Stereoselective synthesis of rubrenoic and nor-rubrenoic acids

Article abstract of DOI:10.1080/00397910701649049

The total stereoselective synthesis of (Z)-rubrenoic I (1a), (Z)-nor-rubrenoic I (17a), (E)-rubrenoic III (3b), and nor-(E)-rubrenoic III (30b) acids was achieved using Suzuki and Stille cross-coupling reactions from readily available starting materials.

Full text of DOI:10.1080/00397910701649049

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Stereoselective Synthesis of Rubrenoic and
nor‐Rubrenoic acids
Lucina G. Sánchez a , Elizabeth N. Castillo a , Hortensia Maldonado a , Daniel
Chávez a , Ratnasamy Somanathan a & Gerardo Aguirre a
a Centro de Graduados e Investigación del Instituto Tecnológico de Tijuana,
Tijuana, México
Version of record first published: 25 Jan 2008.
To cite this article: Lucina G. Sánchez , Elizabeth N. Castillo , Hortensia Maldonado , Daniel Chávez ,
Ratnasamy Somanathan & Gerardo Aguirre (2007): Stereoselective Synthesis of Rubrenoic and nor‐Rubrenoic
acids, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 38:1, 54-71
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Synthetic Communicationsw, 38: 54–71, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701649049
Stereoselective Synthesis of Rubrenoic
and nor-Rubrenoic acids
´
Lucina G. Sanchez, Elizabeth N. Castillo,
Hortensia Maldonado, Daniel Chavez,
´
Ratnasamy Somanathan, and Gerardo Aguirre
´ ´
Centro de Graduados e Investigacion del Instituto Tecnologico de
´
Tijuana, Tijuana, Mexico
Abstract: The total stereoselective synthesis of (Z)-rubrenoic I (1a), (Z)-nor-rubrenoic
I (17a), (E)-rubrenoic III (3b), and nor-(E)-rubrenoic III (30b) acids was achieved
using Suzuki and Stille cross-coupling reactions from readily available starting
materials.
Keywords: rubrenoic acid, Suzuki and Stille cross-coupling reaction
INTRODUCTION
Natural products isolated from marine organisms represent a new source of
pharmacologically active chemical compounds showing impressive in vitro
activities.[1] Rubrenoic acids I–III (1–3) are unique aromatic unsaturated
acids with a hexane or hexene carboxylic acid and a butenyl or butadienyl
side chain (Fig. 1). They have been isolated from the marine bacterium Alter-
omonas rubra, and they demonstrated bronchodilator activity.[2]
Rubrenoic acids 1–3 possess similar structural features to serpentenes
4–5 (Fig. 2), which are polyunsaturated carboxylic acids with 20 carbons.[3,4]
They are isolated from Streptomyces sp. Tu¨ 3851 and show mild antibacterial
activity. Ortho-methyl phenyl alkenoic acids are periodically encountered in
Received in the USA June 26, 2007
Address correspondence to Gerardo Aguirre, Centro de Graduados e Investigacion
´ ´
del Instituto Tecnologico de Tijuana, Apdo. Postal 1166, Tijuana 22500, B.C. Mexico.
´
E-mail: lasvid777@yahoo.com.mx or gaguirre@tectijuana.mx
54

Rubrenoic and nor-Rubrenoic Acids
55
Figure 1. Structure of natural rubrenoic acids I-III (1–3).
Figure 2. Structures of serpentene (4) and all-trans serpentene (5).
nature: o-methylcinnamide (U-77863) from Streptomyces griseoluteus[3]
inhibits cancer invasion and metastasis;[5] 1-hydroxy-2-hydroxymethyl-3-
pent-1-enyl-benzene and 1-hydroxy-2-hydroxymethyl-3-pent-1,3-dienylben-
zene, isolated from deuteromycete, inhibit both the TPA-induced NF-kB
and AP-1.[6] 5-(2-Methylphenyl)-4-pentenoic acid has been isolated from a ter-
restrial Streptomycete,[7] and demetric acid has been isolated from Streptomyces
umbrosus.[8] Even shorter analogs have been described as acyl groups for the
Streptomyces peptides WS 9326A[9,10] and RP 1776.[11]
A previous report on the synthesis of 3a,b led to yields of only 5–20%;
also, the synthesis of pseudorubrenoic acid led to low yield.[12] The biological
activities of these polyunsaturated compounds have not been fully explored
because of the lack of appreciable amounts of material. We therefore
embarked on a project to develop an efficient general synthetic route to
obtain these compounds.
RESULTS AND DISCUSSION
As model compounds, we selected rubrenoic acids I as target molecules to test
our general synthetic route (Scheme 1). Commercially available 2-bromoben-
zyl bromide (6) was converted into the 2-bromobenzyl iodide (7) and then
alkylated with cis-vinyl magnesium bromide (8a) to give the 1-bromo-2-
[(Z)-but-2-enyl]-benzene (9a) in 77% yield (E isomer was not detected by
1H NMR). Interestingly, when compound 7 was alkylated with trans-vinyl
magnesium bromide (8b), a mixture of the isomers 9a/b was obtained in a
40/60 proportion as determined by 1H NMR (integration for benzylic protons).
The ortho-hexane carboxylate fragment was prepared[13,14] from
6-(9-borabicyclo [3.3.1] non-9-yl) propyl hexanoate (12), which was in turn
prepared from commercially available 5-hexen-1-ol followed by oxidation

´
L. G. Sanchez et al.
56
Scheme 1. (a) Nal 2 eq., acetone, room temperature; (b) Cul/THF, 2788C, 08C to
2158C.
and esterification to propyl hex-5-enoate (11). A Suzuki–Miyaura[14] coupling
with 9a, using Pd(dppf)Cl2 as catalyst, gave 6-(2-(Z)-but-2-enyl-phenyl)-
hexanoic acid propyl ester (14a). Hydrolysis gave (Z)-rubrenoic acid I (1a)
in 19% yield. Similarly, acetic acid 5-(9-borabicyclo [3.3.1] non-9-yl)-
pentyl ester (13) coupling to 9a gave nor-(Z)-rubrenoic acid I (17a) in 24%
yield with an additional step, Jones’s oxidation of the primary alcohol
1
(Scheme 2). For both compounds (1a, 17a), the H NMR signals for the
vinylic protons displayed cis stereochemistry (J ¼ 11.2 Hz).
To establish unequivocally the stereochemistry on the double bond, we
prepared the benzylic-deuterated analogs. Thus, 1-bromo-2-[(Z)-1,1-
dideutero-but-2-enyl]-benzene (21a) was prepared from commercially
available ethyl 2-bromobenzoate (18), which was reduced with LiAlD4 to
(2-bromo-phenyl)-dideutero-methanol (19) in 95% yield. Intermediate 19
Scheme 2. (a) CrO3, H2SO4 1.5 M, acetone; (b) bromine–propane, NaHCO3, DMF;
(c) 9-BBN 0.5 M in THF; (d) CsCO3, Ph3As 10% mol, PdCl2(dppf) 5% mol,
DMF–THF–water; (e) LiOH 1 N, CH3OH/THF (2/3 v/v), reflux.

