Synthesis of spirocyclic butenolides by ring closing metathesis

Article abstract of DOI:10.1016/j.tet.2007.03.100

Spirocyclic butenolides were efficiently prepared by a ring closing metathesis strategy.

Full text of DOI:10.1016/j.tet.2007.03.100

Tetrahedron 63 (2007) 4648–4654
Synthesis of spirocyclic butenolides by ring closing metathesis
Uwe Albrechta and Peter Langera,b,
*
aInstitut fu€r Chemie, Universita€t Rostock, Albert-Einstein-Str. 3a, D-18059 Rostock, Germany
bLeibniz-Institut fu€r Katalyse e. V. an der Universita€t Rostock, Albert-Einstein-Str. 29a, D-18059 Rostock, Germany
Received 22 February 2007; revised 15 March 2007; accepted 16 March 2007
Available online 21 March 2007
Abstract—Spirocyclic butenolides were efficiently prepared by a ring closing metathesis strategy.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
(4) in the presence of catalytic amounts of Ti(OiPr)4
€
(Furstner conditions),17 afforded the spirocyclic butenolides
Spirocyclic butenolides are of biological relevance and are
present in a variety of pharmacologically relevant natural
products, such as chlorotricolide,1a,b hydnuferruginine2 or
andirolactone (Fig. 1).3 A general synthetic approach to
spirobutenolides relies on the addition of lithium (Z)-3-
lithioacrylates to aldehydes and ketones.4 Other syntheses
of spirobutenolides, such as andirolactone, rely on the appli-
cation of radical cyclisations,5 the propynoate/cuprate
5a–f. The reaction of vinylmagnesium bromide with 2-meth-
ylcyclohexanone afforded the known18 alcohol 2g with very
good diastereoselectivity. The latter was transformed, via ac-
rylate 3g, into butenolide 5g. Acrylate 3h was prepared from
4-phenylcyclohexanone in one step by reaction of the latter
with vinylmagnesium bromide and subsequent addition of
acrylic acid chloride to the reaction mixture. Ring closing
metathesis afforded butenolide 5h as a diastereomeric mix-
ture (dr¼3:1). Acrylate 3i was prepared in one step from
2,6-dimethylcyclohexanone. However, the ring closing me-
tathesis proved to be unsuccessful, presumably due to steric
effects. Starting with adamantanone, acrylate 3j was pre-
pared and transformed into the known19 butenolide 5j
(Scheme 2). Butenolide 5k was prepared from a-tetralone
(Scheme 3).20 Starting with fluorenone, acrylate 3l was pre-
pared (Scheme 4). However, the ring closing metathesis
proved to be unsuccessful under a variety of conditions.
method,6 palladium-catalysed cyclisations7 and other
8
ꢀ
methods. Marko and Maulide reported the synthesis of
spirocyclic butenolides based on the use of 2-(trimethylsilyl-
oxy)furan as a dianion equivalent.9 The ring closing meta-
thesis (RCM) reaction has found widespread applications
in the synthesis of oxygen and nitrogen heterocycles.10 In
this context, the synthesis of pyrans11 and butenolides was
reported.12,13 Some years ago, we reported the first applica-
tion of RCM to the synthesis of spirocyclic butenolides.14
Recently, Li et al. reported15 a potent synthesis of andirolac-
tone using RCM. Herein, we report full details of our studies.
In summary, we reported the synthesis of pharmacologically
relevant spirocyclic butenolides. A brief comparison of our
method with the one reported by Caine seems to be appropri-
ate. The reaction of cyclohexanone with 3-bromoacrylic acid
afforded spirobutenolide 5a in 48% yield. This compound is
obtained by our method in only 20% yield over 3 steps. On
2. Results and discussion
The reaction of cyclohexanone, cyclopentanone, cyclohep-
tanone, cyclooctanone, cyclodecanone and cyclododeca-
none with vinylmagnesium bromide afforded the alcohols
2a–f, which were transformed, by treatment with acrylic
acid chloride, into the esters 3a–f (Scheme 1, Table 1).16
Ring closing metathesis, using Grubbs’ generation I catalyst
O
O
Me
Me
Keywords: Butenolides; Catalysis; Metathesis; Ruthenium; Spiro com-
pounds.
* Corresponding author. Tel.: +49 381 4986410; fax: +49 381 4986412;
e-mail: peter.langer@uni-rostock.de
andirolactone
Figure 1. Andirolactone.
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.03.100

U. Albrecht, P. Langer / Tetrahedron 63 (2007) 4648–4654
4649
O
O
HO
R3
HO
R3
R1
( )n
R1
( )n
i
i
R2
1k
R2
2a-i
2k (76%)
1a-i
PCy3
Ru
ii
Cl
Cl
ii
Ph
PCy3
O
O
O
O
O
4
O
O
R3
R1
( )n
R3
O
R1
( )n
4
iii
iii
R2
5a-h
R2
3a-i
3k (20%)
5k
Scheme 3. Synthesis of butenolide 5k. (i) H2C]CHMgBr, THF, 0 ꢀC, 16 h;
(ii) H2C]CH(CO)Cl, NEt3, Et2O, 0 ꢀC, 16 h; (iii) 4 (5 mol %), Ti(OiPr)4
(15 mol %), CH2Cl2, 35 ꢀC, 48 h, yield: 61% based on recovered starting
material.
Scheme 1. Synthesis of butenolides 5a–h. (i) H2C]CHMgBr, THF, 0 ꢀC,
16 h; (ii) H2C]CH(CO)Cl, NEt3, Et2O, 0 ꢀC, 16 h; (iii) 4 (10 mol %),
Ti(OiPr)4 (15 mol %), CH2Cl2, 35 ꢀC, 48 h.
Table 1. Products and yields
O
HO
R1
R2
R3
Yielda (%)
i
n
2
3
5
1l
2l (76%)
a
b
c
d
e
f
g
h
i
1
0
2
3
5
7
1
1
1
H
H
H
H
H
H
Me
H
Me
H
H
H
H
H
H
H
Ph
H
H
H
H
H
H
H
H
H
Me
83
58
66
74
59
80
45b
25e
—
43
48
58
45
42
71
57
66
76
78
63
70
80c
80f
0h
ii
30c (85)d
35e
44g
O
O
O
O
iii
a
b
c
d
Isolated yields.
dr>98:2.
dr>98:2.
5l
3l (20%)
Sequential addition of H2C]CHMgBr and H2C]CH(CO)Cl to 1g at
0 ꢀC (no isolation of 2g), dr¼10:1.
Scheme 4. Attempted synthesis of butenolide 5l. (i) H2C]CHMgBr, THF,
0 ꢀC, 16 h; (ii) H2C]CH(CO)Cl, NEt3, Et2O, 0 ꢀC, 16 h; (iii) 4 (5 mol %),
Ti(OiPr)4 (15 mol %), CH2Cl2, 35 ꢀC, 48 h.
e
Sequential addition of H2C]CHMgBr and H2C]CH(CO)Cl to 1h at
0 ꢀC (no isolation of 2h), dr¼3:1 (assignment arbitrary).
dr¼3:1 (assignment arbitrary).
f
g
Sequential addition of H2C]CHMgBr and H2C]CH(CO)Cl to 1i at
0 ꢀC (no isolation of 2i), dr¼10:1.
h
No conversion, adduct was recovered.
containing a substituent at the double bond can be prepared.
This is advantageous, since substituted 3-bromoacrylates are
not always readily available.
OH
O
i
3. Experimental section
1j
2j (25%)
O
3.1. General procedure for the synthesis
of vinylalcohols 2
+
O
O
O
ii
To a THF solution of ketone 1 was added vinylmagnesium
bromide (1 M solution in THF). After stirring for 16 h at
20 ꢀC, an aqueous solution of NH4Cl (50 ml, 1 M) was
added. The organic and the aqueous layers were separated
and the latter was extracted with ether (3ꢁ50 ml). The com-
bined organic layers were dried (MgSO4), filtered and the
filtrate was concentrated in vacuo. The residue was purified
by chromatography (silica gel, petroleum ether/ether¼10:1).
