Rapid Access to Benzofuran-Based Natural Products through a Concise Synthetic Strategy

Article abstract of DOI:10.1002/ejoc.201600154

A concise strategy is described for the synthesis of ailanthoidol (1), egonol (2), homoegonol (3), demethoxyegonol (4), demethoxyhomoegonol (5), and stemofuran A (6). This approach involves a Pd-catalysed domino cyclization/coupling process using triarylbismuth reagents for the generation of the benzofuran core. Subsequent structural modifications then give the final targets. The high yielding synthesis of the recently isolated natural products egonol-9(Z)-12(Z)-linoleate (2a), 7-demethoxyegonol-9(Z)-12(Z)-linoleate (4a), and 7-demethoxy-egonol-9(Z)-oleate (4b) are also reported.

Full text of DOI:10.1002/ejoc.201600154

DOI: 10.1002/ejoc.201600154
Full Paper
Synthesis Design
Rapid Access to Benzofuran-Based Natural Products through a
Concise Synthetic Strategy
Maddali L. N. Rao*[a] and Venneti N. Murty[a]
Abstract: A concise strategy is described for the synthesis of benzofuran core. Subsequent structural modifications then give
ailanthoidol (1), egonol (2), homoegonol (3), demethoxyegonol the final targets. The high yielding synthesis of the recently
(4), demethoxyhomoegonol (5), and stemofuran A (6). This ap- isolated natural products egonol-9(Z)-12(Z)-linoleate (2a), 7-de-
proach involves a Pd-catalysed domino cyclization/coupling methoxyegonol-9(Z)-12(Z)-linoleate (4a), and 7-demethoxy-
process using triarylbismuth reagents for the generation of the egonol-9(Z)-oleate (4b) are also reported.
Introduction
studied in recent times, due to its life-threatening qualities in
Natural products containing benzofuran moieties, including ai-
old age. A few recently isolated natural products, 2a, 4a, and
lanthoidol (1), egonol (2), homoegonol (3), demethoxyegonol
4b, have been studied as potent acetylcholinesterase (AChE)
(4), demethoxyhomoegonol (5), stemofuran A (6), and other
inhibitors (with IC50 = 1.4–3.1 μM
).[2h] It was found that the
related compounds (Figure 1), have attracted attention for me-
dicinal and pharmaceutical applications.[1,3] Ailanthoidol was
isolated from the stem woods of Zanthoxylum ailanthoides, eg-
onol from the seeds of Styrax japonica, and homoegonol from
the glycosidic fraction of the seeds of Styrax officinalis. Further-
more, demethoxyegonol, demethoxyhomoegonol, and stemo-
furan were isolated from Styrax obassia, Styrax japonica, and
length of the side-chain, along with other structural features of
the benzofuran skeleton, had an effect on the inhibitory po-
tency. The importance and relevance of benzofuran derivatives
also warrants to have efficient synthetic routes to these com-
pounds.
In recent years, various strategies have been reported to im-
Stemona collinsae, respectively.[2] The progressive neurodegen- prove the efficiency of natural product syntheses.[4] One such
erative disorder Alzheimer's disease (AD) has been intensely strategy involves the identification of a common core interme-
Figure 1. Benzofuran-containing natural products.
[a] Department of Chemistry, Indian Institute of Technology Kanpur,
diate that can react with complementary structural partners to
provide a pool of synthetic targets in a facile and concise man-
ner. A brief review of the literature revealed that several differ-
ent strategies for the synthesis of the benzofuran core skeleton
are known.[1] Examples include McMurry coupling,[1s] Wittig ole-
Kanpur 208016, India
E-mail: maddali@iitk.ac.in
http://www.iitk.ac.in
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201600154.
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fination,[1t] Sonogashira coupling,[1h] and other methods.[1u] The vinyl)phenols are easily accessible. We planned to evaluate this
popular strategy involving a Sonogashira coupling/cyclization combination for the synthesis of target benzofurans, and the
protocol using ethoxycarbonylethenyl-derived 2-halophenols related retrosynthetic analysis is shown in Scheme 2.
and alkynes (Scheme 1, strategy 1) worked well for ailantho-
idol,[1h,1q] but failed for egonol and other related com-
pounds.[1g] This failure was attributed to the electronic nature
of both the 2-halophenols and the alkynes, and related compli-
cations when applied in a multistep synthesis. Thus, this proto-
col did not facilitate a rapid and concise synthesis of benzo-
furan natural products.
This prompted us to explore the application of a Pd-cata-
lysed domino cyclization/coupling protocol in a pooled ap-
proach (Scheme 1, strategy 2) for the synthesis of benzofuran
natural products 1–5. The strategic use and the relative reactivi-
ties of organometallic reagents and 2-(2,2-dibromovinyl)-
phenols are crucial to achieving success through this approach.
First, the domino cyclization/coupling protocol could be car-
ried out using various organometallic reagents, including mo-
noarylboron,[5a,5b] monoaryltin,[5a] monoarylsilicon,[5c] and tri-
arylbismuth[5d] reagents. It was surprising to note that despite
the availability of these coupling methods, reports of their use
in a concise strategy are conspicuously absent. This increased
our interest for the development of such a strategy. After evalu-
ating various reagents, we converged on the use of triarylbis-
muth reagents; these reagents offer the advantage of threefold
cross-coupling in addition to faster reactivity and high yields.[5d]
The planned divergent route starting from readily available o-
vanillin/salicylaldehyde would provide an easy access to benzo-
furan moieties (13–17), with three different triarylbismuth rea-
We envisaged that this strategy would be more feasible, as gents being used in the key domino cyclization/coupling reac-
various organometallic nucleophiles and 2-(2,2-dibromo- tion (Scheme 2). This was investigated as described below.
Scheme 1. Strategy for the synthesis of benzofurans.
Scheme 2. Retrosynthetic analysis.
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Results and Discussion
13–15, which are key precursors for the synthesis of ailanthoidol
(1), egonol (2), and homoegonol (3), respectively (Scheme 2).
The required triarylbismuth reagents (i.e., TAB-1, TAB-2, and
TAB-3) were prepared using aryl Grignard or aryllithium rea-
gents and bismuth chloride in good to high yields (Scheme 4).
The appropriate aryl bromides were obtained through bromin-
ation of the corresponding arenes following literature proce-
dures.[10] These bismuth reagents were obtained as pure solids.
