate and the solvent removed on a rotary evaporator.
The crude product was purified by column chromatography on sil-
ica gel (solvent: n-hexane/ethyl acetate, 7:4, Rf = 0.27). The product
was received as colourless oil (66 mg, 0.290 mmol, 37%). (b) Acryl-
amide 8a (54 mg, 0.212 mmol) was dissolved in dry dichlorometh-
ane (10 mL) and 5 mol-% of the ruthenium catalyst II (10 mg,
10.6 µmol) were added. The solution was refluxed for 35 d. The
solvent was removed at the rotary evaporator and the crude prod-
uct was purified as described above (30 mg, 0.132 mmol, 62%). (c)
Following GP B, acrylamide 8a (54 mg, 0.212 mmol) and ruthe-
nium catalyst II (10.0 mg, 10.6 µmol) were used. The crude product
was purified as described above (42 mg, 0.185 mmol, 87 %).
(COCH=CH), 139.74 (COCH=CH), 164.62 (CO) ppm. IR: ν =
˜
2984, 2937, 1658, 1614, 1420, 1102 cm–1. MS (CI, isobutane): m/z
(%) = 212.1 (100) [MH]+. HRMS (CI, isobutane): m/z calcd. for
[C11H18NO3]+: 212.1287, found 212.1290.
4,7,7,9,9-Pentamethyl-9,9a-dihydro[1,3]oxazolo[4,3-b][1,3]oxazepin-
5(2H)-one (10d): Following GP B, acrylamide 8d (32 mg,
0.126 mmol) and ruthenium catalyst II (6.0 mg, 6.3 µmol) were
used. The crude product was purified by column chromatography
on silica gel (solvent: n-hexane/ethyl acetate, 7:3, Rf = 0.43) and
obtained as colourless solid (24 mg, 0.107 mmol, 84%), m.p. 53–
1
54 °C. H NMR (500 MHz, CDCl3): δ = 1.31 [s, 3 H, OC(CH3)2-
CH], 1.33 [s, 3 H, OC(CH3)2CH], 1.63 [s, 3 H, OC(CH3)2N], 1.66
[s, 3 H, OC(CH3)2N], 1.98–1.99 [m, 3 H, COC(CH3)=CH], 4.27–
4.32 (m, 1 H, CH2), 4.36–4.41 (m, 1 H, CH2), 4.82 (s, 1 H, NCH),
5.99–6.01 [m, 1 H, COC(CH3)=CH] ppm. 13C NMR (126 MHz,
1H NMR (500 MHz, CDCl3): δ = 1.36 [s, 3 H, SC(CH3)2CH], 1.50 CDCl3): δ = 20.82 [COC(CH3)=CH], 23.65 [OC(CH3)2CH], 27.63
[s, 3 H, SC(CH3)2CH], 1.83 [s, 3 H, SC(CH3)2N], 1.86 [s, 3 H, [OC(CH3)2N], 28.06 [OC(CH3)2N], 28.70 [OC(CH3)2CH], 67.31
SC(CH3)2N], 4.38 (dd, 2J = 18.9, 3J = 2.4 Hz, 1 H, CH2), 4.53 (dd, (CH2), 80.92 [OC(CH3)2CH], 90.56 (NCH), 95.80 [OC(CH3)2N],
3
3
2J = 18.9, J = 2.4 Hz, 1 H, CH2), 4.98 (s, 1 H, NCH), 5.97 (d, J 132.42 [COC(CH3)=CH], 134.95 [COC(CH3)=CH], 166.62 (CO)
3
3
3
= 12.5 Hz, 1 H, COCH=CH), 6.12 (ddd, J = 12.5, J = 2.4, J =
ppm. IR: ν = 2979, 2934, 1661, 1625, 1421, 1146 cm–1. MS (CI,
˜
2.4 Hz, 1 H, COCH=CH) ppm. 13C NMR (126 MHz, CDCl3): δ isobutane): m/z (%) = 226.0 (100) [MH]+. HRMS (CI, isobutane):
= 24.16 [SC(CH3)2CH], 30.22 [SC(CH3)2CH], 31.28 [SC(CH3)2N],
31.72 [SC(CH3)2N], 50.37 [SC(CH3)2CH], 70.03 (CH2), 72.15
[SC(CH3)2N], 97.74 (NCH), 128.06 (COCH=CH), 138.86
m/z calcd. for [C12H20NO3]+: 226.1443, found 226.1444.
