Ph3PAuNTf2 as a superior catalyst for the selective synthesis of 2H-chromenes: Application to the concise synthesis of benzopyran natural products

Article abstract of DOI:10.1002/ejoc.201001674

Ph₃PAuNTf₂ (≈1 mol-%) catalyzes the selective cycloisomerization of substituted aryl propargyl ethers into 2H-chromenes in excellent yields. Benzofuran byproducts are formed only in the case of electron-deficient arenes, in up to 7% relative yield. The Ph ₃PAuNTf₂-catalyzed cyclization of aryl propargyl ethers was applied as a key step to the concise synthesis of the naturally occurring benzopyrans seselin, xanthyletin, precocenes I and II, 8-(3′,3′- dimethylallyl)wenteria chromene, and 2,2-dimethyl-8-prenylchromene-6-propenoic acid. Ph₃PAuNTf₂ is a general, highly efficient, and product-selective catalyst for the clean synthesis of 2H-chromenes from the cycloisomerization of aryl propargyl ethers.The Ph₃PAuNTf ₂-catalyzed cyclization was applied as a key step in the synthesis of several benzopyran-bearing naturally occurring substances. Copyright

Full text of DOI:10.1002/ejoc.201001674

FULL PAPER
DOI: 10.1002/ejoc.201001674
Ph3PAuNTf2 as a Superior Catalyst for the Selective Synthesis of
2H-Chromenes: Application to the Concise Synthesis of Benzopyran
Natural Products
Ioannis N. Lykakis,[a] Christina Efe,[a] Charis Gryparis,[a] and Manolis Stratakis*[a]
Keywords: Homogeneous catalysis / Gold / Chromenes / Cycloisomerization / Natural products
Ph3PAuNTf2 (≈1 mol-%) catalyzes the selective cycloisomeri-
zation of substituted aryl propargyl ethers into 2H-
chromenes in excellent yields. Benzofuran byproducts are
formed only in the case of electron-deficient arenes, in up to
7% relative yield. The Ph3PAuNTf2-catalyzed cyclization of
aryl propargyl ethers was applied as a key step to the concise
synthesis of the naturally occurring benzopyrans seselin,
xanthyletin, precocenes I and II, 8-(3Ј,3Ј-dimethylallyl)wen-
teria chromene, and 2,2-dimethyl-8-prenylchromene-6-pro-
penoic acid.
Introduction
During the last decade, the activation of alkynes by AuI
and AuIII under homogeneous conditions has gained re-
markable attention among organic chemists. The high auro-
philicity of C–C triple bonds allows facile addition of car-
bon- or heteroatom-based nucleophiles to alkynes, provid-
ing an array of novel and unprecedented reaction path-
ways.[1] As a result, the field of homogeneous gold catalysis
has so far witnessed surprising and spectacular achieve-
ments.
Our interest in the use of supported gold nanoparticles
to activate epoxides[2] and alkynes[3] heterogeneously
prompted us to focus on the cycloisomerization of aryl pro-
pargyl ethers catalyzed by AuI under homogeneous condi-
tions, as peculiar results appear in the literature with respect
to product selectivity.[4] This reaction is known to proceed
under extreme thermal conditions[5] or microwave irradia-
tion[6] via intermediate formation of labile ortho-allenyl phe-
Scheme 1. The cycloisomerization of aryl propargyl ethers into 2H-
chromenes and 2-methylbenzofurans.
cently, Banwell[4] used catalyst II (Scheme 2), which is far
more active than I, and it does not require in situ activation
by AgX. Yet, the product selectivity is peculiar with the
majority of substrates, affording primarily 2H-chromenes in
good to moderate yields, whereas other substrates formed
mixtures of 2H-chromenes and 2-methylbenzofurans. Ben-
zofurans are often the major or only products. In addition,
product selectivity does not seem to correlate with the elec-
tronic nature of the aryl rings, as 2-methylbenzofurans are
formed in the cycloisomerization of substrates bearing both
electron-donating and electron-withdrawing substituents.
