Synthesis of functionalized 4a-methyl-1,2,3,4,4a,9,10,10a- octahydrophenanthrenes

Article abstract of DOI:10.1002/(SICI)1522-2675(19990407)82:4<588::AID-HLCA588>3.0.CO;2-V

The title compounds were constructed by a Heck reaction of functionalized aryl halides with homoallylic alcohols followed by Michael addition and subsequent cyclocondensation.

Full text of DOI:10.1002/(SICI)1522-2675(19990407)82:4<588::AID-HLCA588>3.0.CO;2-V

588
Helvetica Chimica Acta ± Vol. 82 (1999)
Synthesis of Functionalized 4a-Methyl-1,2,3,4,4a,9,10,10a-
octahydrophenanthrenes
by Gerald Dyker* and Peter Grundt
Fachbereich 6, Institut für Synthesechemie, Gerhard-Mercator-Universität-Gesamthochschule Duisburg,
Lotharstrasse 1, D-47048 Duisburg
The title compounds were constructed by a Heck reaction of functionalized aryl halides with homoallylic
alcohols followed by Michael addition and subsequent cyclocondensation.
Introduction. ± Abietic acid (1) and salviol (2) are two examples of a widespread
family of diterpenes found in various plants such as juniper, pine tree and sage [1]. A
partially hydrated phenanthrene moiety with a Me group at C(4) is a common
structural unit of these natural products. Recently, we reported on a domino process [2]
combining the Heck reaction [3] with classical carbonyl reactions giving convenient
access to related structures [4]: the Heck reaction with allylic and homoallylic alcohols
as olefinic coupling components leads to carbonyl compounds [5]; this is the basis for
reaction sequences that include the Michael addition, aldol condensation [6], or imine
formation [7] depending on the presence of appropriate functional groups. For
instance, bromoaryl ketone 3.1a (R ˆ H, X ˆ Br) reacts with but-3-en-1-ol (4) under Pd
catalysis and a subsequent Robinson-type annulation is completed under acidic
conditions to give the functionalized hexahydrophenanthrene 5.1 in acceptable yield
(R ˆ H; Scheme 1, Table 1, Entry 1) [4]. In this paper, we report on our attempts to
apply this reaction sequence for the synthesis of corresponding 4a-methylated
phenanthrenes.
Results and Discussion. ± In contrast to the reaction of bromoaryl ketone 3.1a, the
homologues compound (E)-3.2a (R ˆ Me, X ˆ Br) reacted sluggishly, presumably
because of steric hindrance by the additional Me group: 59% of the starting material
was recovered, though partially isomerized to the (Z)-isomer, and only 14% of the
tricyclic annelation product 5.2 was obtained, exclusively in the cis-configuration. The
corresponding iodoaryl ketone (E)-3.2b (R ˆ Me, X ˆ I) is significantly more reactive;

Helvetica Chimica Acta ± Vol. 82 (1999)
589
Scheme 1
a) 1. 1 mmol of 3, 2.5 equiv. of 4, 5 mol-% of Pd(OAc)2, EtN(i-Pr)2, LiCl, 10 ml of DMF, N2, 808, 3 d for Entries
1 and 3, and 5 d for Entry 2; 2. 1 equiv. of conc. HCl, CHCl3, 408, sonication, 4 h (for Entries 1 and 3) or 10 mol-
% of TsOH, CHCl3, reflux, 2 d (for Entry 2).
Table 1. Annelation Reactions of Halogenoaryl Ketones 3 with But-3-en-1-ol (4)
Entry
Substrate
R
X
Yield [%]
5 (cis/trans)
6
1
2
3
3.1a
3.2a
3.2b
H
Me
Me
Br
Br
I
56 (1:4)
14 (cis)
22 (4:1)
±
±
21
an overall yield of 43% for annelation products was attained: the a,b-unsaturated
ketone 5.2 with the cis/trans-ratio of 4:1 (isomers clearly distinguished by NOESY
experiments) as well as the b,g-unsaturated ketone 6.2 (all products are, of course,
racemic).
These results indicate that hydrated phenanthrene derivatives with a Me group at
C(4a) can be constructed by our method, although the yields remain only moderate.
Therefore, we studied a,b-unsaturated esters 7 as alternative coupling components.
With the pentenol 8 as olefinic coupling component, the bromoaryl ketone (E)-7.1a
led to the open-chain product 9.1 in high yield (R ˆ H; Scheme 2, Table 2, Entry 1).
Obviously, the a,b-unsaturated ester moiety is not reactive enough to undergo an
intramolecular Michael addition under the slightly basic conditions of the Heck
reaction nor under the acidic conditions typically applied in the second reaction step
(cf. Scheme 1). The Me-substituted analogue (E)-7.2a reacted in the same way
(Entries 2 and 3), and the corresponding iodo derivative (E)-7.2b was somewhat more
reactive (Entries 5 and 6).
Surprisingly the (Z)-isomers (Z)-7.2a and (Z)-7.2b turned out to be completely
unreactive; the 10% yield of coupling product 9.2 of Entry 10 might be due to an (E/Z)-
isomerization prior to the Heck reaction. An interaction of the intermediary aryl
palladium halide with the ester moiety, which is exclusively restricted to the (Z)-
configuration, seemed to inhibit the coupling reaction.
To increase the reactivity for a cyclization reaction, we transformed the ester 9.2 to
the aldehyde 13.2 in a two-step procedure (Scheme 3). Compound 9.2 was reduced with
LiAlH4, affecting both CˆO groups and resulting in the formation of the diol 12.2. A
double Swern oxidation led to the desired aldehyde 13.2, a sensitive oil with the
tendency for auto-oxidation and polymerization. All attempts to cyclize 13.2 by
Michael addition and subsequent aldol condensation failed: under basic conditions

590
Helvetica Chimica Acta ± Vol. 82 (1999)
Scheme 2
a) 1 mmol of 7, 2.5 equiv. of 8, 5 mol-% of Pd(OAc)2, EtN(i-Pn)2, LiCl, 25 ml of DMF, N2, 808, 3 ± 10 d.
Table 2. Heck Reaction of Halogenoaryl Esters 7 with Pent-4-en-2-ol 8
Entry
Substrate
R
X
t
Yield [%]
9 (E)/(Z)
Recov. 7
1
2
3
4
5
6
7
(E)-7.1a
(E)-7.2a
(E)-7.2a
(Z)-7.2a
(E)-7.2b
(E)-7.2b
(Z)-7.2b
H
Br
Br
Br
Br
I
2 d
3 d
10 d
3 d
3 d
84 (100:0)
62 (87:13)
69 (84:16)
trace
62 (89:11)
77 (82:18)
10 (80:20)
±
20
9
84
19
±
Me
Me
Me
Me
Me
Me
I
I
10 d
3 d
74 (16:84)
10% t-BuOK in THF at room temperature, complete polymerization was observed.
The Lewis acid TiCl4 caused some minor (E/Z)-isomerization. An excess of
concentrated HCl in THF at reflux temperature led to the isolation of the
benzocyclooctene 14.2, obviously the aldol condensation product of the (Z)-isomer
(Z)-13.2. However, under strongly basic conditions (excess NaH in THF/EtOH), the
direct double cyclization of the functionalized esters 9 turned out to be successful:
phenanthrenes 1,3-diones 11 were obtained in acceptable yields. The diastereoisomers
were identified by NOESY spectra; for the trans-annelated products, the NOEꢀs
between Hax C(4) and H C(10a), and between Hax C(10) and H C(4a) (for trans-
11.1), or the Me group at C(4a) (for trans-11.2) are characteristic. The cis-annelated
products were identified by the NOE between H C(10a) and H C(4a) or Me C(4a).
