7
234 J . Org. Chem., Vol. 65, No. 21, 2000
Notes
1
722, 1641, 1548, 1437, 1236, 914 cm-1; 1H NMR (200 MHz,
2.25-2.50 (m, 6H), 2.68 (m, 1H), 5.33-5.37 (m, 2H); 13C NMR
CDCl
7.2 Hz), 3.45 (s, 2H), 3.74 (s, 3H), 4.98 (m, 2H), 5.79 (ddt, 1H,
: C, 65.19; H,
3
) δ 1.41 (m, 2H), 1.61 (m, 2H), 2.05 (m, 2H), 2.55 (t, 2H, J
3
(50 MHz, CDCl ) δ 16.9 (t), 20.8 (q), 24.5 (t), 24.8 (t), 26.6 (t),
)
28.8 (t), 29.3 (d), 36.4 (t), 40.0 (t), 40.7 (t), 42.9 (t), 50.3 (t), 129.3
J ) 17.1, 10.2, 6.7 Hz). Anal. Calcd for C10
H
16
O
3
(d), 130.1 (d), 211.1 (s), 212.1 (s). Anal. Calcd for C16
76.75; H, 10.47. Found: C, 76.65; H, 10.64.
26 2
H O : C,
8
.75. Found: C, 65.37; H, 8.88.
R)-5-Meth yl-7,11-d ioxo-10-m eth oxyca r bon ylh ep ta d eca -
,16-d ien e (13). To a stirred suspension of the keto-ester 7 (121
(
(R)-3-Meth yl-1,12-d ioxocyclop en ta d eca n e (14). A stirred
suspension of a mixture of cyclic olefins 4a and 4b (109 mg, 0.43
mmol) and 5% palladium on charcoal (50 mg) in ethanol (12 mL)
was stirred under hydrogen atmosphere at room temperature
for 5 h. After filtration of the catalyst, the filtrate was concen-
trated in vacuo followed by purification of the residue by MPLC
(EtOAc/hexane 1:5) to give carbocycle 14 (108 mg, 98%) as a
1
mg, 0.66 mmol), potassium carbonate (95 mg, 0.69 mmol), and
tetra-n-butylammonium iodide (13 mg, 0.048 mmol) in DME
(0.40 mL) was added a solution of vinyl ketone 6 (58 mg, 0.38
mmol) in DME (0.70 mL). After being stirred for 1 h, the reaction
mixture was quenched with aq. 1 N hydrochloric acid and
extracted with ethyl acetate (× 2). Combined organic layer was
washed with water and brine and evaporated to dryness.
Purification of the residue by MPLC (EtOAc/hexane 1:5) pro-
vided keto-ester 13 (119 mg, 93%) as a colorless oil along with
white solid; mp 31.2s34.9 °C; R ) 0.42 (EtOAc/hexane 1:5);
f
[R]22 -7.2 (c 0.89, CHCl ); IR (CCl ) 2932, 2858, 1712, 1524
D
3
4
cm-1
1
; H NMR (200 MHz, CDCl ) δ 0.93 (d, 3H, J ) 6.7 Hz),
3
1.22 (m, 11H), 1.68 (m, 6H), 2.34 (m, 8H); 13C NMR (50 MHz,
recovered 7 (40 mg 0.22 mmol); R
f
) 0.37 (EtOAc/hexane 1:5);
); IR (CCl ) 3088, 2978, 2953, 2932,
743, 1720, 1641, 1437, 1373, 1165, 1047, 910 cm ; H NMR
) δ 0.89 (d, 3H, J ) 6.6 Hz), 1.43 (m, 4H), 2.26
m, 15H), 3.55 (t, 1H, J ) 7.1 Hz), 3.73 (s, 3H), 5.01 (m, 4H),
CDCl ) δ 17.3 (t), 21.6 (q), 23.2 (t), 25.1 (t), 26.5 (t), 27.1 (t), 27.2
3
1
9
[
2
R]
D
-1.58 (c 0.57, CHCl
3
4
(t), 27.9 (t), 28.8 (d), 36.3 (t), 41.2 (2C, t), 41.5 (t), 50.0 (t), 211.1
(s), 211.9 (s). Anal. Calcd for C16H28O2: C, 76.14; H, 11.18.
Found: C, 76.00; H, 11.50.
