Silver(I)-catalyzed novel cascade cyclization reactions: Incorporation of allenes into the isochromenes

Article abstract of DOI:10.1021/jo051524q

The silver(I)-catalyzed reaction of alkynones with alcohols represents a general tool for the synthesis of 1-allenyl isochromenes. The reaction most probably proceeds via the formation of benzopyrylium cation, which subsequently undergoes nucleophilic attack of an alcohol to give the annulation products.

Full text of DOI:10.1021/jo051524q

methodology might allow us novel and stereoselective
access to a wide range of 1-allenyl chromenes 3. Thus,
we chose 1a as a model substrate, which was treated
under our previously developed reaction conditions.6,7a
However, none of the reaction conditions gave the desired
products; instead, a mixture of unidentified products was
obtained. The use of AuCl3 catalyst in CH2Cl2 also did
not afford any products.8 We then opted for other catalyst
systems. After detailed investigation on the catalysts and
solvents, we found that silver(I) salts9 in CH2Cl2 gave
very good results (eq 1). We report herein a detailed
account of our results.
Silver(I)-Catalyzed Novel Cascade
Cyclization Reactions: Incorporation of
Allenes into the Isochromenes
Nitin T. Patil, Nirmal K. Pahadi, and
Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science,
Tohoku University, Sendai 980-8578, Japan
yoshi@mail.tains.tohoku.ac.jp
Received July 21, 2005
The results of catalytic activity of various Ag(I) salts
are summarized in Table 1. In the absence of any
catalysts the reaction does not proceed, and the starting
material was recovered (Table 1, entry 1). The reaction
of 1a with 2 equiv of methanol in CH2Cl2 in the presence
The silver(I)-catalyzed reaction of alkynones with alcohols
represents a general tool for the synthesis of 1-allenyl
isochromenes. The reaction most probably proceeds via the
formation of benzopyrylium cation, which subsequently
undergoes nucleophilic attack of an alcohol to give the
annulation products.
(2) (a) Yamamoto, Y.; Al-Masum, M.; Asao, N. J. Am. Chem. Soc.
1994, 116, 6019-6020. (b) Yamamoto, Y.; Al-Masum, M.; Fujiwara,
N. J. Chem. Soc., Chem. Commun. 1996, 381-382. (c) Yamamoto, Y.;
Al-Masum, M.; Takeda, A. J. Chem. Soc., Chem. Commun. 1996, 831-
832. (d) Yamamoto, Y.; Al-Masum, M.; Fujiwara, N.; Asao, N. Tetra-
hedron Lett. 1995, 36, 2811-2814. (e) Yamamoto, Y.; Al-Masum, M.
Synlett 1995, 969-970. (f) Meguro, M.; Kamijo, S.; Yamamoto, Y.
Tetrahedron Lett. 1996, 37, 7453-7456. (g) Besson, L.; Jacques, G.;
Cazes, B. Tetrahedron Lett. 1995, 36, 3853-3856. (h) Trost, B. M.;
Gerusz, V. J. J. Am. Chem. Soc. 1995, 117, 5156-5157. (i) Trost, B.
M.; Jakel, C.; Plietker, B. J. Am. Chem. Soc. 2003, 125, 4438-4439.
(j) Al-Masum, M.; Meguro M.; Yamamoto, Y. Tetrahedron Lett. 1997,
38, 6071-6074. (k) Al-Masum, M.; Yamamoto, Y. J. Am. Chem. Soc.
1998, 120, 3809-3810. For a recent reviews, see: (l) Zimmer, R.;
Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem. Rev. 2000, 100, 3067.
(m) Yamamoto, Y.; Radhakrishnan, U. Chem. Soc. Rev. 1999, 28, 199-
207. (n) Ma, S. Chem. Rev. 2005, 105, 2829-2871.
(3) (a) Franzen, J.; Lofstedt, J.; Dorange, I.; Backvall, J.-E. J. Am.
Chem. Soc. 2002, 124, 11246-11247. (b) Lofstedt, J.; Narhi, K.;
Dorange, I.; Backvall, J.-E. J. Org. Chem. 2003, 68, 7243-7248. (c)
Franzen, J.; Lofstedt, J.; Falk, J.; Backvall, J.-E. J. Am. Chem. Soc.