Initially, we adopted two flexible routes for the synthesis of key
intermediate 10a. The first route, involving a Heck reaction, is
shown in Scheme 3, path a. This route started with the iodina-
tion[6a] of o-vanillin (7a) using ICl/AgNO3 to give the corre-
sponding iodo derivative (i.e., 8a) in 96 % yield. This compound
was subjected to Heck coupling[7] under Pd-catalysed condi-
tions using ethyl acrylate to give cinnamyl ester 9a in 88 %
yield. This aldehyde was subjected to Ramirez olefination[8] to
give the corresponding dibromide (i.e., 10a) in 83 % yield. Thus,
this reaction sequence yielded 10a in 70 % overall yield.
The other synthetic strategy, again starting from o-vanillin
(7a), but involving Wittig olefination, is shown in Scheme 3,
path b. Thus, o-vanillin (7a) was converted into dibromide 11a
in 89 % yield by Ramirez olefination. An attempted formylation
of 11a using a Vilsmeier–Haack reaction failed to give 12a as
the product. We then tested Duff's formylation[9] conditions us-
ing hexamine in trifluoroacetic acid, and under these condi-
tions, 12a was formed in 35 % yield. We were delighted to find
that when this reaction was run in refluxing acetic acid, com-
pound 12a was formed in 70 % yield. It is interesting to note
that dibromide 11a is stable enough to undergo Duff's formyl-
ation in high yield even under relatively harsh conditions. Next,
Wittig reaction of 12a with phosphorane gave cinnamyl ester
10a in 80 % yield. Thus starting from o-vanillin (7a), the key
dibromide (i.e., 10a) was obtained in three steps in 50 % overall
yield.
Thus, two alternative routes (Scheme 3, paths a and b) were
established for the synthesis of dibromide 10a; path a emerged
as the favoured one, with a higher overall yield. Our next chal-
lenge was to subject this intermediate to Pd-catalysed domino
cyclization/coupling with differently functionalized bismuth re-
agents. In this way, we would obtain three 2-arylbenzofurans
Scheme 4. Synthesis of triarylbismuth reagents (NBS = N-bromosuccinimide;
PTSA = p-toluenesulfonic acid; CAN = cerium(IV) ammonium nitrate).
Scheme 3. Two routes for the synthesis of intermediate 10a.
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Having obtained key synthetic intermediate 10a and the tri- This protocol thus proved to be more general in the generation
arylbismuth reagents, we subjected them to a domino cycliza- of diverse 2-arylbenzofuran precursors.
tion/coupling protocol (Scheme 5) under Pd-catalysed coupling
These precursors were then subjected to the required syn-
conditions. To our delight, this domino method involving the thetic modifications to reach the desired target skeletons
1,1-dibromide and the three different bismuth reagents gave (Scheme 6). For example, initial debenzylation of 13 using TiCl4
the corresponding 2-arylbenzofurans (i.e., 13–15) in high yields. gave 18 in 89 % yield. This was then reduced using DIBAL-H
Scheme 5. Synthesis of benzofurans 13–15 through domino cyclization/coupling.
Scheme 6. Synthesis of ailanthoidol (1), egonol (2), and homoegonol (3).
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Scheme 7. Synthesis of demethoxyegonol (4) and demethoxyhomoegonol (5).
Scheme 8. Synthesis of stemofuran A.
(diisobutylaluminium hydride) to give ailanthoidol (1).[1f] forts towards the preparation of demethoxyegonol (4) and de-
Hydrogenation (Pd/C) of benzofuran intermediates 14 and 15 methoxyhomoegonol (5) from salicylaldehyde (Scheme 2).
gave the corresponding reduction products (i.e., 19 and 20) in
quantitative yields. This was followed by the reduction of the
ester group using LiAlH4 to give egonol (2) and homoegonol
(3), respectively, in high yields.
Our concise strategy involving a total of six steps from o-
vanillin allowed the synthesis of ailanthoidol (1), egonol (2), and
homoegonol (3) in high overall yields. The successful applica-
tion of the domino cyclization/coupling protocol to obtain
benzofuran natural products 1–3 encouraged our further ef-
Scheme 9. Synthesis of triarylbismuth reagent TAB-4.
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Scheme 10. Synthesis of recently isolated natural products 2a, 4a, and 4b.
Iodination[6b] of salicylaldehyde (7b) using ICl was accom- study to the preparation of recently isolated natural products
plished, and the corresponding 5-iodosalicylaldehyde (i.e., 8b) egonol-9(Z)-12(Z)-linoleate (2a), 7-demethoxyegonol-9(Z)-12(Z)-
was obtained in 94 % yield (Scheme 7). The Heck coupling of linoleate (4a), and 7-demethoxyegonol-9(Z)-oleate (4b), as
8b was carried out with ethyl acrylate under Pd-catalysed con- shown in Scheme 10. This was based on their importance, as
ditions to give cinnamate ester 9b in 89 % yield. This was then explained in the introduction, and on the easy availability of
converted into dibromide 10b in 70 % yield using the Ramirez egonol (2) and demethoxyegonol (4) by our strategy. We useed
olefination procedure. This 1,1-dibromide was coupled with tri- the Steglich esterification procedure to derivatize these skele-
arylbismuth reagents TAB-2 and TAB-3 under Pd-catalysed tons using linoleic acid and oleic acid and obtained the three
conditions to give 2-arylbenzofurans 16 and 17 in 75 and 77 % natural products 2a, 4a, and 4b (Scheme 10).[1g] Accordingly,
yields, respectively (Scheme 7). These products were then sub- treatment of egonol (2) and demethoxyegonol (4) with linoleic
jected to hydrogenation with Pd/C, followed by reduction with acid, DCC (N,N′-dicyclohexylcarbodiimide), and DMAP (4-di-
LiAlH4 to give demethoxyegonol (4) and demethoxyhomo- methylaminopyridine) gave 2a and 4a, respectively. The corre-
egonol (5), respectively. This synthetic approach involving a to- sponding esterification of demethoxyegonol (4) with oleic acid
tal of six steps from salicylaldehyde provided demethoxyegonol gave 4b. These reactions thus gave three natural products (2a,
(4) and demethoxyhomoegonol (5) in high yields.
4a, and 4b) in high yields.
We decided also to use our method for the synthesis of ste-
mofuran A (6), as shown in Scheme 8. The reported procedure
for the synthesis of this compound involves Suzuki cross-cou-
pling between 2-benzofuranboronic acid and 3,5-dimethoxy-
bromobenzene under Pd-catalysed conditions.[11a] To achieve
the synthesis of 6, we used our method involving coupling be-
tween dibromide 23, obtained from salicylaldehyde (7b), and
triarylbismuth reagent TAB-4. The required bismuth reagent for
this purpose was prepared from the corresponding aryl Grig-
nard reagent in high yield (Scheme 9).