-
1
1
(200 MHz, CDCl
3
(
5
(
3R)-Meth yl-16-a za bicyclo[10.3.1]h exa d eca -1(16),12,14-
tr ien e or (R)-Mu scop yr id in e (1). A solution of the carbocycle
4 (25 mg, 0.10 mmol) in ethanol (5 mL) and hydroxylamine
1
3
3
.79 (ddt, 2H, J ) 17.1, 10.1, 6.7 Hz); C NMR (50 MHz, CDCl )
δ 19.6 (q), 21.7 (t), 22.8 (t), 28.1 (t), 28.7 (t), 31.1 (t), 33.4 (t),
3
1
1
5.9 (t), 40.0 (t), 41.8 (t), 50.1 (t), 52.3 (q), 57.2 (d), 114.5 (t),
14.6 (t), 138.3 (d), 138.5 (d), 167.0 (s), 204.9 (s), 209.5 (s). Anal.
hydrochloride (172 mg, 2.48 mmol) was heated at 150-160 °C
in a sealed tube (capacity 30 mL) for 16 h. After being cooled to
room temperature, the reaction mixture was diluted with ether,
and trace sodium bicarbonate (powder) was added to the
solution. The mixture was filtered by short silica gel column,
and a white precipitate was removed. The filtrate was concen-
trated in vacuo and the residue was purified by MPLC (EtOAc/
Calcd for C20
32 4
H O : C, 71.39; H, 9.59. Found C, 71.28; H, 9.61.
(
R)-5-Meth yl-7,11-d ioxoh ep ta d eca -1,16-d ien e (5). Lithium
chloride (1.14 g, 26.9 mmol) was added to a solution of the keto-
ester 13 (679 mg, 2.0 mmol) in DMPU (3 mL), and the reaction
mixture was heated at 120 °C for 7 h. The reaction was quenched
by addition of water. The organic layer was extracted with ethyl
acetate (× 2) and washed with water and brine. Evaporation of
the solvent in vacuo followed by purification of the residue by
MPLC (EtOAc/hexane 1:5) gave dimethylene 5 (404 mg, 72%)
hexane 1:5) to give (+)-muscopyridine 1 (14 mg, 61%) as a
23
colorless oil; R
f
) 0.62 (EtOAc/hexane 1:5); [R]
D
+12.5 (c 1.80,
), lit.,4 [R]
23
), lit.,5 [R]
25
CHCl
.90, CHCl ); IR (CCl
200 MHz, CDCl ) δ 1.06 (d, 3H, J ) 6.8 Hz), 0.88-1.31 (m, 13H),
.80 (m, 2H), 2.04 (m, 1H), 2.50 (dd, 1H, J ) 13.1, 10.1 Hz),
.85 (m, 2H), 6.94 (dd, 2H, J ) 7.6, 2.1 Hz), 7.48 (t, 1H, J ) 7.6
3
D
+17.1 (c 1.92, CHCl
3
D
+13.3 (c
-1
1
0
3
4
) 2928, 2858, 1576, 1454 cm ; H NMR
2
2
as a colorless oil; R
.64, CHCl ); IR (CCl
cm ; H NMR (200 MHz, CDCl
f
) 0.40 (EtOAc/hexane 1:5); [R]
) 3088, 2953, 1716, 1641, 1410, 1371, 998
) δ 0.89 (d, 3H, J ) 6.6 Hz),
.56 (m, 9H), 2.12 (m, 4H), 2.40 (m, 8H), 4.99 (m, 4H), 5.78 (ddt,
H, J ) 17.1, 10.1, 6.7 Hz); 13C NMR (50 MHz, CDCl
) δ 17.7
D
+3.18 (c
(
3
0
3
4
1
2
-
1
1
3
1
2
13
Hz); C NMR (50 MHz, CDCl
3
) δ 22.1 (q), 22.8 (t), 25.0 (t), 26.0
t), 26.1 (t), 26.3 (t), 27.8 (t), 33.5 (d), 34.0 (t), 36.9 (t), 45.3 (t),
3
(
(t), 19.6 (q), 23.2 (t), 28.4 (t), 28.7 (d), 31.2 (t), 33.5 (t), 36.0 (t),
1
20.2 (d), 120.5 (d), 136.1 (d), 160.7 (s), 161.5 (s). Picrolonic acid
4
1
1.5 (t), 42.1 (t), 42.6 (t), 50.1 (t), 114.5 (t), 114.6 (t), 138.4 (d),
38.6 (d), 210.4 (s), 210.6 (s). Anal. Calcd for C18 : C, 77.64;
4
salt of 1 was prepared according to the literature precedent and
had mp 161-163 °C (lit., 163-165 °C).