nols, resulting from
a
[3,3] Claisen rearrangement
(Scheme 1). Apart from several milder versions of this reac-
tion using metal-catalyzed procedures (e.g., Pd, Pt, Hg, Ag,
etc.),[7] it was also found that AuI catalyzes the cyclization
of aryl propargyl ethers.[4,8–10]
The initial report by the group of Echavarren[8] made use
of precatalyst I (Scheme 2), which requires stoichiometric
amount of silver salts to abstract a chloride ion and to gen-
erate the catalytically active Ph3PAu+ species in situ. Sur-
prisingly, dimeric byproducts that arise from a Ag+-cata-
lyzed pathway are also formed in various yields. More re-
Scheme 2. AuI catalysts used in the cycloisomerization of aryl pro-
pargyl ethers.
Ph3PAuNTf2 (III) is a highly active and air-stable catalyst
for alkyne activation that was introduced by Gagosz.[9] Re-
garding its use in the cycloisomerization of aryl propargyl
ethers, only two specific reaction examples have been re-
ported so far,[9,10] which yield exclusively 2H-chromenes.
Yet, the generality, scope, and limitations, as well as the
product selectivity (2H-chromenes vs. 2-methylbenzo-
[a] Department of Chemistry, University of Crete,
Voutes 71003, Iraklion, Greece
Fax: +30-2810-545001
E-mail: stratakis@chemistry.uoc.gr
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001674.
2334
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2334–2338

Ph3PAuNTf2-Catalyzed Synthesis of 2H-Chromenes
furans), in the isomerization of aryl propargyl ethers cata-
lyzed by III is unknown.
Results and Discussion
In this paper, we undertook a systematic examination of
the cyclization of aryl propargyl ethers by using III (Ga-
gosz’s catalyst). The two preliminary examples[9,10] revealed
that III might be a promising and general catalyst for such a
purpose. More specifically, the steric and electronic factors
governing product selectivity were initially addressed. Ad-
ditionally, as the 2H-chromene moiety appears in a vast
number of naturally occurring and pharmaceutically rel-
evant substances, several applications of this key reaction
in natural product synthesis were achieved.
As a first step, the results concerning the influence of
stereoelectronic factors are presented in Scheme 3. By using
III (1 mol-%) in dry dichloromethane, the cyclization pro-
ceeded smoothly at room temperature, and 2H-chromenes
were exclusively formed in excellent yields for electron-rich
arenes. For electron deficient arenes (i.e., 7–9), the reaction
rate was slower, as expected, and in certain cases up to
4 mol-% of Ph3PAuNTf2 and refluxing conditions (1,2-
dichloroethane, DCE) were necessary to drive the reaction
to completion. Yet, primarily 2H-chromenes were formed,
with 2-methylbenzofurans being formed in up to 7% rela-
tive yield and only for those substrates in which the aryl
group bears strong electron-withdrawing substituents (o-
COOMe, p-NO2, p-CN). Moreover, for slow-reacting sub-
strates 7–9, if the solvent is not dry, competing Au-catalyzed
hydration[11] occurs, forming the corresponding ketones as
byproducts in up to 25% relative yield.