Rubrenoic and nor-Rubrenoic Acids
57
.
Scheme 3. (a) LiAlD4/THF; (b) CeCl3 7H2O, Nal, acetonitrile; (c) Cul/THF,
2788C, 08C to 2158C.
was converted to 1-bromo-2-(iodo-dideutero-methyl)-benzene (20) and
alkylated with cis-vinyl magnesium bromide (8a) to give 1-bromo-2-[(Z)-1,
1-dideutero-but-2-enyl]-benzene (21a) in 72% yield. Alkylation was also
performed with trans-vinyl magnesium bromide (8b) then to give 1-bromo-
2-[(Z/E)-1,1-dideutero-but-2-enyl]-benzene (21a/b) as a cis/trans mixture
in 72% yield (Scheme 3).
As expected, the 1H NMR spectrum of the deuterated compounds 21a/b
was complex. All the NMR signals appear as a multiplet at 5.55 ppm (both cis
and trans vinylic protons). However, in double resonance using irradiation of
the methyl protons, the spectrum simplifies, and it was possible to see the four
doublets for the cis and trans vinylic protons (Table 1). Similarly, decoupling
of the vinylic protons resulted in a spectrum with two singlets for the methyls.
Integration of the well-separated signals for the allylic methyls (dH 1.57 for cis
and 1.62 for trans) indicated a 40:60 ratio for the isomers Z/E, respectively.
This was confirmed by analysis of the gas chromatography/electron impact
mass spectrometry (GC/EIMS) chromatogram.
Careful analysis of 13C NMR spectra for compound 21a and the mixture
of compounds 21a/b showed different signals for the vinylic methyls, dC 13.4
corresponding to the cis isomer and dC 13.6/18.4 for the cis/trans mixture
(Table 2). These results are in agreement with 13C NMR data reported in
Table 1. Partial 1H NMR data of the mixture of 1-bromo-2-[(E/
Z)-1,1-dideutero-but-2-enyl]-benzene (21a/b) in a double reson-
ance experiment (200 MHz, CDCl3)
Multiplicity
d (ppm)
J (Hz)
Configuration
d
d
d
d
5.74
5.72
5.68
5.67
9.4
16.2
15.2
7.4
cis
trans
trans
cis

´
L. G. Sanchez et al.
58
Table 2. Partial 13C NMR data of the 1-bromo-2-[(Z)-1,1-dideu-
tero-but-2-enyl]-benzene (21a) and the mixture of 1-bromo-2-[(Z/
E)-1,1-dideutero-but-2-enyl]-benzene (21a/b) (50 MHz, CDCl3)
compound
d (ppm)
Configuration
21a
21a/b
13.4
13.6/18.4
cis
cis/trans
the literature, where the signal for the vinylic methyl in cis position is found
ca. 5.3 ppm upfield from the trans.[15,16]
To obtain rubrenoic acid III (3), the general synthetic route described in
Scheme 4 was followed. o-Bromoenzaldehyde was coupled with 6-(9-borabi-
cyclo [3.3.1] non-9-yl) propyl hexanoate (12) using the Suzuki–Miyaura
method[14] to give the intermediate propyl 6-(2-formylphenyl) hexanoate
(22) in 85% yield. The intermediate 22 when treated with triphenyl iodo-
methyl phosphonium iodide (24) gave the 6-[2-Z-(2-iodo-vinyl)-phenyl]-
hexanoic acid propyl ester (25a) in 50% yield.[17] Stille coupling
reaction[18] with tributylvinyltin gave the 6-(2-Z-buta-1,3-dienyl-phenyl)-
hexanoic acid propyl ester (27a) in 65% yield. We found than the cis
compound spontaneously isomerizes in the presence of light to the trans
isomer 6-(2-E-buta-1,3-dienyl-phenyl)-hexanoic acid propyl ester (27b). We
carried out the Stille coupling reaction in the absence of light, and then
immediately analyzed it by high performance liquid chromatography
(HPLC). From this, we obtained a mixture of 27a and 27b in a ratio of
30/70 (Z/E), respectively. After few hours under daylight, only the trans
isomer could be detected in the HPLC. This result is different from a
previous work,[3] which reported the separation of both isomers. Finally,
hydrolysis of the protecting group gave E-rubrenoic acid III (3b) in 19%
overall yield. On the other hand, when the intermediate 22 was treated
under White’s conditions,[19] the mixture of Z/E iodo-alkene 25a/b was
obtained, and only 27b was recovered after Stille coupling reaction.[18]
Thus, only the E-rubrenoic acid III (3b) could be obtained.
The nor-rubrenoic acid III (30b) was obtained in a fashion similar to the
synthesis of E-rubrenoic acid III (3b), but in this case hydrolysis of acetic acid
5-(2-E-buta-1,3-dienyl-phenyl)-pentyl ester (28b) gave 5-(2-E-buta-1,3-
dienyl-phenyl)-pentan-1-ol (29b) in 95% yield. Lastly, Jones’s oxidation of
29b led to the nor-E-rubrenoic acid III (30b) in 22% overall yield (Scheme 4).
In summary, we have developed an efficient synthetic route to
(Z)-rubrenoic and nor-(Z)-rubrenoic acids I with overall yields of 19%

Rubrenoic and nor-Rubrenoic Acids
59
Scheme 4. (a) CsCO3, Ph3As 10% mol, PdCl2(dppf) 5% mol, DMF–THF–water; (b)
Ph3PþCH2l.l2 (24) NaHMDS 1.0 M, rt, HMPA 2788C; (c) CrCl2, CHl3/THF, 08C; (d)
Cul 10% mol, Pd(PPh3)4 5% mol, [CH3(CH2)3]3Sn CH55CH2 rt; (e) CH2Cl2, l2, l; (f)
LiOH 1 N, CH3OH/THF (2/3 v/v) reflux; (g) CrO3, H2SO4 1.5 M; acetone.
and 24%, respectively. Studies of the butenyl chain with deuterated benzylic
positions and double-irradiation NMR experiments corroborated the
cis stereochemistry in the double bond as well as chemical shifts on 13C
NMR. (E)-rubrenoic acid and nor-(E)-rubrenoic acids III were obtained
in overall yields of 19% and 22%, respectively. Both the rubrenoic acids and
nor-rubrenoic acids (I and III) can be synthesized in reasonable amounts for
further biological studies. Our stereoselective synthetic methodology also
provides a route to other similar polyunsaturated benzene compounds.
EXPERIMENTAL
General Methods
Melting points were determined on a Fisher–Johns melting-point apparatus
and are uncorrected. Infrared (IR) spectra were taken on a Perkin-Elmer