Due to their unstable nature, compounds 2 had to be used
immediately after their preparation. Elemental analyses
and high-resolution mass data could, in some cases, not be
obtained.
3j (35%)
5j (65%)
Scheme 2. Synthesis of butenolide 5j. (i) (1) H2C]CHMgBr, THF, 0 ꢀC,
16 h; (2) H2C]CH(CO)Cl, 0 ꢀC, 16 h; (ii) 4 (10 mol %), Ti(OiPr)4
(15 mol %), CH2Cl2, 35 ꢀC, 48 h.
the other hand, the methods reported herein complement
the method of Caine, since a Grignard rather than a (highly
reactive and very basic) dilithio reagent was employed. It
was recently shown by Li et al.15 that spirocyclic butenolides

4650
U. Albrecht, P. Langer / Tetrahedron 63 (2007) 4648–4654
3.1.1. 1-Vinyl-1-cyclohexanol (2a). Starting with 1a
(1.96 g, 20.0 mmol), dissolved in THF (20 ml), and vinyl-
magnesium bromide (30 ml, 30.0 mmol, 1 M), 2a was
isolated (2.09 g, 83%) as a colourless oil. 1H NMR
(CDCl3, 250 MHz): d 1.18–1.30 (m, 1H, CH2), 1.38–1.75
bromide (7.5 ml, 7.5 mmol), 2e was isolated (0.54 g, 59%)
as a colourless oil. H NMR (CDCl3, 250 MHz): d 1.39–
1
2
3
1.76 (m, 18H, CH2), 5.00 (dd, J¼2.0 Hz, Jcis¼11.0 Hz,
1H, CH2), 5.21 (dd, 2J¼2.0 Hz, 3Jtrans¼17.0 Hz, 1H, CH2),
3
3
5.99 (dd, Jcis¼11.0 Hz, Jtrans¼17.0 Hz, 1H, CH). 13C
NMR (CDCl3, 50 MHz): d 21.2, 23.6, 26.2, 26.9, 34.3
(CH2), 76.4 (C), 111.0 (CH2), 145.5 (CH). IR (KBr): ~n
3394 (s), 2981 (m), 2924 (s), 2866 (s), 2849 (s), 1483 (s),
1444 (m), 1413 (w) cmꢂ1. Anal. Calcd for C14H26O: C
79.06, H 12.16; found: C 79.25, H 12.44.
3
(m, 9H, CH2), 5.01 (dd, Jcis¼11.0 Hz, 2J¼1.0 Hz, 1H,
3
CH2), 5.22 (dd, Jtrans¼17.0 Hz, 2J¼1.0 Hz, 1H, CH2),
3
3
5.95 (dd, Jtrans¼17.0 Hz, Jcis¼11.0 Hz, 1H, CH). 13C
NMR (CDCl3, 75 MHz): d 21.9, 26.9, 37.4 (CH2), 71.6
(C), 111.3 (CH2), 145.9 (CH). IR (KBr): ~n 3392 (s), 3085
(w), 2980 (w), 2963 (s), 2933 (s), 2859 (s), 1698 (m), 1639
(m), 1449 (s), 1415 (s), 1405 (s) cmꢂ1. MS (EI, 70 eV):
m/z (%)¼126 (8, M+), 111 (20), 98 (16, [Mꢂethylene]+),
83 (80), 41 (100). The spectroscopic data are identical to
those reported in the literature.21
3.1.6. 1-Vinyl-1-cyclododecanol (2f). Starting with 1f
(1.82 g, 10.0 mmol), dissolved in THF (20 ml), and vinyl-
magnesium bromide (15 ml, 1 M), 2f was isolated (1.78 g,
8.0 mmol, 80%) as a colourless oil. 1H NMR (CDCl3,
250 MHz): d 1.36–1.63 (m, 22H, CH2), 5.02 (dd,
3
2
3.1.2. 1-Vinyl-1-cyclopentanol (2b). Starting with 1b
(0.42 g, 10.0 mmol), dissolved in THF (20 ml), and vinyl-
magnesium bromide (15 ml, 15.0 mmol, 1 M), 2b was iso-
2J¼1.0 Hz, Jcis¼11.0 Hz, 1H, CH2), 5.20 (dd, J¼1.0 Hz,
3Jtrans¼17.0 Hz, 1H, CH2), 5.98 (dd, Jcis¼11.0 Hz,
3
3Jtrans¼17.0 Hz, 1H, CH). 13C NMR (CDCl3, 50 MHz):
d 19.6, 22.1, 22.6, 25.9, 26.4, 34.7 (CH2), 75.5 (C), 111.1
(CH2), 145.3 (CH). MS (EI, 70 eV): m/z (%)¼210 (28,
M+), 182 (24, [Mꢂethylene]+), 152 (28), 111 (44), 83 (100).
IR (KBr): ~n 3380 (s), 2939 (s), 2905 (s), 2863 (s), 2849 (s),
1470 (s), 1444 (w), 1413 (w), 1404 (w) cmꢂ1. Anal. Calcd
for C12H22O: C 71.03, H 7.95; found: C 70.98, H 7.92.
1
lated (0.65 g, 58%) as a colourless oil. H NMR (CDCl3,
300 MHz): d 1.64–1.71 (m, 6H, CH2), 1.85–189 (m, 2H,
2
3
CH2), 5.02 (dd, J¼1.0 Hz, Jcis¼11.0 Hz, 1H, CH2), 5.26
3
(dd, 2J¼1.0 Hz, Jtrans¼17.0 Hz, 1H, CH2), 6.02 (dd,
3Jcis¼11.0 Hz, 3Jtrans¼17.0 Hz, 1H, CH). 13C NMR (CDCl3,
75 MHz): d 23.6, 40.1 (CH2), 82.1 (C), 111.0 (CH2), 144.4
(CH). IR (KBr): ~n 3589 (s), 3088 (w), 3008 (w), 2963 (s),
2875 (m), 1641 (w), 1412 (m) cmꢂ1. MS (EI, 70 eV): m/z
(%)¼112 (12, M+), 97 (56), 84 (100, [Mꢂethylene]+), 70
(32), 55 (60). Anal. Calcd for C7H12O: C 74.95, H 10.78;
found: C 74.46, H 10.45. The spectroscopic data are identi-
cal to those reported in the literature.21
3.1.7. 2-Methyl-1-vinyl-1-cyclohexanol (2g). Starting
with 1g (1.12 g, 10.0 mmol), dissolved in THF (20 ml),
and vinylmagnesium bromide (20 ml, 20.0 mmol, 1 M),
2g was isolated (0.69 g, 4.9 mmol, 49%, syn/anti>30:1)
as
a
colourless oil. 1H NMR (CDCl3, 250 MHz):
3
d 0.77 (d, J¼6.0 Hz, 3H, CH3), 1.20–1.70 (m, 9H, CH,
3
2
3.1.3. 1-Vinyl-1-cycloheptanol (2c). Starting with 1c
(1.13 g, 10.0 mmol), dissolved in THF (20 ml), and vinyl-
magnesium bromide (12 ml, 12.0 mmol, 1 M), 2c was iso-
CH2), 5.02 (dd, Jcis¼11.0 Hz, J¼2.0 Hz, 1H, CH2), 5.20
(dd, Jtrans¼17.0 Hz, 2J¼2.0 Hz, 1H, CH2), 5.79 (dd,
3
3Jtrans¼17.0 Hz, Jcis¼11.0 Hz, 1H, CH). 13C NMR
3
1
lated (0.92 g, 66%) as a colourless oil. H NMR (CDCl3,
250 MHz): d 1.37–1.73 (m, 10H, CH2), 4.94 (dd,
(CDCl3, 50 MHz): d 15.4 (CH3), 21.4, 25.9, 29.8, 38.6
(CH2), 38.7 (CH), 74.1 (C), 111.3 (CH2), 146.2 (CH). MS
(EI, 70 eV): m/z (%)¼140 (8, M+), 112 (28, [Mꢂethylene]+),
97 (30), 83 (100), 70 (60). IR (KBr): ~n 3486 (s), 2962 (m),
3
2
2J¼1.0 Hz, Jcis¼11.0 Hz, 1H, CH2), 5.17 (dd, J¼1.0 Hz,
3Jtrans¼17.0 Hz, 1H, CH2), 5.99 (dd, Jcis¼11.0 Hz,
3
3Jtrans¼17.0 Hz, 1H, CH). 13C NMR (CDCl3, 50 MHz):
d 22.1, 29.5, 41.1 (CH2), 75.5 (C), 110.1 (CH2), 146.6
(CH). IR (KBr): ~n 3385 (s), 3168 (w), 2978 (m), 2925 (s),
2857 (m), 1640 (w), 1460 (w), 1446 (w) cmꢂ1. MS (EI,
70 eV): m/z (%)¼140 (4, M+), 122 (24), 112 (100,
[Mꢂethylene]+), 97 (76), 83 (68). The spectroscopic data
are identical to those reported in the literature.22
2932 (s), 2854 (m), 1459 (w), 1447 (w), 1407 (w) cmꢂ1
.
