Synthesis of selenium-containing bicyclic β-lactams via alkene metathesis

Article abstract of DOI:10.1039/b902698c

The stereoselective insertion of allyl-seleno moieties at the C(4) position of azetidinones and further ring-closing metathesis afforded novel selenium-containing bicyclic β-lactams. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b902698c

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Synthesis of selenium-containing bicyclic b-lactams via alkene metathesis†
Dinesh R. Garud,a Deepali D. Garuda and Mamoru Koketsu*b
Received 9th February 2009, Accepted 26th March 2009
First published as an Advance Article on the web 28th April 2009
DOI: 10.1039/b902698c
The stereoselective insertion of allyl-seleno moieties at the C(4) position of azetidinones and further
ring-closing metathesis afforded novel selenium-containing bicyclic b-lactams.
resulting from the chemoselective cleavage of the C–Se bond by
piperazine. The glycosyl selenolate anion can react with various
Introduction
The b-lactam (2-azetidinone) skeleton is the key structural element
of the most widely employed class of antibacterial agents, the b-
lactam antibiotics.1 However, very few reports are available in
the literature for the synthesis of selenium-containing bicyclic b-
lactams due to difficulties involved in their preparation.2 Recently,
we have reported the trimethylsilylethyl (TSE)-protection3 and
iodocyclization approaches4 for the synthesis of a variety of
selenium-containing b-lactams. In continuation of the above in-
vestigations, we were interested in finding a new synthetic strategy
for the preparation of novel bicyclic b-lactams. The generation of
b-lactam arrays by ring-closing metathesis (RCM) has received
considerable attention over the past few years (Fig. 1).5 However,
it is surprising to note that the RCM of allyl-seleno compounds
has never been described thus far.6 We describe herein, for the
first time, RCM of allyl-seleno compounds in the formation of
selenium-containing bicyclic b-lactams.
electrophilic coupling partners in high yields, with complete
retention of stereochemistry. Inspired by the chemistry of this
method, we have designed novel selenating reagents 2a and 2b
as depicted in Scheme 1 for the first approach. The treatment
of potassium p-methylselenobenzoate 17 with allyl bromide or 4-
bromo-1-butene resulted in the formation of the novel selenating
reagents 2a or 2b, respectively (Scheme 1). These reagents have the
carbonyl carbon as the reactive site and should be susceptible to
nucleophilic attack by amine, thereby producing alkeneselenolate
anion. This anion is expected to react with electrophilic sites,
allowing the incorporation of the alkene-seleno moiety onto the
b-lactam skeleton.
Fig. 1 Ruthenium and molybdenum carbene complexes used in ring-clos-
ing metathesis (RCM) reactions.
Scheme 1 Synthesis of selenating reagents 2 and key intermediates 4.
The reaction with commercially available, optically pure, 4-
acetoxyazetidinone, was studied to find applications for the
newly synthesized selenating reagents 2a and 2b. The treatment
of selenating reagents 2a or 2b with commercially available,
optically pure, 4-acetoxyazetidinone resulted in the formation of
the corresponding previously unknown key intermediates 3a or 3b
having alkene-seleno moieties at the C(4) position of the azeti-
dinones with complete retention of configuration (Scheme 1).
The relative configuration of 3a or 3b was concluded based on
Results and discussion
The most difficult task in the present synthesis was the insertion of
the alkene-seleno moieties at the C(4) position of the azetidinones.
For this we considered two approaches. Recently, a novel method
for seleno-glycosidation using p-methylselenobenzoate 1 was
reported.7 The method features the in situ production of glycosyl
selenolate anion from the corresponding p-toluoylselenoglycoside
the coupling constant between protons C-3 and C-4 (JH3-H4
=
aDepartment of Chemistry, Faculty of Engineering, Gifu University, Gifu
501-1193, Japan
2.3 Hz). This is in agreement with those of similar compounds
in the literature.3,4,8 Subsequent treatment of 3a or 3b with either
bDepartment of Materials Science and Technology, Faculty of Engineering,
Gifu University, Gifu 501-1193, Japan. E-mail: koketsu@gifu-u.ac.jp;
Fax: +81-58-293-2619; Tel: +81-58-293-2619
◦
sodium hydride in THF at 0 C or lithium hexamethyldisilazide
(LHMDS) in THF at -78 ◦C followed by an activated electrophile
afforded the corresponding previously unknown key intermediates
(4a–4e) in 24–82% yields (Scheme 1).
† Electronic supplementary information (ESI) available: Experimental
details for the synthesis and 1H and 13C NMR spectra of compounds.
See DOI: 10.1039/b902698c
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Recently, we have shown that compound 5 is an important
starting material for the synthesis of a variety of selenium-
containing bicyclic b-lactams.3 For the second approach, it was
considered that the compound 5 could be an important starting
material for the synthesis of the variety of key intermediates 4
via compounds 6. For this the N-alkylation of the compound 5
was carried out with alkene bromides either with sodium hydride
in THF at 0 ◦C or LHMDS in THF at -78 ◦C to afford the
corresponding N-alkylated compounds 6a–6c (Scheme 2).
was found to be effective and a cyclized product, i.e. selenazepine
8a was obtained in 36% yield (Table 2, entry 3). The loading of
10 mol% of catalyst B gave the best results (Table 2, entry 4).
Since it was found that the allyl-seleno moiety was compatible
with Grubbs 2nd gen. catalyst B, reaction of the other key
intermediates 4b–4h or 7b and 7f was carried out under similar
reaction conditions and the results are shown in Table 2. The
treatment of 4b or 4f with 10 mol% of catalyst B afforded the
corresponding methyl-substituted selenazepines 8b or 8c in high
yields (Table 2, entries 5 and 6). The hydroxy group in 7b or 7f
was also well tolerated under these reaction conditions giving 8d
or 8e in high yields (Table 2, entries 7 and 8). Attempting to
prepare a highly functionalized selenazepine 8f was unsuccessful
and only the starting material was recovered (Table 2, entry 9). The
RCM of 4c, 4h and 4d afforded the corresponding eight-membered
selenium heterocycles i.e. 1,3-selenazocine 8g–8i (Table 2, entries
10, 11 and 12). Furthermore 4e afforded nine-membered selenium
heterocycle i.e. 1,3-selenazonine 8j (Table 2, entry 13). The
synthesis of higher-membered selenium heterocycles has been
found to be very difficult. To the best of our knowledge, there are
only four reports on the preparation of seven-membered selenium-
containing heterocycles, that is, 1,3-selenazepines.3,4,9 Whereas,
the eight- or nine-membered selenium heterocycles such as 1,3-
selenazocine or 1,3-selenazonine, respectively, have never been
described in the literature thus far. The present RCM approach
allows the synthesis of previously inaccessible selenium-containing
heterocycles.
Scheme 2
Next, deprotection of the TSE-group of 6a-6c followed by in
situ alkylation of the selenolate anion was tried for the synthesis
of key intermediates 4 (Table 1). After screening of several reaction
conditions (for details see the ESI†), we found that the treatment
of 6a–6c with 2.5 equiv. of TBAF resulted in the deprotection of
the TSE-group. Furthermore, in situ alkylation with alkyl halide
readily afforded the key intermediates 4a–4c and 4f–4h along
with the TBS-deprotected intermediates 7b and 7f–7h, respectively
(Table 1). The diselenide was formed as a by-product (entries 1, 4
and 5). A longer reaction time afforded the TBS-deprotected key
intermediate 7 in high yields (entries 3 and 7).