It is worthy to emphasize that in the presence of catalyst
II substrate 5 provides[4] a mixture of 2H-chromene and its
isomeric benzofuran in moderate yield, whereas naphthyl
ether 4 yields exclusively the corresponding benzofuran. On
the other hand, in the presence of III (current study) only
2H-chromenes are formed. Moreover, although in the pres-
ence of catalyst III byproduct 7b is formed in 6% relative
yield, under II catalysis it becomes the major product by
far (80%). The reaction works equally well and selectively
with internal alkynes 10–12, yielding exclusively 2H-
chromenes. Finally, more hindered gem-dimethyl derivatives
13 and 14 cleanly provide cyclized products 13a and 14a,
respectively, in excellent yields. It is worthy to note that sub-
strate 13 does not cyclize under oxidative AuIII catalytic
conditions (HAuCl4/tBuOOH).[12]
The product selectivity could possibly be rationalized in
terms of the reduced tendency of cyclized Au complex IV
(Scheme 4) to decompose[4,13] into ortho-allenyl phenolate
V, the established[5] precursor of benzofurans (and 2H-
chromenes as well) under thermal conditions. This explana-
tion is in agreement with the observation that benzofurans
are detected only for electron-deficient arenes 7–9, where
the p- or o-electron-withdrawing substituents stabilize inter-
mediate phenolate V through resonance, thus providing the
driving force for the minor benzofuran-forming pathway.
Scheme 3. Cyclization of substituted aryl propargyl ethers cata-
lyzed by Ph3PAuNTf2 (III).
Eur. J. Org. Chem. 2011, 2334–2338
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2335

I. N. Lykakis, C. Efe, C. Gryparis, M. Stratakis,
FULL PAPER
uct(s). Previous reported attempts to achieve the same Heck
coupling met with limited success;[22] we believe this is due
to the choice of solvent (DMF vs. toluene). Plicatin B
cleanly afforded propargyl ether 20 (91% isolated yield)
upon treatment with 3-chloro-3-methyl-1-butyne in the
presence of a catalytic amount of CuCl2.[14] Then, the cycli-
zation of 20 with catalyst III (1 mol-%) afforded 2H-
chromene 21 in almost quantitative isolated yield; 2H-
chromene 21 is the known natural product 8-(3Ј,3Ј-dimeth-
ylallyl)wenteria chromene.[23] Finally, 21 was smoothly hy-
drolyzed with aqueous KOH in MeOH[21] to afford 22 in
excellent overall yield. Both syntheses of 21 and 22 are the
first in the literature. Notably, the Au-catalyzed cyclization
of 20 was clean, without formation of any byproducts from
the interference of the proximal double bond on the prenyl
chain.[24]
Scheme 4. Rational pathway for the formation of benzofuran by-
products in the case of electron-deficient arenes.
To explore this highly selective cyclization in natural
product synthesis, we initially achieved the concise synthe-
ses of precocenes I and II, seselin, and xanthyletin
(Scheme 5). Thus, propargyl ether 15[14] afforded a mixture
of 15a (precocene I) and its regioisomeric 15b in 83% iso-
lated yield, and in a relative ratio 15a/15b = 3:1. The cycli-
zation of 15 under thermal conditions (boiling N,N-dieth-
ylaniline) is known[15] to afford 15a and 15b in a relative
ratio of ca. 1:1. Similarly, 16[14] afforded only regioisomer
16a (precocene II)[16] in excellent yield. Moreover, the py-
ranocoumarins xanthyletin (17a) and seselin (17b),[17] com-
pounds with surprisingly rich biological activities,[18] were
synthesized in excellent yield from the smooth cyclization
of 17.[14] Their relative product ratio was 17a/17b = 40:60.
Seselin and xanthyletin can be easily separated by column
chromatography.
Scheme 6. Concise synthesis of naturally occurring 8-(3Ј,3Ј-dimeth-
ylallyl)wenteria chromene (21) and 2,2-dimethyl-8-prenylchromene-
6-propenoic acid (22).
Conclusions
Scheme 5. Syntheses of precocenes I and II, seselin, and xanthyl-
etin.
In conclusion, we have shown that Ph3PAuNTf2 is a sim-
ple, general, efficient, and highly product-selective catalyst
for the synthesis of 2H-chromenes from aryl propargyl
ethers. The Au-catalyzed cyclization was applied as a key
step to the concise synthesis of several benzopyran-bearing
natural products from simple precursors. We believe that
based on our work, Ph3PAuNTf2 will become the catalyst
of choice for the synthesis of 2H-chromenes.