The stereochemical assignment is based on the identity of
the spectroscopic data to those reported in the literature.23
3.1.8. 1-Vinyl-1,2,3,4-tetrahydro-1-naphthol (2k). Start-
ing with tetralone (3.65 g, 25.0 mmol), dissolved in THF
(50 ml), and vinylmagnesium bromide (30 ml, 30.0 mmol,
1
1 M), 2k was isolated (3.31 g, 76%) as a colourless oil. H
3.1.4. 1-Vinyl-1-cyclooctanol (2d). Starting with 1d
(1.26 g, 10.0 mmol), dissolved in THF (20 ml), and vinyl-
magnesium bromide (20 ml, 20.0 mmol, 1 M), 2d was
isolated (1.14 g, 74%) as a colourless oil. 1H NMR
(CDCl3, 250 MHz): d 1.41–1.81 (m, 14H, CH2), 5.01 (dd,
NMR (CDCl3, 300 MHz): d 1.81–1.97 (m, 4H, CH2), 2.76–
2.81 (m, 2H, CH2), 5.18 (dd, 2J¼1.0 Hz, 3Jcis¼11.0 Hz, 1H,
CH2), 5.27 (dd, 2J¼1.0 Hz, 3Jtrans¼17.0 Hz, 1H, CH2), 6.00
3
3
(dd, Jcis¼11.0 Hz, Jtrans¼17.0 Hz, 1H, CH). 13C NMR
(CDCl3, 75 MHz): d 19.3, 29.9, 37.7 (CH2), 73.3 (C), 113.1
(CH2), 126.2, 127.5, 127.9, 129.0 (CH), 137.0, 139.7 (C),
144.8 (CH). IR (KBr): ~n 3548 (s), 3072 (w), 3018 (w), 2936
(s), 2867 (w), 1640 (w), 1488 (w), 1450 (w), 1405 (w), 1395
(w) cmꢂ1. MS (EI, 70 eV): m/z (%)¼174 (36, M+), 146 (100,
[Mꢂethylene]+), 131 (52), 128 (36), 115 (32).
3
2
2J¼1.0 Hz, Jcis¼11.0 Hz, 1H, CH2), 5.20 (dd, J¼1.0 Hz,
3
3Jtrans¼17.0 Hz, 1H, CH2), 5.96 (dd, Jcis¼11.0 Hz,
3Jtrans¼17.0 Hz, 1H, CH). 13C NMR (CDCl3, 50 MHz):
d 22.0, 24.7, 28.2, 36.2 (CH2), 75.2 (C), 111.3 (CH2),
145.8 (CH). IR (KBr): ~n 3383 (s), 3007 (w), 2922 (s),
2853 (m), 1640 (w), 1472 (w), 1448 (w), 1410 (w) cmꢂ1
.
MS (EI, 70 eV): m/z (%)¼154 (4, M+), 125 (12), 111 (56),
3.1.9. 9-Vinyl-9H-fluoren-9-ol (2l). Starting with fluor-
enone (1.82 g, 10.0 mmol), dissolved in THF (30 ml), and
vinylmagnesium bromide (12 ml, 12.0 mmol, 1 M), 2l
97 (24), 83 (100).
1
3.1.5. 1-Vinyl-1-cyclodecanol (2e). Starting with 1e (0.77 g,
5.0 mmol), dissolved in THF (10 ml), and vinylmagnesium
was isolated (1.50 g, 72%) as a colourless oil. H NMR
(CDCl3, 300 MHz): d 5.20 (dd, J¼1.0 Hz, Jcis¼11.0 Hz,
2
3

U. Albrecht, P. Langer / Tetrahedron 63 (2007) 4648–4654
4651
1H, CH2), 5.53 (dd, 2J¼1.0 Hz, 3Jtrans¼17.0 Hz, 1H, CH2),
(CH2), 129.6 (CH), 129.9 (CH2), 140.1 (CH), 165.2 (CO).
IR (KBr): ~n 2958 (m), 2926 (s), 2871 (w), 2854 (w), 1727
(m), 1403 (m) cmꢂ1. MS (EI, 70 eV): m/z (%)¼166
(2, M+), 111 (4), 94 (64), 79 (24), 55 (100). HRMS
(EI, 70 eV) calcd for C10H14O2 [M+]: 166.0994; found:
m/z¼166.0994ꢃ2 ppm.
3
3
5.96 (dd, Jcis¼11.0 Hz, Jtrans¼17.0 Hz, 1H, CH), 7.29–
2
3
7.37 (m, 4H, CH), 7.43 (dd, J¼1.0 Hz, J¼7.0 Hz, 2H,
2
3
CH), 7.61 (dd, J¼1.0 Hz, J¼7.0 Hz, 2H, CH). 13C NMR
(CDCl3, 75 MHz): d 82.4 (C), 113.5 (CH2), 120.1, 124.4,
128.1, 129.2, 139.1 (CH), 139.5, 147.9 (C). IR (KBr): ~n
3511 (w), 3298 (s), 3093 (w), 1449 (s), 1205 (w) cmꢂ1
.
MS (EI, 70 eV): m/z (%)¼208 (100, M+), 189 (12), 180
(52, [Mꢂethylene]+), 165 (64), 152 (72). Anal. Calcd for
C15H12O: C 86.51, H 5.81; found: C 86.23, H 6.17.
3.3.3. 1-Vinyl-1-cycloheptylacrylate (3c). The reaction
was carried out following general procedure A. Starting
with 2c (0.70 g, 5.0 mmol), dissolved in ether (25 ml),
NEt3 (0.76 g, 7.5 mmol) and acrylic acid chloride (0.68 g,
7.5 mmol), 3c was isolated (0.56 g, 2.9 mmol, 58%) as a
3.2. General procedure A for the synthesis
of vinylacrylates 3
1
colourless oil. H NMR (CDCl3, 250 MHz): d 1.35–1.64
(m, 8H, CH2), 1.92 (dd, J¼9.0 Hz, 2H, CH2), 2.15 (dd,
3
3
To an ether solution of 2 was added triethylamine (NEt3) and
acrylic acid chloride at 0 ꢀC. After stirring at 20 ꢀC for 24 h,
the suspension was filtered and the filtrate was concentrated
in vacuo. The residue was purified by chromatography (silica
gel, petroleum ether/ether¼20:1).