The key intermediates, 4 and 7, were next applied to ring-
closing metathesis (RCM) to deliver selenium-containing bicyclic
b-lactams (Table 2). Our initial attempts to bring about the
cyclization of the key intermediate 4a using 10 mol% Schrock
catalyst C (Table 2, entry 1) or 10 mol% Grubbs 1st gen. catalyst
A (Table 2, entry 2) in toluene were unsuccessful and only the
starting material was recovered (for details see the ESI†). However,
the use of 5 mol% Grubbs 2nd gen. catalyst B in the RCM reaction
Conclusions
In conclusion, we have developed a pivotal approach to a variety of
selenium-containing b-lactams, featuring selenating reagents (2a
and 2b) and ring-closing metathesis reactions. Further expansion
of the current strategies is in progress.
Experimental
All reactions were performed in round-bottom flasks fitted with
balloons filled with argon, unless otherwise specified. Transfer
Table 1 Synthesis of key intermediates 4 and 7
Yield (%)a
Entry
Starting
R1
CH2CH CH2
R2
CH2CH CH2
Time
4
7
71 (4a)b
66 (4b)
3 (4b)
trace (7a)
17 (7b)
87 (7b)
— (7c)
trace (7d)
14 (7f)
66 (7f)
35 (7g)
16 (7h)
=
=
1
2
3
4
5
6
7
8
9
6a
6b
6b
6a
6b
6a
6a
6b
6c
15 min
15 min
45 min
18 h
=
=
CH2CH CH2
CH2(CH3)C CH2
=
=
CH2CH CH2
CH2(CH3)C CH2
CH2CH CH2
10 (4c)b
trace (4d)b
78 (4f)
=
=
CH2CH2CH CH2
=
=
CH2(CH3)C CH2
CH2CH2CH CH2
18 h
=
=
=
CH2CH CH2
CH2(CH3)C CH2
15 min
45 min
1 h
=
CH2CH CH2
CH2(CH3)C CH2
27 (4f)
58 (4g)
76 (4h)
=
=
CH2(CH3)C CH2
CH2(CH3)C CH2
CH2CH CH2
=
=
CH2CH2CH CH2
1 h
a Isolated yields. b Corresponding diselenide was obtained as a by-product.
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Table 2 Ring-closing metathesis of 4 and 7a
Entry
Starting
Catalyst (10 mol%)
Time
Product
Yield of 8 (%)b
1
2
3
4
C
A
2 days
4 days
2 days
2 h
0c
tracec
36d
B (5 mol%)
B
78
5
6
7
8
9
B
B
B
B
B
2 h
92
75
82
74
0c
2 h
2 h
2 h
2 days
10
B
4 h
68
11
12
B
B
2 h
4 h
74
91
13
B
2 h
74
a All reactions were carried out on ca. 0.05 mmol scale in toluene at reflux. b Isolated yields. c Starting material was recovered quantitatively. d Starting
material was recovered in 56% yield.
of air- and moisture-sensitive liquids was performed via cannula
under a positive pressure of argon. TLC analysis was performed
on Merck TLC (silica gel 60F254 on glass plate). Evaporation
and condensation were carried out in vacuo. The compounds 11
and 52 were prepared according to the literature. Silica gel 60 N
(spherical, neutral) manufactured by Kanto Chemical Co. Inc.
was used for flash column chromatography. DMF and toluene
were deoxygenated prior to use. Tetramethylammonium fluoride
and methyl hydrazine were purchased from Tokyo Chemical
Industry Ltd. Grubbs 1st gen. catalyst, Grubbs 2nd gen. catalyst,
LHMDS (1.0 M THF solution) and 3-bromo-2-methyl-propene
were purchased from Aldrich Chemical Company. Schrock’s
catalyst was purchased from Strem Chemicals. 4-Bromo-1-butene
was purchased from Alfa Aesar Company. (3R,4R)-4-Acetoxy-
3-[(R)-(tert-butyldimethylsilyloxy)ethyl]-2-azetidinone, allyl bro-
mide and caesium carbonate were purchased from Wako Pure
Chemical Industries Ltd. NaH was purchased from Nacalai
Tesque Inc.
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Melting points were measured by a Yanagimoto micromelting
point apparatus (uncorrected). Optical rotation was recorded
by Union PM-201 Automatic Digital Polarimeter (Horiba) at
28 ◦C. IR spectra were measured on a JASCO FT/IR-410 Fourier
transform infrared spectrometer. The 1H NMR, 13C NMR spectra
or 77Se NMR spectra were measured on JEOL:JNM ECX-400P,
JEOL:JNM ECA-500, JEOL:JNM ECA-600 spectrometers in
CDCl3. Chemical shifts of protons are reported in d values
referred to TMS as an internal standard. The 77Se chemical
shifts were expressed in d values deshielded with respect to neat
The isolated yields and the spectral data for 3a–3b are as follows
(3S,4R)-4-Allylseleno-3-[(R)-tert-butyldimethylsilyloxyethyl]-2-
azetidinone (3a). Yield: 26%; Mp. 58–59 ◦C; IR (neat): 2955,
1766, 1723, 1654, 1637, 1374, 1250, 958, 835 cm-1; 1H NMR
(CDCl3): d 0.07 (s, 3H), 0.08 (s, 3H), 0.87 (s, 9H), 1.23 (d, J =
6.3 Hz, 3H), 3.24 (s, 1H), 3.28–3.40 (m, 2H), 4.22–4.28 (m, 1H),
2
4.97 (d, J = 2.3 Hz, J(77Se-1H) = 18.9 Hz, 1H), 5.04 (d, J =
9.7 Hz, 1H), 5.14 (dd, J = 1.1, 17.2 Hz, 1H), 5.92–6.00 (m, 1H),
6.18 (brs, 1H); 13C NMR (CDCl3): d -5.12, -4.33, 17.9, 22.2, 25.7,
26.4, 46.8, 64.7, 67.0, 116.9, 135.4, 167.2; 77Se NMR (CDCl3): d
310.5; HRMS: m/z = 292.0272 calcd. for C10H18NO2SeSi, found
292.0231.
1
Me2Se. J(77Se-1H) values are observed as 77Se satellites of the
1H NMR spectra. MS and HRMS were measured on a JEOL
JMS-700.
(3S,4R)-4-(3-Buteneseleno)-3-[(R)-tert-butyldimethylsilyloxy-
ethyl]-2-azetidinone (3b). Yield 92%; Mp. 70–71 ◦C; IR (neat):
General preparation of Se-alkene p-methylselenobenzoate (2)
1
2952, 1761, 1672, 1567, 1386, 1257, 1095, 832 cm-1; H NMR
To
a
solution of potassium p-methylselenobenzoate
1
(CDCl3): d 0.07 (s, 3H), 0.08 (s, 3H), 0.88 (s, 9H), 1.24 (d, J =
(12.65 mmol) in degassed DMF (50 mL) was added alkyl bromide
(18.97 mmol) under an argon atmosphere, and the mixture was
stirred for 1 h (TLC; CHCl3:n-hexane = 1:5). The reaction mixture
was filtered through celite and washed with CHCl3. The combined
filtrate and washings were extracted with CHCl3 and washed
with water and brine. The organic layer was dried over Na2SO4
and concentrated. The resulted residue was purified by column
chromatography on silica gel (CHCl3:n-hexane = 1:15 → 1:10 →
1:5) to give 2.