´
L. G. Sanchez et al.
60
1
FT-IR 1600 spectrometer. H (200-MHz) and 13C NMR (75-MHz) spectra
were recorded on a Bruker Avance DPX 300-MHz spectrometer. Spectra
were run in CDCl3 with tetramethylsilane (TMS) used as internal standard.
Mass spectra were obtained on a Hewlett Packard 5989 MS spectrometer at
70 eV by direct insertion. The high resolution mass spectrometry (HRMS)
(FABþ) data was obtained on a Finnigan MAT-90 instrument, and elementary
analyses for carbon and hydrogen were conducted by Galbraith Laboratories,
Inc. (Knoxville, TN). Reagents were acquired from Aldrich and used as
received: 9-BBN (0.05 M solution in THF), 2-bromobenzyl bromide, benzal-
dehyde 2-bromine, ethyl 2-bromobenzoate, PdCl2 (dppf), Ph3As, Cs2CO3,
NaHMDS (1.0 M solution in THF), hexamethylphosphoramide (HMPA),
Pd(PPh3)4, CrCl2, LiAlD4, 5-hexen-1-ol, cis-1-bromo-1-propene, trans-1-
bromo-1-propene, 1-bromo-propane, and 4-pentenyl acetate.
2-Bromobenzyl Iodide (7)
A solution of 2-bromobenzyl bromide (6) (1.00 g, 4.0 mmol) was added
dropwise to a solution of sodium iodine (1.20 g, 8.00 mmol) in acetone
(40 mL). The mixture was vigorously stirred for 5 min, in which time the
mixture turned orange with formation of a white precipitate (NaBr). The
reaction was complete in 21 hr. The solid was collected by filtration and
washed twice with acetone, and the filtrate was concentrated under reduced
pressure, dissolved in water, and extracted with ethyl ether (50 mL). The
organic phase was washed with brine, dried under anhydrous MgSO4, and
filtered, and solvent was removed under reduced pressure to give an
amber color solid (1.12 g, 94%), melting point 42–448C. IR (KBr):
3065, 2926, 1152, 573 cm21 1H NMR (200 MHz, CDCl3): d 7.53 (1H,
;
dd, J ¼ 8.2, 1.8 Hz, Ar); 7.44 (1H, dd, J ¼ 7.6, 1.6 Hz, Ar); 7.25 (1H,
dt, J ¼ 7.8, 1.2 Hz, Ar); 7.12 (1H, dt, J ¼ 7.6, 1.8 Hz, Ar); 4.54 (2H, s,
-CH2-l); 13C NMR (50 MHz, CDCl3): d 133.6, 130.6, 129.6, 128.0,
124.1, 5.7; m/z (EIMS) 298 Mþþ2 (8), 296 Mþ (8), 169 (100),
127 (47), 89 (55). Anal. calcd. for C7H6BrI: C, 28.31; H, 2.04. Found: C,
28.48; H, 2.22.
cis-Propenyl Magnesium Bromide (8a) Grignard Reagent
In a dry Schlenk flask (100 mL), magnesium (0.245 g, 10.10 mmol), and
iodine in catalytic amounts were placed under an inert atmosphere in
tetrahydrofuran (THF) (50 mL). The solution was stirred for 10 min at room
temperature, and then a solution of cis-bromo-1-propene was added (1.22 g,
10.10 mmol). The reaction mixture was stirred at reflux temperature for
30 min. The crude product was used in the next step of the procedure.

Rubrenoic and nor-Rubrenoic Acids
61
1-Bromo-2-[(Z)-but-2-enyl]-benzene (9a)
A suspension of 2-bromobenzyl iodide (7) (0.500 g, 1.684 mmol) in THF
(40 mL) was treated with copper iodide (0.034 g, 0.178 mmol) under an
inert atmosphere at 2788C. Then a solution of Grignard reagent 8a was
added dropwise by syringe. The reaction mixture was stirred for 17 h at
2108C. The reaction was quenched by addition of NH4Cl (10 mL) and
extracted with ethyl ether (3 ꢀ 30 mL). The organic layer was washed
twice with brine and dried over anhydrous MgSO4. The solvent was
removed under reduced pressure and purified by flash column chromatography
on silica gel (90:10 hexanes–petroleum ether) to give a clear yellow oil
product (0.27 g, 77%). IR (film): 3062–3020, 2916–2854, 1468–1441,
1
1021, 750 cm21. H NMR (200 MHz, CDCl3): d 7.53 (1H, d, J ¼ 7.6 Hz,
Ar); 7.23 (2H, m, Ar); 7.06 (1H, dd, J ¼ 8.2, 3.4 Hz, Ar); 5.54 (2H, m,
-CH2-CH55CH-CH3); 3.50 (2H, d, J ¼ 6.4 Hz, -CH2-CH55CH-CH3); 1.73
(3H, d, J ¼ 6.0 Hz, -CH55CH-CH3); 13C NMR (50 MHz, CDCl3): d 140.4,
132.7, 130.0, 127.5, 127.4, 127.3, 125.8, 124.5, 33.6, 13.0; m/z (EIMS) 212
Mþþ2 (36), 210 Mþ (37), 131 (93), 116 (100), 91 (57). Anal. calcd. for
C10H11Br: C, 56.90; H, 5.25. Found: C, 57.02; H, 5.38.
1-Bromo-2-[(Z/E)-but-2-enyl]-benzene (9a/b)
This compound was synthesized following the same procedure described for
compound 9a using a solution of Grignard reagent 8b and compound 7 to give
a clear yellow oil product (77%). Z/E 40:60. IR (film): 3058–3014 (C55C-H);
2918–2854 (C-H); 1467–1438 (-CH2-); 1024 (Ar-Br); 966 (CH55CH); 747
1
(C-H) cm21. H NMR (200 MHz, CDCl3): d 7.52 (1H, d, J ¼ 7.6 Hz, Ar);
7.21 (2H, m, Ar); 7.03 (1H, m, Ar); 5.56 (2H, m, -CH2-CH55CH-CH3);
3.50 (2H, d, J ¼ 6.4 Hz, -CH2-CH55CH-); 3.42 (2H,d, J ¼ 6.4 Hz, -CH2-
CH55CH-); 1.73 (3H, d, J ¼ 6.0 Hz -CH55CH-CH3). 13C NMR (50 MHz,
CDCl3): d 140.4, 132.7, 130.0, 127.5, 127.4 127.3, 125.8, 124.5, 36.4, 33.6,
19.0, 13.0. m/z (EIMS) 212 Mþþ2 (36), 210 Mþ (37), 131 (93), 116 (100),
91 (57). Purity determined by GC-EIMS Z/E 55:37 (92%).
Hex-5-enoic Acid (10)
A solution of chromium trioxide (6.250 g, 62.5 mmol) in aqueous 1.5 M
sulfuric acid (100 mL, 150 mmol) at 08C was treated with a solution of
5-hexen-1-ol (1.662 g, 16.6 mmol) in acetone (200 mL) by dropwise
addition over 6 h. The reaction was complete in 8 h at 58C and diluted with
ethyl ether (150 mL). The organic phase was washed with a brine solution
(3 ꢀ 100 mL). The organic phase was concentrated under reduced pressure
and dissolved in ethyl ether (100 mL). The solution was washed with 1M
NaOH (2 ꢀ 75 mL), then washed and acidified with 6 M sulfuric acid
(50 mL), and extracted again with ethyl ether (3 ꢀ 75 mL). The organic