6,6-Dimethyl-5a,6-dihydro[1,3]oxazepino[2,3-c][1,4]benzothiazin-
1(4H)-one (11a): Following GP B, acrylamide 9a (30 mg,
0.104 mmol) and ruthenium catalyst II (5.0 mg, 5.2 µmol) were
used. The crude product was purified by column chromatography
on silica gel (solvent: n-hexane/ethyl acetate, 7:3, Rf = 0.43) and
(COCH=CH), 166.13 (CO) ppm. IR: ν = 2984, 2964, 2926, 1651,
˜
1621, 1397, 1373, 1347, 1167, 1149 cm–1. MS (CI, isobutane): m/z
(%) = 228.1 (100) [MH]+. HRMS (CI, isobutane): m/z calcd. for
[C12H20NO2S]+: 228.1058, found 228.1058.
1
obtained as a colourless oil (22 mg, 0.084 mmol, 82%). H NMR
4,7,7,9,9-Pentamethyl-9,9a-dihydro[1,3]thiazolo[4,3-b][1,3]oxazepin-
5(2H)-one (10b): Following GP B, acrylamide 8b (57 mg,
0.213 mmol) and ruthenium catalyst II (10.0 mg, 10.6 µmol) were
used. The crude product was purified by column chromatography
on silica gel (solvent: n-hexane/ethyl acetate, 7:3, Rf = 0.75). The
product was received as a clear oil (43.0 mg, 178.2 µmol, 84%).
(500 MHz, CDCl3): δ = 1.09 (s, 3 H, CH3), 1.44 (s, 3 H, CH3), 4.48
2
3
4
2
(ddd, J = 19.1, J = 2.4, J = 2.4 Hz, 1 H, CH2), 4.65 (ddd, J =
19.1, 3J = 2.4, 4J = 2.4 Hz, 1 H, CH2), 5.35 (s, 1 H, NCH), 6.18
(ddd, 3J = 12.7, 3J = 2.4, 3J = 2.4 Hz, 1 H, COCH=CH), 6.30 (ddd,
4
4
3
3J = 12.7, J = 2.4, J = 2.4 Hz, 1 H, COCH=CH), 7.07 (ddd, J
3
4
3
= 7.4, J = 7.4, J = 1.0 Hz, 1 H, p-CHArN), 7.23 (ddd, J = 7.8,
1H NMR (500 MHz, CDCl3): δ = 1.36 [s, 3 H, SC(CH3)2CH], 1.54 3J = 7.8,4, J = 1.4 Hz, 1 H, p-CHArS), 7.30 (dd, 3J = 7.7, 4J =
[s, 3 H, SC(CH3)2CH], 1.85 [s, 3 H, SC(CH3)2N], 1.99 [s, 3 H, 1.4 Hz, 1 H, o-CHArS), 7.76 (dd, 3J = 8.2, 4J = 1.0 Hz, 1 H, o-
SC(CH3)2N], 1.99 [s, 3 H, COC(CH3)=CH], 4.28–4.31 (m, 2 H,
CHArN) ppm. 13C NMR (126 MHz, CDCl3): δ = 21.05 (CH3),
CH2), 4.99 (s, 1 H, NCH), 5.94–5.98 [m, 1 H, COC(CH3)=CH] 26.37 (CH3), 46.12 [C(CH3)2], 71.13 (CH2), 92.53 (NCH), 125.11
ppm. 13C NMR (126 MHz, CDCl3): δ = 19.55 [COC(CH3)=CH], (p-CHArN), 126.39 (p-CHArS), 126.66 (COCH=CH), 126.71
23.71 [SC(CH3)2CH], 30.17 [SC(CH3)2CH], 31.67 [SC(CH3)2N], (CArS), 126.85 (o-CHArN), 130.04 (o-CHArS), 136.39 (CArN),
32.11 [SC(CH3)2N], 51.05 [SC(CH3)2CH], 64.42 (CH2), 72.85 139.73 (COCH=CH), 166.92 (CO) ppm. IR: ν = 3062, 2978, 2929,
˜
[SC(CH3)2N], 95.77 (NCH), 128.83 [COC(CH3)=CH], 138.92
[COC(CH )=CH], 168.67 (CO) ppm. IR: ν = 3046, 2981, 2928,
2836, 1662, 1474, 1322, 750 cm–1. MS (CI, isobutane): m/z (%) =
262.1 (100) [MH]+ . HRMS (CI, isobutane): calcd. for
˜
3
2865, 1657, 1632, 1657, 1632, 1391, 1373, 1168, 1139 cm–1. MS (CI, [C14H16NO2S]+: 262.0896, found 262.0901.