6.3 Hz, 3H), 2.41–2.53 (m, 2H), 2.75 (t, J = 7.4 Hz, 2H), 3.21
2
(s, 1H), 4.23–4.28 (m, 1H), 4.99 (d, J = 1.7 Hz, J(77Se-1H) =
26.9 Hz, 1H), 5.05–5.13 (m, 2H), 5.77–5.87 (m, 1H), 5.92 (brs,
1H); 13C NMR (CDCl3): d -5.07, -4.31, 17.9, 22.1, 22.2, 25.7,
34.8, 46.4, 64.8, 67.4, 116.4, 136.9, 167.0; 77Se NMR (CDCl3): d
277.3; HRMS: m/z = 306.0429 calcd. for C11H20NO2SeSi, found
306.0420.
General procedure for the N-alkylation reaction of 3
The isolated yield and the spectral data for 2a and 2b are as
follows:
Method A. To a suspension of NaH (60% in mineral oil,
2.07 mmol) in 5 mL of THF at 0 ◦C was added compound 3
(1.38 mmol) in 15 mL THF over 15 minutes. The mixture was
stirred at 0 ◦C for an additional 15 min, then alkyl bromide
(2.07 mmol) was added dropwise. The reaction mixture was stirred
at r.t. for 1 hour to 3 days and then taken up in 10 mL of ammonium
chloride solution. The organic layer was washed with 10 mL of
a saturated solution of sodium bicarbonate. The aqueous layer
was extracted 3 times with 20 mL of diethyl ether each time. The
combined organic layers were dried (Na2SO4) and concentrated.
The residue was purified by column chromatography (SiO2:
hexane/diethyl ether = 15/1) to afford compound 4.
Se-Allyl 4-methylbenzoselenoate (2a). Yield: 87%; IR (neat):
2921, 1682, 1661, 1604, 1203, 1172, 887 cm-1; 1H NMR (CDCl3):
2
d 2.39 (s, 3H), 3.71 (d, J = 8.0 Hz, J(77Se-1H) = 14.0 Hz, 2H),
5.05 (d, J = 9.2 Hz, 1H), 5.26 (dd, J = 1.1, 17.2 Hz, 1H), 5.92–
6.02 (m, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.78 (d, J = 8.0 Hz, 2H);
13C NMR (CDCl3): d 21.7, 27.7, 117.3, 127.3, 129.4, 134.6, 136.4,
144.6, 193.7; 77Se NMR (CDCl3): d 553.3; HRMS (EI): m/z =
240.0053 calcd. for C11H12OSe, found 240.0042.
Se-3-Butenyl 4-methylbenzoselenoate (2b). Yield: 83%; IR
(neat): 2924, 1681, 1661, 1604, 1406, 1202, 1172, 886 cm-1; H
1
NMR (CDCl3): d 2.38 (s, 3H), 2.48–2.54 (m, 2H), 3.13 (t, J =
Method B. Lithium bis(trimethylsilyl)amide (0.66 mmol, 1.0
M solution in THF) was added dropwise to a stirred solution of
compound 3 (0.55 mmol) in THF (10 mL) at -78 ◦C under an
argon atmosphere. The resultant solution was stirred at -78 ◦C
for 10 minutes. Alkyl bromide (2.76 mmol) was added over
5 minutes and the resulting mixture allowed to warm to ambient
temperature overnight. The resulting mixture was quenched with
10% HCl and extracted with diethyl ether. The combined organic
extracts were dried (Na2SO4) and concentrated in vacuo to afford a
residue that was further subjected to flash chromatography (SiO2:
hexane/diethyl ether = 15/1) to afford the title compound 4 as
clear oil
2
6.9 Hz, J(77Se-1H) = 26.3 Hz, 2H), 5.05 (dd, J = 1.7, 10.3 Hz,
1H), 5.10 (dd, J = 1.7, 17.2 Hz, 1H), 5.80–5.90 (m, 1H), 7.22 (d,
J = 8.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3):
d 21.6, 24.4, 34.5, 116.0, 127.2, 129.3, 136.5, 137.2, 144.4, 194.0;
77Se NMR (CDCl3): d 521.1; HRMS (EI): m/z = 254.0210 calcd.
for C12H14OSe, found 254.0197.
Typical procedure for the preparation of 4-alkylseleno-2-azeti-
dinone (3). To stirred solution of selenium reagent 2 (3.83 mmol)
and Cs2CO3 (3.83 mmol) in dry DMF (5 mL) at r.t. was added
methyl hydrazine (3.83 mmol) under an argon atmosphere. After
stirring at this temperature for 10 minutes, (3R,4R)-4-acetoxy-3-
[(R)-(tert-butyldimethylsilyloxy)ethyl]-2-azetidinone (3.48 mmol)
was added and stirring continued for an additional 30 min. The
reaction mixture was extracted with dichloromethane and washed
with water. The combined organic extracts were dried (Na2SO4)
and concentrated in vacuo to afford a residue that was further
subjected to flash chromatography (SiO2: hexane/diethyl ether =
5/1) to afford compound 3.
The isolated yields and the spectral data for 4a–e are as follows:
(3S,4R)-1-Allyl-4-(allylseleno)-3-[(R)-1-tert-butyldimethylsily-
loxyethyl]-2-azetidinone (4a). Method A; Yield: 24%; IR (neat):
2928, 1763, 1633, 1388, 1251, 1065, 836 cm-1; 1H NMR (CDCl3):
d 0.06 (s, 3H), 0.08 (s, 3H), 0.87 (s, 9H), 1.22 (d, J = 6.2 Hz,
3H), 3.20–3.30 (m, 3H), 3.50 (dd, J = 7.5, 15.8 Hz, 1H), 4.08 (dd,
J = 4.8, 15.8 Hz, 1H), 4.24–4.30 (m, 1H), 4.92 (d, J = 2.1 Hz,
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2J(77Se-1H) = 19.9 Hz, 1H), 5.04 (d, J = 9.7 Hz, 1H), 5.10 (dd,
J = 1.4, 17.2 Hz, 1H), 5.21 (dd, J = 1.4, 10.3 Hz, 1H), 5.29 (dd,
J = 1.4, 17.2 Hz, 1H), 5.74–5.82 (m, 1H), 5.86–5.93 (m, 1H);
13C NMR (CDCl3): d -4.80, -4.61, 17.9, 22.3, 25.8, 42.7, 51.8,
64.7, 65.7, 117.2, 118.6, 131.8, 134.6, 166.2; 77Se NMR (CDCl3): d
235.6; HRMS: m/z = 332.0585 calcd. for C13H22NO2SeSi, found
332.0587.
General procedure for the N-alkylation reaction of 5
Method A. To a suspension of NaH (60% in mineral oil,
1.84 mmol) in 5 mL of THF at 0 ◦C was added (3S,4R)-3-
[(R)-tert-butyldimethylsilyloxyethyl]-4-[2-(trimethylsilyl)ethylse-
leno]-2-azetidinone 5 (1.22 mmol) in 15 mL THF over 15 minutes.