As a final target, we applied the Ph3PAuNTf2-catalyzed
cyclization as a key step in the concise synthesis of naturally
occurring
2,2-dimethyl-8-prenylchromene-6-propenoic
acid[19] (22, Scheme 6). This compound was synthesized in
five linear steps in 50% overall yield by using p-iodophenol
as the starting material. p-Iodophenol underwent ortho-pre-
nylation[20] (Na/Et2O, then prenyl bromide) to form 18[21]
in 78% isolated yield. Subsequently, 18 was transformed
into 19 (plicatin B) by Heck coupling [Pd(OAc)2, tri(o-tol-
yl)phosphane, Et3N, DMF] with methyl acrylate in excel-
Experimental Section
General: The reactions were monitored by thin-layer chromatog-
lent isolated yield (87%), without formation of any byprod- raphy (TLC) carried out on silica gel plates (60F-254) with UV
2336
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2334–2338

Ph3PAuNTf2-Catalyzed Synthesis of 2H-Chromenes
light as the visualizing method and an acidic mixture of phos-
phomolybdic acid/cerium(IV) sulfate accompanied by heating of
the plate as a developing system. Flash column chromatography
was carried out on SiO2 (silica gel 60, particle size 0.040–0.063 mm)
with the specified eluent. NMR spectra were recorded with a
Bruker DPX-300 instrument. Electrospray ionization (ESI) mass
spectrometry (MS) experiments were performed with a GC–MS QP
5050 Shimadzu single-quadrupole mass spectrometer. GC analyzes
and kinetics were performed by using a Shimadzu GC-17A model
equipped with a 60-m HP-5 capillary column.
CDCl3): δ = 7.63 (d, J = 16.0 Hz, 1 H), 7.53 (d, J = 9.0 Hz, 1 H),
7.31 (s, 1 H), 7.30 (d, J = 9.0 Hz, 1 H), 6.30 (d, J = 16.0 Hz, 1 H),
5.25 (br. t, J = 7.5 Hz, 1 H), 3.78 (s, 3 H), 3.29 (d, J = 7.5 Hz, 2
H), 2.61 (s, 1 H), 1.74 (br. s, 3 H), 1.69 (br. s, 3 H), 1.69 (s, 6 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 167.7, 155.7, 144.9, 133.6,
132.8, 129.4, 127.9, 126.5, 122.1, 117.8, 115.4, 85.7, 74.2, 72.0, 51.5,
29.6, 28.7, 25.7, 17.8 ppm. HRMS: calcd. for [C20H24O3 + H]
313.180; found 313.179.
(E)-Methyl 3-[2,2-Dimethyl-8-(3-methylbut-2-en-1-yl)-2H-chromen-
6-yl]acrylate [8-(3Ј,3Ј-dimethylallyl)wenteria Chromene (21)]: Natu-
rally occurring 21[23] was isolated in 95% yield after a 2-h reaction
at 25 °C with Ph3PAuNTf2 (1 mol-%) according to the typical pro-
Typical Procedure for the AuI-Catalyzed Cyclization: To a solution
of aryl propargyl ether 2 (73 mg, 0.5 mmol) in dry dichloromethane
(1 mL) was added Ph3PAuNTf2 (1.3 mg, ≈1 mol-%) at ambient
temperature. After disappearance of the starting material (TLC
and/or GC analysis), the reaction was concentrated under vacuum,
and the residue was purified by chromatography (hexane/ethyl acet-