Eur. J. Org. Chem. 2008, 3859–3867
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3865

M. Watzke, K. Schulz, K. Johannes, P. Ullrich, J. Martens
FULL PAPER
2,6,6-Trimethyl-5a,6-dihydro[1,3]oxazepino[2,3-c][1,4]benzothiazin-
1(4H)-one (11b): Following GP B, acrylamide 9b (18 mg,
0.059 mmol) and ruthenium catalyst II (3.0 mg, 3.2 µmol) were
used. The crude product was purified by column chromatography
on silica gel (solvent: n-hexane/ethyl acetate, 8:2, Rf = 0.31) and
obtained as a colourless oil (5 mg, 0.018 mmol, 31%). 1H NMR
(500 MHz, CDCl3): δ = 1.11 (s, 3 H, CH3), 1.45 (s, 3 H, CH3), 2.09
[s, 3 H, COC(CH3)=CH], 4.32–4.37 (m, 1 H, CH2), 4.47–4.53 (m,
1 H , C H 2 ) , 5 . 2 8 ( s, 1 H , N C H ) , 6 . 1 7 – 6 . 2 1 [ m , 1 H ,
Acknowledgments
We are indebted to Ludmila Hermann for the preparative assist-
ance. The ruthenium catalyst II was generously supplied by Evonik
Degussa GmbH and the silica gel by Grace GmbH & Co.
KG. K. S. and K. J. gratefully acknowledge the Heinz-Neumüller-
Stiftung for a doctoral fellowship.
3
3
4
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COC(CH3)=CH], 7.10 (ddd, J = 7.4, J = 7.4, J = 1.1 Hz, 1 H,
p-CHArN), 7.23 (ddd, 3J = 7.8, 3J = 7.8, 4J = 1.5 Hz, 1 H, p-
3
4
CHArS), 7.33 (dd, J = 7.7, J = 1.5 Hz, 1 H, o-CHArS), 7.71 (dd,
3J = 8.2, J = 0.9 Hz, 1 H, o-CHArN) ppm. 13C NMR (126 MHz,
4
CDCl3): δ = 20.73 [COC(CH3)=CH], 22.31 (CH3), 27.05 (CH3),
46.59 [C(CH3)2], 65.86 (CH2), 90.36 (NCH), 125.44 (p-CHArN),
126.36 (p-CHArS), 126.92 (o-CHArN), 127.64 (CArS), 130.09 (o-
CHArS), 130.88 [COC(CH3)=CH], 136.20 [COC(CH3)=CH],
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41, 1619–1630.
136.27 (CArN), 169.65 (CO) ppm. IR: ν = 3099, 2978, 2927, 2869,
˜
1662, 1474, 1290, 748 cm–1. MS (CI, isobutane): m/z (%) = 276.1
(100) [MH]+. HRMS (CI, isobutane): calcd. for [C15H18NO2S]+:
276.1053, found 276.1057.