The mixture was stirred at 0 ◦C for an additional 15 min, then
alkyl bromide (1.84 mmol) was added dropwise. The reaction
mixture was stirred at r.t. for 1 hour to 3 days and then taken
up in 10 mL of ammonium chloride solution. The organic layer
was washed with 10 mL of a saturated solution of sodium
bicarbonate. The aqueous layer was extracted 3 times with 20 mL
of diethyl ether each time. The combined organic layers were dried
(Na2SO4) and concentrated. The residue was purified by column
chromatography (SiO2: hexane/diethyl ether = 15/1) to afford
compound 6.
(3S,4R)-4-(Allylseleno)-3-[(R)-1-tert-butyldimethylsilyloxy-
ethyl]-1-(2-methylallyl)-2-azetidinone (4b). Method A; Yield:
47%; IR (CHCl3): 2955, 1758, 1633, 1462, 1387, 1254, 836 cm-1;
1H NMR (CDCl3): d 0.06 (s, 3H), 0.09 (s, 3H), 0.88 (s, 9H), 1.24
(d, J = 6.3 Hz, 3H), 1.76 (s, 3H), 3.19–3.30 (m, 3H), 3.45 (d, J =
16.0 Hz, 1H), 3.97 (d, J = 15.5 Hz, 1H), 4.22–4.31 (m, 1H), 4.88
(d, J = 1.7 Hz, 1H), 4.92 (s, 1H), 4.96 (s, 1H), 5.03 (d, J = 9.7 Hz,
1H), 5.08 (d, J = 16.7 Hz, 1H), 5.84–5.93 (m, 1H); 13C NMR
(CDCl3): d -4.81, -4.49, 18.0, 20.6, 22.3, 25.8, 26.0, 46.0, 52.4,
65.0, 65.8, 113.4, 117.2, 134.6, 139.6, 166.5; 77Se NMR (CDCl3): d
233.7; HRMS: m/z = 346.0742 calcd. for C14H24NO2SeSi, found
346.0760.
Method B. Lithium bis(trimethylsilyl)amide (1.46 mmol,
1.0 M solution in THF) was added dropwise to a stirred
solution of (3S,4R)-3-[(R)-tert-butyldimethylsilyloxyethyl]-4-[2-
(trimethylsilyl)ethylseleno]-2-azetidinone 5 (1.22 mmol) in THF
(10 mL) at -78 ◦C under an argon atmosphere. The resultant
solution was stirred at -78 ◦C for 10 minutes. Alkyl bromide
(12.2 mmol) was added over 5 minutes and the resulting mixture
allowed to warm to ambient temperature overnight. The resulting
mixture was quenched with 10% HCl and extracted with diethyl
ether. The combined organic extracts were dried (Na2SO4) and
concentrated in vacuo to afford a residue that was further subjected
to flash chromatography (SiO2: hexane/diethyl ether = 15/1) to
afford the title compound 6 as a clear oil.
(3S,4R)-1-Allyl-4-(3-butenylseleno)-3-[(R)-1-tert-butyldime-
thylsilyloxyethyl]-2-azetidinone (4c). Method A; Yield: 51%; IR
1
(neat): 2955, 1762, 1643, 1387, 1252, 1063, 836 cm-1; H NMR
(CDCl3): d 0.07 (s, 3H), 0.09 (s, 3H), 0.88 (s, 9H), 1.24 (d,
J = 6.4 Hz, 3H), 2.38–2.50 (m, 2H), 2.58–2.71 (m, 2H), 3.19
(s, 1H), 3.49 (dd, J = 7.3, 15.6 Hz, 1H), 4.09 (dd, J = 4.6,
2
15.6 Hz, 1H), 4.23–4.31 (m, 1H), 4.91 (d, J = 2.3 Hz, J(77Se-
1H) = 27.0 Hz, 1H), 5.02–5.12 (m, 2H), 5.20 (d, J = 10.1 Hz,
1H), 5.28 (d, J = 17.0 Hz, 1H), 5.71–5.86 (m, 2H); 13C NMR
(CDCl3): d -4.81, -4.60, 18.0, 21.6, 22.3, 25.8, 34.7, 42.7, 51.5,
64.7, 65.9, 116.2, 118.6, 131.6, 136.8, 166.2; 77Se NMR (CDCl3): d
213.0; HRMS: m/z = 346.0742 calcd. for C14H24NO2SeSi, found
346.0724.
The isolated yields and the spectral data for 6a–c are as follows:
(3S,4R)-1-Allyl-3-[(R)-tert-butyldimethylsilyloxyethyl]-4-[2-
(trimethylsilyl)ethylseleno]-2-azetidinone (6a). Method A; Yield:
64%; IR (neat): 2953, 2360, 1763, 1644, 1539, 1387, 1249, 837 cm-1;
1H NMR (CDCl3): d 0.00 (s, 9H), 0.04 (s, 3H), 0.06 (s, 3H), 0.86
(s, 9H), 0.90–1.00 (m, 2H), 1.22 (d, J = 6.3 Hz, 3H), 2.56–2.67 (m,
2H), 3.17 (t, J = 2.2 Hz, 1H), 3.48 (dd, J = 6.3, 14.8 Hz, 1H), 4.06
(dd, J = 5.2, 16.1 Hz, 1H), 4.22–4.27 (m, 1H), 4.88 (d, J = 2.3 Hz,
2J(77Se-1H) = 21.8 Hz, 1H), 5.17 (dd, J = 1.1, 10.4 Hz, 1H), 5.24
(dd, J = 1.1, 17.1 Hz, 1H), 5.71–5.80 (m, 1H); 13C NMR (CDCl3):
d -4.82, -4.58, -1.91, 18.0, 18.2, 18.7, 22.3, 25.8, 42.7, 51.6, 64.8,
65.8, 118.5, 131.8, 166.3; 77Se NMR (CDCl3): d 262.9; HRMS:
m/z = 392.0980 calcd. for C15H30NO2SeSi2, found 392.0976.
(3S,4R)-4-(3-Butenylseleno)-3-[(R)-1-tert-butyldimethylsily-
loxyethyl]-1-(2-methylallyl)-2-azetidinone (4d). Method A;
Yield: 82%; IR (neat): 2955, 1762, 1657, 1641, 1471, 1387, 1254,
1
1054, 836 cm-1; H NMR (CDCl3): d 0.06 (s, 3H), 0.09 (s, 3H),
0.88 (s, 9H), 1.25 (d, J = 6.3 Hz, 3H), 1.75 (s, 3H), 2.40–2.47
(m, 2H), 2.59–2.69 (m, 2H), 3.21 (t, J = 2.3 Hz,1H), 3.41 (d,
J = 16.0 Hz, 1H), 3.99 (d, J = 16.0 Hz, 1H), 4.25–4.31 (m, 1H),
4.87 (d, J = 2.3 Hz, 1H), 4.91 (s, 1H), 4.95 (s, 1H), 5.03–5.12 (m,
2H), 5.75–5.85 (m, 1H); 13C NMR (CDCl3): d -4.82, -4.54, 18.0,
20.5, 21.9, 22.3, 25.8, 34.6, 45.9, 52.2, 65.1, 66.0, 113.3, 116.2,
136.8, 139.3, 166.3; 77Se NMR (CDCl3): d 211.8; HRMS: m/z =
360.0898 calcd. for C15H26NO2SeSi, found 360.0887.