´
L. G. Sanchez et al.
62
phase was washed with water and brine, dried over anhydrous MgSO4, and
filtered, and the solvent was removed under reduced pressure and purified
by flash column chromatography on silica gel (90:10 hexanes–ethyl
acetate) to give a colorless liquid (yield, 1.118 g, 60%). IR (film): 3215,
1
3077, 2936, 1711, 1642, 1245 cm21; H NMR (200 MHz, CDCl3): d 11.2
(1H, bs, COOH); 5.77 (1H, ddt, J ¼ 17.2, 10.2, 6.6 Hz, -CH55CH2); 5.01
(2H, m, -CH55CH2); 2.36 (2H, t, J ¼ 7.4 Hz, -CH2-COOH); 2.11 (2H, c,
J ¼ 7.0, 6.6 Hz, 55CH-CH2-CH2-); 1.73 (2H, q, J ¼ 7.0, 6.8 Hz, -CH2-CH2-
CH2-); 13C NMR (50 MHz, CDCl3): d 179.9, 137.2, 115.3, 33.3, 32.9, 23.7.
Propyl Hex-5-enoate (11)
NaHCO3 (20 eq., 1.68 g) and 1-bromo-propane (10 eq., 0.907 mL) were added
to a solution of hex-5-enoic acid (10) (0.114 g, 1.0 mmol) in DMF (5 mL).
The reaction mixture was stirred at room temperature for 24 h, quenched
with water (50 mL), and then extracted with ethyl ether (3 ꢀ 50 mL). The
organic phase was washed with brine, dried over anhydrous MgSO4, and
filtered, and solvent was removed under pressure to give a light yellow
liquid product (0.1342 g, 86%). IR (film): 3077, 2968, 1736, 1684,
1
1173 cm21; H NMR (200 MHz, CDCl3): d 5.78 (1H, ddt, J ¼ 17.0, 11.2,
6.6 Hz, CH255CH-); 5.01 (1H, dd, J ¼ 17.2, 1.6 Hz, CH255CH-); 4.97 (1H,
dd, J ¼ 11.2, 1.2 Hz, CH255CH-), 4.03 (2H, t, J ¼ 6.6 Hz, -CO2-CH2-CH2-);
2.31 (2H, t, J ¼ 7.8 Hz, -CH2-CO2-CH2 -); 2.08 (2H, c, J ¼ 6.8, 6.4 Hz,
55CH-CH2-CH2-); 1.69 (2H, q, J ¼ 7.0 Hz, -CH2-CH2-CH2-CO2-CH2); 1.65
(2H, sext, J ¼ 7.4 Hz, -CH2-CO2-CH2-CH2-CH3); 0.94 (3H, t, J ¼ 7.6 Hz,
-CH2-CO2-CH2-CH2-CH3); 13C NMR (50 MHz, CDCl3): d 173.4, 137.4,
115.0, 65.7, 33.5, 33.0, 24.1, 21.9, 10.4. Anal. calcd. for C9H16O2: C,
69.19; H, 10.32. Found: C, 69.29; H, 9.42.
6-(9-Borabicyclo [3.3.1] non-9-yl)-propyl Hexanoate (12)
A solution of propyl hex-5-enoate (11) (0.569 g, 4.44 mmol) in THF (4 mL)
was cooled to 08C, and a solution of 9-BBN (0.5 M solution in THF,
8.9 mL, 4.44 mmol) was added dropwise during 15 min. The solution was
warmed to room temperature and stirred for 4 h. The crude product was
used in situ in the Suzuki coupling procedure in the next step.
Acetic Acid 5-(9-Borabicyclo [3.3.1] non-9-yl)-pentyl Ester (13)
This compound was synthesized following the same procedure described for
compound 12 but using 4-pentenyl acetate. In this reaction, the 9-BBN was
added at 2108C for 5 min and stirred at room temperature for 4 h.

Rubrenoic and nor-Rubrenoic Acids
63
General Procedure of the Suzuki–Miyaura Cross-coupling
6-(2-(Z)-but-2-enyl-phenyl)-hexanoic Acid Propyl Ester (14a)
A suspension of compound 9a (0.455 g, 2.15 mmol), Cs2CO3 (1.26 g,
3.87 mmol, 1.8 eq.), PdCl2 (dppf) (0.078 g, 0.107 mmol, 5% mol), and
Ph3As (0.066 g, 0.215 mmol, 10% mol) in DMF (10 mL) was placed in a
dry round-bottom flask (50 mL). The solution was stirred for 5 min, during
which time the mixture turned orange. Water (0.46 mL, 25.8 mmol, 12
eq.), and then a solution of compounds 12/THF (2.58 mmol) were added.
The solution was stirred for 5 min, and then more water was added
(0.37 mL, 20.64 mmol, 12 eq.). Then the reaction mixture was stirred for
4 h. The reaction was quenched by addition of water (100 mL). After
regular extraction with ethyl ether (3 ꢀ 50 mL), the organic phase was
washed with aqueous 10% HCl solution (1 ꢀ 50 mL), 10% NH4OH
(1 ꢀ 50 mL), water (2 ꢀ 50 mL), and brine, dried over anhydrous MgSO4,
and filtered. The solvent was removed under vacuum, and the product was
purified by flash-column chromatography on silica gel (90:10 petroleum
ether–ethyl acetate) to give a light yellow liquid product (0.198 g, 53%).
1
IR (film): 2932, 1735, 1175, 749 cm21; H NMR (200 MHz, CDCl3): d
7.05 (4H, m, Ar); 5.46 (2H, m, Ar-CH2-CH55CH-CH3); 3.95 (2H, t,
J ¼ 7.0 Hz, -O-CH2); 3.31 (2H, d, J ¼ 5.6 Hz, Ar-CH2-CH55CH); 2.54
(2H, t, J ¼ 8.2 Hz, Ar-CH2-CH2-); 2.24 (2H, t, J ¼ 7.6 Hz, CH2-C55O);
1.66 (3H, d, J ¼ 5.8 Hz, CH55CH-CH3); 1.62 (8H, m, -CH2); 0.86 (3H, t,
J ¼ 7.8 Hz, CH2-CH3); 13C NMR (50 MHz, CDCl3): d 173.8, 140.4, 138.8,
129.2, 129.1, 126.1, 126.1, 124.5, 66.0, 34.6, 32.9, 30.9, 30.6, 29.5, 25.2,
22.3, 13.2, 10.7. Anal. calcd. for C19H28O2: C, 79.12; H, 9.78. Found: C,
79.21; H, 9.90.
Acetic Acid 5-(2-But-2-enyl-phenyl)-pentyl Ester (15a)
This compound was synthesized following the same procedure described for
the Suzuki–Miyaura coupling in compound 14a using the compounds 9a and
13 to give a light yellow liquid product (50%). IR (film): 2933–2859 (C-H);
1739 (C55O); 1238 (C-O-C); 1041 (CH-O-CH2-); 751 (C-H) cm21. 1H NMR
(200 MHz, CDCl3): d 7.15 (4H, m, Ar); 5.54 (2H, m, Ar-CH2-CH55CH-CH3);
4.08 (2H, t, J ¼ 4.6 Hz, -CH2-O-C55O-CH3); 3.40 (2H, d, J ¼ 4.4 Hz, Ar-
CH2-CH55CH-); 2.64 (2H, t, J ¼ 5.6 Hz, Ar-CH2-CH2); 2.05 (3H, s,
-C55O-CH3); 1.75 (3H, d, J ¼ 3.8 Hz, -CH55CH-CH3); 1.42 (6H, m, -CH2-).
13C NMR (50 MHz, CDCl3): d 170.7, 139.9, 138.4, 132.5, 130.2, 128.9,
128.8, 125.8, 124.2, 64.3, 32.6, 30.5, 30.3, 28.5, 26.0, 21.0, 12.9. m/z
(EIMS): 260 (Mþ), 129 (100). Anal. calcd. for C17H24O2: C, 78.42; H, 9.29.
Found: C, 78.57; H, 9.16.