3J¼7.0 Hz, 2H, CH2), 5.05 (d, Jcis¼8.0 Hz, 1H, CH2),
5.11 (d, 3Jtrans¼15.0 Hz, 1H, CH2), 5.72 (dd, 3Jcis¼10.0 Hz,
2J¼2.0 Hz, 1H, CH2), 5.70–6.11 (m, 2H, CH), 6.31 (dd,
2
3Jtrans¼16.0 Hz, J¼2.0 Hz, 1H, CH2). 13C NMR (CDCl3,
50 MHz): d 22.3, 29.1, 38.2 (CH2), 86.1 (C), 112.3, 129.5
(CH2), 129.8, 142.6 (CH), 164.9 (CO). IR (KBr): ~n 2982
(s), 2859 (w), 1725 (s), 1687 (w), 1637 (w), 1619 (w),
3.3. General procedure B for the synthesis
of vinylacrylates 3
1460 (w), 1447 (w), 1402 (m) cmꢂ1
.
To a THF solution of 2 was added vinylmagnesium bromide
(1 M solution in THF) at 0 ꢀC. After stirring for 16 h at 20 ꢀC
the solution was cooled to 0 ꢀC and acrylic acid chloride was
added. The solution was stirred for 16 h at 20 ꢀC. To the so-
lution was added an aqueous solution of NH4Cl (50 ml,
1 M). The organic and the aqueous layers were separated
and the latter was extracted with ether (3ꢁ50 ml). The com-
bined organic layers were dried (MgSO4), filtered and the fil-
trate was concentrated in vacuo. The residue was purified by
chromatography (silica gel, petroleum ether/ether¼20:1).
3.3.4. 1-Vinyl-1-cyclooctylacrylate (3d). The reaction was
carried out following general procedure A. Starting with 2d
(0.77 g, 5.0 mmol), dissolved in ether (25 ml), NEt3 (0.76 g,
7.5 mmol) and acrylic acid chloride (0.68 g, 7.5 mmol), 3d
1
was isolated (0.47 g, 45%) as a colourless oil. H NMR
(CDCl3, 250 MHz): d 1.38–1.71 (m, 10H, CH2), 1.93 (dd,
3J¼7.0 Hz, 2H, CH2), 2.24 (dd, 3J¼7.0 Hz, 2H, CH2), 5.10–
3
2
5.16 (m, 2H, CH2), 5.71 (dd, Jcis¼12.0 Hz, J¼1 Hz, 1H,
3
CH2), 5.98–6.12 (m, 2H, CH), 6.29 (dd, Jtrans¼17.0 Hz,
2J¼2.0 Hz, 1H, CH2). 13C NMR (CDCl3, 50 MHz): d 21.4,
24.7, 28.0, 32.4 (CH2), 86.0 (C), 113.4, 129.5 (CH2),
129.9, 141.9 (CH), 164.8 (CO). IR (KBr): ~n 2925 (s), 2855
(s), 1723 (s), 1636 (m), 1476 (m), 1446 (m), 1402 (s)
cmꢂ1. MS (EI, 70 eV): m/z (%)¼208 (12, M+), 136 (32),
108 (32), 95 (20), 81 (20), 55 (100).
Due to their unstable nature, compounds 3 had to be used
immediately after their preparation. Elemental analyses and
high-resolution mass data could not be obtained.
3.3.1. 1-Vinyl-1-cyclohexylacrylate (3a). The reaction was
carried out following general procedure A. Starting with 2a
(0.63 g, 5.0 mmol), dissolved in ether (25 ml), NEt3 (0.76 g,
7.5 mmol) and acrylic acid chloride (0.68 g, 7.5 mmol), 3a
3.3.5. 1-Vinyl-1-cyclodecylacrylate (3e). The reaction was
carried out following general procedure A. Starting with 2e
(0.43 g, 2.4 mmol), dissolved in ether (15 ml), NEt3 (0.31 g,
3.1 mmol) and acrylic acid chloride (0.26 g, 2.8 mmol), 3e
1
was isolated (0.38 g, 43%) as a colourless oil. H NMR
1
(CDCl3, 250 MHz): d 1.25–1.30 (m, 1H, CH2), 1.49–1.62
(m, 7H, CH2), 2.21–2.24 (m, 2H, CH2), 5.10–5.20 (m, 2H,
CH2), 5.75 (dd, 3Jcis¼10.0 Hz, 2J¼1.6 Hz, 1H, CH2), 6.01–
6.18 (m, 2H, CH), 6.34 (dd, 3Jtrans¼17.0 Hz, 2J¼2.0 Hz, 1H,
CH2). 13C NMR (CDCl3, 50 MHz): d 21.8, 25.3, 34.8 (CH2),
82.0 (C), 113.6, 129.7 (CH2), 129.8, 141.7 (CH), 164.8
(CO). IR (KBr): ~n 2935 (s), 2862 (w), 1725 (s), 1638 (w),
1620 (w), 1449 (w), 1402 (m) cmꢂ1. MS (EI, 70 eV): m/z
(%)¼179 (4, M+), 153 (6), 108 (84), 79 (30), 55 (100).
was isolated (0.23 g, 42%) as a colourless oil. H NMR
(CDCl3, 250 MHz): d 1.30–1.70 (m, 14H, CH2), 1.78–1.95
(m, 2H, CH2), 2.20–2.34 (m, 2H, CH2), 5.10–5.17 (m, 2H,
3
CH2), 5.72 (dd, Jcis¼11.0 Hz, 2J¼2.0 Hz, 1H, CH2),
3
5.97–6.09 (m, 2H, CH), 6.30 (dd, Jtrans¼18.0 Hz,
2J¼2.0 Hz, 1H, CH2). 13C NMR (CDCl3, 50 MHz): d 20.5,
23.9, 26.1, 26.2, 30.6 (CH2), 86.7 (C), 113.6, 129.6 (CH2),
129.8, 141.6 (CH), 164.7 (CO). IR (KBr): ~n 2927 (s), 2866
(m), 2850 (m), 1766 (m), 1730 (s), 1484 (m), 1445 (m)
cmꢂ1. MS (EI, 70 eV): m/z (%)¼208 (12, M+), 165 (32),
151 (36), 137 (24), 97 (100).
3.3.2. 1-Vinyl-1-cyclopentylacrylate (3b). The reaction
was carried out following general procedure A. Starting
with 2b (0.45 g, 4.0 mmol), dissolved in ether (20 ml),
NEt3 (0.61 g, 6.0 mmol) and acrylic acid chloride (0.51 g,
5.6 mmol), 3b was isolated (0.32 g, 48%) as a colourless
oil. 1H NMR (CDCl3, 250 MHz): d 1.55–2.04 (m, 6H,
CH2), 2.06–2.18 (m, 2H, CH2), 5.07–5.17 (m, 2H, CH2),
3.3.6. 1-Vinyl-1-cyclododecylacrylate (3f). The reaction
was carried out following general procedure A. Starting
with 3f (0.21 g, 1.0 mmol), dissolved in ether (10 ml),
NEt3 (0.13 g, 1.3 mmol) and acrylic acid chloride (0.12 g,
1.3 mmol), 3f was isolated (0.19 g, 0.7 mmol, 71%) as a col-
2
1
5.75 (3Jcis¼10.0 Hz, J¼2.0 Hz, 1H, CH2), 6.01–6.22 (m,
ourless oil. H NMR (CDCl3, 250 MHz): d 1.12–1.22 (m,
18H, CH2), 1.59–1.65 (m, 2H, CH2), 2.05–2.19 (m, 2H,
3
2
2H, CH), 6.33 (dd, Jtrans¼17.0 Hz, J¼2.0 Hz, 1H, CH2).