ate, 50:1) through a short pad of silica gel to yield 2a (69 mg, 95%
1
cedure conditions. H NMR (300 MHz, CDCl3): δ = 7.58 (d, J =
16.0 Hz, 1 H), 7.15 (d, J = 1.5 Hz, 1 H), 7.01 (d, J = 1.5 Hz, 1 H),
6.30 (d, J = 10.0 Hz, 1 H), 6.26 (d, J = 15.5 Hz, 1 H), 5.63 (d, J =
10.0 Hz, 1 H), 5.25 (br. t, J = 7.5 Hz, 1 H), 3.78 (s, 3 H), 3.25 (d,
J = 7.5 Hz, 2 H), 1.73 (br. s, 3 H), 1.72 (br. s, 3 H), 1.42 (s, 6 H)
yield). 1H NMR (300 MHz, CDCl3): δ = 6.90 (dd, J = 8.0, 2.0 Hz, ppm. 13C NMR (75 MHz, CDCl3): δ = 167.9, 152.8, 145.1, 132.6,
1 H), 6.78 (s, 1 H), 6.68 (d, J = 8.0 Hz, 1 H), 6.39 (br. d, J = 9.5 Hz, 131.0, 129.7, 129.5, 126.6, 124.1, 122.1, 122.0, 121.0, 114.6, 76.9,
1 H), 5.76 (dt, J = 9.5, 3.5 Hz, 1 H), 4.78 (m, 2 H), 2.25 (s, 3 H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 151.9, 130.5, 129.5, 127.1,
124.7, 122.2, 122.0, 115.4, 65.5, 20.5 ppm.
51.5, 28.2, 28.1, 25.8, 17.8 ppm.
2,2-Dimethyl-8-prenylchromene-6-propenoic Acid (22): An aqueous
solution of 10% NaOH (1 mL) was added to a solution of 21
(16 mg, 0.05 mmol) in methanol (1 mL). The reaction mixture was
heated to 50 °C for 1 h. At that time, TLC revealed clean hydrolysis
of 21. Then, most of the methanol was evaporated under vacuum,
and ethyl acetate was added. The organic layer was washed with
1 n HCl. After solvent evaporation, the residue was purified by
chromatography (hexane/ethyl acetate, 4:1) to afford 22[19] (13 mg,
86% yield). 1H NMR (300 MHz, CDCl3): δ = 7.68 (d, J = 16.0 Hz,
4-Iodo-2-(3-methylbut-2-en-1-yl)phenol (18): To a solution of 4-
iodophenol (1 g, 4.5 mmol) in dry diethyl ether (15 mL) was care-
fully added small pieces of Na metal (0.21 g, 9.0 mmol) at 0 °C.
After 3 h, prenyl bromide (0.74 g, 5 mmol) was added, and the re-
action mixture was vigorously stirred at 25 °C for 8 h. Then, 10%
aq. HCl was added, and the resulting solution was extracted with
diethyl ether. The residue was purified by chromatography (hexane/
ethyl acetate, 15:1) to afford prenylated phenol 18[21] (1.01 g, 78% 1 H), 7.18 (d, J = 1.5 Hz, 1 H), 7.04 (d, J = 1.5 Hz, 1 H), 6.31 (d,
1
yield). H NMR (300 MHz, CDCl3): δ = 7.38 (s, 1 H), 7.36 (d, J J = 10.0 Hz, 1 H), 6.27 (d, J = 15.5 Hz, 1 H), 5.65 (d, J = 10.0 Hz,
= 8.5 Hz, 1 H), 6.56 (d, J = 8.5 Hz, 1 H), 5.26 (br. t, J = 7.0 Hz,
1 H), 5.26 (br. t, J = 7.5 Hz, 1 H), 3.26 (d, J = 7.5 Hz, 2 H), 1.74
1 H), 5.17 (s, 1 H, -OH), 3.28 (d, J = 7.0 Hz, 2 H), 1.77 (br. s, 3 (br. s, 3 H), 1.73 (br. s, 3 H), 1.43 (s, 6 H) ppm. 13C NMR (75 MHz,
H), 1.76 (br. s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 154.2,
CDCl3): δ = 172.5, 153.3, 147.2, 132.7, 131.1, 129.9, 129.8, 126.2,
138.4, 136.2, 135.6, 129.7, 120.8, 118.0, 82.8, 29.4, 25.8, 17.9 ppm.