(3S,4R)-3-[(R)-tert-Butyldimethylsilyloxyethyl]-1-(2-methyl-
allyl)-4-[2-(trimethylsilyl)ethylseleno]-2-azetidinone
(6b). Me-
thod A; Yield: 84%; IR (neat): 2954, 1764, 1658, 1472, 1386,
1
1249, 838 cm-1; H NMR (CDCl3): d 0.00 (s, 9H), 0.04 (s, 3H),
(3S,4R)-1-(3-Butenyl)-4-(3-butenylseleno)-3-[(R)-1-tert-butyl-
dimethylsilyloxyethyl]-2-azetidinone (4e). Method B; Yield: 38%;
IR (neat): 2954, 1759, 1641, 1393, 1253, 1059, 836 cm-1; 1H NMR
(CDCl3): d 0.07 (s, 3H), 0.08 (s, 3H), 0.88 (s, 9H), 1.24 (d, J =
6.3 Hz, 3H), 2.30–2.49 (m, 4H), 2.59–2.70 (m, 2H), 2.97–3.04
(m, 1H), 3.17 (t, J = 1.8 Hz, 1H), 3.41–3.48 (m, 1H), 4.19–
0.08 (s, 3H), 0.86 (s, 9H), 0.90–1.03 (m, 2H), 1.24 (d, J = 6.0 Hz,
3H), 1.73 (s, 3H), 2.53–2.68 (m, 2H), 3.16–3.22 (m, 1H), 3.43 (d,
J = 15.5 Hz, 1H), 3.98 (d, J = 15.5 Hz, 1H), 4.22–4.30 (m, 1H),
4.85 (d, J = 1.8 Hz, 1H), 4.88 (s, 1H), 4.92 (s, 1H); 13C NMR
(CDCl3): d -4.82, -4.59, -2.00, 18.0, 18.5, 18.7, 20.5, 22.3, 25.8,
45.9, 52.3, 65.1, 65.7, 113.1, 139.4, 166.4; 77Se NMR (CDCl3): d
262.9; HRMS: m/z = 406.1137 calcd. for C16H32NO2SeSi2, found
406.1127.
2
4.25 (m, 1H), 4.86 (d, J = 1.7 Hz, J(77Se-1H) = 30.9 Hz, 1H),
5.03–5.15 (m, 4H), 5.76–5.85 (m, 2H); 13C NMR (CDCl3): d
-4.82, -4.52, 17.9, 21.0, 22.4, 25.7, 32.2, 34.6, 39.7, 52.0, 65.1,
65.9, 116.3, 117.0, 134.9, 136.8, 166.3; 77Se NMR (CDCl3): d
212.1; HRMS: m/z = 360.0898 calcd. for C15H26NO2SeSi, found
360.0890
(3S,4R)-1-(3-Butenyl)-3-[(R)-tert-butyldimethylsilyloxyethyl]-
4-[2-(trimethylsilyl)ethylseleno]-2-azetidinone (6c). Method A;
Yield: 14%; Method B; Yield: 45%; IR (neat): 2953, 1758, 1643,
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1472, 1393, 1249, 838 cm-1; 1H NMR (CDCl3): d 0.02 (s, 9H), 0.06
(s, 3H), 0.08 (s, 3H), 0.88 (s, 9H), 0.92–1.01 (m, 2H), 1.24 (d, J =
6.3 Hz, 3H), 2.28–2.41 (m, 2H), 2.55–2.70 (m, 2H), 2.96–3.05 (m,
1H), 3.18 (s, 1H), 3.40–3.48 (m, 1H), 4.17–4.26 (m, 1H), 4.85 (d,
J = 1.7 Hz, 2J(77Se-1H) = 28.1 Hz, 1H), 5.06 (dd, J = 1.1, 10.3 Hz,
1H), 5.12 (dd, J = 1.1, 17.2 Hz, 1H), 5.72–5.83 (m, 1H); 13C NMR
(CDCl3): d -4.83, -4.50, -1.90, 17.5, 18.0, 18.6, 22.4, 25.8, 32.2,
39.7, 52.2, 65.2, 65.8, 117.0, 135.0, 166.4; 77Se NMR (CDCl3): d
262.1; HRMS: m/z = 406.1137 calcd. for C16H32NO2SeSi2, found
406.1134.
3.19–3.30 (m, 3H), 3.50 (dd, J = 6.8, 16.1 Hz, 1H), 4.05 (dd, J =
5.1, 16.1 Hz, 1H), 4.24–4.31 (m, 1H), 4.84 (s, 1H), 4.89 (s, 1H), 4.93
(d, J = 2.3 Hz, 2J(77Se-1H) = 22.9 Hz, 1H), 5.20 (d, J = 10.3 Hz,
1H), 5.27 (d, J = 17.2 Hz, 1H), 5.73–5.82 (m, 1H); 13C NMR
(CDCl3): d -4.80, -4.62, 17.9, 21.1, 22.2, 25.8, 30.9, 42.8, 52.0,
64.6, 65.8, 113.9, 118.5, 131.9, 141.7, 166.3; 77Se NMR (CDCl3): d
221.0; HRMS: m/z = 346.0742 calcd. for C14H24NO2SeSi, found
346.0727.
(3S,4R)-1-Allyl-3-[(R)-1-hydroxyethyl]-4-(2-methylallylseleno)-
2-azetidinone (7f). Table 1, Entry 6; Yield: 14%; Entry 7; Yield:
66%; IR (neat): 3419, 2969, 1740, 1644, 1589, 1427, 1375, 1244,
865 cm-1; 1H NMR (CDCl3): d 1.26 (d, J = 6.3 Hz, 3H), 1.84 (s,
3H), 2.64 (brs, 1H), 3.19–3.35 (m, 3H), 3.47 (dd, J = 6.3, 16.0 Hz,
1H), 4.05 (d, J = 4.6, 16.0 Hz, 1H), 4.19–4.26 (m, 1H), 4.82 (s,
1H), 4.85 (d, J = 2.3 Hz, 1H), 4.88 (s, 1H), 5.19 (d, J = 10.3 Hz,
1H), 5.28 (d, J = 17.2 Hz, 1H), 5.70–5.80 (m, 1H); 13C NMR
(CDCl3): d 20.9, 21.1, 31.0, 42.6, 52.2, 64.2, 65.6, 114.0, 118.1,
131.4, 141.7, 166.5; 77Se NMR (CDCl3): d 228.5; HRMS: m/z =
289.0581 calcd. for C12H19NO2Se, found 289.0591.
Typical procedure for the synthesis of 4 and 7
To a stirred solution of 6 (0.22 mmol) and alkyl bromide
(2.23 mmol) in degassed dry DMF (2 mL) was added TBAF (1
M solution in THF, 0.56 mmol) at r.t. with argon bubbling into
the reaction mixture. The stirring was continued for the above
mentioned time and then the reaction mixture was extracted with
chloroform and washed with water. The combined organic layers
were dried (Na2SO4) and concentrated. The residue was purified
by column chromatography (SiO2: hexane/diethyl ether = 15/1)
to afford compounds 4, 7 or corresponding diselenide.