13C NMR (CDCl3, 50 MHz): d 23.2, 37.6, 90.7 (C), 113.1
3
CH2), 5.09–5.18 (m, 2H, CH2), 5.74 (dd, Jcis¼11.0 Hz,

4652
U. Albrecht, P. Langer / Tetrahedron 63 (2007) 4648–4654
2J¼2.0 Hz, 1H, CH2), 5.92–6.10 (m, 2H, CH), 6.32 (dd,
6H, CH3, syn/anti), 0.96 (d, 3J¼7.0 Hz, 6H, CH3, syn/
anti), 1.28–1.54 (m, 6H, CH2, syn/anti), 1.64–1.78 (m, 2H,
CH, syn/anti), 4.94–5.32 (m, 3H, CH2, syn/anti), 5.56–
5.82 (m, 1H, CH2, syn/anti), 6.05–6.18 (m, 1H, CH, syn/
anti), 6.32–6.53 (m, 1H, CH, syn/anti). 13C NMR (CDCl3,
75 MHz): 15.5, 17.0 (CH3), 25.4, 25.7, 29.6, 30.1 (CH2),
37.1, 42.5 (CH), 88.17, 88.18 (C), 109.2, 112.2, 129.3,
129.4 (CH2), 129.9, 130.5, 141.3, 144.5 (CH), 164.3,
165.1 (C). IR (KBr): ~n 2966 (m), 2931 (s), 2878 (w), 2858
(w), 1726 (s), 1637 (w), 1621 (w), 1458 (m), 1405 (m)
cmꢂ1. The stereochemical assignment is based on analogy
to the synthesis of 2g.
2
3Jtrans¼18.0 Hz, J¼2.0 Hz, 1H, CH2). 13C NMR (CDCl3,
50 MHz): d 18.9, 21.9, 22.3, 26.1, 30.9 (CH2), 85.6 (C),
113.8 (CH2), 129.7 (CH), 129.8 (CH2), 141.2 (CH), 164.8
(CO). IR (KBr): ~n 2947 (s), 2906 (s), 2864 (m), 2852 (m),
1724 (s), 1711 (s), 1471 (m), 1401 (m) cmꢂ1. MS (EI,
70 eV): m/z (%)¼264 (4, M+), 209 (8), 192 (36), 95 (20),
55 (100).
3.3.7. 2-Methyl-1-vinyl-1-cyclohexylacrylate (3g). The re-
action was carried out following general procedure A. Start-
ing with 2g (0.42 g, 4.0 mmol), dissolved in ether (20 ml),
NEt3 (0.93 g, 9.2 mmol) and acrylic acid chloride (0.72 g,
8.0 mmol), 3g was isolated (0.23 g, 1.2 mmol, 30%,
3.3.10. 2-Vinyl-2-adamantanylacrylate (3j). The reaction
was carried out following general procedure B. Starting
with adamantanone (0.75 g, 5.0 mmol), vinylmagnesium
bromide (7 ml, 7.0 mmol, 1 M) and acrylic acid chloride
(0.63 g, 7.0 mmol) in THF (25 ml), 3j was isolated
(0.41 g, 1.8 mmol, 35%) as a colourless oil. In addition, 2j
(0.22 g, 1.2 mmol, 25%) was isolated.
1
dr>98:2) as a colourless oil. H NMR (CDCl3, 250 MHz):
d 0.94 (d, J¼3.0 Hz, 3H, CH3), 1.24–1.36 (m, 2H, CH2),
3
1.44–1.57 (m, 6H, CH2), 1.66–1.69 (m, 1H, CH), 5.03
3
(dd, Jtrans¼18.0 Hz, 2J¼1.0 Hz, 1H, CH2), 5.13 (dd,
3Jcis¼11.0 Hz, 2J¼1.0 Hz, 1H, CH2), 5.77 (dd,
3Jcis¼12.0 Hz, 2J¼1.0 Hz, 1H, CH2), 5.99–6.16 (m, 2H,
3
2
CH), 6.36 (dd, Jtrans¼19.0 Hz, J¼1.0 Hz, 1H, CH2). 13C
NMR (CDCl3, 50 MHz): d 15.5 (CH3), 21.3, 25.4, 30.4,
32.3 (CH2), 41.8 (CH), 84.6 (C), 112.7, 129.7 (CH2),
129.8, 141.5 (CH), 164.9 (CO). IR (KBr): ~n 3089 (w),
3030 (w), 2970 (s), 2933 (s), 2859 (s), 1725 (s), 1637 (m),
1620 (m), 1603 (w), 1448 (s), 1403 (s) cmꢂ1. MS (EI,
70 eV): m/z (%)¼193 (32, M+), 176 (24), 121 (32), 95
(24), 55 (100).
1
Data of 3j. H NMR (CDCl3, 300 MHz): d 1.66–2.16 (m,
14H, CH, CH2), 5.27 (dd, J¼1.0 Hz, Jcis¼11.0 Hz, 1H,
2
3
3
CH2), 5.33 (dd, 2J¼1.0 Hz, Jtrans¼18.0 Hz, 1H, CH2),
2
3
5.75 (dd, J¼2.0 Hz, Jcis¼11.0 Hz, 1H, CH2), 6.08 (dd,
3
3Jtrans¼18.0 Hz, Jcis¼11.0 Hz, 1H, CH), 6.26–6.39 (m,
2H, CH, CH2). 13C NMR (CDCl3, 75 MHz): 26.8, 27.2
(CH), 32.9, 34.3 (CH2), 35.1 (CH), 37.7 (CH2), 85.3 (C),
115.7, 129.6 (CH2), 130.0, 140.6 (CH), 164.5 (C). IR
(KBr): ~n 2909 (s), 2859 (m), 1723 (s), 1657 (w), 1619 (w),
1453 (s), 1402 (s) cmꢂ1. Anal. Calcd for C15H20O2: C
77.55, H 8.68; found: C 77.44, H 8.68.
3.3.8. 4-Phenyl-1-vinyl-1-cyclohexylacrylate (3h). The re-
action was carried out following general procedure B. Start-
ing with 4-phenylcyclohexanone (1h) (0.87 g, 5.0 mmol),
vinylmagnesium bromide (7 ml, 7.0 mmol, 1 M) and acrylic
acid chloride (0.63 g, 7.0 mmol) in THF (25 ml), 3h was iso-
lated (0.46 g, 35%, dr¼3:1) as a colourless oil. The stereo-
chemistry could not be unambiguously assigned. A small
selectivity in favour of the syn diastereomer was observed
in the reaction of lithiated 3-bromoacrylic acid with 4-tert-
butylcyclohexanone (equatorial attack of the organolithium
reagent to give an axial alcohol). The reaction of phenylmag-
nesium bromide with 4-phenylcyclohexanone has also been
reported.24 1H NMR (CDCl3, 300 MHz): d 1.55–1.74 (m,
3H, CH2), 1.77–1.93 (m, 3H, CH2), 2.50–2.65 (m, 3H,
Data of 2-vinyl-2-adamantanol (2j). 1H NMR (CDCl3,
300 MHz): d 1.57–1.60 (m, 2H, CH), 1.70–1.75 (m, 2H,
3
CH), 1.82–1.90 (m, 4H, CH2), 2.26 (d, J¼12.0 Hz, 2H,
3
2
CH2), 5.16 (dd, Jcis¼11.0 Hz, J¼2.0 Hz, 1H, CH2), 5.35
3
(dd, Jtrans¼17.0 Hz, 2J¼2.0 Hz, 1H, CH2), 6.27 (dd,
3
3Jtrans¼17.0 Hz, Jcis¼11.0 Hz, 1H, CH). 13C NMR
(CDCl3, 75 MHz): 27.6, 27.8 (CH2), 33.2, 35.1 (CH), 38.2
(CH2), 38.4 (CH), 74.7 (C), 113.9 (CH), 145.2 (CH2). IR
(KBr): ~n 3365 (s), 2902 (s), 2857 (s), 1636 (w), 1453 (s)
cmꢂ1. MS (EI, 70 eV): m/z (%)¼178 (100, M+), 163 (14),
148 (17), 135 (31), 121 (19), 108 (21). HRMS (EI, 70 eV)
calcd for C12H18O [M+]: 178.1358; found: m/z¼
178.1358ꢃ2 ppm. The spectroscopic data are identical to
those reported in the literature.25
3
3
CH, CH2), 5.16 (dd, Jtrans¼18.0 Hz, Jcis¼12.0 Hz, 1H,
3
3
CH2), 5.38 (dd, Jtrans¼18.0 Hz, Jcis¼12.0 Hz, 1H, CH2),
3
2
5.75 (dd, Jcis¼12.0 Hz, J¼1.0 Hz, 1H, CH2), 6.00–6.43
(m, 3H, CH), 7.17–7.19 (m, 5H, CH). 13C NMR (CDCl3,
75 MHz): d 28.9, 30.4, 34.7, 35.4 (CH2), 43.1 (CH), 81.0,
81.7 (C), 113.3, 117.1 (CH2), 126.0, 126.6, 128.3, 129.7,
129.8, 129.2, 138.9, 141.8 (CH), 145.9 (C), 164.7 (CO). IR
(KBr): ~n 3028 (s), 2935 (m), 2863 (w), 1722 (s), 1635 (w),
1620 (w), 1494 (w), 1450 (m), 1402 (s) cmꢂ1. MS (EI,
70 eV): m/z (%)¼256 (M+, 8), 184 (87), 156 (54), 139
(21), 117 (23), 104 (100). Anal. Calcd for C17H20O2: C
79.65, H 7.86; found: C 79.47, H 7.76.