For 11.1, the trans-isomer clearly predominates; in contrast, for the Me-substituted
derivative 11.2, the cis-isomer is favored. This finding represents a significant drawback
for plans to apply this method to natural product synthesis, since most target molecules
of this type are trans-annelated. However, the acidity of H C(10a) allows epimeriza-
tion at this center and might help to solve this synthetic problem.
Experimental Part
1. General. Anal. TLC: precoated plastic sheets POLYGRAM SIL G/UV254 from Macherey-Nagel. M.p.
(uncorr.): Reichert Thermovar. IR: Perkin-Elmer 983. UV/VIS: Perkin-Elmer 554; MeCN as solvent. NMR:
Bruker DRX 500, Bruker WM 300. 1H-NMR spectra (500 MHz or 300 MHz): in CDCl3 (if not mentioned
otherwise), TMS internal standard. 13C-NMR Spectra (125.8 MHz or 75.5 MHz): using CDCl3 as solvent and
internal standard. MS: MAT 311A (70 eV).
2. Synthesis of the Coupling Components. 2.1. Ethyl (E)-3-(2-Bromophenyl)prop-2-enoate ((E)-7.1a). A
suspension of 3.70 g (20.0 mmol) of 2-bromobenzaldehyde, 4.92 g (21.0 mmol) of triethyl phosphonoacetate

Helvetica Chimica Acta ± Vol. 82 (1999)
591
Scheme 3
a) 5 Equiv. of NaH, trace amount of EtOH, THF, room temperature, 16 h; b) LiAlH4, Et2O, reflux, 2 h. c) Swern
oxidation, 608, 1 h.
and 526 mg (22.0 mmol) of LiOH in 25 ml of THF was stirred for 3 h at r.t. After filtration through silica gel, the
solvent was evaporated and the product mixture fractionated by flash chromatography (FC). TLC (silica gel;
petroleum ether/t-BuOMe 5:1): Rf 0.66 ((E)-7.1a), 0.11, 0.00. The fraction with Rf 0.66 gave 4.79 g (94%) of
(E)-7.1a. Colorless oil. NMR Spectra are in accord with the reported data [8]. 1H-NMR (300 MHz): 1.33 (t, J ˆ
7.1, 3 H); 4.26 (q, J ˆ 7.1, 2 H); 6.37 (d, J ˆ 15.9,
H
C(2)); 7.19 (t, J ˆ 7.8, 1 H); 7.29 (t, J ˆ 8.2, 1 H);
7.57 (m, 1 H); 7.60 (m, 1 H); 8.03 (d, J ˆ 15.9,
H
C(3)). 13C-NMR (75.5 MHz): 14.31 (q); 60.69 (t);
121.18 (d, C(2)); 125.29 (s, C 2')); 127.70, 127.77, 131.13, 133.43 (4d); 134.60 (s, C(1')); 142.91 (d, C(3));
166.37 (s, C(1)).
2.2. Ethyl 3-Arylbut-2-enoates (7.2). General Procedure: A 1.6m soln. of BuLi (8.0 ml, 12 mmol) in hexane
was added dropwise at 08 under N2 to a soln. of 2.81 g (12.5 mmol) of triethyl phosphonoacetate in 20 ml of dry
THF. After 30 min stirring at r. t., 10.0 mmol of the acetophenone in 5 ml of dry THF were added, and the
reaction mixture was stirred for another 2 d. After hydrolysis with 15 ml of 1m HCl and extracting with AcOEt
(3 Â 10 ml), the combined org. layer was filtered through silica gel. The solvent was evaporated and the product
mixture fractionated by FC.
2.2.1. Ethyl 3-(2-Bromophenyl)but-2-enoate (7.2a): 2-Bromoacetophenone (1.99 g, 10.0 mmol) was treated
with triethyl phosphonoacetate according to the General Procedure. TLC (silica gel; petroleum ether/t-BuOMe
10:1): Rf 0.68, 0.57 ((E)-7.2a), 0.44 ((Z)-7.2a), 0.00. The first fraction with Rf 0.57 gave 1.62 g (60%) of (E)-7.2a.
Colorless oil. UV/VIS: 224 (4.05), 243 (3.84, sh). IR (film): 3056w, 2979w, 1715s, 1641m, 1558w, 1466m, 1432w,
1366w, 1339w, 1287m, 1246m, 1176s, 1121w, 1091w, 1042w, 1026w, 878w, 760m, 656m. 1H-NMR (500 MHz):
1.31 (t, J ˆ 7.2, 3 H); 2.48 (d, J ˆ 1.5, H C(4)); 4.22 (q, J ˆ 7.2, 2 H); 5.80 (q, J ˆ 1.5, H C(2)); 7.15 (m, 1 H);

592
Helvetica Chimica Acta ± Vol. 82 (1999)
7.16 (m, 1 H); 7.28 (td, J ˆ 7.5, 1.2, 1 H); 7.55 (m, 1 H). NOE (500 MHz); spin saturation at 2.48:
2.48 ( 100.0%, 3 H); 4.22 (‡ 0.9%, 2 H); 5.80 (‡ 1.0%, 1 H); 7.15 (‡ 1.1 %, 1 H). 13C-NMR (125 MHz):
14.25(q); 20.32 (q, C(4)); 59.93(t); 120.46 (d, C(2)); 120.62 (s, C(1')); 127.32, 128.81, 129.09, 132.96(4d); 144.64,
‡
‡
156.94(s); 166.26 (s, C(1)). EI-MS: 270/268 (4/4, M ), 225/223 (20/21, [M C2H5O] ), 190(12), 189(77, [M
‡
‡
‡
Br] ), 162(20), 161(100, [M Br C2H4] ), 144(13, [M Br C2H5O] ), 117(18), 116(58), 115(78),
105(12), 89(13), 58(14), 39(11). Anal. calc. for C12H13BrO2 (269.14): C 53.55, H 4.87; found C 53.76,
H 4.87. Second fraction: 833 mg (31%) of (Z)-7.2a.
Data of (Z)-7.2a: Colorless oil. IR (film): 3053w, 2981m, 2908w, 1723s, 1646w, 1589w, 1563w, 1469m, 1428m,
1372m, 1352w, 1279m, 1233s, 1164s, 1121w, 1093w, 1046m, 1025m, 947w, 868w, 756m. UV/VIS: 217(4.15).
1H-NMR (500 MHz): 1.04 (t, J ˆ 7.1, 3 H); 2.14 (d, J ˆ 1.5, Me C(4)); 3.96 (q, J ˆ 7.1, 2 H); 5.99 (q, J ˆ 1.5,
H
C(2)); 7.06 (dd, J ˆ 7.5, 1.7, 1 H); 7.14 (m, 1 H); 7.29 (td, J ˆ 7.5, 1.2, 1 H); 7.55 (dd, J ˆ 7.9, 1.1, 1 H). NOE
(500 MHz); spin saturation at 2.14: 2.14 ( 100.0%, 3 H); 5.99 (‡ 5.0%, H C(2)); 7.06 (‡ 1.2%, 1 H).