The isolated yields and the spectral data for 4, 7 and diselenide
are as follows:
(3S,4R)-3-[(R)-1-tert-Butyldimethylsilyloxyethyl]-1-(2-methyl-
allyl)-4-(2-methylallylseleno)-2-azetidinone (4g). Table 1, Entry
8; Yield: 58%; IR (neat): 2955, 1763, 1657, 1471, 1375, 1253,
1
836 cm-1; H NMR (CDCl3): d 0.04 (s, 3H), 0.08 (s, 3H), 0.87
(s, 9H), 1.21 (d, J = 6.3 Hz, 3H), 1.75 (s, 3H), 1.85 (s, 3H), 3.17 (d,
J = 12.0 Hz, 1H), 3.21–3.30 (m, 2H), 3.42 (d, J = 16.0 Hz, 1H),
3.96 (d, J = 16.0 Hz, 1H), 4.23–4.31 (m, 1H), 4.82 (s, 1H), 4.86 (s,
1H), 4.88 (d, J = 2.3 Hz, 1H), 4.90 (s, 1H), 4.95 (s, 1H); 13C NMR
(CDCl3): d -4.86, -4.49, 18.0, 20.6, 21.1, 22.2, 25.8, 31.1, 46.0,
52.6, 64.9, 65.7, 113.3, 113.9, 139.6, 141.6, 166.5; 77Se NMR
(CDCl3): d 219.1; HRMS: m/z = 360.0898 calcd. for C15H26NO2-
SeSi, found 360.0893.
Diselenide a. Table 1, Entry 1; Yield: 9%; IR (neat): 2954, 1767,
1644, 1539, 1384, 1255, 837 cm-1; 1H NMR (CDCl3): d 0.06 (s, 3H),
0.08 (s, 3H), 0.87 (s, 9H), 1.22 (d, J = 6.4 Hz, 3H), 3.29 (s, 1H),
3.45 (dd, J = 7.3, 15.5 Hz, 1H), 4.10 (dd, J = 5.0, 15.5 Hz, 1H),
4.26–4.32 (m, 1H), 5.02 (d, J = 1.9 Hz, 2J(77Se-1H) = 40.8 Hz, 1H),
5.22 (d, J = 10.0 Hz, 1H), 5.30 (d, J = 16.9 Hz, 1H), 5.70–5.80
(m, 1H); 13C NMR (CDCl3): d -4.83, -4.64, 18.0, 22.4, 25.8, 43.0,
53.5, 64.4, 66.8, 119.4, 131.1, 165.7; 77Se NMR (CDCl3): d 320.4;
HRMS: m/z = 637.1100 calcd. for C24H43N2O478Se80SeSi2, found
637.1107.
(3S,4R)-3-[(R)-1-Hydroxyethyl]-1-(2-methylallyl)-4-(2-me-
thylallylseleno)-2-azetidinone (7g). Table 1, Entry 8; Yield: 35%;
IR (neat): 3419, 2969, 1746, 1657, 1538, 1375, 1247, 861 cm-1; 1H
NMR (CDCl3): d 1.27 (d, J = 6.3 Hz, 3H), 1.72 (s, 3H), 1.84
(s, 3H), 2.14 (brs, 1H), 3.20 (d, J = 12.0 Hz, 1H), 3.27 (d, J =
12.0 Hz, 1H), 3.30–3.33 (m, 1H), 3.36 (d, J = 16.1 Hz, 1H), 4.02
(d, J = 16.1 Hz, 1H), 4.20–4.29 (m, 1H), 4.78–4.84 (m, 2H), 4.87
(s, 1H), 4.91 (s, 1H), 4.94 (s, 1H); 13C NMR (CDCl3): d 20.2, 21.0,
21.1, 31.1, 46.1, 52.3, 64.4, 65.5, 113.7, 114.0, 139.3, 141.7, 166.5;
77Se NMR (CDCl3): d 222.7; HRMS: m/z = 303.0738 calcd. for
C13H21NO2Se, found 303.0732.
(3S,4R)-4-(Allylseleno)-3-[(R)-1-hydroxyethyl]-1-(2-methyl-
allyl)-2-azetidinone (7b). Table 1, Entry 2; Yield: 17%; Entry 3;
Yield: 87%; IR (neat): 3419, 2928, 1740, 1656, 1633, 1542, 1377,
1240, 815 cm-1; 1H NMR (CDCl3): d 1.31 (d, J = 7.5 Hz, 3H), 1.75
(s, 3H), 2.04 (brs, 1H), 3.21–3.34 (m, 3H), 3.40 (d, J = 15.5 Hz,
1H), 4.03 (d, J = 15.5 Hz, 1H), 4.23–4.32 (m, 1H), 4.84 (d, J =
1.7 Hz, 2J(77Se-1H) = 22.4 Hz, 1H), 4.93 (s, 1H), 4.96 (s, 1H), 5.04
(d, J = 9.7 Hz, 1H), 5.12 (d, J = 17.2 Hz, 1H), 5.84–5.95 (m, 1H);
13C NMR (CDCl3): d 20.2, 21.1, 26.0, 46.1, 52.1, 64.5, 65.5, 113.7,
117.3, 134.6, 139.3, 166.5; 77Se NMR (CDCl3): d 238.7; HRMS:
m/z = 289.0581 calcd. for C12H19NO2Se, found 289.0596.
(3S,4R)-4-Allylseleno-1-(3-butenyl)-3-[(R)-1-tert-butyldime-
thylsilyloxyethyl]-2-azetidinone (4h). Table 1, Entry 9; Yield:
76%; IR (neat): 2954, 1760, 1633, 1393, 1253, 1060, 836 cm-1;
1H NMR (CDCl3): d 0.06 (s, 3H), 0.08 (s, 3H), 0.88 (s, 9H), 1.24
(d, J = 6.3 Hz, 3H), 2.31–2.37 (m, 2H), 2.95–3.04 (m, 1H), 3.21–
3.29 (m, 3H), 3.37–3.46 (m, 1H), 4.19–4.27 (m, 1H), 4.87 (d, J =
2.3 Hz, 2J(77Se-1H) = 30.8 Hz, 1H), 5.02–5.18 (m, 4H), 5.75–5.84
(m, 1H), 5.88–5.98 (m, 1H); 13C NMR (CDCl3): d -4.84, -4.53,
17.9, 22.3, 25.3, 25.7, 32.2, 39.8, 52.4, 65.0, 65.8, 117.0, 117.1,
134.8, 136.9, 166.4; 77Se NMR (CDCl3): d 238.5; HRMS: m/z =
346.0742 calcd. for C14H24NO2SeSi, found 346.0733.
Diselenide b. Table 1, Entry 5; Yield: 12%; IR (neat): 2954,
1766, 1658, 1471, 1377, 1256, 836 cm-1; 1H NMR (CDCl3): d 0.06
(s, 3H), 0.09 (s, 3H), 0.87 (s, 9H), 1.24 (d, J = 6.4 Hz, 3H), 1.76 (s,
3H), 3.32 (s, 1H), 3.39 (d, J = 16.0 Hz, 1H), 3.99 (d, J = 16.0 Hz,
1H), 4.27–4.33 (m, 1H), 4.92 (s, 1H), 4.95–5.00 (m, 2H); 13C NMR
(CDCl3): d -4.82, -4.47, 18.1, 20.7, 22.5, 25.8, 46.2, 54.3, 64.8,
t
66.9, 114.0, 138.8, 165.8; MS (EI): m/z = 667 [M+ - Bu].