The cross-coupling of dibromide 23 was carried out with
TAB-4 under Pd-catalysed conditions. This gave the corre-
sponding 2-arylbenzofuran precursor (i.e., 24) in 70 % yield. It
was demethylated using BBr3 to give stemofuran A (6) in high
yield (Scheme 8). It is important to note that intermediate 24
could also be converted to stemofuran C through alkylation
and demethylation procedures.[11a] The stemofuran A skeleton
has wider applicability in the synthesis of natural products such
as machaeriol B and D.[11b–11d]
Conclusions
We have successfully demonstrated a concise strategy for the
synthesis of medicinally important ailanthoidol (1), egonol (2),
homoegonol (3), demethoxyegonol (4), demethoxyhomoeg-
onol (5), and stemofuran A (6). Using our strategy, which in-
volves 2-(2,2-dibromovinyl)phenol and coupling with a triaryl-
bismuth reagent for the generation of the benzofuran core, it
was possible to access a variety of benzofuran natural products
in a concise manner. We have also demonstrated the synthesis
of three recently isolated natural products, egonol-9(Z)-12(Z)-
linoleate (2a), 7-demethoxyegonol-9(Z)-12(Z)-linoleate (4a), and
7-demethoxy-egonol-9(Z)-oleate (4b), all in high yields. The
synthetic potential of triarylbismuths in threefold cross-cou-
pling combined with divergent reactivity is noteworthy. The
strategy described here, using 1,1-dibromide and triarylbismuth
reagents, is expected to serve as a robust method for the gener-
The success of the domino cyclization/coupling protocol for ation of benzofuran scaffolds with a broad scope and applica-
the preparation of natural products 1–6 led us to extend this bility in organic synthesis.
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(100 mL). Acetic acid (30 mL) was then added. The mixture was
stirred for 15 min at room temp., and then heated at 130 °C for
12 h. After that, the mixture was brought to room temp., HCl (50 %
aq.; 10 mL) was added, and the mixture was stirred for 45 min. It
was then neutralized with NaHCO3 solution, and extracted with
ethyl acetate. The organic phase was washed with brine, and dried
with anhydrous MgSO4. The crude product was purified by silica
gel column chromatography (chloroform) to give compound 12a
(1.53 g, 70 %) as a yellowish-red solid, m.p. 184–186 °C. 1H NMR
(500 MHz, CDCl3): δ = 9.84 (s, 1 H), 7.89 (s, 1 H), 7.63 (s, 1 H), 7.40
(s, 1 H), 6.40 (s, 1 H), 3.99 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 190.71, 148.79, 147.03, 130.55, 128.90, 126.96, 121.82, 107.95,
Experimental Section
General Remarks: NMR spectra were recorded with JEOL–Lambda
(500 MHz and 400 MHz) spectrometers with CDCl3, [D6]DMSO, and
CD3OD as solvents, and with tetramethylsilane as an internal stand-
ard. HRMS spectra were recorded with a Waters ESI-QTOF instru-
ment. IR spectra were recorded with a Bruker Vector 22 FTIR spec-
trometer. All solvents were distilled using standard drying methods.
The couplings were carried out under a nitrogen atmosphere in
oven-dried Schlenk tubes.
Compound 9a:
A mixture of 5-iodo-o-vanillin (8a; 2.5 g,
8.99 mmol), ethyl acrylate (1.8 g, 17.98 mmol), Pd(OAc)2 (101 mg,
0.44 mmol), tri(o-tolyl)phosphine (547 mg, 1.79 mmol), and triethyl-
amine (4.54 g, 44.95 mmol) in dry acetonitrile (35 mL) was put
under a nitrogen atmosphere in an oven-dried round-bottomed
flask. The reaction mixture was stirred at 90 °C for 9 h. After this
time, the solvent was removed, and the mixture was extracted with
ethyl acetate. The organic extract was washed with water and brine,
dried using MgSO4, and concentrated. The crude product was puri-
fied by silica gel column chromatography (EtOAc/hexane, 40:60) to
give 9a (1.97 g, 88 %) as a pale yellow solid, m.p. 122–124 °C. 1H
NMR (400 MHz, CDCl3): δ = 11.33 (s, 1 H), 9.93 (s, 1 H), 7.63 (d, J =
16.00 Hz, 1 H), 7.34 (d, J = 1.84 Hz, 1 H), 7.26 (s, 1 H), 6.35 (d, J =
16.04 Hz, 1 H), 4.27 (q, J = 7.32 Hz, 2 H), 3.96 (s, 3 H), 1.34 (t, J =
7.32 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 196.26, 166.74,
153.45, 148.82, 142.89, 126.53, 125.44, 120.41, 117.40, 115.18, 60.61,
91.89, 56.39 ppm. IR (KBr): ν = 3130, 1670, 1589, 1492, 1460, 1433,
˜
1287, 1150, 708 cm–1. HRMS (ESI): calcd. for C10H12Br2NO3 [M +
NH4]+ 351.9184; found 351.9182.
General Procedure for Domino Cyclization/Coupling: 1,1-Di-
bromide (0.825 mmol), BiAr3 (0.250 mmol), Cs2CO3 (1.5 mmol),
Pd(PPh3)4 (0.022 mmol), and DMF (5 mL) were put into an oven-
dried Schlenk tube under a nitrogen atmosphere. The mixture was
heated in an oil bath at 90 °C for 4 h. The reaction mixture was
then cooled to room temp., and extracted with ethyl acetate. The
organic phase was washed with water followed by brine, dried with
MgSO4, and concentrated. The crude product was purified by silica
gel column chromatography to give the benzofuran product. This
procedure was followed for the preparation of benzofurans 13–17
and 24.
56.32, 14.30 ppm. IR (KBr): ν = 2980, 2882, 1707, 1633, 1474, 1276,
˜
Compound 13:[1f] Colourless solid (277 mg, 80 %), m.p. 128–130 °C.
1H NMR (500 MHz, CDCl3): δ = 7.75 (d, J = 16.05 Hz, 1 H), 7.46–7.44
(m, 2 H), 7.39–7.32 (m, 6 H), 6.96–6.93 (m, 2 H), 6.88 (s, 1 H), 6.41
(d, J = 16.05 Hz, 1 H), 5.21 (s, 2 H), 4.28 (q, J = 7.16 Hz, 2 H), 4.06
(s, 3 H), 3.99 (s, 3 H), 1.35 (t, J = 7.17 Hz, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 167.18, 157.16, 149.74, 148.90, 145.36, 145.28,
145.14, 136.71, 131.34, 130.52, 128.60, 127.96, 127.26, 123.29,
118.14, 116.88, 114.51, 113.79, 108.57, 105.05, 100.45, 70.92, 60.45,
1166, 1180, 868, 758 cm–1. HRMS (ESI): calcd. for C13H13O5 [M – H]–
249.0763; found 249.0764.