13C-NMR (75.5 MHz): 13.84 (q); 25.94 (q, C(4)); 59.68 (t); 119.72 (d, C(2)); 120.21 (s, C(2')); 127.08, 127.74,
‡
128.49, 132.33 (4d); 142.46, 154.50 (2s); 164.93 (s, C(1)). EI-MS: 225/223 (16/17, [M C2H5O]H ), 190(15),
‡
‡
‡
189(89, [M Br] ), 162(21), 161(100, [M Br C2H4] ), 144(11, [M Br C2H5O] ), 117(19), 116(57),
115(80), 105(14), 91(12), 89(14), 58(14), 39(13). Anal. calc. for C12H13BrO2 (269.14): C 53.55, H 4.87; found
C 53.55, H 4.85.
2.2.2. Ethyl 3-(2-Iodophenyl)butenoate (7.2b): 2-Iodoacetophenone (2.46 g, 10.0 mmol) was treated with
triethyl phosphonoacetate according to the General Procedure. TLC (silica gel; petroleum ether/t-BuOMe
10:1): Rf 0.77, 0.70 ((E)-7.2b), 0.66, 0.54 ((Z)-7.2b), 0.33, 0.00. The first fraction with Rf 0.70 gave 1.97 g (62%)
of (E)-7.2b. Colorless oil. UV/VIS: 222 (4.25, sh). IR (film): 3055w, 2979m, 1712s, 1641m, 1582w, 1554w, 1461m,
1428m, 1366m, 1338m, 1284m, 1245m, 1177s, 1115w, 1088w, 1042m, 1014m, 945w, 877m, 760m, 742w, 647m.
1H-NMR (300 MHz): 1.32 (t, J ˆ 7.1, 3 H); 2.45 (d, J ˆ 1.4, 3 H C(4)); 4.22 (q, J ˆ 7.1, 2 H); 5.75 (q, J ˆ 1.4,
H
C(2)); 6.99 (m, 1 H); 7.12 (dd, J ˆ 7.6, 1.7, 1 H); 7.33 (td, J ˆ 7.5, 1.2, 1 H); 7.84 (dd, J ˆ 7.9, 1.2, 1 H).
13C-NMR (75.5 MHz): 14.32 (q); 20.68 (q, C(4)); 59.99 (t); 95.25 (s, C 2'); 120.81 (d, C(2); 127.85, 128.17,
‡
‡
129.07, 139.56 (d); 148.82, 159.13, 166.33 (s). EI-MS: 316 (0.26, M ), 271 (12), 189 (65, [M I] ), 162 (14),
161 (100, [M
‡
‡
I
C2H4] ), 144 (30, [M
I
C2H5O] ), 117 (11), 116 (25), 115 (71), 105 (11). Anal. calc. for
C12H13IO2 (316.14): C 45.59, H 4.14; found C 45.60, H 4.11.
Second fraction: 840 mg (27%) of (Z)-7.2b. Colorless oil. UV/VIS: 221 (4.08). IR (film): 3051w, 2980m,
2906w, 1724s, 1645m, 1584w, 1465m, 1440m, 1426m, 1371m, 1351w, 1279m, 1231s, 1159s, 1116w, 1090w, 1046m,
1012m, 959w, 867w, 756m, 646m. 1H-NMR (300 MHz): 1.04 (t, J ˆ 7.1, 3 H); 2.13 (d, J ˆ 1.5, Me C(4));
3.97 (q, J ˆ 7.1, 2 H); 5.98 (q, J ˆ 1.5, H C(2)); 6.98 (ddd, J ˆ 7.8, 7.4, 1.7, 1 H); 7.05 (dd, J ˆ 7.6, 1.7, 1 H);
7.34 (td, J ˆ 7.5, 1.2, 1 H); 7.83 (dd, J ˆ 7.9, 1.1, 1 H). 13C-NMR (75.5 MHz): 13.90 (q); 26.13 (q, C(4));
59.74 (t); 95.15 (s, C(2')); 119.87 (d, C(2)); 126.78, 127.95, 128.44, 138.83 (4d); 146.70, 156.99 (2s);
‡
‡
‡
164.85 (s, C(1)). EI-MS: 316 (0.07, M ), 271 (6), 189 (59, [M I] ), 162 (11), 161 (100, [M
I
C2H4] ),
‡
144 (17, [M
I
C2H5O] ), 117 (7), 116 (16), 115 (53), 105 (10), 91 (7), 89 (7), 63 (5), 39 (5). Anal. calc. for
C12H13IO2 (316.14): C 45.59, H 4.14; found C 45.51, H 4.11.
2.3. 4-Arylpent-3-en-2-ones (3.2). General Procedure. A soln. of 5 mmol of (E)-7.2a or (E)-7.2b, and 1.56 g
(7.50 mmol) dimethyltitanocene [9] in 25 ml of dry THF was heated under N2 at reflux temp. for 64 h. After
hydrolysis with 10 ml of 1m HCl for 1 h at r. t. and extracting twice with 20 ml of methyl-t-BuOMe, the combined
org. layer was filtered through silica. The solvent was evaporated, and the crude product mixture was purified by
bulb-to-bulb distillation at 1258/0.5 mbar. The distillate was further purified by FC.
2.3.1. (E)-4-(2-Bromophenyl)pent-3-en-2-one ((E)-3.2a). The ester (E)-7.2a (1.35 g, 5.00 mmol) was
treated with dimethyltitanocene according to the General Procedure. TLC (silica gel, petroleum ether/6:1):
Rf 0.89, 0.85, 0.78 ((E)-7.2a), 0.56 ((E)-3.2a), 0.37, 0.00. The first fraction with Rf 0.78 gave 609 mg (45%) of
recovered starting material (E)-7.2a. Second fraction with Rf 0.56: 542 mg (45%; 83% based on recovered
starting material) of (E)-3.2a. Slightly yellow oil. UV/VIS: 223 (4.18), 251 (3.94, sh). IR (film): 3054w, 3003w,
2959w, 2916w, 1686s, 1616s, 1559w, 1467m, 1424m, 1371m, 1356m, 1284w, 1262w, 1244w, 1179m, 1121w,
1091w, 1027m, 963w, 857w, 755m, 724w, 671w, 639w. 1H-NMR (300 MHz): 2.27 (s, 3 H C(1)); 2.44 (d,
J ˆ 1.4, 3 H C(5)); 6.18 (q, J ˆ 1.4, H C(3)); 7.13 ± 7.20 (m, 2 H); 7.31 (m, 1 H); 7.60 (m, 1 H). 13C-NMR
(75.5 MHz): 20.73 (q, C(5)); 32.03 (q, C(1)); 120.75 (s, C(2')); 127.39, 127.50, 128.84, 129.14, 133.08 (5d);
‡
‡
144.87 (s, C(1')); 154.92 (s, C(4)); 198.80 (s, C(2)). EI-MS: 240/238 (7/7, M ), 225/223 (5/6, [M Me] ),
‡
‡
160 (16), 159 (100, [M Br] ), 144 (16), 116 (54), 115 (37), 89 (8), 58 (8), 43 (32, [C2H3O] ). Anal. calc. for
C11H11BrO (239.11): C 55.25, H 4.64; found C 55.40, H 4.64.