(3S,4R)-1-Allyl-3-[(R)-1-tert-butyldimethylsilyloxyethyl]-4-(2-
methylallylseleno)-2-azetidinone (4f). Table 1, Entry 6; Yield:
78%; Entry 7; Yield: 27%; IR (CHCl3): 2955, 2360, 1755, 1644,
1471, 1389, 1253, 1064, 756 cm-1; 1H NMR (CDCl3): d 0.06 (s, 3H),
0.08 (s, 3H), 0.87 (s, 9H), 1.21 (d, J = 6.3 Hz, 3H), 1.86 (s, 3H),
(3S,4R)-4-Allylseleno-1-(3-butenyl)-3-[(R)-1-hydroxyethyl]-2-
azetidinone (7h). Table 1, Entry 9; Yield: 16%; IR (neat): 3419,
2968, 1737, 1634, 1402, 1241, 1043, 862 cm-1; 1H NMR (CDCl3):
2596 | Org. Biomol. Chem., 2009, 7, 2591–2598
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d 1.32 (d, J = 6.3 Hz, 3H), 2.27–2.41 (m, 2H), 2.96–3.04 (m, 1H),
5.84 (t, J = 7.9 Hz, 1H); 13C NMR (CDCl3): d 16.2, 21.4, 23.0,
45.1, 49.2, 64.6, 68.0, 126.1, 134.0, 166.2; 77Se NMR (CDCl3): d
367.4; HRMS: m/z = 261.0268 calcd. for C10H15NO2Se, found
261.0225.
3.25–3.34 (m, 3H), 3.45–3.53 (m, 1H), 4.17–4.24 (m, 1H), 4.83
2
(d, J = 1.7 Hz, J(77Se-1H) = 20.6 Hz, 1H), 5.03–5.19 (m, 4H),
5.72–5.84 (m, 1H), 5.89–5.99 (m, 1H); 13C NMR (CDCl3): d 21.1,
25.5, 32.0, 39.7, 52.3, 64.9, 65.8, 117.3, 117.4, 134.8, 134.9, 166.2;
77Se NMR (CDCl3): d 238.5; HRMS: m/z = 289.0581 calcd. for
C12H19NO2Se, found 289.0583.
(7R,8S)-8-[(R)-1-Hydroxyethyl]-4-methyl-1-aza-6-selenabi-
cyclo[5.2.0]non-3-en-9-one (8e). Yield: 74%; Mp. 110–111 ◦C; IR
(KBr): 3365, 2927, 1737, 1676, 1655, 1399, 1289, 1152, 840 cm-1;
1H NMR (CDCl3): d 1.30 (d, J = 6.3 Hz, 3H), 1.70 (brs, 1H), 1.86
(s, 3H), 3.19–3.26 (m, 2H), 3.40 (d, J = 13.2 Hz, 1H), 3.75 (dd,
J = 5.2, 16.0 Hz, 1H), 4.19–4.26 (m, 2H), 5.06 (d, J = 1.7 Hz,
2J(77Se-1H) = 18.3 Hz, 1H), 5.31 (t, J = 5.2 Hz, 1H); 13C NMR
(CDCl3): d 21.5, 22.8, 24.2, 39.7, 49.1, 64.6, 67.7, 117.5, 142.9,
165.4; 77Se NMR (CDCl3): d 341.0; HRMS: m/z = 261.0268 calcd.
for C10H15NO2Se, found 261.0223.
Typical procedure for the RCM reaction
10 mol% of catalyst B was added to the compound 4 or
7 (0.05 mmol) in toluene (2 mL). The mixture was allowed
to stir for 2–4 days under reflux prior to destruction of the
catalyst by exposure to air. The mixture was evaporated and
chromatographed to afford compound 8.
The isolated yields and the spectral data for 8a–j are as follows:
(8R,9S)-9-[(R)-1-tert-Butyldimethylsilyloxyethyl]-1-aza-7-se-
lenabicyclo[6.2.0]dec-3-en-10-one (8g). Yield: 68%; IR (CHCl3):
2953, 1758, 1692, 1566, 1486, 1255, 836 cm-1; 1H NMR (CDCl3):
d 0.06 (s, 6H), 0.86 (s, 9H), 1.21 (d, J = 6.4 Hz, 3H), 2.66–2.78
(m, 3H), 2.82–2.97 (m, 2H), 3.67 (dd, J = 10.0, 13.2 Hz, 1H), 3.94
(dd, J = 6.9, 13.2 Hz, 1H), 4.21–4.28 (m, 1H), 5.00 (d, J = 2.3 Hz,
2J(77Se-1H) = 23.0 Hz, 1H), 5.53–5.61 (m, 1H), 5.90–5.99 (m, 1H);
13C NMR (CDCl3): d -5.19, -4.30, 17.9, 22.1, 23.6, 25.7, 30.7,
35.7, 50.3, 62.6, 64.5, 122.6, 135.0, 164.8; HRMS: m/z = 318.0429
calcd. for C12H20NO2SeSi, found 318.0405.
(7R,8S)-8-[(R)-1-tert-Butyldimethylsilyloxyethyl]-1-aza-6-
selenabicyclo[5.2.0]non-3-en-9-one (8a). Yield: 78%; IR (neat):
2954, 1762, 1652, 1471, 1396, 1252, 836 cm-1; 1H NMR (CDCl3):
d 0.06 (s, 3H), 0.08 (s, 3H), 0.86 (s, 9H), 1.22 (d, J = 6.3 Hz, 3H),
3.10 (dd, J = 8.6, 14.3 Hz, 1H), 3.26 (dd, J = 1.7, 3.4 Hz, 1H),
3.56 (dd, J = 6.3, 14.3 Hz, 1H), 3.68 (dt, J = 1.7, 17.2 Hz, 1H),
4.21–4.26 (m, 1H), 4.37 (dd, J = 5.8, 17.2 Hz, 1H), 5.10 (d, J =
1.7 Hz, 2J(77Se-1H) = 30.9 Hz, 1H), 5.44–5.49 (m, 1H), 6.09–6.19
(m, 1H); 13C NMR (CDCl3): d -5.14, -4.22, 16.3, 17.9, 22.5, 25.7,
40.5, 49.5, 64.8, 68.5, 125.3, 132.0, 166.2; 77Se NMR (CDCl3): d
359.4; HRMS: m/z = 304.0272 calcd. for C11H18NO2SeSi, found
304.0258.