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L. G. Sanchez et al.
64
(Z)-Rubrenoic Acid I (1a)
Saponification
A solution of 1 N LiOH (0.71 mL) was added to a solution of compound
14a (0.064 g, 0.22 mmol) in CH3OH/THF (2/3 v/v) (10 mL), and the
reaction mixture was stirred and refluxed for 3 h. Then aqueous 2 N HCl
(50 mL) was added, and the product was extracted with ethyl acetate
(3 ꢀ 30 mL) and dried over anhydrous MgSO4. The solvent was evaporated
under reduced pressure and purified by flash column chromatography on
silica-gel dichloromethane to give an oily product (0.51 g, 95%). IR (film):
1
3200, 3075, 2933, 1710 cm21; H NMR (200 MHz, CDCl3): d 7.05 (4H, m,
Ar); 5.46 (2H, m, -CH2-CH55CH-CH3); 3.31 (2H, d, J ¼ 5.8 Hz, Ar-CH2-
CH55CH); 2.55 (2H, t, J ¼ 8.6 Hz, Ar-CH2-CH2-); 2.30 (2H, t, J ¼ 6.6 Hz,
-CH2-COOH); 1.67 (3H, d, J ¼ 5.8 Hz, -CH55CH-CH3); 1.54 (6H, m,
-CH2-); 13C NMR (50 MHz, CDCl3): d 179.1, 140.0, 138.5, 128.8 (3C),
125.8, 125.7, 124.2, 33.4, 32.6, 30.5, 30.3, 29.1, 24.5, 12.9. m/z [HRMS
(FABþ)] calc. for C15H21O2 [M þ H] 233.1542. Found: 245.1508. Anal.
calcd. for C16H22O2: C, 78.01; H, 9.00. Found: C, 78.57; H, 9.13.
5-(2-But-2-enyl-phenyl)-pentan-1-ol (16a)
This compound was obtained following the same procedure described for
compound 1a using the compound 15a to give an oil (63%). IR (film): 3355
(-OH); 2930–2860 (C-H); 1457 (C55C); 1049 (CH-O-CH2-); 751 (C-H)
1
cm21. H NMR (200 MHz, CDCl3): d 7.13 (4H, m, Ar); 5.54 (2H, m, Ar-
CH2-CH55CH-CH3); 3.64 (2H, t, J ¼ 6.4 Hz, -CH2-OH); 3.39 (2H, d,
J ¼ 6.2 Hz, Ar-CH2-CH55CH-); 2.63 (2H, t, J ¼ 8.0 Hz, Ar-CH2-CH2-);
1.74 (3H, d, J ¼ 5.2 Hz, -CH55CH-CH3); 1.60 (4H, m, -CH2-CH2-CH2-);
1.46 (2H, m, -CH2-CH2-CH2). 13C NMR (50 MHz, CDCl3): d 140.7, 139.0,
129.4, 129.3, 129.2, 126.3, 126.2, 124.7, 63.1, 33.1, 32.9, 30.9, 30.5, 26.1,
13.1. m/z (EIMS) 218 Mþ (30) 129 (100). Anal. calcd. for C15H22O: C,
82.52; H, 10.16. Found: C, 82.61; H, 10.28.
nor-(Z)-Rubrenoic Acid I (17a)
This compound was obtained following the same procedure described for
compound 10 using the compound 16a to give an oily product (73%). IR
(film): 3339 (-OH); 3060 (C55C-H); 2922 (C-H); 1708 (COOH); 1411
1
(-CH2-); 1285 (C-0); 751 (C-H) cm21. H NMR (200 MHz, CDCl3): d 7.16
(4H, m, Ar); 5.49 (2H, m, Ar-CH2-CH55CH-CH3); 3.39 (2H, d, J ¼ 6.4 Hz,
Ar-CH2-CH55CH-); 2.61 (2H, t, J ¼ 8.4 Hz, Ar-CH2-CH2); 2.42 (2H, t,
J ¼ 7.0 Hz, -CH2-COOH); 1.75 (3H, d, J ¼ 6.2 Hz, -CH55CH-CH3); 1.69
(4H, m, -CH2-CH2-). 13C NMR (50 MHz, CDCl3): d 179.0, 139.6, 138.5,
128.9, 128.8, 128.1, 125.9, 125.8, 124.3, 33.9, 32.4, 30.3, 24.7, 12.9. m/z