124.4, 122.0, 121.9, 121.0, 114.0, 77.0, 28.2, 28.0, 25.8, 17.9 ppm.
(E)-Methyl 3-[4-Hydroxy-3-(3-methylbut-2-en-1-yl)phenyl]acrylate Supporting Information (see also the footnote on the first page of
1
[plicatin B (19)): A mixture of 18 (576 mg, 2.0 mmol), methyl acry-
late (900 μL, 10.0 mmol), Et3N (340 μL, 2.5 mmol), Pd(OAc)2
(68 mg, 0.3 mmol), and tri-ortho-tolylphosphane (368 mg,
1.2 mmol) in dry DMF (6 mL) was flushed with argon and then
heated to 100 °C (sealed tube) for 40 h. Afterwards, dichlorometh-
ane (30 mL) was added, and the reaction mixture was washed with
H2O (3ϫ10 mL). The organic layer was dried with MgSO4, fil-
tered, and concentrated under vacuum. The residue was purified
by flash column chromatography (hexane/EtOAc, 6:1), affording
naturally occurring 19[22] (428 mg, 87% yield). 1H NMR
(300 MHz, CDCl3): δ = 7.62 (d, J = 16.0 Hz, 1 H), 7.27 (s, 1 H),
7.25 (d, J = 8.0 Hz, 1 H), 6.82 (d, J = 8.0 Hz, 1 H), 6.27 (d, J =
16.0 Hz, 1 H), 5.31 (br. t, J = 7.0 Hz, 1 H), 3.79 (s, 3 H), 3.24 (d,
J = 7.0 Hz, 2 H), 1.76 (br. s, 3 H), 1.74 (br. s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 168.3, 156.8, 145.4, 134.5, 130.0, 127.9,
127.6, 126.6, 121.3, 115.9, 114.4, 51.6, 29.0, 25.7, 17.8 ppm.
this article): Experimental procedures, copies of the H/13C NMR
spectra, and selected HRMS data.
Acknowledgments
We thank ProFI (ITE, Heraklion, Greece) for obtaining some
HRMS spectra.
[1] a) E. Jimenez-Nunez, A. M. Echavarren, Chem. Rev. 2008, 108,
3326–3350; b) D. J. Gorin, B. D. Sherry, F. D. Toste, Chem. Rev.
2008, 108, 3351–3378; c) Z. Li, C. Brouwer, C. He, Chem. Rev.
2008, 108, 3239–3265; d) N. D. Shapiro, F. D. Toste, Synlett
2010, 675–691; e) H. C. Shen, Tetrahedron 2008, 64, 3885–3903;
f) A. Fürstner, P. W. Davies, Angew. Chem. Int. Ed. 2007, 46,
3410–3449; g) A. Fürstner, Chem. Soc. Rev. 2009, 38, 3208–
3221; h) A. S. K. Hashmi, Chem. Rev. 2007, 107, 3180–3211; i)
A. S. K. Hashmi, Angew. Chem. Int. Ed. 2010, 49, 5232–5241;
j) V. Lopez-Carrillo, A. M. Echavarren, J. Am. Chem. Soc.
2010, 132, 9292–9294; k) I. D. Jurberg, Y. Odabachian, F. Ga-
gosz, J. Am. Chem. Soc. 2010, 132, 3543–3552; l) B. Bolte, Y.
Odabachian, F. Gagosz, J. Am. Chem. Soc. 2010, 132, 7294–
7296; m) A. K. Buzas, F. M. Istrate, F. Gagosz, Angew. Chem.
Int. Ed. 2007, 46, 1141–1144; n) T. de Haro, C. Nevado, J. Am.