Compound 10a
Route A: A solution of CBr4 (5.56 g, 16.78 mmol) in CH2Cl2 (100 mL)
was put into a 250 mL round-bottomed flask, and cooled to 0 °C.
A solution of PPh3 (8.80 g, 33.57 mmol) in CH2Cl2 (25 mL) was
added dropwise over about 15 min. The resulting mixture was
stirred for 30 min, and then triethylamine (3.39 g, 33.57 mmol) was
added, followed by a solution of compound 9a (1.4 g, 5.59 mmol)
in CH2Cl2 (25 mL). The mixture was then brought to room temp.,
and stirred for a further 9 h. Hexane (50 mL) was then added. The
resulting suspension was filtered through 100–200 silica, and the
filtrate was concentrated. The crude product was purified by silica
gel column chromatography (EtOAc/hexane 30:70) to give 10a
(1.88 g, 83 %) as a pale yellow solid, m.p. 103–105 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.63–7.59 (m, 2 H), 7.54 (d, J = 1.84 Hz, 1 H),
7.00 (d, J = 1.84 Hz, 1 H), 6.29 (d, J = 16.04 Hz, 1 H), 6.10 (s, 1 H),
4.26 (q, J = 7.17 Hz, 2 H), 3.93 (s, 3 H), 1.33 (t, J = 7.1 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 167.09, 146.62, 145.20, 144.34,
131.08, 126.12, 122.17, 121.98, 116.32, 108.84, 91.19, 60.45, 56.16,
56.18, 56.05, 14.36 ppm. IR (KBr): ν = 3420, 2929, 1712, 1631, 1510,
˜
1480, 1271, 1173, 1113, 849 cm–1. HRMS (ESI): calcd. for C28H27O6
[M + H]+ 459.1808; found 459.1801.
Compound 14:[1g] Colourless solid (209 mg, 76 %), m.p. 165–167 °C.
1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 16.04 Hz, 1 H), 7.40 (dd,
J = 8.24, J = 1.36 Hz, 1 H), 7.32–7.31 (m, 2 H), 6.96 (s, 1 H), 6.88 (d,
J = 8.24 Hz, 1 H), 6.84 (s, 1 H), 6.40 (d, J = 16.48 Hz, 1 H), 6.01 (s, 2
H), 4.28 (q, J = 7.17 Hz, 2 H), 4.06 (s, 3 H), 1.35 (t, J = 7.1 Hz, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 167.15, 156.93, 148.30, 148.11,
145.32, 145.09, 131.26, 130.55, 124.10, 119.42, 116.91, 114.50,
108.67, 105.56, 105.24, 101.39, 100.45, 60.43, 56.10, 14.34 ppm. IR
(KBr): ν = 2904, 1702, 1635, 1500, 1472, 1287, 1231, 1173, 1150,
˜
1022, 930, 843 cm–1. HRMS (ESI): calcd. for C21H19O6 [M + H]+
367.1182; found 367.1184.
14.34 ppm. IR (KBr): ν = 3518, 1705, 1637, 1600, 1489, 1453, 1277,
˜
1176, 1072, 833 cm–1. HRMS (ESI): calcd. for C14H15Br2O4 [M + H]+
404.9337; found 404.9332.
Compound 15: Colourless solid (221 mg, 77 %), m.p. 139–141 °C.
1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 16.04 Hz, 1 H), 7.45 (dd,
J = 8.44, J = 2.06 Hz, 1 H), 7.35 (d, J = 1.84 Hz, 1 H), 7.31 (br. s, 1
H), 6.96 (d, J = 0.92 Hz, 1 H), 6.93 (d, J = 8.24 Hz, 1 H), 6.89 (s, 1 H),
6.41 (d, J = 16.04 Hz, 1 H), 4.28 (q, J = 7.17 Hz, 2 H), 4.06 (s, 3 H),
3.99 (s, 3 H), 3.93 (s, 3 H), 1.35 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 167.15, 157.19, 149.82, 149.15, 145.34, 145.29,
145.13, 131.36, 130.53, 122.89, 118.23, 116.89, 114.46, 111.23,
Route B: A solution of compound 12a (1 g, 2.97 mmol) in THF
(60 mL) was put into a round-bottomed flask (100 mL), and (carb-
ethoxymethylene)triphenylphosphorane (3.11 g, 8.93 mmol) was
added. The mixture was heated at reflux for 6 h. After the reaction
was complete, the solvent was evaporated, and the product was
extracted with ethyl acetate. The organic extract was washed with
brine, dried with MgSO4, and concentrated. The crude product was
purified by silica gel column chromatography (EtOAc/hexane, 5:95)
to give compound 10a (0.96 g, 80 %) as a pale yellow solid, m.p.
103–105 °C.
108.11, 105.07, 100.36, 60.43, 56.05, 55.96, 14.34 ppm. IR (KBr): ν =
˜
3011, 2989, 1710, 1637, 1610, 1576, 1271, 1174, 1141, 1022 cm–1
.
HRMS (ESI): calcd. for C22H23O6 [M + H]+ 383.1495; found 383.1493.
Compound 12a: A mixture of compound 11a (2 g, 6.49 mmol) and
hexamine (2.73 g, 19.48 mmol) was put into a round-bottomed flask
Compound 16: Off-white solid (189 mg, 75 %), m.p. 164–165 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.78 (d, J = 16.12 Hz, 1 H), 7.70 (s, 1 H),
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7.48–7.43 (m, 2 H), 7.39 (dd, J = 8.28, J = 1.7 Hz, 1 H), 7.30 (d, J =
1.48 Hz, 1 H), 6.89 (d, J = 8.32 Hz, 1 H), 6.86 (s, 1 H), 6.43 (d, J =
16.12 Hz, 1 H), 6.02 (s, 2 H), 4.28 (q, J = 7.16 Hz, 2 H), 1.35 (t, J =
133.80, 131.39, 130.18, 129.59, 121.66, 118.45, 116.41, 111.49,
109.17, 104.92, 100.73, 62.14, 56.26 ppm. IR (KBr): ν = 3327, 2936,
˜
1602, 1516, 1478, 1442, 1423, 1378, 1340, 1277, 11167, 1128, 995
7.08 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 167.22, 156.96, 967 cm–1. HRMS (ESI): calcd. for C19H17O5 [M – H]– 325.1076; found
155.74, 148.32, 148.15, 145.08, 129.96, 129.68, 124.22, 124.03,
120.85, 119.32, 116.87, 111.45, 108.74, 105.47, 101.40, 100.06, 60.41,
325.1076.