2.3.2. (E)-4-(2-Iodophenyl)pent-3-en-2-one ((E)-3.2b). The ester (E)-7.2b (1.90 g, 6.00 mmol) was treated
with 1.42 g (6.82 mmol) of dimethyltitanocene according to the General Procedure. TLC (silica gel; petroleum

Helvetica Chimica Acta ± Vol. 82 (1999)
593
ether/t-BuOMe 5:1): Rf 0.70 ((E)-7.2b), 0.56 ((E)-3.2b), 0.00. The first fraction with Rf 0.70 gave 793 mg (42%)
of recovered starting material (E)-7.2b. Second fraction with Rf 0.56: 864 mg (50%; 86% based on recovered
starting material) of (E)-3.2b. Yellow oil. UV/VIS: 228 (4.11), 268 (3.56, sh). IR (film): 3051w, 3002w, 1688s,
1613s, 1554w, 1461m, 1428m, 1355m, 1282w, 1258w, 1244w, 1182m, 1039w, 1014m, 963w, 857w, 756m, 721w, 662m.
1H-NMR (300 MHz): 2.28 (s, 3H C(1)); 2.41 (d, J ˆ 1.4, 3H C(5)); 6.13 (q, J ˆ 1.3, H C(3)); 6.99 (td, J ˆ
7.4, 1.7, 1 H); 7.13 (ddd, J ˆ 7.5, 1.8, 0.2, 1 H); 7.34 (td, J ˆ 7.5, 1.2, 1 H); 7.85 (ddd, J ˆ 7.9, 1.2, 0.3, 1 H).
13C-NMR (75.5 MHz): 20.95 (q, C(5)); 31.97 (q, C(1)); 95.35 (s, C(2')); 127.57, 127.72, 128.14, 129.05,
‡
139.44 (5d); 148.66 (s, C(1')); 157.10 (s, C(4)); 198.79 (s, C(2)). EI-MS: 286 (0.5, M ), 160 (17), 159 (100,
‡
‡
[M I] ), 144 (31), 117 (5), 116 (23), 115 (39), 91 (9), 89 (8), 63 (6), 43 (39, C2H3O ), 39 (6). Anal. calc. for
C11H11IO (286.11): C 46.18, H 3.88; found: C 46.45, H 3.84.
3. Palladium-Catalyzed Coupling Reactions and Subsequent Carbonyl Reactions.
3.1. General Procedure for the Palladium-Catalyzed Coupling Reactions. A mixture of 1.00 mmol of the
ketone 3.2 or the esters 7, 180 mg (2.50 mmol) of butenol 4 or pentenol 8, 11.2 mg (50 mmol, 5 mol-%)
Pd(OAc)2, 1.0 g (8.0 mmol) of EtN(i-Pr)2, and 42 mg (1.0 mmol) of LiCl in dry DMF (10 ml for 3.2 and 25 ml in
the case of 7) in a sealed tube was stirred under N2 at 808 for 2 ± 10 d. After addition of 50 ml of H2O, the
mixture was extracted three times with t-BuOMe (3 Â 20 ml), the combined org. layer was washed with 50 ml of
H2O, and the H2O layer re-extracted with 10 ml of AcOEt. After filtering the combined org. layer through silica
gel, the soln. was concentrated at 508/0.5 mbar by bulb-to-bulb distillation. For coupling reactions with ketones
3.2, the crude product mixture was treated under acidic conditions in CHCl3 before the reaction mixture was
fractionated by FC.
3.2. Coupling Reaction of 3.2a with But-3-en-1-ol (4; Entry 2 of Table 1): The ketone (E)-3.2a (239 mg,
1.00 mmol) and butenol 4 (180 mg, 2.50 mmol) were coupled under palladium catalysis according to the General
Procedure (reaction time: 3 d). The crude product mixture was treated with 19 mg (10 mol-%) TsOH in 10 ml of
CHCl3 for 2 d at reflux temp. After neutralization with 100 mg of NaHCO3, the soln. was filtered through silica
gel and concentrated. TLC (silica gel; petroleum ether/t-BuOMe 1:2): Rf 0.88, 0.81, 0.73 ((E)-3.2a, (E)-3.2c
(X ˆ H)), 0.62 ((Z)-3.2a), 0.50 (cis-5.2), 0.35, 0.27, 0.00. FC was performed with petroleum ether/t-BuOMe
15:1. First fraction: 97 mg of a mixture of starting material ((E)-3.2a) and (E)-4-phenylpent-3-en-2-one ((E)-
3.2c; X ˆ H) in the ratio 7.5:1.0. Second fraction: 52 mg (22%) of isomerized starting material ((Z)-3.2a) as a
brown oil. UV/VIS: 220 (4.20), 249 (3.74, sh). IR (film): 2970w, 1688s, 1665s, 1618s, 1587w, 1467m, 1424m,
1
1370w, 1356m, 1260w, 1179m, 1094w, 1025s, 963w, 859w, 800w, 759s, 725w, 669m, 657m. H-NMR (300 MHz):
1.83 (s, 3 H C(1)); 2.14 (d, J ˆ 1.5, 3 H C(5)); 6.23 (q, J ˆ 1.4,
H
C(3)); 7.09 (dd, J ˆ 7.5, 1.7, 1 H);
7.18 (t, J ˆ 7.7, 1 H); 7.32 (dd, J ˆ 7.5, 1.2, 1 H); 7.58 (d, J ˆ 8.5, 1 H). 13C-NMR (75.5 MHz): 26.30 (q, C(5));
29.66 (q, C(1)); 120.30 (s, C(2')); 127.51, 128.19, 129.00, 129.16, 132.72 (5d); 142.09 (s, C(1')); 151.90 (s, C(4));
‡
‡
197.81 (s, C(2)). EI-MS: 240/238 (2.5/2.5, M ), 160 (14), 159 (100, [M Br] ), 144 (12), 116 (39), 115 (29),
89 (7), 58 (8), 43 (32). Anal. calc. for C11H11BrO (239.11): C 55.25, H 4.64; found: C 55.05, H 4.60.
Third fraction: 30 mg (14%) of (4aR*,10aR*)-3,4,4a,9,10,10a-hexahydro-4a-methylphenanthren-3-one (cis-
5.2). Colorless oil. UV/VIS: 212 (4.10), 228 (3.89, sh), 264 (2.84), 272 (2.77). IR (film): 3020w, 2933m, 2874m,
1676s, 1488m, 1445m, 1386m, 1331w, 1292w, 1250w, 1177w, 1141w, 1092w, 1076w, 1042w, 946w, 899w, 885w, 839w,
809w, 761m, 729m. 1H-NMR (500 MHz): 1.42 (s, 3 H); 1.88 (m, Hax C(10)); 2.13 (m, Heq C(10)); 2.57 (d, J ˆ
16.2, HA C(4)); 2.60 (m, H C(10a)); 2.85 (m, 2 H C(9)); 2.88 (d, J ˆ 16.2, HB C(4)); 5.99 (dd, J ˆ 10.1, 2.0,
H
C(2)); 6.87 (dd, J ˆ 10.1, 4.0, H C(1)); 7.06 (dd, J ˆ 7.6, 0.9, 1 H); 7.11 (t, J ˆ 7.3, 1.3, 1 H); 7.18 (t, J ˆ 7.1,
1 H); 7.28 (dd, J ˆ 7.9, 1.1, 1 H). 13C-NMR (125.8 MHz): 24.34 (t, C(10)); 28.81 (t, C(9)); 29.45 (q);
39.38 (s, C(4a)); 43.43 (d, C(10a)); 50.05 (t, C(4)); 126.13, 126.56, 126.68 (3d); 128.99 (d, C(2)); 129.17 (d);
‡
‡
134.76, 141.87 (2s); 152.36 (d, C(1)); 198.89 (s, C(3)). EI-MS: 213 (14, [M ‡ 1] ), 212 (86, M ), 198 (16),
‡
197 (100, [M Me] ), 179(22), 169(23), 155(15), 153(10), 142(13), 141(24), 129(21), 128(21), 115(21),
91(13), 81(16). Anal. calc. for C15H16O (212.29): C 84.87, H 7.60; found: C 84.80, H 7.59.