6,6-Dimethyl-6,6a-dihydro[1,3]oxazepino[2,3-c][1,4]benzoxazin-
11(8H)-one (11c): Following GP B, acrylamide 9c (30 mg,
0.109 mmol) and ruthenium catalyst II (5.2 mg, 5.4 µmol) were
used. The crude product was purified by column chromatography
on silica gel (solvent: n-hexane/ethyl acetate, 7:3, Rf = 0.21) and
obtained as a colourless solid (22 mg, 0.089 mmol, 82%), m.p. 112–
1
116 °C. H NMR (500 MHz, CDCl3): δ = 1.32 (s, 3 H, CH3), 1.41
(s, 3 H, CH3), 4.46 (ddd, 2J = 18.1, 3J = 3.3, 4J = 1.6 Hz, 1 H,
2
3
4
CH2), 4.57 (ddd, J = 18.1, J = 2.8, J = 1.9 Hz, 1 H, CH2), 5.09
(s, 1 H, NCH), 6.19–6.22 (m, 1 H, COCH=CH), 6.25–6.29 (m, 1 H,
COCH=CH), 6.91 (dd, 3J = 7.9, J = 1.7 Hz, 1 H, o-CHArO), 6.96
4
(ddd, J = 7.7, J = 7.7, J = 1.7 Hz, 1 H, p-CHArO), 7.01 (ddd, 3J
3
3
4
3
4
3
4
= 7.6, J = 7.5, J = 1.5 Hz, 1 H, p-CHArN), 8.56 (dd, J = 8.3, J
= 1.6 Hz, 1 H, o-CHArN) ppm. 13C NMR (126 MHz, CDCl3): δ =
22.52 (CH3), 24.01 (CH3), 69.22 (CH2), 74.67 [C(CH3)2], 86.09
(NCH), 117.93 (o-CHArO), 120.57 (o-CHArN), 121.76 (p-CHArO),
124.70 (p-CHArN), 125.88 (CArN), 127.75 (COCH=CH), 137.87
(COCH=CH), 143.88 (CArO), 167.30 (CO) ppm. IR: ν = 3137,
˜
[9] R. P. Elander, Appl. Microbiol. Biotechnol. 2003, 61, 385–392.
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2989, 2924, 1659, 1489, 1263, 757 cm–1. MS (CI, isobutane): m/z
(%) = 246.1 (100) [MH]+. HRMS (CI, isobutane): calcd. for
[C14H16NO3]+: 246.1125, found 246.1130.
6,6,10-Trimethyl-6,6a-dihydro[1,3]oxazepino[2,3-c][1,4]benzoxazin-
11(8H)-one (11d): Following GP B, acrylamide 9d (52 mg,
0.181 mmol) and ruthenium catalyst II (8.6 mg, 9.1 µmol) were
used. The crude product was purified by column chromatography
on silica gel (solvent: n-hexane/ethyl acetate, 8:2, Rf = 0.32) and
obtained as a colourless solid (36 mg, 0.139 mmol, 77%), m.p. 118–
1
120 °C. H NMR (500 MHz, CDCl3): δ = 1.25 (s, 3 H, CH3), 1.48
(s, 3 H, CH3), 2.12 [s, 3 H, COC(CH3)=CH], 4.14–4.19 (m, 1 H,
CH2), 4.24 (dd, 2J = 13.4, 3J = 7.0 Hz, 1 H, CH2), 4.92 (s, 1 H,
NCH), 6.09–6.13 [m, 1 H, COC(CH3)=CH], 6.91–6.95 (m, 2 H, o-
CHArO, p-CHArO), 7.01 (ddd, 3J = 7.7, 3J = 7.7, 4J = 1.6 Hz), 1 H, [12] a) I. Hayakawa, S. Atarashi, S. Yokohama, M. Imamura, K.
p-CHArN, 8.57–8.60 (m, 1 H, o-CHArN) ppm. 13C NMR
(126 MHz, CDCl3): δ = 18.76 [COC(CH3)=CH], 23.26 (CH3),
24.19 (CH3), 62.23 (CH2), 73.54 [C(CH3)2], 83.03 (NCH), 118.00
(o-CHArO), 119.23 (o-CHArN), 121.45 (p-CHArO), 123.59 (CArN),
124.78 (p-CHArN), 127.81 [COC(CH3)=CH], 139.71 [COC-
Sakano, M. Furukawa, Antimicrob. Agents Chemother. 1986,
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Angew. Chem. Int. Ed. Engl. 1967, 6, 907–919.
(CH3)=CH], 143.16 (CArO), 170.06 (CO) ppm. IR: ν = 3163, 2990,
˜
2910, 1655, 1492, 1255, 765 cm–1. MS (CI, isobutane): m/z (%) =
246.1 (100) [MH]+. HRMS (CI, isobutane): calcd. for [C14H16-
NO3]+: 246.1125, found 246.1130.
3866
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3859–3867

α,β-Unsaturated δ-Oxacaprolactams
[16] H. Gröger, J. Martens, Sulfur Lett. 1996, 19, 197–206.
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[20] CCDC-686787 contains the supplementary crystallographic
data for 11d. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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Received: March 7, 2008
Published Online: June 25, 2008
Eur. J. Org. Chem. 2008, 3859–3867
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3867