Compound 19:[1g] Compound 14 (0.120 g, 0.327 mmol) was put
into a round-bottomed flask (50 mL) containing methanol (10 mL).
Pd/C (10 %; 0.012 g) was added, and the mixture was stirred at
room temp. under a hydrogen atmosphere (balloon) for 4 h. The
14.35 ppm. IR (KBr): ν = 2986, 2906 1697, 1632, 1499, 1467, 1450,
˜
1292, 1266, 1236, 1178, 929, 791 cm–1. HRMS (ESI): calcd. for
C20H17O5 [M + H]+ 337.1076; found 337.1073.
Compound 17: Pale yellow solid (203 mg, 77 %), m.p. 161–163 °C. mixture was then filtered through a bed of silica gel, and the filtrate
1H NMR (500 MHz, CDCl3): δ = 7.79 (d, J = 15.9 Hz, 1 H), 7.71 (br. s,
was concentrated. The crude product was purified by column chro-
1 H), 7.50–7.43 (m, 3 H), 7.36 (d, J = 2.15 Hz, 1 H), 6.95 (d, J = matography (EtOAc/hexane, 20:80) to give compound 19 (0.120 g,
8.55 Hz, 1 H), 6.91 (s, 1 H), 6.43 (d, J = 16.15 Hz, 1 H), 4.28 (q, J =
99 %) as a colourless solid, m.p. 96–98 °C. 1H NMR (500 MHz, CDCl3):
7.12 Hz, 2 H), 3.99 (s, 3 H), 3.94 (s, 3 H), 1.35 (t, J = 7.02 Hz, 3 H)
δ = 7.39 (dd, J = 7.9, J = 1.82 Hz, 1 H), 7.31 (d, J = 1.85 Hz, 1 H),
ppm. 13C NMR (125 MHz, CDCl3): δ = 167.23, 157.19, 155.81, 149.85, 6.97 (br. s, 1 H), 6.86 (d, J = 7.95 Hz, 1 H), 6.79 (s, 1 H), 6.63 (br. s, 1
149.23, 145.13, 130.09, 129.69, 123.98, 123.02, 120.79, 118.13,
116.89, 111.45, 111.36, 108.07, 99.92, 60.41, 56.01, 14.36 ppm. IR
H), 6.00 (s, 2 H), 4.14 (q, J = 7.13 Hz, 2 H), 4.02 (s, 3 H), 3.01 (t, J =
7.92 Hz, 2 H), 2.66 (t, J = 7.92 Hz, 2 H), 1.24 (t, J = 7.02 Hz, 3 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 172.99, 156.14, 148.03, 147.98,
(KBr): ν = 2928, 1701, 1633, 1511, 1265, 1170, 1139, 1023, 793 cm–1
.
˜
HRMS (ESI): calcd. for C21H21O5 [M + H]+ 353.1389; found 353.1387. 144.78, 142.57, 136.32, 131.04, 124.63, 119.20, 112.26, 108.60,
107.24, 105.53, 101.29, 100.36, 60.41, 56.11, 36.54, 31.33, 14.22 ppm.
Compound 24:[11a] Colourless liquid (133 mg, 70 %). 1H NMR
(400 MHz, CDCl3): δ = 7.58 (d, J = 6.88 Hz, 1 H), 7.52 (d, J = 8.24 Hz,
1 H), 7.29 (td, J = 7.66, J = 1.52 Hz, 1 H), 7.23 (td, J = 7.56, J =
0.92 Hz, 1 H), 7.03 (d, J = 2.28 Hz, 2 H), 7.01 (d, J = 0.92 Hz, 1 H),
IR (KBr): ν = 2904, 1725, 1619, 1600, 1501, 1475, 1365, 1259, 1228,
˜
1189, 1039, 739, 861 cm–1. HRMS (ESI): calcd. for C21H21O6 [M + H]+
369.1338; found 369.1331.
6.48 (t, J = 2.28 Hz, 1 H), 3.88 (s, 6 H) ppm. 13C NMR (100 MHz, Compound 20: Compound 15 (0.150 g, 0.392 mmol) was dissolved
CDCl3): δ = 161.09, 155.70, 154.80, 132.22, 129.09, 124.37, 122.94, in methanol (10 mL) in a round-bottomed flask (100 mL), and Pd/C
120.94, 111.17, 103.02, 101.82, 101.05, 55.49 ppm. IR (KBr): ν = 3052,
(10 %; 15 mg) was added. The mixture was stirred at room temp.
for 4 h under a hydrogen atmosphere (balloon). The mixture was
filtered through a bed of silica gel, and the filtrate was concen-
trated. The crude product was purified by silica gel column chroma-
tography (EtOAc/hexane, 20:80) to give compound 20 (0.149 g,
99 %) as a colourless solid, m.p. 101–103 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.45 (dd, J = 8.24, J = 1.84 Hz, 1 H), 7.36 (d, J = 1.84 Hz,
1 H), 6.98 (br. s, 1 H), 6.92 (d, J = 8.68 Hz, 1 H), 6.83 (s, 1 H), 6.63
(br. s, 1 H), 4.14 (q, J = 7.17 Hz, 2 H), 4.03 (s, 3 H), 3.98 (s, 3 H), 3.93
(s, 3 H), 3.02 (t, J = 8 Hz, 2 H), 2.67 (t, J = 8.02 Hz, 2 H), 1.24 (t, J =
7.1 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 173.00, 156.39,
149.51, 149.08, 144.77, 142.60, 136.30, 131.14, 123.42, 118.05,
112.22, 111.20, 108.07, 107.02, 100.27, 60.43, 56.05, 55.95, 36.55,
˜
2950, 1600, 1450, 1360, 1250, 1230, 1199, 930 cm–1. HRMS (EI):
calcd. for C16H14O3 [M]+ 254.0942; found 254.0949.
Compound 18:[1a] Compound 13 (0.100 g, 0.218 mmol) was dis-
solved in dry CH2Cl2 (15 mL) in a round-bottomed flask (100 mL),
and the solution was cooled to 0 °C. A solution of TiCl4 (0.050 g,
0.262 mmol) in CH2Cl2 (5 mL) was added dropwise. The mixture
was stirred for 6 h at room temp. It was then poured into ice-water,
and extracted with CH2Cl2. The organic phase was concentrated.