H
30
O
2
4
H, 10.86. Found: C, 77.65; H, 10.74.
R)-3-Meth yl-1,12-d ioxocyclop en ta d eca -6-en e (4). To a
Cr yst a llogr a p h ic d a t a of p icr olon ic a cid sa lt of 1 (23
(
°
C): yellow crystals (from n-hexane and 1,2-dichloroethane);
formula C26 , fw ) 495.58; triclinic, space group P1 (no.
), a ) 11.439(4) Å, b ) 11.722(4) Å, c ) 10.697(5) Å; R ) 95.05-
solution of bis(tricyclohexylphosphine)benzylideneruthenium
dichloride 3 (25 mg, 0.030 mmol) in dry degassed dichlo-
romethane (100 mL) was added a solution of dimethylene 5 (171
mg, 0.616 mmol) in dichloromethane (80 mL) via a dropping
funnel over a period of 2 h. The resulting purple solution was
stirred for 16.5 h at 40 °C and then concentrated under reduced
pressure to afford an oily brown residue. Purification of the
residue by silica gel column (EtOAc/hexane 1:5) gave cyclic
olefins 4a (104 mg, 67%) and 4b (35 mg, 23%) as a colorless oil.
33 5 5
H N O
2
3
(
3) deg., â ) 115.12(3) deg., γ ) 88.53(3) deg.; V ) 1293.5(9) Å ,
3
-1
Z ) 2, Dcalcd ) 1.272 g/cm , µ(Mo KR) ) 0.90 mm . A total of
reflection 5293, 1726 (I > 3.00σ(I)) were used in refinement: R
)
w
0.091, R ) 0.128. The reflection intensities were collected
on a Rigaku AFC7S diffractometer with a rotating anode (50
kV, 30 mA) using graphite monochromated Mo KR (λ ) 0.7107
Å).
Major cyclic olefin 4a had R
13.5 (c 0.71, CHCl ); IR (CCl
371 cm ; H NMR (500 MHz, CDCl
Hz), 1.26-1.56 (m, 6H), 1.85-1.93 (m, 3H), 2.00-2.15 (m, 6H),
.30-2.43 (m, 7H), 5.31-5.33 (m, 2H); 13C NMR (50 MHz,
CDCl ) δ 17.1 (t), 19.7 (q), 23.9 (t), 27.9 (t), 28.3 (t), 29.7 (t), 31.9
d), 35.9 (t), 40.9 (2C, t), 42.8 (t), 51.0 (t), 130.8 (d), 131.2 (d),
f
) 0.33 (EtOAc/hexane 1:5); [R]22
) 2932, 2862, 1712, 1462, 1404,
) δ 0.91 (d, 3H, J ) 6.5
D
+
1
3
4
-
1
1
Ack n ow led gm en t. This work was partially sup-
ported by the J apan Association of Chemistry.
3
2
3
Su p p or tin g In for m a tion Ava ila ble: An ORTEP drawing
of picrolonic acid salt of 1 and tables of X-ray crystallographic
(
2
10.8 (s), 211.9 (s). Minor cyclic olefin 4b had R
f
) 0.36 (EtOAc/
4
1
13
data and copies of H and C NMR spectra of all compounds
described in the Experimental Section. This material is
available free of charge via the Internet at http://pubs.acs.org.
2
0
hexane 1:5); [R]
2
δ 0.94 (d, 3H, J ) 7.0 Hz), 1.13 (m, 1H), 1.23-1.33 (m, 3H), 1.52-
1
D
-8.8 (c 0.27, CHCl
3
); IR (CCl ) 3007, 2934,
-
1 1
3
862, 1712, 1462, 1435, 1371 cm ; H NMR (500 MHz, CDCl )
.57 (m, 2H), 1.86-2.03 (m, 7H), 2.16 (dd, 1H, J ) 15.3, 5.3 Hz),
J O000785R