(8R,9S)-9-[(R)-1-tert-Butyldimethylsilyloxyethyl]-1-aza-7-sele-
nabicyclo[6.2.0]dec-4-en-10-one (8h). Yield: 74%; IR (CHCl3):
1
2952, 1760, 1690, 1598, 1461, 1375, 1256, 1057, 836 cm-1; H
NMR (CDCl3): d 0.05 (s, 3H), 0.07 (s, 3H), 0.87 (s, 9H), 1.19
(d, J = 6.3 Hz, 3H), 2.26–2.34 (m, 1H), 2.45–2.54 (m, 1H), 3.01 (t,
J = 12.0 Hz, 1H), 3.13–3.18 (m, 1H), 3.25 (dd, J = 8.1, 12.0 Hz,
1H), 3.64 (dd, J = 9.7, 12.0 Hz, 1H), 3.82–3.88 (m, 1H), 4.21–4.27
(m, 1H), 5.10 (d, J = 2.3 Hz, 1H), 5.66–5.74 (m, 1H), 5.92–5.99
(m, 1H); 13C NMR (CDCl3): d -4.94, -4.36, 17.8, 18.7, 22.4, 25.2,
25.7, 42.9, 49.4, 64.7, 64.8, 128.6, 130.2, 168.2; HRMS: m/z =
318.0429 calcd. for C12H20NO2SeSi, found 318.0403.
(7R,8S)-8-[(R)-1-tert-Butyldimethylsilyloxyethyl]-3-methyl-1-
aza-6-selenabicyclo[5.2.0]non-3-en-9-one (8b). Yield: 92%; IR
1
(KBr): 2955, 1760, 1661, 1471, 1400, 1256, 1135, 838 cm-1; H
NMR (CDCl3): d 0.06 (s, 3H), 0.07 (s, 3H), 0.86 (s, 9H), 1.20 (d,
J = 6.3 Hz, 3H), 1.73 (s, 3H), 3.02 (dd, J = 9.2, 14.3 Hz, 1H),
3.23–3.26 (m, 1H), 3.54 (dd, J = 6.9, 14.3 Hz, 1H), 3.60 (d, J =
2
17.2 Hz, 1H), 4.20–4.29 (m, 2H), 5.08 (d, J = 1.7 Hz, J(77Se-
1H) = 29.3 Hz, 1H), 5.84 (t, J = 7.4 Hz, 1H); 13C NMR (CDCl3):
d -5.15, -4.25, 16.4, 17.9, 22.4, 23.1, 25.7, 44.9, 48.9, 64.7, 68.5,
126.3, 133.8, 166.3; 77Se NMR (CDCl3): d 361.6; HRMS: m/z =
318.0429 calcd. for C12H20NO2SeSi, found 318.0412.
(8R,9S)-9-[(R)-1-tert-Butyldimethylsilyloxyethyl]-3-methyl-1-
aza-7-selenabicyclo[6.2.0]dec-3-en-10-one (8i). Yield: 91%; IR
(CHCl3): 2954, 1758, 1670, 1461, 1377, 1255, 1064, 836 cm-1; 1H
NMR (CDCl3): d 0.07 (s, 3H), 0.08 (s, 3H), 0.88 (s, 9H), 1.21 (d,
J = 6.3 Hz, 3H), 1.77 (s, 3H), 2.58–2.86 (m, 4H), 2.94–2.97 (m,
1H), 3.75–3.82 (m, 2H), 4.23–4.29 (m, 1H), 4.93 (d, J = 2.3 Hz,
1H), 5.60 (t, J = 9.2 Hz, 1H); 13C NMR (CDCl3): d -4.77, -4.67,
18.0, 22.1, 22.8, 24.6, 25.8, 31.6, 40.6, 50.4, 62.9, 64.7, 128.9, 130.8,
165.2; 77Se NMR (CDCl3): d 299.4; HRMS: m/z = 332.0585 calcd.
for C13H22NO2SeSi, found 332.0543.
(7R,8S)-8-[(R)-1-tert-Butyldimethylsilyloxyethyl]-4-methyl-1-
aza-6-selenabicyclo[5.2.0]non-3-en-9-one (8c). Yield: 75%; Mp.
48–49 ◦C; IR (KBr): 2958, 1754, 1733, 1655, 1542, 1400, 1256,
1
1136, 839 cm-1; H NMR (CDCl3): d 0.05 (s, 3H), 0.06 (s, 3H),
0.86 (s, 9H), 1.20 (d, J = 6.3 Hz, 3H), 1.86 (s, 3H), 3.15–3.21 (m,
2H), 3.40 (d, J = 13.2 Hz, 1H), 3.68 (dd, J = 5.8, 16.0 Hz, 1H),
4.17–4.25 (m, 2H), 5.04 (d, J = 1.7 Hz, 2J(77Se-1H) = 20.0 Hz, 1H),
5.29 (t, J = 5.8 Hz, 1H); 13C NMR (CDCl3): d -5.16, -4.24, 17.8,
22.6, 22.9, 24.2, 25.6, 39.5, 49.1, 64.7, 68.2, 117.4, 142.9, 165.5;
77Se NMR (CDCl3): d 335.9; HRMS: m/z = 318.0429 calcd. for
C12H20NO2SeSi, found 318.0389.
(9R,10S)-10-[(R)-1-tert-Butyldimethylsilyloxyethyl]-1-aza-8-
selenabicyclo[7.2.0]undec-4-en-11-one (8j). Yield: 74%; Mp. 77–
78 ◦C; IR (CHCl3): 2952, 1749, 1652, 1564, 1463, 1393, 1249, 1059,
833 cm-1; 1H NMR (CDCl3): d 0.05 (s, 3H), 0.06 (s, 3H), 0.86 (s,
9H), 1.22 (d, J = 6.3 Hz, 3H), 2.46–2.56 (m, 3H), 2.60–2.73 (m,
2H), 2.76–2.82 (m, 1H), 3.03 (dt, J = 5.7, 14.3 Hz, 1H), 3.19 (t,
J = 2.3 Hz, 1H), 3.62–3.69 (m, 1H), 4.22–4.29 (m, 1H), 4.99 (d,
J = 1.7 Hz, 1H), 5.58–5.69 (m, 2H); 13C NMR (CDCl3): d -5.13,
-4.26, 17.9, 21.9, 22.2, 25.0, 25.7, 29.1, 40.6, 51.1, 64.6, 64.7, 129.4,
130.4, 167.3; HRMS: m/z = 332.0585 calcd. for C13H22NO2SeSi,
found 332.0551.
(7R,8S)-8-[(R)-1-Hydroxyethyl]-3-methyl-1-aza-6-selenabi-
cyclo[5.2.0]non-3-en-9-one (8d). Yield: 82%; Mp. 97–98 ◦C; IR
(KBr): 3365, 2969, 1747, 1715, 1663, 1445, 1376, 1121, 835 cm-1;
1H NMR (CDCl3): d 1.31 (d, J = 6.3 Hz, 3H), 1.74 (s, 3H), 1.94
(brs, 1H), 3.04 (dd, J = 8.6, 14.4 Hz, 1H), 3.33 (dd, J = 1.7, 5.1 Hz,
1H), 3.54 (dd, J = 5.1, 13.7 Hz, 1H), 3.67 (d, J = 17.2 Hz, 1H),
4.20–4.31 (m, 2H), 5.10 (d, J = 1.8 Hz, 2J(77Se-1H) = 30.9 Hz, 1H),
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5 For selected publications see: C. A. Tarling, A. B. Holmes, R. E.
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6 Only one report showing that the PhSe group is compatible with Grubbs
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Acknowledgements
This work was supported by a Grant-in-Aid for Science Research
from the Ministry of Education, Culture, Sports, Science, and
Technology of Japan (No. 20590005) for which we are grateful.
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2598 | Org. Biomol. Chem., 2009, 7, 2591–2598
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