The crude product was purified by column chromatography (EtOAc/
hexane, 35:65) to give compound 14 (72 mg, 89 %) as a pale yellow
solid, m.p. 135–138 °C. 1H NMR (500 MHz, CDCl3): δ = 7.75 (d, J =
16 Hz, 1 H), 7.40 (dd, J = 8.3, J = 2 Hz, 1 H), 7.36 (d, J = 2 Hz, 1 H),
7.31 (s, 1 H), 6.98 (d, J = 8.3 Hz, 1 H), 6.96 (s, 1 H), 6.86 (s, 1 H), 6.41
(d, J = 16 Hz, 1 H), 4.28 (q, J = 7.15 Hz, 2 H), 4.06 (s, 3 H), 3.99 (s, 3
H), 1.35 (t, J = 7.15 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
167.18, 157.28, 146.69, 146.55, 145.37, 145.23, 131.36, 130.50,
31.35, 14.22 ppm. IR (KBr): ν = 2935, 1731, 1600, 1512, 1461, 1484,
˜
1272, 1251, 1141, 1025, 857 cm–1. HRMS (ESI): calcd. for C22H25O6
[M + H]+ 385.1651; found 385.1650.
Compound 2:[1g] LiAlH4 (0.041 g, 1.086 mmol) was dissolved in dry
122.41, 118.97, 116.85, 114.77, 114.46, 107.51, 104.96, 100.11, 60.44, THF (15 mL) in a round-bottomed flask (100 mL), and the solution
56.12, 56.02, 14.34 ppm. IR (KBr): ν = 3403, 2938, 1708, 1634, 1509, was cooled to 0 °C. Compound 19 (0.100 g, 0.271 mmol) was added
˜
1277, 1171, 1145, 1037 cm–1. HRMS (ESI): calcd. for C21H21O6 [M +
H]+ 369.1338; found 369.1338.
dropwise, and then the resulting mixture was stirred at room temp.
for 2 h. After the conversion was complete, the mixture was
quenched with saturated aq. NH4Cl, and extracted with ethyl acet-
ate. The organic extract was concentrated, and the crude product
was purified by column chromatography (EtOAc/CHCl3, 5:95) to give
compound 2 (84 mg, 95 %) as a colourless solid, m.p. 117–119 °C.
1H NMR (500 MHz, CDCl3): δ = 7.40 (dd, J = 8.1, J = 1.65 Hz, 1 H),
7.32 (d, J = 1.5 Hz, 1 H), 6.97 (br. s, 1 H), 6.86 (d, J = 7.95 Hz, 1 H),
6.79 (s, 1 H), 6.63 (d, J = 1.55 Hz, 1 H), 6.00 (s, 2 H), 4.03 (s, 3 H),
3.71 (t, J = 6.4 Hz, 2 H), 2.78 (t, J = 7.62 Hz, 2 H), 1.97–1.93 (m, 2 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 156.09, 148.04, 147.97, 144.78,
142.45, 137.50, 131.03, 124.70, 119.20, 112.30, 108.61, 107.41,
Compound 1:[1a,1f] Compound 18 (50 mg, 0.136 mmol) was dis-
solved in dry THF (10 mL) in a round-bottomed flask (50 mL). DIBAL-
H (1
M solution in hexane; 0.543 mL, 0.543 mmol) was then added
at –78 °C, and the mixture was stirred for 2 h at –78 °C. At this
temperature, the mixture was then quenched with saturated
Na2SO4 solution. The mixture was brought to room temp., and ex-
tracted with ethyl acetate. The combined organic extracts were
dried with anhydrous MgSO4, and concentrated. The crude product
was purified by silica gel column chromatography (EtOAc/hexane,
60:40) to give compound 1 (0.042 g, 95 %) as a colourless solid,
m.p. 199–201 °C. 1H NMR (400 MHz, [D6]DMSO): δ = 9.45 (s, 1 H),
7.38 (br. s, 1 H), 7.32 (d, J = 8.72 Hz, 1 H), 7.17 (d, J = 6.84 Hz, 2 H),
7.00 (br. s, 1 H), 6.88 (d, J = 8.24 Hz, 1 H), 6.60 (d, J = 16.48 Hz, 1
H), 6.38 (dt, J = 16.04, J = 5.04 Hz, 1 H), 4.86 (t, J = 5.48 Hz, 1 H),
105.54, 101.29, 100.34, 62.30, 56.15, 34.67, 32.42 ppm. IR (KBr): ν =
˜
3333, 2927, 1599, 1502, 1261, 1230, 1039 cm–1. HRMS (ESI): calcd.
for C19H19O5 [M + H]+ 327.1232; found 327.1234.
Compound 3:[1d] The above procedure was used to obtain com-
4.14 (t, J = 4.56 Hz, 2 H), 3.98 (s, 3 H), 3.87 (s, 3 H) ppm. 13C NMR pound 3 from compound 20 (0.100 g, 0.260 mmol). Compound 3
(100 MHz, [D6]DMSO): δ = 156.80, 148.49, 148.19, 145.18, 142.99, (85 mg, 95 %) was isolated as a colourless solid, m.p. 114–116 °C.
Eur. J. Org. Chem. 2016, 2177–2186
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1H NMR (400 MHz, CDCl3): δ = 7.45 (dd, J = 8.48, J = 2.06 Hz, 1 H),
7.36 (d, J = 2.28 Hz, 1 H), 6.98 (br. s, 1 H), 6.92 (d, J = 8.24 Hz, 1 H),
40.80 ppm. IR (KBr): ν = 3214, 2895, 1612, 1576, 1500, 1488, 1466,
˜
1449, 1251, 1234, 1039, 930, 798 cm–1. HRMS (ESI): calcd. for
6.83 (s, 1 H), 6.64 (br. s, 1 H), 4.04 (s, 3 H), 3.98 (s, 3 H), 3.93 (s, 3 H), C18H15O4 [M – H]+ 295.0970; found 295.0975.
3.71 (t, J = 6.4 Hz, 2 H), 2.78 (t, J = 7.78 Hz, 2 H), 1.98–1.91 (m, 2 H)
Compound 5:[1p] The procedures given above were followed to
ppm. 13C NMR (100 MHz, CDCl3): δ = 156.32, 149.49, 149.08, 144.75,
give compound 5 (83 mg, 94 %) as an off-white solid, m.p. 102–
142.47, 137.48, 131.11, 123.47, 118.04, 112.25, 111.21, 108.09,
1
104 °C. H NMR (500 MHz, CDCl3): δ = 7.43–7.40 (m, 2 H), 7.36 (br.