Chem. Soc. 2010, 132, 1512–1513; o) P. Garcia, M. Malacria,
C. Aubert, V. Gandon, L. Fensterbank, ChemCatChem 2010,
2, 493–497; p) M. N. Hopkinson, J. E. Ross, G. T. Giufreddi,
A. D. Gee, V. Gouverneur, Org. Lett. 2010, 12, 4904–4907; q)
(E)-Methyl 3-{3-(3-Methylbut-2-en-1-yl)-4-[(2-methylbut-3-yn-2-yl)-
oxy]phenyl}acrylate (20): In a flame-dried flask was placed (19
(246 mg, 1 mmol) and anhydrous CH3CN (2 mL). At 0 °C was sub-
sequently added DBU (0.18 mL, 1.2 mmol), CuCl2·2H2O (1 mol-
%), and 3-chloro-3-methyl-1-butyne (135 μL, 1.2 mmol). The pro-
gress of the reaction was monitored by TLC, and the reaction was
complete after 3 h at room temperature. Diethyl ether was added,
and the organic layer was washed with dilute HCl and brine. Pro-
pargyl ether 20 (283 mg) was isolated in 91% yield after chromato-
graphic purification (hexane/EtOAc, 20:1). 1H NMR (300 MHz,
Eur. J. Org. Chem. 2011, 2334–2338
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2337

I. N. Lykakis, C. Efe, C. Gryparis, M. Stratakis,
FULL PAPER
R. S. Menon, M. G. Banwell, Org. Biomol. Chem. 2010, 8,
[13] C. Ferrer, A. M. Echavarren, Angew. Chem. Int. Ed. 2006, 45,
1105–1109.
5483–5485.
[14] Propargyl ethers 15–17 were prepared by a CuII-catalyzed cou-
pling of 3-chloro-3-methyl-1-butyne with the corresponding
phenols: J. D. Godfrey, R. H. Mueller, T. C. Sedergran, N.
Soundararajan, V. J. Colandrea, Tetrahedron Lett. 1994, 35,
6405–6408.
[2]
[3]
[4]
C. Raptis, H. Garcia, M. Stratakis, Angew. Chem. Int. Ed. 2009,
48, 3133–3136.
C. Efe, I. N. Lykakis, M. Stratakis, Chem. Commun. 2011, 47,
803–805.
R. S. Menon, A. D. Findlay, A. C. Bissember, M. G. Banwell,
J. Org. Chem. 2009, 74, 8901–8903.
R. P. Lutz, Chem. Rev. 1984, 84, 205–247.
a) K. Subburaj, R. Katoch, M. G. Murugesh, G. K. Trivedi,
Tetrahedron 1997, 53, 12621–12628; b) M. Bruder, S. J. Smith,
A. J. Blake, C. J. Moody, Org. Biomol. Chem. 2009, 7, 2127–
2134; c) J. Garcia, S. Barluenga, K. Beebe, L. Neckers, N.
Winssinger, Chem. Eur. J. 2010, 16, 9767–9771.
[15] W. K. Anderson, E. J. LaVoie, P. G. Whitkop, J. Org. Chem.
1974, 39, 881–884.
[5]
[6]
[16] Previous alternative methodologies for the syntheses of preco-
cenes I and II: a) T. Timar, J. C. Jaszberenyi, J. Heterocycl.
Chem. 1988, 25, 871–877; b) E. Lamcharfi, L. Menguy, H. Za-
marlik, Synth. Commun. 1993, 23, 3019–3028; c) S. Bissada,
C. K. Lau, M. A. Bernstein, C. Dufresne, Can. J. Chem. 1994,
72, 1866–1869.
[7] a) C. Jia, W. Lu, J. Oyamada, T. Kitamura, K. Matsuda, M.
Irie, Y. Fujiwara, J. Am. Chem. Soc. 2000, 122, 7252–7263; b)
S. J. Pastine, S. W. Youn, D. Sames, Org. Lett. 2003, 5, 1055–
1058; c) A. Fürstner, V. Mamane, Chem. Commun. 2003, 2112–
2113; d) N. Chatani, H. Inoue, T. Ikeda, S. Murai, J. Org.