3.3. Coupling Reaction of 3.2b with 4 (Entry 3 of Table 1). The ketone (E)-3.2b (286 mg, 1.00 mmol) and
180 mg (2.50 mmol) of 4 were coupled under palladium catalysis according to the General Procedure (reaction
time: 3 d). The crude product mixture was treated with 0.1 g of conc. HCl in 10 ml of CHCl3 in the ultrasonic
bath for 4 h at 408. After neutralization with 100 mg of NaHCO3, the soln. was filtered through silica gel and
concentrated. TLC (silica gel; petroleum ether/t-BuOMe 1:2): Rf 0.81, 0.66(6), 0.57 (trans-5.2), 0.48 (cis-5.2),
0.19, 0.00. FC was performed with petroleum ether/t-BuOMe 10:1. First fraction: 44 mg (21%) of 2,3,4,4a,9,10-
hexahydro-4a-methylphenanthren-3-one (6). Slightly yellow oil. IR (film): 3055w, 3018m, 2960s, 2930s, 2843m,
1715s, 1600w, 1487w, 1444w, 1398m, 1377m, 1350m, 1307m, 1242m, 1179w, 1151w, 1076w, 1039m, 1005m, 969w,
937w, 867w, 837w, 766s, 737m, 704m, 669m. 1H-NMR (500 MHz, CDCl3): 1.36 (d, J ˆ 0.8, 3 H); 2.50 (m,
2 H C(10)), 2.59 (dd, J ˆ 13.8, 0.8, Hax C(4)); 2.82 ± 3.02 (m, 2 H C(2), Heq C(4), 2 H C(9)); 5.55 (m,

594
H
Helvetica Chimica Acta ± Vol. 82 (1999)
C(1)); 7.10 ± 7.15 (m, 2 H); 7.20 ± 7.25 (m, 2 H). 1H-NMR (500 MHz, C6D6): 1.17 (d, J ˆ 0.8, 3 H);
2.07 (ddd, J ˆ 13.1, 4.8, 2.8, Heq C(10)); 2.16 (m, Hax C(10)); 2.22 (dd, J ˆ 13.5, 0.8, Hax C(4)); 2.52 (ddd,
J ˆ 21.9, 3.9, 2.2, HA (2)); 2.56 ± 2.65 (m, HB C(2), 2 H C(9)); 2.78 (d, J ˆ 13.5); 5.04 (m, H C(1)); 6.90 ±
6.92 (m, H C(5), H C(8)); 6.98 (t, J ˆ 7.3, 1 H); 7.02 (t, J ˆ 7.5, 1 H). 13C-NMR (75.5 MHz, C6D6): 29.36
(q, Me); 30.04 (t, C(10)); 32.00 (t, C(9)); 39.63 (t, C(2)); 41.76 (s, C(4a)); 53.82 (t, C(4)); 116.80 (d, C(1));
‡
126.09, 126.66, 126.99, 129.03(4d); 135.88, 143.66, 143.93(3s); 207.07 (s, C(3)). EI-MS: 213 (9, [M ‡ 1] ),
‡
‡
212 (55, M ), 198(16), 197(100, [M Me] ), 170(31), 169(71), 155(21), 154(14), 153(14), 152(10), 141(28),
128(19), 115(15), 91(10). HR-MS: calc. for C15H16O (212.29): 212.12012; found 212.12018.
Second fraction: 10.1 mg (5%) of (4aR*,10aS*)-3,4,4a,9,10,10a-hexahydro-4a-methylphenanthren-3-one
(trans-5.2). Slightly yellow oil. UV/VIS: 212(4.11), 230 (3.93, sh), 272(2.80), 334(2.80). IR (film): 3023w,
2935m, 1675s, 1487m, 1446w, 1384w, 1324w, 1264w, 1240w, 1167w, 1065w, 1043w, 1027w, 882w, 801w, 759m, 721w.
1H-NMR (500 MHz): 1.15 (d, J ˆ 1.1, 3 H); 1.95 (m, 1 H, Hax C(10)); 2.04 (m, Heq C(10)); 2.53 (dq, J ˆ 16.1,
1.1, Hax C(4)); 2.82 (m, H C(10a)); 3.02 (m, 2 H C(9)); 3.12 (d, J ˆ 16.1, Heq C(4)); 6.12 (ddd, J ˆ 9.9, 3.1,
1.1, H C(2)); 6.78 (dd, J ˆ 9.0, 2.0, H C(1)); 7.11 ± 7.21 (m, 4 H). 13C-NMR (75.5 MHz): 22.82(q); 23.49
(t, C(10)); 28.94 (t, C(9)); 40.39 (s, C(4a)); 42.23 (d, C(10a)); 51.17 (t, C(4)); 123.97, 126.18, 126.38 (3d);
‡
129.31 (d, C(2)); 129.69(d); 134.44, 144.52(s); 153.31 (d, C(1)); 199.41 (s, C(3)). EI-MS: 213(11, [M ‡ 1] ),
‡
‡
212(63, M ), 198(15), 197(100, [M Me] ), 179(12), 169(30), 157(12), 155(11), 142(11), 141(17), 129(16),
115(16), 91(12), 81(22). Anal. calc. for C15H16O (212.29): C 84.87, H 7.60; found: C 84.65, H 7.54.
Third fraction: 38 mg (18%) of cis-5.2 as a colorless oil (for spectroscopic data, see 3.2).
3.4. Coupling Reaction of (E)-7.1a with Pent-4-en-2-ol (8; Entry 1 of Table 2). The ester (E)-7.1a (255 mg,
1.00 mmol) and pentenol 8 (215 mg, 2.50 mmol) were coupled under Pd catalysis according to the General
Procedure (reaction time: 2 d). TLC (silica gel; petroleum ether/t-BuOMe 1:1): Rf 0.50 ((E)-9.1), 0.20, 0.00. FC
is performed with petroleum ether/t-BuOMe 3:1 to give 218 mg (84%) of ethyl (E)-3-bromo-3-[2-(4-
oxophenyl)phenyl]prop-2-enoate ((E)-9.1). Colorless oil. UV/VIS: 221 (4.17), 228 (4.06, sh), 276 (4.28). IR
(film): 3065w, 2961m, 1706m, 1628m, 1599w, 1481w, 1363m, 1261s, 1158s, 1097s, 1030s, 866w, 766m. 1H-NMR
(300 MHz): 1.35 (t, J ˆ 7.1, 3 H); 1.85 (m, 2 H); 2.12 (s, 3 H); 2.47 (t, J ˆ 7.1, 2 H); 2.76 (t, J ˆ 7.7, 2 H);
4.29 (t, J ˆ 7.1, 2 H); 6.37 (d, J ˆ 15.7, 1 H); 7.17 ± 7.33 (m, 3 H); 7.56 (dd, J ˆ 7.7, 0.9, 1 H); 8.01 (d, J ˆ 15.8,
1 H). 13C-NMR (75.5 MHz): 14.26 (q); 25.17 (t); 29.80 (q); 32.24, 42.69, 60.41 (3t); 119.70, 126.58, 126.61,
‡
129.98, 130.01 (5d); 133.02, 141.22 (2s); 141.79 (d); 166.85, 208.08 (2s). EI-MS: 260 (16, M ), 214 (28,
‡
‡
[M C2H6O] ), 203(23), 157(27), 144(26), 131(20), 130(22), 129(100, C9H5O ), 128(40), 116(13), 115(24),
‡
43(38, MeCO ). Anal. calc. for C16H20O3 (260.33): C 73.82, H 7.74; found C 73.58, H 7.80.