3.3.11. 1-Vinyl-1-tetrahydronaphthylacrylate (3k). The
reaction was carried out following general procedure A.
Starting with 2k (0.87 g, 5.0 mmol), dissolved in ether
(25 ml), NEt3 (0.61 g, 6.0 mmol) and acrylic acid chloride
(0.50 g, 5.5 mmol), 3k was isolated (0.23 g, 1.0 mmol,
20%) as a colourless oil. 1H NMR (CDCl3, 250 MHz):
3
3
d 1.87 (tt, J¼6.0 Hz, 2H, CH2), 2.61 (t, J¼6.0 Hz, 2H,
3
CH2), 2.81 (t, J¼6.0 Hz, 2H, CH2), 4.90–4.93 (m, 2H,
3
3.3.9. 2,6-Dimethyl-1-vinyl-cyclohexylacrylate (3i). The
reaction was carried out following general procedure B.
Starting with 2,6-dimethylcyclohexanone (1i) (1.26 g,
10.0 mmol), vinylmagnesium bromide (12 ml, 12.0 mmol,
1 M) and acrylic acid chloride (1.08 g, 12.0 mmol) in THF
(40 ml), 3i was isolated (0.91 g, 44%, dr¼10:1) as a colour-
CH2), 5.85 (dd, Jcis¼11.0 Hz, 2J¼2.0 Hz, 1H, CH2),
3
2
6.12–6.23 (m, 2H, CH), 6.46 (dd, Jtrans¼17 Hz, J¼2 Hz,
1H, CH2), 7.09–7.22 (m, 3H, CH), 7.60–7.64 (m, 1H, CH).
13C NMR (CDCl3, 50 MHz): d 22.9, 26.6, 30.2 (CH2),
61.4 (C), 116.9, 124.1, 126.1, 127.5, 128.4, 128.9 (CH),
130.7 (CH2), 134.8 (C), 137.9 (CH2), 139.4 (C), 166.2
(CO). IR (KBr): ~n 3494 (s), 3439 (s), 3064 (w), 3033 (w),
1
3
less oil. H NMR (CDCl3, 300 MHz): d 0.79 (d, J¼7 Hz,

U. Albrecht, P. Langer / Tetrahedron 63 (2007) 4648–4654
4653
2933 (s), 2867 (s), 2840 (s), 1724 (s), 1684 (s), 1635 (s),
1619 (m), 1603 (w), 1485 (m), 1455 (m), 1406 (s) cmꢂ1
(CH2), 92.0 (C), 118.9, 161.6 (CH), 172.6 (CO). IR (KBr):
~n 3082 (w), 2928 (s), 2859 (s), 1847 (w), 1828 (w), 1761
.
MS (EI, 70 eV): m/z (%)¼228 (44, M+), 173 (40), 156
(s), 1746 (s), 1637 (w), 1604 (w), 1460 (s), 1446 (s) cmꢂ1
.
(100), 141 (36), 129 (76).
MS (EI, 70 eV): m/z (%)¼166 (16, M+), 138 (76), 109
(24), 97 (72), 81 (100). The spectroscopic data are identical
with those reported in the literature.27
3.3.12. 9-Vinyl-9H-fluoren-9-yl-acrylate (3l). The reaction
was carried out following general procedure A. Starting with
2l (1.04 g, 5.0 mmol), dissolved in THF (25 ml), NEt3
(0.61 g, 6.0 mmol) and acrylic acid chloride (0.50 g,
5.5 mmol), 3l was isolated (0.19 g, 0.7 mmol, 14%) as a
3.4.4. 1-Oxaspiro[4.7]dodec-3-en-2-one (5d). Starting with
3d (0.11 g, 0.55 mmol), dissolved in CH2Cl2 (10 ml),
Ti(OiPr)4 (0.02 g, 0.08 mmol), dissolved in CH2Cl2 (5 ml),
and 4 (0.04 g, 0.05 mmol), dissolved in CH2Cl2 (5 ml), 5d
1
colourless solid. H NMR (CDCl3, 250 MHz): d 5.44 (d,
3Jcis¼7.0 Hz, 1H, CH2), 5.89 (dd, 3Jcis¼11.0 Hz, 2J¼2.0 Hz,
1
was isolated (0.08 g, 78%) as a colourless oil. H NMR
3
3
1H, CH), 6.24 (dd, Jtrans¼17.0 Hz, Jcis¼11.0 Hz, 1H,
(CDCl3, 250 MHz): d 1.49–1.93 (m, 12H, CH2), 1.96–2.01
(m, 2H, CH2), 5.96 (d, 3J¼6.0 Hz, 1H, CH), 7.52 (d,
3J¼6.0 Hz, 1H, CH). 13C NMR (CDCl3, 50 MHz): d 22.4,
24.4, 27.8, 33.4 (CH2), 92.1 (C), 119.6, 161.1 (CH), 172.5
(CO). IR (KBr): ~n 3080 (w), 2925 (s), 2857 (w), 1863 (w),
1474 (m), 1449 (m) cmꢂ1. MS (EI, 70 eV): m/z (%)¼180
(16, M+), 151 (24), 135 (28), 108 (24), 97 (100). Anal. Calcd
for C11H16O2: C 73.30, H 8.95; found: C 73.72, H 9.37.
3
2
CH2), 6.51 (dd, Jtrans¼17.0 Hz, J¼2 Hz, 1H, CH2), 6.74
(t, 3J¼6.0 Hz, 1H, CH), 7.24–7.39 (m, 6H, CH), 7.66–7.71
(m, 3H, CH). MS (EI, 70 eV): m/z (%)¼262 (76, M+), 207
(92), 189 (80), 179 (100), 165 (20).
3.4. General procedure for the synthesis of spirocyclic
butenolides 5
To a CH2Cl2 solution (30 ml) of 3 was added Ti(OiPr)4 and
the solution was stirred for 1 h at 35 ꢀC. A CH2Cl2 solution
of 4 was subsequently added and the reaction mixture was
stirred at 35 ꢀC for 48 h. The solvent was removed in vacuo
and the residue was purified by column chromatography
(silica gel, petroleum ether/ether¼3:1).
3.4.5. 1-Oxaspiro[4.9]tetradec-3-en-2-one (5e). Starting
with 5e (0.12 g, 0.52 mmol), dissolved in CH2Cl2 (10 ml),
Ti(OiPr)4 (0.02 g, 0.08 mmol), dissolved in CH2Cl2 (5 ml),
and 4 (0.04 g, 0.05 mmol), dissolved in CH2Cl2 (5 ml), 5e
was isolated (0.07 g, 0.3 mmol, 63%) as a colourless oil.