Chem. 2000, 65, 4913–4918; e) J. S. Yadav, B. S. V. Reddy, B.
Padmavani, M. K. Gupta, Tetrahedron Lett. 2004, 45, 7577–
7579; f) M. Nishizawa, H. Takao, V. K. Yadav, H. Imagawa, T.
Sugihara, Org. Lett. 2003, 5, 4563–4565; g) M. Bandini, E.
Emer, S. Tommasi, A. Umani-Ronchi, Eur. J. Org. Chem. 2006,
3527–3544; h) U. Koch-Pomeranz, H.-J. Hansen, H. Schmid,
Helv. Chim. Acta 1973, 56, 2981–3004.
[17] Previous syntheses of seselin and xanthyletin using alternative
approaches: a) K. C. Nicolaou, J. A. Pfefferkorn, G.-Q. Cao,
Angew. Chem. Int. Ed. 2000, 39, 734–739; b) P. C. Bulman Page,
L. F. Appleby, D. Day, Y. Chan, B. R. Buckley, S. M. Allin,
M. J. McKenzie, Org. Lett. 2009, 11, 1991–1993.
[18] a) P. Magiatis, E. Melliou, A.-L. Skaltsounis, S. Mitaku, S.
Leonce, P. Renard, A. Pierre, G. Atassi, J. Nat. Prod. 1998, 61,
982–986; b) R. S. Mali, P. P. Joshi, P. K. Sandhu, A. Manekar-
Tilve, J. Chem. Soc. Perkin Trans. 1 2002, 371–376.
[19] A. H. Banskota, Y. Tezuka, J. K. Prasain, K. Matsushige, I.
Saiki, S. Kadota, J. Nat. Prod. 1998, 61, 896–900.
[20] S. Bouzbouz, B. Kirschleger, Synthesis 1994, 714–718.
[21] Y. Uto, A. Hirata, T. Fujita, S. Takubo, H. Nagasawa, H. Hori,
J. Org. Chem. 2002, 67, 2355–2357.
[8] C. Nevado, A. M. Echavarren, Chem. Eur. J. 2005, 11, 3155–
3164.
[9] N. Mezailles, L. Ricard, F. Gagosz, Org. Lett. 2005, 7, 4133–
[22] R. W. Bates, C. J. Gabel, J. Ji, T. Rama-Devi, Tetrahedron 1995,
4136.
51, 8199–8212.
[10] a) N. R. Curtis, J. C. Prodger, G. Rassias, A. J. Walker, Tetrahe-
dron Lett. 2008, 49, 6279–6281; b) G. Rassias, N. G. Stevenson,
N. R. Curtis, J. M. Northall, M. Gray, J. C. Prodger, A. J.
Walker, Org. Process Res. Dev. 2010, 14, 92–98.
[11] a) A. Leyva, A. Corma, J. Org. Chem. 2009, 74, 2067–2074; b)
N. Marion, R. S. Ramon, S. P. Nolan, J. Am. Chem. Soc. 2009,
131, 448–449.
[23] F. Bohlmann, C. Zdero, R. M. King, H. Robinson, Phytochem-
istry 1984, 23, 1135–1137.
[24] Substrate 20 can be formally considered as an 1,8-enyne, and
such compounds are known to undergo Au-catalyzed intramo-
lecular cycloisomerization: a) F.-D. Boyer, X. Le Goff, I.
Hanna, J. Org. Chem. 2008, 73, 5163–5166; b) Y. Odabachian,
F. Gagosz, Adv. Synth. Catal. 2009, 351, 379–386.
Received: December 14, 2010
[12] H. A. Wegner, S. Ahles, M. Neuburger, Chem. Eur. J. 2008, 14,
11310–11313.
Published Online: March 10, 2011
2338
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2334–2338