3.5. Coupling Reaction of (E)-7.2b with Pent-4-en-2-ol (8; Entry 6 of Table 2). The ester (E)-7.2b (316 mg,
1.00 mmol) and 8 (215 mg, 2.50 mmol) were coupled under Pd catalysis according to the General Procedure
(reaction time: 10 d). TLC (silica, petroleum ether/t-BuOMe 2:1): Rf 0.70, 0.35 ((E)-9.2), 0.28 ((Z)-9.2), 0.10,
0.00. FC was performed with petroleum ether/t-BuOMe 4:1; first fraction: 173 mg (63%) of (E)-9.2. Colorless
oil. UV/VIS: 211 (4.39), 245 (3.92). IR (film): 3058w, 2980w, 2938w, 1711s, 1640m, 1599m, 1482w, 1443m,
1366m, 1337m, 1274m, 1174s, 1115w, 1095w, 1073w, 1042m, 946w, 878w, 765m, 704w. 1H-NMR (300 MHz):
1.31 (t, J ˆ 7.1, 3 H); 1.85 (m, 2 H); 2.12 (s, 3 H); 2.43 (t, J ˆ 7.3, 2 H); 2.45 (d, J ˆ 1.4, 3 H); 2.59 (m, 2 H);
4.21 (q, J ˆ 7.1, 2 H); 5.76 (q, J ˆ 1.4, 1 H); 7.05 (d, J ˆ 8.0, 1 H); 7.10 ± 7.27 (m, 3 H). 13C-NMR (125.8 MHz):
14.31, 21.49 (2q); 25.14(t); 29.83(q); 32.06, 43.17, 59.85 (3t); 119.69, 126.01, 127.34, 127.82, 129.28 (5d); 137.82,
‡
‡
‡
143.79, 157.93, 166.48, 208.34 (5s). EI-MS: 274 (3, M ), 229 (19, [M C2H5O] ), 228 (38, [M C2H6O] ),
‡
200(11), 171(35), 158(35), 145(12), 144(19), 143 (100, C10H7O ), 142(42), 141(14), 129(27), 128(36),
115(15), 43(40, CH3CO ). Anal. calc. for C17H22O3 (274.36): C 74.42, H 8.08; found C 74.40, H 8.02.
‡
Second fraction: 39 mg (14%) of ((Z)-9.2). Slightly yellow oil. UV/VIS: 208(4.34, sh). IR (film): 2981m,
1714s, 1642m, 1486w, 1442m, 1372m, 1278m, 1231m, 1158s, 1115w, 1046m, 947w, 870w, 756w. 1H-NMR
(300 MHz): 1.02 (t, J ˆ 7.1, 3 H); 1.84 (m, 2 H); 2.10 (s, 3 H); 2.14 (d, J ˆ 1.5, 3 H); 2.44 ± 2.53 (m, 4 H); 3.95
(q, J ˆ 7.1, 2 H); 5.97 (q, J ˆ 1.5, 1 H); 6.96 (dd, J ˆ 8.0, 1.1, 1 H); 7.17 ± 7.26 (m, 3 H). 13C-NMR (125.8 MHz):
13.92(q); 24.50(t); 27.63, 29.81(2q); 31.91, 43.18, 59.61(t); 119.11, 125.83, 126.38, 127.30, 128.59(5d); 136.90,
‡
‡
‡
141.09, 156.14, 165.38, 208.63(5s). EI-MS: 274 (5, M ), 229 (23, [M C2H5O] ), 228 (38, [M C2H6O] ),
‡
217(23), 171(30), 161(11), 158(20), 145(14), 144(18), 143 (100, C10H7O ), 142(31), 141(11), 129(23),
128(28), 115(13), 43(32) [CH3CO ]. Anal. calc. for C17H22O3 (274.36): C 74.42, H 8.08; found: C 74.42, H 8.05.
‡
3.6. 1,2,3,4,4a,9,10,10a-Octahydrophenanthrene-1,3-dione (11.1): A soln. of 195 mg (750 mmol) of (E)-9.1 in
1 ml of dry THF/5 ml of dry EtOH was added to a suspension of 86 mg (3.75 mmol) of NaH (applied as a 60%
mixture with mineral oil) in 10 ml of dry THF. After stirring for 16 h at r.t., the mixture was hydrolyzed dropwise
with 10 ml 1m HCl and extracted with AcOEt (3 Â 20 ml). The combined org. layer was filtered through silica
gel and the solvent removed in vacuo. TLC (silica gel, petroleum ether/AcOEt 1:2): Rf 0.78, 0.34, 0.21 (11.1),

Helvetica Chimica Acta ± Vol. 82 (1999)
595
0.00. Purification by FC gave 94 mg (59%) of 11.1. Colorless solid. M.p. 1978. According to 1H-NMR
((D6)DMSO) the cis/trans-ratio is 1:8. The minor cis-isomer was detected by the s of H C(2) at 5.26 ppm (enol
tautomer in (D6)DMSO). IR (KBr): 3058w, 2923m, 2892m, 2541m, 1615s, 1524s, 1482s, 1367s, 1309s, 1224s,
1
1176m, 1131m, 1110w, 1074w, 1040w, 1006w, 972m, 953m, 923m, 826w, 761w, 748m, 433w. H-NMR (500 MHz,
CDCl3; keto/enol ratio 6:1): signals of the keto form: 1.76 (m, Hax C(10)); 2.43 (ddt, J ˆ 13.8, 5.2, 3.3,
Heq C(10)); 2.60 (dd, J ˆ 12.1, 3.0, H C(10a)); 2.67 (dd, J ˆ 15.9, 13.2, Hax C(4)); 2.93 (m, 2 H C(9));
3.07 (td, J ˆ 12.9, 4.0, H C(4a)); 3.44 (ddd, J ˆ 16.1, 4.3, 1.5, Heq C(4)); 3.52 (dd, J ˆ 17.5, 1.5, Heq C(2));
1
3.58 (d, J ˆ 17.5, Hax C(2)); 7.16 ± 7.25 (m, 4 H); typical signal of the enol form: 5.61 (s, H C(2)). H-NMR
(500 MHz, (D6)DMSO; exclusively signals of the enol form are detected): 1.37 (m, Hax C(10)); 2.19 (t, J ˆ
11.3,
H
C(10a)); 2.34 ± 2.43 (m, Hax C(4), Heq C(10)); 2.82 (m, 2 H C(9)); 3.00 (td, J ˆ 12.0, 4.1,
H
H
C(4a)); 3.07 (dd, J ˆ 16.8, 4.5, Heq C(4)); 5.32 (s, H C(2)); 7.09 ± 7.17 (m, 3 H); 7.30 (d, J ˆ 7.5,
C(5)); 11.16 (s, OH). 13C-NMR (125.8 MHz, CDCl3): 21.82 (t, C(10)); 28.87 (t, C(9)); 35.80 (d, C(4a));
46.43 (t, C(4)); 51.74 (d, C(10a)); 57.59 (t, C(2)); 126.13, 126.52, 127.02, 129.48 (4d); 136.00, 136.82, 203.31,
‡
203.59 (4s). EI-MS: 214 (14, M ), 186(12), 185(13), 157(79), 144(37), 143(20), 141(11), 130(60), 129(100),
128(69), 116(14), 115(44), 91(12), 77(10), 71(10), 64(10), 63(11), 51(14), 40(15). Anal. calc. for C14H14O2
(214.26): C 78.48, H 6.59; found: C 78.48, H 6.61.