1H NMR (CDCl3, 250 MHz): d 1.56–1.91 (m, 16H, CH2),
1.93–1.98 (m, 2H, CH2), 5.96 (d, 3J¼6.0 Hz, 1H, CH),
7.50 (d, 3J¼6.0 Hz, 1H, CH). 13C NMR (CDCl3, 50 MHz):
d 21.6, 23.2, 25.6, 26.4, 31.5 (CH2), 92.7 (C), 119.8, 161.0
(CH), 172.5 (CO). IR (KBr): ~n 2987 (m), 2917 (s), 2865
(m), 2844 (m), 1814 (s), 1484 (m) cmꢂ1. MS (EI, 70 eV):
m/z (%)¼208 (8), 165 (32), 151 (36), 109 (24), 97 (100).
Anal. Calcd for C13H20O2: C 74.96, H 9.68; found: C
74.54, H 9.87.
3.4.1. 1-Oxaspiro[4.5]dec-3-en-2-one (5a). Starting with
3a (0.18 g, 1.00 mmol), dissolved in CH2Cl2 (30 ml),
Ti(OiPr)4 (0.04 g, 0.15 mmol), dissolved in CH2Cl2 (5 ml),
and 4 (0.08 g, 0.10 mmol), dissolved in CH2Cl2 (5 ml), 5a
1
was isolated (0.06 g, 57%) as a colourless oil. H NMR
(CDCl3, 250 MHz): d 1.57–1.80 (m, 10H, CH2), 5.99 (d,
3
3J¼6.0 Hz, 1H, CH), 7.44 (d, J¼6.0 Hz, 1H, CH). 13C
NMR (CDCl3, 50 MHz): d 22.4, 24.6, 34.5, 88.6 (C),
120.1, 160.6 (CH), 172.6 (CO). IR (KBr): ~n 3083 (w),
2937 (s), 2861 (m), 1883 (m), 1766 (s), 1750 (s), 1449
(m), 1430 (w), 1403 (m) cmꢂ1. The spectroscopic data are
identical with those reported in the literature.26
3.4.6. 1-Oxaspiro[4.11]hexadec-3-en-2-one (5f). Starting
with 3f (0.18 g, 0.67 mmol), dissolved in CH2Cl2 (40 ml),
Ti(OiPr)4 (0.04 g, 0.15 mmol), dissolved in CH2Cl2 (5 ml),
and 4 (0.08 g, 0.10 mmol), dissolved in CH2Cl2 (5 ml), 5f
was isolated (0.11 g, 0.5 mmol, 70%) as a colourless solid.
1H NMR (CDCl3, 250 MHz): d 1.23–1.40 (m, 13H, CH2),
1.41–1.60 (m, 7H, CH2), 1.70–1.82 (m, 2H, CH2), 5.95 (d,
3.4.2. 1-Oxaspiro[4.4]non-3-en-2-one (5b). Starting with
3b (0.17 g, 1.00 mmol), dissolved in CH2Cl2 (40 ml),
Ti(OiPr)4 (0.04 g, 0.15 mmol), dissolved in CH2Cl2 (5 ml),
and 4 (0.08 g, 0.10 mmol), dissolved in CH2Cl2 (5 ml), 5b
3
3J¼6.0 Hz, 1H, CH), 7.48 (d, J¼6.0 Hz, 1H, CH). 13C
NMR (CDCl3, 50 MHz): d 19.9, 21.8, 22.3, 25.7, 26.0,
31.9 (CH2), 91.9 (C), 119.8, 160.8 (CH), 172.4 (CO). IR
(KBr): ~n 3088 (w), 2957 (s), 2937 (s), 2864 (m), 2847 (m),
1743 (s), 1472 (s), 1444 (m) cmꢂ1. MS (EI, 70 eV): m/z
(%)¼236 (100, M+), 208 (16), 179 (12), 165 (28), 151
(28). HRMS (EI, 70 eV) calcd for C15H24O2 [M+]:
236.1776; found: m/z¼236.1776ꢃ2 ppm. Anal. Calcd for
C15H24O2: C 76.23, H 10.24; found: C 76.10, H 10.76.
1
was isolated (0.09 g, 66%) as a colourless oil. H NMR
(CDCl3, 250 MHz): d 1.78–1.98 (m, 8H, CH2), 5.96 (d,
3
3J¼6.0 Hz, 1H, CH), 7.36 (d, J¼6.0 Hz, 1H, CH). 13C
NMR (CDCl3, 50 MHz): d 24.6, 36.7 (CH2), 96.7 (C), 120.1,
159.0 (CH), 172.5 (CO). IR (KBr): ~n 3084 (w), 2965 (s),
2877 (m), 1746 (s), 1602 (w), 1452 (w), 1434 (w) cmꢂ1
.
MS (EI, 70 eV): m/z (%)¼138 (100, M+), 109 (12), 94
(24), 82 (50), 81 (54). HRMS (EI, 70 eV) calcd for
C8H10O2 [M+]: 138.0681; found: m/z¼138.0681ꢃ2 ppm.
3.4.7. 5-Methyl-1-oxaspiro[4.5]dec-3-en-2-one (5g). Start-
ing with 3g (0.05 g, 0.26 mmol), dissolved in CH2Cl2
(10 ml), Ti(OiPr)4 (0.01 g, 0.04 mmol), dissolved in
CH2Cl2 (5 ml), and 4 (0.03 g, 0.03 mmol), dissolved in
CH2Cl2 (5 ml), 5g was isolated (0.032 g, 80%, dr >98:2)
as a colourless oil. 1H NMR (CDCl3, 250 MHz): d 0.71 (d,
3J¼7.0 Hz, 3H, CH3), 1.24–1.36 (m, 3H, CH2), 1.58–1.82
3.4.3. 1-Oxaspiro[4.6]undec-3-en-2-one (5c). Starting with
3c (0.21 g, 1.07 mmol), dissolved in CH2Cl2 (20 ml),
Ti(OiPr)4 (0.04 g, 0.15 mmol), dissolved in CH2Cl2 (5 ml),
and 4 (0.08 g, 0.10 mmol), dissolved in CH2Cl2 (5 ml), 5c
was isolated (0.14 g, 0.8 mmol, 76%) as a colourless oil.
1H NMR (CDCl3, 250 MHz): d 1.51–1.86 (m, 12H, CH2),
5.99 (d, 3J¼6.0 Hz, 1H, CH), 7.45 (d, 3J¼6.0 Hz, 1H,
CH). 13C NMR (CDCl3, 50 MHz): d 22.6, 28.8, 37.5
3
(m, 6H, CH2, CH), 5.99 (d, J¼6.0 Hz, 1H, CH), 7.26 (d,
3J¼6.0 Hz, 1H, CH). 13C NMR (CDCl3, 50 MHz): d 14.9
(CH3), 22.0, 25.3, 30.5, 35.4 (CH2), 36.8 (CH), 80.5 (C),

4654
U. Albrecht, P. Langer / Tetrahedron 63 (2007) 4648–4654
120.3, 160.8 (CH), 173.2 (CO). IR (KBr): ~n 2957 (w), 2917
(s), 2849 (s), 1632 (w), 1463 (w), 1261 (w) cmꢂ1
References and notes
.
1. (a) Ireland, R. E.; Thompson, W. J. J. Org. Chem. 1979, 44,
3041; (b) Ireland, R. E.; Varney, M. D. J. Org. Chem. 1986,
51, 635.
2. Gripenberg, J. Acta Chem. Scand. 1981, 35, 513.
3. Avcibasi, H.; Anil, H. Phytochemistry 1987, 26, 2852.
4. Caine, D.; Frobese, A. S. Tetrahedron Lett. 1978, 52, 5167.
5. Srikrishna, A.; Sharma, G. V. Tetrahedron Lett. 1988, 29, 6487.
6. Krause, N. Liebigs Ann. Chem. 1990, 603.
7. Larock, R. C.; Stinn, D. E.; Kuo, M. Y. Tetrahedron Lett. 1990,
31, 17.