107.17, 100.24, 62.28, 56.05, 55.95, 34.66, 32.43 ppm. IR (KBr): ν =
˜
s, 2 H), 7.09 (dd, J = 8.25, J = 1.8 Hz, 1 H), 6.93 (d, J = 8.2 Hz, 1 H),
6.85 (s, 1 H), 3.99 (s, 3 H), 3.93 (s, 3 H), 3.70 (t, J = 6.42 Hz, 2 H), 2.80
(t, J = 7.62 Hz, 2 H), 1.97–1.91 (m, 2 H), 1.30 (br. s, 1 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 156.19, 153.37, 149.51, 149.17, 136.38,
129.61, 124.48, 123.65, 119.95, 117.88, 111.35, 110.70, 108.03, 99.84,
3363, 3286, 2922, 2853, 1602, 1516, 1486, 1273, 1214, 1140, 1025,
859, 791 cm–1. HRMS (EI): calcd. for C20H23O5 [M + H]+ 343.1545;
found 343.1544.
Compound 9b:[7] A mixture of compound 8b (2.0 g, 8.06 mmol),
ethyl acrylate (1.61 g. 16.13 mmol), palladium acetate (90 mg, 62.28, 55.99, 34.76, 32.00 ppm. IR (KBr): ν = 3360, 2939, 1512, 1469,
˜
0.403 mmol), tri-o-tolylphosphine (490 mg, 1.612 mmol), and trieth- 1447, 1253, 1142, 1020, 800 cm–1. HRMS (ESI): calcd. for C19H21O4
ylamine (4.07 g, 40.3 mmol) in dry acetonitrile (60 mL) was stirred [M + H]+ 313.1440; found 313.1447.
at 90 °C for 9 h in a two-necked round-bottomed flask (100 mL).
Stemofuran A (6):[11a] Compound 24 (0.140 g, 0.550 mmol) was
The mixture was then concentrated under reduced pressure, and
dissolved in CH2Cl2 (20 mL) in a round-bottomed flask (100 mL),
extracted with ethyl acetate. The organic phase was washed with
and the solution was cooled to –78 °C. BBr3 (0.16 mL, 1.652 mmol)
dilute HCl, followed by brine, and concentrated. The crude product
was added dropwise. The reaction mixture brought to room temp.,
was purified by silica gel column chromatography (EtOAc/hexane,
and stirred for 24 h. The mixture was then cooled to 0 °C, quenched
with water (5 mL), and extracted with ethyl acetate. The organic
extract was dried with anhydrous MgSO4, and concentrated. The
crude product was purified by column chromatography (EtOAc/hex-
5:95) to give compound 9b (1.57 g, 89 %) as a pale yellow solid,
1
m.p. 92–94 °C. H NMR (400 MHz, CDCl3): δ = 11.19 (s, 1 H), 9.92 (s,
1 H), 7.72–7.70 (m, 2 H), 7.64 (d, J = 16.48 Hz, 1 H), 7.02 (d, J =
8.24 Hz, 1 H), 6.36 (d, J = 16.04 Hz, 1 H), 4.26 (q, J = 7.17 Hz, 2 H),
ane, 25:75) to give compound 6 (118 mg, 95 %) as an off-white
1.33 (t, J = 7.32 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 196.28,
1
solid, m.p. 181–182 °C. H NMR (500 MHz, CD3OD): δ = 7.56 (d, J =
166.78, 162.99, 142.43, 135.66, 133.82, 126.73, 120.54, 118.58,
6.1 Hz, 1 H), 7.47 (d, J = 7.95 Hz, 1 H), 7.27–7.19 (m, 2 H), 7.03 (br.
117.43, 60.58, 14.30 ppm. IR (KBr): ν = 2993, 2870, 1701, 1639, 1662,
s, 1 H), 6.84–6.83 (m, 2 H), 6.30–6.29 (m, 1 H) ppm. 13C NMR
(125 MHz, CD3OD): δ = 160.02, 157.37, 156.05, 133.39, 130.53,
125.34, 124.00, 121.92, 111.79, 104.42, 104.11, 102.27 ppm. IR (KBr):
˜
1580, 1489, 1378, 1184, 1161, 983, 838, 750, 552 cm–1. HRMS (ESI):
calcd. for C12H11O4 [M – H]– 219.0657; found 219.0648.
Compound 10b: The procedure used for compound 10a was fol-
lowed, using CBr4 (4.5 g, 13.62 mmol), CH2Cl2 (60 mL), PPh3 (7.14 g,
27.24 mmol), NEt3 (2.75 g, 27.24 mmol), and compound 9b (1 g,
4.54 mmol). The crude product was purified by column chromatog-
raphy using 30 % EtOAc/hexane to give compound 10b (1.2 g,
70 %) as a pale yellow solid, m.p. 140–142 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.75 (d, J = 1.96 Hz, 1 H), 7.62 (d, J = 15.84 Hz, 1 H),
7.54 (s, 1 H), 7.40 (dd, J = 8.28, J = 2.2 Hz, 1 H), 6.86 (d, J = 8.32 Hz,
1 H), 6.31 (d, J = 15.88 Hz, 1 H), 5.91 (s, 1 H), 4.26 (q, J = 7.2 Hz, 2
H), 1.34 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
167.38, 154.51, 143.92, 131.56, 129.78, 129.37, 127.17, 123.32,
ν = 3201, 2923, 1605, 1573, 1503, 1449, 1351, 1158 cm–1. HRMS
˜
(ESI): calcd. for C14H11O3 [M + H]+ 227.0708; found 227.0705.
Compound 2a: Compound 2 (34 mg, 0.104 mmol) was put into a
round-bottomed flask (100 mL), and DCC (54 mg, 0.260 mmol) and
DMAP (32 mg, 0.260 mmol) in CH2Cl2 (10 mL) were added, along
with linoleic acid (58 mg, 0.208 mmol). The mixture was heated at
reflux for 9 h. It was then brought to room temp., and filtered
through a bed of Celite. The Celite was washed with CH2Cl2, and
the filtrate was concentrated. The crude product was purified by
column chromatography (EtOAc/hexane, 5:95) to give compound
1
2a (55 mg, 90 %) as a colourless oil. H NMR (500 MHz, CDCl3): δ =
116.40, 116.29, 92.90, 60.57, 14.32 ppm. IR (KBr): ν = 3322, 1677,
˜
7.39 (dd, J = 8.15, J = 1.6 Hz, 1 H), 7.32 (d, J = 1.4 Hz, 1 H), 6.95 (s,
1 H), 6.87 (d, J = 8 Hz, 1 H), 6.78 (s, 1 H), 6.60 (s, 1 H), 6.00 (s, 2 H),
5.39–5.31 (m, 4 H), 4.12 (t, J = 6.57 Hz, 2 H), 4.03 (s, 3 H), 2.78–2.73
1663, 1631, 1598, 1428, 1366, 1261, 1188, 760, 742 cm–1. HRMS
(ESI): calcd. for C13H13Br2O3 [M + H]+ 374.9231; found 374.9236.