2003, 125, 14140-14148.
(4) Nakamura, H.; Onagi, S.; Kamakura, T. J. Org. Chem. 2005,
70, 2357-2360 and reference cited therein.
(5) Shin, C.; Chavre, S. N.; Pae, A. N.; Cha, J. H.; Koh, H. Y.; Chang,
M. H.; Choi, J. H.; Cho, Y. S. Org. Lett. 2005, 7, 3283-3285.
(6) Asao, N.; Nogami, T.; Takahashi, K.; Yamamoto, Y. J. Am. Chem.
Soc. 2002, 124, 764-765.
(7) (a) Patil, N. T.; Yamamoto, Y. J. Org. Chem. 2004, 69, 5139-
5142. For other reports on synthesis of the cyclic alkenyl ethers, see:
(b) Barluenga, J.; Vazquez-Villa, H.; Ballesteros, A.; Gonzalez, J. M.
J. Am. Chem. Soc. 2003, 125, 9028-9029. (c) Mondal, S.; Nogami, T.;
Asao, N.; Yamamoto, Y. J. Org. Chem. 2003, 68, 9496-9498. (d) Yue,
D.; Ca, N. D.; Larock, R. C. Org. Lett. 2004, 6, 1581-1584. (e) Wei,
L.-L.; Wei, L.-M.; Pan, W.-B.; Wu, M.-J. Synlett 2004, 1497-1502. For
a similar process, see: (f) Miyakoshi, N.; Aburano, D.; Mukai, C. J.
Org. Chem. 2005, 70, 6045-6052.
(8) (a) Yao, T.; Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2004,
126, 11164-11165. (b) Yao, T.; Zhang, X.; Larock, R. C. J. Org. Chem.
2005, 70, 7679-7685. For homogeneous gold-catalyzed reactions, see
also: (c) Hashmi, A. S. K. Gold Bull. 2004, 37, 51-65.
(9) Silver(I) salts acts as a Lewis acid as well as a transition metal
catalyst. See: Yao, X.; Li C.-J. J. Org. Chem. 2005, 70, 5752-5755
and references therein.
Allenes are a common structural unit found in many
biologically and medicinally important natural and non-
natural products, and therefore they have received
considerable attention in organic synthesis.1 Apart from
their occurrence in some natural compounds, allenes
nowadays are considered as a versatile functional group
that acts as an electrophile2 as well as nucleophile3
depending on the catalyst and reaction conditions leading
to the formation of highly substituted carbon centers. It
is thus not surprising that many new synthetic methods
have been developed for their syntheses.4 We envisaged
that syntheses of highly substituted heterocycles can be
achieved if the method permitting the introduction of
allene moiety into heterocycles could be found.5
Recently, we reported a new method for the one-pot
synthesis of cyclic alkenyl ethers from acetylenic alde-
hydes by using Pd(OAc)26 and CuI7a catalysts. With this
in mind, we envisioned that a substrate of type 1 would
undergo cyclization with alcohols, and if successful this
(1) Taylor, D. R. Chem. Rev. 1967, 67, 317. (b) Rutledge, T. F.
Acetylenes and Allenes; Reinhold: New York, 1969. (c) Patai, S. The
Chemistry of Ketenes, Allenes, and Related Compounds; Wiley: Chich-
ester, 1980. (d) Landor, S. R. The Chemistry of the Allenes; Academic
Press: London, 1982. (e) Coppola, G. M.; Schuster, H. F. Allenes in
Organic Synthesis; Wiley: New York, 1984. (f) Krause, N.; Hashmi,
A. S. K. Modern Allene Chemistry; Wiley-VCH: Weinheim, Germany,
2004. (g) Pasto, D. J. Tetrahedron 1984, 40, 2805. (h) Marshall, J. A.
Chem. Rev. 1996, 96, 31. (i) Wang, K. K. Chem. Rev. 1996, 96, 207. (j)
Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34, 535. (k) Tius, M. A.
Acc. Chem. Res. 2003, 36, 284. (l) Brandsma, L.; Nedolya, N. A.
Synthesis 2004, 735. (m) Hoffman-Roder, A.; Krause, N. Angew. Chem.,
Int. Ed. 2004, 43, 1196-1216.
10.1021/jo051524q CCC: $30.25 © 2005 American Chemical Society
Published on Web 11/03/2005
10096
J. Org. Chem. 2005, 70, 10096-10098