8. (a) Orduna, A.; Zepeda, G.; Tamariz, J. Synthesis 1993, 375;
(b) Quayle, P.; Ward, E. L. Tetrahedron Lett. 1994, 35, 8883;
(c) Planas, M.; Segura, C.; Ventura, M.; Ortuno, R. M. Synth.
Commun. 1994, 24, 651.
3.4.8. 8-Phenyloxaspiro[4.5]dec-3-en-2-one (5h). Starting
with 3h (0.20 g, 0.78 mmol), dissolved in CH2Cl2 (20 ml),
Ti(OiPr)4 (0.03 g, 0.12 mmol), dissolved in CH2Cl2 (5 ml),
and 4 (0.06 g, 0.08 mmol), dissolved in 5 ml of CH2Cl2,
5h was isolated (0.143 g, 80%, dr¼3:1) as a colourless solid.
The stereochemistry could not be unambiguously assigned
1
(see 3h). H NMR (CDCl3, 300 MHz): d 1.66–2.19 (m,
8H, CH2), 2.53–2.61 (m, 1H, CH, syn/anti), 2.65–2.75 (m,
3
1H, CH, syn/anti), 6.03 (d, J¼6.0 Hz, 1H, CH, syn), 6.10
(d, 3J¼6.0 Hz, 1H, CH, anti), 7.20–7.35 (m, 5H, CH), 7.40
3
3
(d, J¼6.0 Hz, 1H, CH, syn), 7.88 (d, J¼6.0 Hz, 1H, CH,
anti). 13C NMR (CDCl3, 75 MHz): d 29.6, 31.0, 34.6, 35.3
(CH2), 42.4, 42.8 (CH), 87.4, 88.8 (C), 120.3, 120.9, 126.3,
126.5, 126.7, 126.8, 128.5, 128.6 (CH), 145.0, 146.2 (C),
158.2, 161.2 (CH), 171.9, 172.5 (C). IR (KBr): ~n 3089 (w),
2933 (m), 2861 (w), 1750 (s), 1601 (w), 1494 (w), 1449
(w) cmꢂ1. UV–vis (MeCN): lmax (log 3)¼208.55 (4.23) nm.
MS (EI, 70 eV): m/z (%)¼228 (M+, 100), 183 (11), 156 (51),
130 (29), 117 (67), 104 (99). HRMS (EI, 70 eV) calcd for
C15H16O2 [M+]: 228.1150; found: m/z¼228.1150ꢃ2 ppm.
ꢀ
9. Maulide, N.; Marko, I. E. Org. Lett. 2006, 8, 3705.
10. Reviews: (a) Schuster, M.; Blechert, S. Angew. Chem. 1997,
109, 2124; Angew. Chem., Int. Ed. 1997, 36, 2036; (b)
Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998, 371;
(c) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413.
11. Schmidt, B.; Wildemann, H. Eur. J. Org. Chem. 2000, 3145.
12. Ghosh, A. K.; Cappiello, J.; Shin, D. Tetrahedron Lett. 1998,
4651.
3.4.9. Adamantanone-spirobutenolide 5j. Starting with 3j
(0.20 g, 0.85 mmol), dissolved in CH2Cl2 (30 ml), Ti(OiPr)4
(0.04 g, 0.15 mmol), dissolved in CH2Cl2 (5 ml) and 4
(0.08 g, 0.10 mmol), dissolved in CH2Cl2 (5 ml), 5j was
isolated (0.11 g, 65%) as a colourless solid. 1H NMR
(CDCl3, 300 MHz): d 1.68–2.31 (m, 14H, CH, CH2), 6.05
(d, Jcis¼6.0 Hz, 1H, CH), 7.87 (d, Jcis¼6.0 Hz, 1H, CH).
13C NMR (CDCl3, 75 MHz): d 26.1, 26.8 (CH), 33.6, 35.0
(CH2), 36.8 (CH), 37.2 (CH2), 92.8 (C), 120.5, 159.1 (CH),
172.1 (C). IR (KBr): ~n 3078 (w), 2938 (s), 2917 (s), 2863
(m), 1738 (s), 1595 (w), 1454 (w) cmꢂ1. MS (EI, 70 eV):
m/z (%)¼204 (M+, 100), 176 (4), 148 (6), 110 (5), 95 (11).
HRMS (EI, 70 eV) calcd for C13H16O2 [M+]: 204.1150;
found: m/z¼204.1150ꢃ2 ppm [M+]. The spectroscopic
data are identical with those reported in the literature.19
13. (a) Bassindale, M. J.; Hamley, P.; Leitner, A.; Harrity, J. P. A.
Tetrahedron Lett. 1999, 3247; (b) Michaut, M.; Santelli, M.;
Parrain, J.-L. J. Organomet. Chem. 2000, 606, 93.
14. Langer, P.; Albrecht, U. Synlett 2002, 1841.
15. Li, Y.; Zhang, T.; Li, Y.-L. Tetrahedron Lett. 2007, 48, 1503.
16. (a) Herz, W.; Juo, R.-R. J. Org. Chem. 1985, 50, 618; (b) Wang,
C.; Russell. J. Org. Chem. 1999, 64, 2066.
17. F€urstner, A.; Langermann, K. J. Am. Chem. Soc. 1997, 119,
9130.
18. Molander, G. A.; Burkhardt, E. R.; Weinig, P. J. Org. Chem.
1990, 55, 4990.
19. Van Haard, P. M. M. Tetrahedron Lett. 1975, 10, 803.
3
3
ꢀ
20. Carda, M.; Castillo, E.; Rodrıguez, S.; Uriel, S.; Marco, J. A.
Synlett 1999, 1639.
21. Konzelman, L. M.; Conley, R. T. J. Org. Chem. 1968, 33,
3828.
22. Thummel, R. P.; Rickborn, B. B. J. Org. Chem. 1971, 36,
3.4.10. 5,6-Benzo[e]-1-oxaspiro[4.5]dec-3-en-2-one (5k).
Starting with 3k (0.11 g, 0.50 mmol), dissolved in CH2Cl2
(20 ml), Ti(OiPr)4 (0.02 g, 0.08 mmol), dissolved in
CH2Cl2 (5 ml) and 4 (0.04 g, 0.05 mmol), dissolved in
CH2Cl2 (5 ml), 5k was isolated (yield: 60% based on recov-
ered starting material) as a colourless oil. The spectroscopic
data are identical with those reported in the literature.20
1365.
23. Crabbe, P.; Dollat, J.-M.; Gallina, J.; Luche, J.-L.; Velarde, E.;
ꢀ
Maddox, M. L.; Tokes, L. J. Chem. Soc., Perkin Trans. 1 1978,
€ ꢁ
730. See also: Ref. 18.
24. (a) Levine, S. G.; Ng, A. S. J. Org. Chem. 1985, 50, 390; For an
independent synthesis of 2h, see: (b) Fleming, I.; Terrett, N. K.
J. Organomet. Chem. 1984, 264, 99.
25. Prakash, G. K. S.; Reddy, V. P.; Rasul, G.; Casanova, J.; Olah,
G. A. J. Am. Chem. Soc. 1992, 114, 3076.
Acknowledgements
26. (a) Bonete, P.; Najera, C. J. Org. Chem. 1994, 59, 3202; (b)
Torii, S.; Okamoto, T.; Tanaka, H. J. Org. Chem. 1974, 39,
2486.
We are grateful to Dr. Holm Frauendorf for MS measure-
ments. Financial support by the Deutsche Forschungsge-
meinschaft is gratefully acknowledged.
27. El Ali, B.; Alper, H. J. Org. Chem. 1991, 56, 5357.