Compound 4:[1m] Compound 16 (0.170 g, 0.505 mmol) was dis- (m, 4 H), 2.31 (t, J = 7.45 Hz, 2 H), 2.06–1.97 (m, 6 H), 1.64–1.60 (m,
solved in ethyl acetate (10 mL) in a round-bottomed flask (50 mL), 2 H), 1.36–1.26 (m, 14 H), 0.89 (t, J = 6.7 Hz, 3 H) ppm. 13C NMR
and Pd/C (10 %; 17 mg) was added. The mixture was stirred at room (125 MHz, CDCl3): δ = 173.90, 156.12, 148.04, 147.98, 144.79, 142.50,
temp. for 3 h under a hydrogen atmosphere (balloon). The product
was filtered through a bed of silica gel, and the filtrate was concen-
trated. The crude material was purified by silica gel column chroma-
136.93, 131.05, 130.20, 130.02, 128.04, 127.88, 124.68, 119.20,
112.33, 108.60, 107.38, 105.54, 101.29, 100.32, 63.60, 56.16, 34.36,
32.53, 31.51, 30.74, 29.59, 29.32, 29.18, 29.15, 29.12, 27.18, 25.61,
tography (EtOAc/hexane, 7:93) to give a colourless solid (0.162 mg, 25.00, 22.55, 14.06 ppm. IR (KBr): ν = 3008, 2927, 2854, 1734, 1600,
˜
95 %), m.p. 90–92 °C.
1476, 1365, 1251, 1146, 1039, 930, 819, 741 cm–1. HRMS (EI): calcd.
for C37H49O6 [M + H]+ 589.3529; found 589.3528. This procedure
was followed for the preparation of compound 4a and compound
4b.
A portion of this product (0.100 g, 0.295 mmol) was reduced as
follows. It was treated with LiAlH4 (0.045 g, 1.182 mmol) in dry THF
(20 mL) at 0 °C, and then the mixture was stirred at room temp. for
3 h. After usual workup, the crude product was purified by column
Compound 4a: Colourless oil (47 mg, 83 %). 1H NMR (500 MHz,
CDCl3): δ = 7.40–7.37 (m, 2 H), 7.34 (br. s, 1 H), 7.30 (br. s, 1 H), 7.07
(d, J = 8.55 Hz, 1 H), 6.88 (d, J = 8.25 Hz, 1 H), 6.80 (s, 1 H), 6.01 (s,
2 H), 5.37–5.32 (m, 4 H), 4.11 (t, J = 6.57 Hz, 2 H), 2.77 (t, J = 7.32 Hz,
4 H), 2.30 (t, J = 7.47 Hz, 2 H), 2.06–1.98 (m, 6 H), 1.62–1.60 (m, 2
H), 1.36–1.25 (m, 14 H), 0.88 (t, J = 6.87 Hz, 3 H) ppm. 13C NMR
chromatography (EtOAc/hexane, 35:65) to give compound
4
(80 mg, 92 %) as a colourless solid, m.p. 116–118 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.40–7.36 (m, 3 H), 7.30 (d, J = 1.48 Hz, 1 H),
7.09 (dd, J = 8.32, J = 1.7 Hz, 1 H), 6.88 (d, J = 8.04 Hz, 1 H), 6.81 (s,
1 H), 6.01 (s, 2 H), 3.70 (t, J = 6.34 Hz, 2 H), 2.80 (t, J = 7.68 Hz, 2
H), 1.97–1.92 (m, 2 H), 1.55 (s, 1 H) ppm. 13C NMR (125 MHz, CDCl3): (125 MHz, CDCl3): δ = 173.92, 156.03, 153.36, 148.07, 147.97, 135.87,
δ = 156.38, 154.14, 148.07, 139.19, 129.45, 124.63, 121.83, 119.15,
130.20, 130.03, 129.50, 128.02, 127.88, 124.84, 124.54, 119.99,
117.73, 110.91, 108.69, 105.43, 101.33, 100.15, 74.65, 61.57, 119.07, 110.74, 108.67, 105.43, 101.30, 99.97, 63.58, 34.36, 32.13,
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31.51, 30.82, 29.59, 29.33, 29.18, 29.14, 27.18, 25.61, 25.00, 22.55,
14.06 ppm. IR (KBr): ν = 3009, 2926, 2855, 1736, 1489, 1469, 1234,
˜
1192, 1040, 932, 802 cm–1. HRMS (ESI): calcd. for C36H46NaO4 [M +
Na]+ 581.3243; found 581.3242.
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Compound 4b: Colourless oil (51 mg, 90 %). 1H NMR (500 MHz,
CDCl3): δ = 7.40–7.36 (m, 2 H), 7.34 (br. s, 1 H), 7.30 (d, J = 1.55 Hz,
1 H), 7.07 (d, J = 8.25 Hz, 1 H), 6.88 (d, J = 8.25 Hz, 1 H), 6.80 (s, 1
H), 6.01 (s, 2 H), 5.37–5.33 (m, 2 H), 4.11 (t, J = 6.55 Hz, 2 H), 2.77
(t, J = 7.47 Hz, 2 H), 2.30 (t, J = 7.47 Hz, 2 H), 2.05–1.96 (m, 6 H),
1.64–1.61 (m, 2 H), 1.30–1.26 (m, 20 H), 0.89–0.86 (m, 3 H) ppm. 13
C
NMR (125 MHz, CDCl3): δ = 173.92, 156.03, 153.37, 148.08, 147.97,
135.87, 129.99, 129.73, 129.50, 124.85, 124.54, 119.99, 119.07,
110.74, 108.67, 105.43, 101.29, 99.97, 63.57, 34.36, 32.13, 31.88,
30.82, 29.75, 29.69, 29.60, 29.50, 29.30, 29.18, 29.14, 29.11, 27.20,
27.15, 25.00, 22.67, 14.09 ppm. IR (KBr): ν = 2922, 2851, 1733, 1500,
˜
1468, 1253, 1041, 1024, 929, 799, 874, 813, 799 cm–1. HRMS (ESI):
calcd. for C36H49O5 [M + H]+ 561.3580; found 561.3587.
Acknowledgments
The authors acknowledge financial support from the Council of
Scientific and Industrial Research (CSIR), New Delhi [grant num-
ber 02(0091)/12/EMR-II]. V. N. M. acknowledges CSIR for a re-
search fellowship.
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Keywords: Homogeneous catalysis · Palladium · Bismuth ·
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Received: February 15, 2016
Published Online: March 30, 2016
Eur. J. Org. Chem. 2016, 2177–2186
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