Rubrenoic and nor-Rubrenoic Acids
65
[HRMS (FABþ)] calc. for C14H19O2 [M þ H] 219.1385. Found: 219.1415.
Anal. calcd. for C15H20O2: C, 77.55; H, 8.68. Found: C, 77.75; H, 8.89.
(2-Bromo-phenyl)-dideutero-methanol (19)
A suspension of LiAlD4 (1.08 g, 25.72 mmol) and dry THF (150 mL) was
added dropwise to a solution of ethyl 2-bromobenzoate (18) (2.94 g,
12.86 mmol) in dry THF (50 mL) at 08C in a dry round-bottom flask
(250 mL). The solution was stirred for 12 h, in which time the mixture
turned gray. This was then added dropwise to a solution of 3 M NaOH,
which resulted in a white suspension. The solid was collected by filtration,
washed twice with ethyl ether, dried under anhydrous MgSO4, and filtered,
and solvent was removed under reduced pressure to give a white solid,
yield 95%, mp 73–748C. IR (film): 3332; 3061–3027; 2199–2090; 1227;
1
666 (C-Br) cm21. H NMR (200 MHz, CDCl3): d 7.47 (1H, dd, J ¼ 7.6,
1.4 Hz, Ar); 7.40 (1H, dd, J ¼ 7.6, 1.8 Hz, Ar); 7.31 (1H, td, J ¼ 7.6,
1.2 Hz, Ar); 7.09 (1H, td, J ¼ 7.2, 1.8 Hz, Ar); 1.99 (1H, bs, -OH). 13C
NMR (50 MHz, CDCl3): d 142.0, 132.7, 129.2, 129.1, 127.7, 122.7.
1-Bromo-2-(iodo-dideutero-methyl)-benzene (20)
Compound 19 (0.189 g, 1 mmol) and NaI (0.179 g, 1.2 mmol) in acetonitrile
.
(10 mL) were placed in a dry round-bottom flask (50 mL), to which CeCl3
7
H2O (0.560 g, 1.5 mmol) was added, and the resulting mixture was stirred for
24 h at reflux. The mixture was diluted with ethylic and treated with 0.5 N
HCL (15 mL). The organic layer was separated, and the aqueuos phase was
extracted ethylic ether (2 ꢀ 20 mL). The combined organic phase was
washed with a solution of saturated NaHCO3 and brine, dried under
anhydrous MgSO4, and filtered. Solvent was removed under reduced
pressure to give an amber-colored solid (72%), mp 39–408C. IR (film):
1
3026; 2922; 2172; 548 cm21. H NMR (200 MHz, CDCl3): d 7.47 (1H, dd,
J ¼ 8.0, 1.2 Hz, Ar); 7.40 (1H, dd, J ¼ 7.8, 2.2 Hz, Ar); 7.25 (1H, td,
J ¼ 7.6, 1.2 Hz, Ar); 7.09 (1H, td, J ¼ 7.8, 1.8 Hz, Ar). 13C NMR (50 MHz,
CDCl3): d 139.6, 132.6, 129.24, 129.1, 127.7, 122.7, 40.1.
1-Bromo-2-[(Z)-1,1-dideutero-but-2-enyl]-benzene (21a)
This compound was synthesized following the same procedure described for
compound 9a using a solution of Grignard reagent 8a and compound 20 to
1
give a yellow oily product (72%). IR (film): 3018; 2196; 745; 653 cm21. H
NMR (200 MHz, CDCl3): d 7.46 (1H, dt, J ¼ 7.8, 0.8 Hz, Ar); 7.17 (1H, td,
J ¼ 4.0, 0.8 Hz, Ar); 7.15 (2H, m, Ar); 6.98 (1H, dt, J ¼ 7.4, 4.8 Hz, 1H,
Ar); 5.54 (2H, m, CH55CH); 1.66 (3H, d, J ¼ 7.8 Hz, CH55CH-CH3). 13C
NMR (50 MHz, CDCl3): d 140.0, 132.7, 130.8, 130.1, 127.7, 127.5, 127.3,
125.9, 40.0, 13.4. Purity determined by GC-EIMS, 88%.

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L. G. Sanchez et al.
66
1-Bromo-2-[(Z/E)-1,1-dideutero-but-2-enyl]-benzene (21a/b)
This compound was synthesized following the same procedure described for
compound 9a using a solution of Grignard reagent 8b and the compound 20 to
give a yellow oil product (72%). Z/E 40:60. IR (film): 2924; 939; 745;
1
653 cm21. H NMR (200 MHz, CDCl3): d 7.52 (2H, m, Ar); 7.19 (4H, m,
Ar); 7.05 (2H, m, Ar); 5.55 (4H, m, -Ar-CD2-CH55CH-CH3); 1.60 (6H, m,
CH55CH-CH3). 13C NMR (50 MHz, CDCl3): d 138.2, 138.0, 132.9, 132.7,
128.4, 127.9, 127.8, 127.6, 127.5, 126.1, 125.9, 124.5, 124.2, 18.4, 13.6.
Propyl 6-(2-Formylphenyl) Hexanoate (22)
This compound was synthesized following the same procedure described for
the Suzuki–Miyaura coupling in compound 14a. The solution of benzal-
dehyde-2-bromine (0.318 g, 1.72 mmol), Cs2CO3 (1.008 g, 3.096 mmol, 1.8
eq.), PdCl2 (dppf) (0.063 g, 0.086 mmol, 5% mol), and Ph3As (0.053 g,
0.172 mmol, 10 mol) in DMF (10 mL) was stirred with a suspension of
9-BBN-H/THF 12 (2.58 mmol) to give a light yellow liquid product
(0.386 g, 85%). IR (film): 2930, 1734, 1696, 1185, 754 cm21 1H NMR
;
(200 MHz, CDCl3): d 10.25 (1H, s, Ar-CHO); 7.82 (1H, dd, J ¼ 7.4,
1.4 Hz, Ar); 7.49 (1H, td, J ¼ 7.4, 1.4 Hz, Ar); 7.35 (1H, td, J ¼ 7.2,
1.4 Hz, Ar); 7.25 (1H, d, J ¼ 7.8 Hz, Ar); 4.02 (2H, t, J ¼ 6.8 Hz, -O-CH2);
3.03 (2H, t, J ¼ 7.6 Hz, Ar-CH2); 2.31 (2H, t, J ¼ 7.8 Hz, CH2-COO-);
1.65 (6H, m, -CH2-); 1.45 (2H, m, -CH2-); 0.93 (3H, t, J ¼ 7.6 Hz, -CH2-
CH3); 13C NMR (50 MHz, CDCl3): d 191.9, 173.4, 145.0, 133.4, 133.4,
133.3, 131.6, 130.6, 126.2, 65.7, 34.1, 32.3, 31.8, 28.9, 24.7, 21.9, 10.7.
Anal. calcd. for C16H22O3: C, 73.25; H, 8.45. Found: C, 73.33; H, 8.57.
Acetic Acid 5-(2-Formyl-phenyl)-pentyl Ester (23)
This compound was synthesized following the same procedure described for
the Suzuki–Miyaura coupling in compound 22 using compound 13 to give a
light yellow liquid product (50%). IR (film): 2933–2859 (C-H); 1736 (C55O);
1697 (C55O); 1241 (C-O-C); 1041 (CH-O-CH2-); 756 (C-H) cm21. 1H NMR
(200 MHz, CDCl3): d 10.24 (1H, s, CHO); 7.81 (1H, dd, J ¼ 7.4, 1.6 Hz, Ar);
7.50 (1H, td, J ¼ 7.4, 1.6 Hz, Ar); 7.36 (1H, td, J ¼ 7.8, 1.2 Hz, Ar); 7.26 (1H,
dd, J ¼ 7.4, 1.2 Hz, Ar); 4.05 (2H, t, J ¼ 6.6 Hz, -CH2-O-C55O); 3.04 (2H, t,
J ¼ 8.2 Hz, Ar-CH2-); 2.40 (2H, t, J ¼ 6.6 Hz, CH2-C55O); 2.04 (3H, s,
-O ¼ C-CH3); 1.55 (6H, ma, -CH2-). 13C NMR (50 MHz, CDCl3): d 191.9,
144.9, 133.4, 133.4, 131.8, 130.7, 126.2, 64.2, 41.6, 32.4, 31.7, 28.4, 27.1,
24.7, 20.9. Anal. calcd. for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.92;
H, 7.84.