3.7. 1,2,3,4,4a,9,10,10a-Octahydro-4a-methylphenanthrene-1,3-dione (11.2). A soln. of 187 mg (682 mmol) of
(E)-9.2 in 1 ml of dry THF/5 ml of dry EtOH was added to a suspension of 86 mg (3.75 mmol) of NaH (applied
as 60% mixture with mineral oil) in 10 ml of dry THF. After stirring for 16 h at r. t., the mixture was hydrolyzed
dropwise with 10 ml, 1m HCl and extracted with AcOEt (3 Â 20 ml). The combined org. layer was filtered
through silica gel and the solvent removed in vacuo. TLC (silica gel; petroleum ether/AcOEt 1:2): Rf 0.92, 0.75,
0.30 (trans-11.2), 0.21 (cis-11.2), 0.00. Purification by FC gave 84 mg (54%) of 11.2 with the cis/trans-ratio 3:1. A
pure sample of trans-11.2 was obtained by crystallization from petroleum ether/AcOEt 4:1. Slightly yellow solid.
M.p. 788. IR (KBr): 3406m, 3060m, 3018m, 2964s, 1702w, 1605s, 1490m, 1445m, 1409m, 1374m, 1338m, 1255s,
1222s, 1175s, 1145w, 1126w, 1089w, 1067w, 1043w, 995w, 942w, 851w, 831w, 796w, 761s, 724w, 685w, 649w, 565w,
451w. 1H-NMR (500 MHz, CDCl3; keto/enol ratio 12:1) signals of the keto form: 1.05 (s, 3 H); 1.87
(m, Hax C(10)); 2.27 (ddt, J ˆ 14.1, 6.2, 1.4, Heq C(10)); 2.83 (d, J ˆ 15.1, Hax C(4)); 2.87 ± 3.02 (m,
2 H C(9), H C(10a)); 3.32 (dd, J ˆ 15.0, 2.1, Heq C(4)); 3.42 (dd, J ˆ 17.6, 2.1, Heq C(2)); 3.54 (d, J ˆ
17.6, Hax C(2)); 7.13 ± 7.25 (m, 4 H); selected signals of the enol form: 1.20 (s, 3 H); 5.61 (s, H C(2)).
13C-NMR (125.8 MHz, CDCl3): signals of the keto form: 17.80 (t, C(10)); 25.02(q); 28.84(t, C(9));
36.91 (s, C(4a)); 54.48 (t, C(4)); 55.09 (d, C(10a)); 57.62 (t, C(2)); 125.54, 126.60, 126.77, 129.72 (4d); 135.15,
‡
‡
142.01, 203.57, 203.84 (4s). EI-MS: 228 (64, M ), 213 (34, [M Me] ), 171(61), 158(23), 144(34), 143(100),
142(28), 141(18), 130(21), 129(54), 128(54), 115(26). Anal. calc. for C15H16O2 (228.29): C 78.92, H 7.06;
found: C 78.92, H 7.06.
cis-11.2: 1H-NMR (500 MHz, CDCl3; keto/enol ratio 3:4): selected signals of the keto form: 1.38 (s, 3 H);
2.68 (d, J ˆ 15.8, HA C(4)); 3.19 (d, J ˆ 15.5, HB C(4)); selected signals of the enol form: 1.45 (s, 3 H);
2.48 (d, J ˆ 17.6, HA C(4)); 2.73 (d, J ˆ 17.6, HB C(4)); 5.54 (s, H C(2)); 7.95 (br. s, OH). 13C-NMR
(125.8 MHz, CDCl3): signals of the keto form: 21.96, 27.64 (2t); 29.66 (q); 36.53 (s, C(4a)); 52.64, 55.96(t);
56.07 (d, C(10a)); 126.02, 126.84, 126.92, 129.67 (4d); 134.75, 140.16, 202.61, 207.08 (4s); signals of the enol
form: 23.69 (t); 27.77 (q, Me); 29.57(t); 37.99 (s, C(4a)); 45.17 (t, C(4)); 49.51 (d, C(10a)); 102.80 (d, C(2));
126.10, 126.24, 126.55, 129.32 (4d); 134.97, 142.40, 191.16, 192.49 (4s).
3.8. (E)-3-[2-(4-Hydroxy-1-pentyl)phenyl]but-2-en-1-ol ((E)-12.2). A soln. of 846 mg (3.08 mmol) of (E)-
9.2 was added dropwise at 08 to a suspension of 96 mg (2.5 mmol) of LiAlH4 in 25 ml of dry Et2O. After stirring
for 2 h at reflux the mixture was cooled to r. t. and hydrolyzed with 300 ml of H2O, 100 ml of 15 weight-% aq.
NaOH soln., and again with 300 ml of H2O. The precipitate was filtered off through silica gel and the solvent
removed in vacuo. TLC (silica gel, petroleum ether/AcOEt 1:2): Rf 0.34 ((E)-12.2), 0.00. Purification by FC
gave 633 mg (88%) of (E)-12.2. Colorless oil. IR (film): 3316 s (br.), 3059m, 3014m, 2931s, 2864s, 1658w, 1599w,
1483s, 1443s, 1374m, 1333w, 1212w, 1170w, 1129m, 1068m, 1008s, 942m, 860w, 808w, 759s, 704m. 1H-NMR
(300 MHz): 1.08 (d, J ˆ 6.2, 3 H); 1.44 (m, 2 H); 1.65 (m, 2 H); 1.96 (t, J ˆ 0.6, 3 H); 2.51 (m, 1 H);
2.67 (m, 1 H); 2.75 ± 3.45 (br., 2 OH); 3.79 (q, J ˆ 6.2, 1 H); 4.26 (m, 2 H); 5.51 (m, 1 H); 7.03 (d, J ˆ 7.1,
1 H); 7.07 ± 7.25 (m, 3 H). 13C-NMR (75.5 MHz): 18.93, 23.68(q); 27.71, 32.97, 38.93, 59.13(3t); 67.27,
‡
125.64, 126.86, 128.18, 128.24, 129.25(6d); 138.90, 139.19, 144.43(3s). EI-MS: 234 (0.33; M ), 183(14),
159(13), 158(34), 157(15), 156(25), 155(25), 147(13), 146(11), 145(38), 144(19), 143(100), 142(26),
141(26), 131(32), 130(18), 129(51), 128(42), 117(26), 115(22), 91(26), 45(11), 43(11). Anal. calc. for
C15H22O2 (234.34): C 76.88, H 9.46; found: C 76.79, H 9.47.