Rubrenoic and nor-Rubrenoic Acids
67
Triphenyl Iodomethyl Phosphonium Iodide (24)
Iodoform (4.02 g, 15 mmol) was added to a solution of triphenyl phosphine
(5.00 g, 19.06 mmol) in toluene (20 mL). The suspension was stirred at reflux
temperature for 16 h. The solvent was removed at reduced pressure, and the
product was washed with ethyl ether to give a white solid product (6.45 g,
81%, mp 180–1818C). IR (film): 2910–2845, 1430, 779–682 cm21; 1H NMR
(200 MHz, CDCl3): d 7.77 (15H, m, -Ar); 4.85 (2H, d, J ¼ 8.6 Hz, P-CH2-).
6-[2-Z-(2-iodo-vinyl)-phenyl]-hexanoic Acid Propyl Ester (25a)
A suspension of salt 24 (2.65 g, 5.00 mmol) in THF (5 mL) was added to a
solution of NaHMDS 1.0 M (0.917 g, 1.014 mL, 5 mmol). The solution was
stirred at room temperature under argon atmosphere. The mixture was
stirred for 5 min at 2788C, and then HMPA (1.74 mL, 10 mmol) and a
solution of compound 22 (0.262 g, 1 mmol) in THF (1.0 mL) were added.
The reaction mixture was maintained at 2788C for 1 h, and then water
(5 mL) was added; the product was extracted with ethyl ether (3 ꢀ 30 mL).
The organic phase was washed with brine, dried over anhydrous MgSO4,
and filtered, and the solvent was evaporated under reduced pressure. The
residue was purified by column chromatography on silica gel with a
mixture of petroleum ether and dichloromethane to give a light yellow
1
liquid product (0.189 g, 50%). IR (film): 2919, 1733, 1173 cm21; H NMR
(200 MHz, CDCl3): d 7.29 (1H, d, J ¼ 8.4 Hz, Ar-CH55CH-I); 7.18 (4H,
m, Ar); 6.59 (1H, d, J ¼ 8.4 Hz, Ar-CH55CH-I); 3.95 (2H, t, J ¼ 6.6 Hz, -
O-CH2-); 2.47 (2H, t, J ¼ 8.2 Hz, Ar-CH2-); 2.23 (2H, t, J ¼ 7.6 Hz, CH2-
COO); 1.58 (6H, m, -CH2); 1.30 (2H, m, -CH2-); 0.86 (3H, t, J ¼ 7.4 Hz,
CH2-CH3); 13C NMR (50 MHz, CDCl3): d 173.4, 141.0, 139.0, 137.0,
129.0, 128.7, 128.1, 125.5, 83.8, 65.9, 34.4, 33.4, 30.4, 29.1, 25.0, 22.2,
10.6. Anal. calcd. for C17H23IO2: C, 52.86; H, 6.00. Found: C, 52.92; H, 6.12.
6-[2-E/Z-(2-Iodo-vinyl)-phenyl]-hexanoic Acid Propyl Ester (25a/b)
A solution of CrCl2 (0.737 g, 6 mmol) in THF (5 mL) was cooled to 08C. Then
a solution of compound 22 (0.65 g, 1.0 mmol) and CHI3 (0.787 g, 2.0 mmol) in
dry THF (5 mL) was added. The mixture was stirred to room temperature and
extracted with ethyl ether (3 ꢀ 30 mL); the organic phase was washed, dried
over anhydrous MgSO4, and filtered. The solvent was evaporated to give a
yellow liquid product (0.148 g, 52%). IR (film): 3062, 2934, 1732,
1178 cm21
;
1H NMR (200 MHz, CDCl3): d 7.56 (1H, d, J ¼ 14.6 Hz,
Ar-CH55CH-Itrans); 7.20 (1H, d, J ¼ 8.4 Hz, Ar-CH55CH-Icis); 7.14 (8H, m,
Ar); 6.59 (1H, d, J ¼ 14.6 Hz, Ar-CH55CH-Itrans); 6.56 (1H, d,
J ¼ 8.4 Hz, Ar-CH55CH-Icis); 3.94 (2H, t, J ¼ 6.6 Hz, -O-CH2-); 3.93 (2H,
t, J ¼ 6.6 Hz, -O-CH2-); 2.55 (2H, t, J ¼ 8.2 Hz, Ar-CH2-); 2.45 (2H, t,
J ¼ 8.2 Hz, Ar-CH2-); 2.22 (2H, t, J ¼ 7.6 Hz, CH2-COO); 2.21 (2H, t,

´
L. G. Sanchez et al.
68
J ¼ 7.6 Hz, -CH2-COO); 1.56 (12H, m, -CH2-); 1.30 (4H, m, -CH2-); 0.85 (6H,
t, J ¼ 7.8 Hz, -CH2-CH3). 13C NMR (50 MHz, CDCl3): d 173.7, 143.2, 139.3,
136.6, 129.6, 128.4, 126.4, 125.4, 126.2, 84.1, 66.1, 34.5, 33.3, 30.9, 29.2, 29.2,
25.1, 22.3, 10.8.
Acetic Acid 5-[2-(Z-2-Iodo-vinyl)-phenyl]-pentyl Ester (26a)
This compound was synthesized following the same procedure described for
the compound 25a using compound 23 and the salt 24 to give a light yellow
liquid product (50%). IR (film): 3062; 2928; 1736; 1204; 753 cm21. 1H NMR
(200 MHz, CDCl3): d 7.19 (1H, d, J ¼ 8.0 Hz, Ar-CH55CH-I); 7.05 (4H, m,
Ar); 6.48 (1H, d, J ¼ 8.4 Hz, Ar-CH55CH-I); 3.86 (2H, t, J ¼ 6.6 Hz, -O-
CH2-); 2.37 (2H, t, J ¼ 7.6 Hz, Ar-CH2-); 1.85 (3H, s, -O-CO-CH3); 1.35
(6H, m, -CH2-). 13C NMR (50 MHz, CDCl3): d 171.0, 140.1, 139.0, 136.7,
129.1, 128.7, 128.5, 125.6, 84.0, 64.6, 33.5, 28.6, 22.2, 21.4. Anal. calcd.
for C15H19IO2: C, 50.29; H, 5.35. Found: C, 50.20; H, 5.48.
General Procedure for Stille Coupling
6-(2-Z/E-Buta-1,3-dienyl-phenyl)-hexanoic Acid Propyl Ester (27a/b)
Compound 25a (0.199 g, 0.519 mmol), cooper iodide (0.009 g, 0.051 mmol,
10% mol), Pd (PPh3)4 (0.030 g, 0.026 mmol. 5% mol), and tributylvinyltin
(0.20 mL, 0.214 g, 0.67 mmol) in DMF (5 mL) were dissolved in a Schlenk
flask (100 mL) under an inert atmosphere. The reaction mixture was stirred
for 21 h at room temperature and quenched with water. The product was
extracted with ethyl ether (3 ꢀ 30 mL) and dried over anhydrous MgSO4.
The solvent was removed, and the product was purified by flash-column
chromatography on silica gel (95:5 ether petroleum–ethyl acetate) to give a
light green liquid product (0.096 g, 65%). IR (film): 3023, 2935, 1732,
1
1177 cm21. H NMR (200 MHz, CDCl3): d 7.56 (2H, m, Ar); 7.14 (2H, m,
Ar); 6.75 (1H, dd, J ¼ 15.0, 9.6 Hz, Ar-CH55CH-); 6.73 (1H, d,
J ¼ 15.0 Hz, Ar-CH55CH-); 6.54 (1H, ddd, J ¼ 17.0, 9.2, 9.2 Hz,
-CH55CH2); 5.32 (1H, dd, J ¼ 16.2, 2.2 Hz, -CH55CH2); 5.16 (1H, dd,
J ¼ 10.0, 2.2 Hz, -CH55CH2); 4.02 (2H, t, J ¼ 6.6 Hz, -O-CH2-); 2.67 (2H,
t, J ¼ 8.0 Hz, Ar-CH2-); 2.30 (2H, t, J ¼ 7.8 Hz, -CH2-CO); 1.62 (6H, m,
-CH2-); 1.40 (2H, m, -CH2-); 0.95 (3H, t, J ¼ 7.6 Hz, CH2-CH3); 13C NMR
(50 MHz, CDCl3): d 173.8, 140.1, 137.5, 135.5, 131.0, 130.2, 129.7, 127.6,
126.2, 125.6, 117.5, 66.1, 34.6, 33.4, 31.0, 29.2, 25.2, 22.3, 10.7.
Acetic acid 5-(2Z/E-Buta-1,3-dienyl-phenyl)-pentyl Ester (28a/b)
This compound was synthesized following the same procedure described for
Stille coupling using the compound 26a to give a light green liquid product