596
Helvetica Chimica Acta ± Vol. 82 (1999)
3.9. 3-[2-(4-Oxo-1-pentyl)phenyl]but-2-enal (13.2). A soln. of 881 mg (11.3 mmol) dry DMSO in 1 ml dry of
CH2Cl2 was added at 608 under N2 to a soln. of 713 mg (5.63 mmol) of oxalyl chloride in 20 ml of dry CH2Cl2.
After stirring for 30 min, a soln. of 601 mg (2.56 mmol) of diol 12.2 in 5 ml of dry CH2Cl2 was added, and stirring
was continued for 1 h at 608. The mixture was treated with 1.0 ml (8.0 mmol) of Et3N, hydrolyzed at r. t. with
10 ml of H2O. The org. layer was washed with 10 ml of 1m HCl and with 10 ml of sat. aq. NaHCO3 soln., and
filtered through silica. TLC (silica gel; petroleum ether/t-BuOMe 2:1): Rf 0.81, 0.72, 0.32, 0.29 (13.2), 0.11, 0.00.
The solvent was removed in vacuo and purification by FC afforded 433 mg (73%) of 13.2 with a (E)/(Z)-ratio
of 3:1 as a yellow oil. Because of its tendency to decompose at r. t. in the presence of air, 13.2 was immediately
cyclized under appropriate conditions (see 3.10).
1
Selected spectroscopic data of 13.2: H-NMR (500 MHz): (E)-13.2: 1.85 (m, 2 H); 2.12 (d, J ˆ 0.7, 3 H);
2.45 (t, J ˆ 7.1, 2 H); 2.48 (d, J ˆ 1.4, 3 H); 2.59 (m, 2 H); 5.94 (dd, J ˆ 8.0, 1.4, 1 H); 7.07 (d, J ˆ 7.5, 1 H);
7.19 ± 7.29 (m, 3 H); 10.16 (d, J ˆ 8.0, CHO); (Z)-13.2: selected signals: 2.26 (d, J ˆ 1.4, 3 H); 6.16 (dq, J ˆ 8.4,
1.4, 1 H); 9.23 (d, J ˆ 8.4, 1 H). 13C-NMR (125.8 MHz): (E)-13.2: 20.00(q); 25.11(t); 29.96(q); 32.08,
42.93 (2t); 126.16, 126.86, 128.36, 129.52, 130.20 (5d); 137.36, 142.53, 160.98 (3s); 193.31(d); 208.25(s); (Z)-
13.2: 24.77(t); 27.39, 29.94(q); 32.01, 42.98 (2t); 126.13, 128.02, 128.47, 129.23, 129.93 (5d); 138.07, 138.16,
‡
163.25 (3s); 190.97(d); 208.14(s). EI-MS: 229 (1.7, M ), 211(13), 203(12), 158(12), 157(11), 156(25),
146(41), 145(16), 144(100), 142(10), 141(20), 130(28), 129(11), 128(40), 127(31), 126(10), 118(11),
116(18), 114(28), 90(23), 76(12), 70(11), 42(72).
3.10. 1-(5,6-Dihydro-10-methylbenzocycloocten-7-yl)ethanone (14.2). A soln. of 117 mg (500 mmol) of 13.2
and 1.0 ml (12 mmol) of conc. HCl in 25 ml of THF was heated for 5 d at 808. TLC (silica gel; petroleum ether/t-
BuOMe 2:1): Rf 0.93, 0.85, 0.67, 0.52 (14.2), 0.19, 0.11, 0.00. The fraction with Rf 0.52 yielded 39 mg (37%) of
14.2. Colorless solid. M.p. 488. IR (film): 2965m, 2934m, 1662s, 1628m, 1569w, 1491w, 1430m, 1375m, 1355m,
1246s, 1218w, 1195w, 1143w, 1125w, 1030w, 947w, 876w, 841w, 797w, 765m, 754m. UV/VIS: 206 (4.13, sh),
229(3.86), 288(3.70). 1H-NMR (500 MHz): 2.18 (t, J ˆ 1.6, 3 H); 2.20 (s, 3 H); 2.73 (tt, J ˆ 6.5, 1.6, 2 H C(6));
3.00 (br., s, 2H C(5)); 6.07 (m, H C(9)); 6.78 (m, H C(8)); 7.18 ± 7.25 (m, 4 H). 13C-NMR (125.8 MHz):
25.93, 26.11 (2q); 30.14 (t, C(5)); 31.39 (t, C(6)); 122.98 (d, C(9)); 125.77, 126.68, 127.92, 128.94 (4d);
‡
136.76 (d, C(8)); 139.23, 140.05, 140.09, 201.13 (4s). EI-MS: 212 (31, M ), 197(19), 184(14), 170(15),
‡
169(100, [M MeCO] ), 155(26), 155(26), 154(42), 153(27), 152(18), 145(19), 141(30), 129(19), 128(25),
‡
115(21), 43 (42, MeCO ). HR-MS: calc. for C15H16O (212.29): 212.1201; found: 212.1202.
Financial support of the Fonds der Chemischen Industrie and of the Deutsche Forschungsgemeinschaft and a
generous donation of palladium acetate from Degussa AG are gratefully acknowledged.
REFERENCES
[1] a) Dictionary of Natural Products, Chapman & Hall, London, 1994; b) T. Hayashi, T. Handa, M. Ohashi, H.
Kakisawa, H.-Y. Hsu, Y. P. Chen, J. Chem. Soc., Chem. Commun. 1971, 541.
[2] L. F. Tietze, U. Beifuss, Angew. Chem. 1993, 105, 137; Angew. Chem. Int. Ed. Engl. 1993, 32, 131.
[3] J. Tsuji, Palladium Reagents and Catalysts: Innovations in Organic Synthesis, Wiley, Chichester, 1995.
[4] G. Dyker, P. Grundt, H. Markwitz, G. Henkel, J. Org. Chem. 1998, 63, 6043.
[5] a) J. B. Melpolder, R. F. Heck, J. Org. Chem. 1976, 41, 265; b) A. J. Chalk, S. A. Magennis, J. Org. Chem.
1976, 41, 273, 1206; c) Y. Tamaru, Y. Yamada, Z. Yoshida, J. Org. Chem. 1978, 43, 3396; d) W. Smadja, S.
Czernecki, G. Ville, C. Georgoulis, Organometallics 1987, 6, 166; e) R. C. Larock, W.-Y. Leung, S. Stolz-
Dunn, Tetrahedron Lett. 1989, 30, 6629; f) S.-K. Kang, K.-Y. Jung, C.-H. Park, E.-Y. Namkoong, T.-H. Kim,
Tetrahedron Lett. 1995, 36, 6287.
[6] G. Dyker, P. Grundt, Tetrahedron Lett. 1996, 37, 619.
[7] G. Dyker, H. Markwitz, Synthesis 1998, in press.
[8] a) M. L. Hammond, R. A. Zambias, M. N. Chang, N. P. Jensen, J. McDonald, J. Med. Chem. 1990, 33, 909;
Â
b) C. N. Robinson, J. L. Horton, D. O. Foshee, J. W. Jones, S. H. Hanissian, C. D. Slater, J. Org. Chem. 1986,
51, 3535.
[9] K. von Clauss, H. Bestian, Liebigs Ann. Chem. 1962, 654, 8 ± 19.
Received January 21, 1999