Rubrenoic and nor-Rubrenoic Acids
69
(0.024 g, 65%). IR (film): 2933–2859 (C-H); 1739 (C55O); 1238 (C-O-C);
1042 (CH-O-CH2-); 997 (C55C); 751 (C-H) cm21 1H NMR (200 MHz,
.
CDCl3): d 7.48 (2H, m, Ar); 7.15 (4H, m, Ar-CH55CH-CH55CH2); 6.96
(1H, dd, J ¼ 17.6, 10.6 Hz, Ar-CH55CH-CH55CH2); 5.64 (1H, dd,
J ¼ 17.0, 1.6 Hz, -CH55CH2); 5.28 (1H, dd, J ¼ 11.0, 1.2 Hz, -CH55CH2);
4.04 (2H, m, -CH2-O-); 2.68 (2H, t, J ¼ 7.4, Ar-CH2-); 2.03 (3H, s, -O55C-
CH3); 1.67 (4H, m, -CH2-). 1.41 (2H, m, -CH2-). 13C NMR (50 MHz,
CDCl3): d 171.2, 139.8, 136.4, 134.6, 133.0, 129.5, 129.0, 127.8, 126.3,
125.8, 115.5, 64.7, 34.6, 31.0, 28.8, 26.2, 21.4. m/z (EIMS) 232 [M]þ (17),
143 (100).
(E)-Rubrenoic Acid III (3b)
This compound was obtained following the same procedure described for
compound 1a using the compound 27b to give a liquid product (0.078 g,
;
95%). IR (film): 3200, 3060, 2960, 1709, 1094–1019 cm21 1H NMR
(200 MHz, CDCl3): d 7.43 (2H, m, Ar); 7.15 (m, 4H, Ar-CH55CH-
CH55CH2); 6.96 (1H, dd, J ¼ 17.6, 11.0 Hz, Ar-CH55CH-CH55CH2); 5.62
(1H, dd, J ¼ 15.8, 1.4 Hz, Ar-CH55CH-CH55CH2); 5.27 (1H, dd, J ¼ 9.4,
1.4 Hz, Ar-CH55CH-CH55CH2); 2.67 (2H, t, J ¼ 8.0 Hz, Ar-CH2-CH2-);
2.34 (2H, t, J ¼ 7.4 Hz, -CH2-C55O-); 1.62 (4H, m, -CH2-); 1.41 (2H, m,
-CH2-); 13C NMR (50 MHz, CDCl3): d 180.2, 139.8, 136.3, 134.6, 129.5,
129.4, 127.8, 126.3, 126.2, 125.8, 115.6, 34.3, 33.6, 31.0, 29.2, 24.8. m/z
[HRMS (FABþ)] calc. for C16H21O2 [M þ H] 245.1542. Found: 245.1566.
Anal. calcd. for C16H20O2: C, 78.65; H, 8.25. Found: C, 78.86; H, 8.37.
5-(2-E-Buta-1,3-dienyl-phenyl)-pentan-1-ol (29b)
This compound was obtained following the same procedure described for
compound 1a using the compound 28b to give a crystalline liquid product
(95%). IR (film): 3345 (-OH); 2932 (C-H); 1451 (C55C); 1048 (CH-O-);
1
752 (C-H) cm21. H NMR (200 MHz, CDCl3): d 7.48 (2H, m, Ar); 7.18
(4H, m, Ar-CH55CH-CH55CH2); 7.00 (1H, dd, J ¼ 17.2, 11.0 Hz, Ar-
CH55CH-); 5.64 (1H, dd, J ¼ 17.2, 1.6 Hz, -CH55CH2); 5.28 (1H, dd,
J ¼ 11.0, 1.4 Hz, -CH55CH2); 3.63 (2H, t, J ¼ 6.2 Hz, -CH2-O-); 2.68 (2H,
t, J ¼ 7.0 Hz, Ar-CH2); 1.60 (4H, m, -CH2-); 1.42 (2H, m, -CH2-). 13C
NMR (50 MHz, CDCl3): d 136.4, 134.6, 133.0, 123.0, 129.6 128.9, 128.8,
127.8 126.2, 125.7, 115.4, 63.1, 34.7, 33.7, 31.2, 26.0. Anal. calcd. for
C15H20O: C, 83.28; H, 9.32. Found: C, 83.40; H, 9.40.
nor-(E)-Rubrenoic Acid III (30b)
This compound was obtained following the same procedure described for
compound 10 using the compound 29b to give a liquid product (69%). IR
1
(film): 3224 (-OH); 2934 (C-H); 1709 (COOH) cm21. H NMR (200 MHz,

´
L. G. Sanchez et al.
70
CDCl3): d 7.44 (2H, m, Ar); 7.19 (3H, m, Ar-CH55CH-CH55CH2); 6.99 (1H,
dd, J ¼ 17.2, 9.0 Hz, Ar-CH55CH-); 5.64 (1H, dd, J ¼ 17.2, 1.4 Hz,
-CH55CH2); 5.29 (1H, dd, J ¼ 10.8, 1.4 Hz, -CH55CH2); 2.81 (2H, t,
J ¼ 7.4 Hz, Ar-CH2-); 2.40 (2H, t, J ¼ 7.4 Hz, -CH2-COOH); 1.69 (4H, m,
-CH2-CH2-). 13C NMR (50 MHz, CDCl3): d 179.0, 134.6, 133.0, 129.5,
128.9, 128.8, 127.8, 126.4, 126.1, 125.9, 115.6, 34.3, 30.7, 30.2, 24.7. m/z
[HRMS (FABþ)] calc. for C15H19O2 [M þ H] 231.1385. Found: 231.1410.
Anal. calcd. for C15H18O2: C, 78.23; H, 7.88. Found: C, 78.41; H, 8.09.
ACKNOWLEDGMENT
We gratefully acknowledge support for this project from Consejo del Sistema
´ ´
Nacional de Educacion Tecnologica (COSNET) 491-02-P (2002) and a
´
graduate fellowship from Consejo Nacional de Ciencia y Tecnologıa
(CONACyT) for L. G. S.
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