TABLE 1. Effect of Various Ag(I) Salts on Cyclizationa
TABLE 2. AgSbF6-Catalyzed Cyclization of Alkynonesa
entry
catalyst (5%)
yield (%)b
1
2
3
4
5
6
7
none
0c
AgOTf
AgSbF6
AgClO4
AgBF4
AgPF6
Ag2SO4
94
100 (95)d
48
56
79
0c
a Methanol (2 equiv) was added to a solution of 1 and catalyst
(5 mol%) in CH2Cl2, and the mixture was heated at 35 °C for 16
h. b Yields were determined by 1H NMR spectroscopy with dibro-
momethane as an internal standard. c Starting material recovered.
d Isolated yields are shown in parentheses.
of AgOTf (5 mol %) at 35 °C gave the desired product 3a
in 94% yield (entry 2). In the case of AgSbF6, the reaction
proceeded well, leading to the formation of 3a in quan-
titative yield (entry 3). However, silver(I) salts such as
AgClO4, AgBF4, and AgPF6 were not very effective
(entries 4-6). The catalyst Ag2SO4 does not promote the
reaction at all (entry 7).
Since the optimal reaction conditions were in hand for
the silver-catalyzed annulations, the reaction of 1 with
various alcohols 2 was carried out, and the results are
summarized in Table 2. The reaction of 1a with 2b was
conducted with AgSbF6 (5 mol %) in CH2Cl2 at 35 °C.
The substrate 1a was consumed in 16 h, and the
annulation product 3b was obtained in 93% isolated yield
(Table 2, entry 1). Similarly, the homoallyl alcohol 2c and
3-phenyl-2-propyn-1-ol 2d reacted smoothly, with 1a
giving the corresponding annulation products in 95 and
78% yield, respectively (entries 2 and 3). It was possible
to use a secondary alcohol, for instance 2-propanol 2e,
for the reaction. Thus, when 1a was treated with 2e
under the standard conditions, 3e was obtained in 92%
yield (entry 4). However, the reaction of bulky tert-butyl
alcohol 2f with 1a did not lead to the desired product;
instead, a complex mixture of unidentified materials was
obtained (entry 5). The reaction of R-phenylmethyl
alcohol 2g with 1a gave the product 3g with slightly
lower yield (entry 6). The steric hindrance around the
alcohol functionality seems to diminish the yield of
annulation products. When 1b and 1c were treated with
methanol and 2-propanol under the standard conditions,
the corresponding products 3h-k were obtained in high
yields (entries 7-10). As shown in entries 11 and 12, the
substrates 1d and 1e underwent smooth annulation
reactions with MeOH to produce 3l and 3m in 65 and
93% yield, respectively. It should be noted that terminal
alkynes or -TMS substituted alkynes (R ) H, TMS) did
not give the corresponding desired products under the
present reaction conditions.10 Similar to the previously
reported case, no formation of a regioisomeric product
due to 5-exo-dig cyclization was observed in any of the
cases.7a,11
a The reactions of 1 (0.2 mmol) with alcohol 2 (0.4 mmol) in the
presence of AgSbF6 (5 mol %) were carried out at 35 °C in CH2Cl2.
b Isolated yields. c A mixture of unidentified products was obtained.
standard conditions (eq 2). No formation of the corre-
1
sponding 1-allenyl chromene was detected by H NMR
spectrum of the crude product.
A plausible mechanism for the silver(I)-catalyzed an-
nulation is depicted in Scheme 1. The reaction most
probably proceeds through the benzopyrylium cation I,
(10) The reason for the failure of reaction in the case of terminal
alkynes (R ) H) and TMS (R ) TMS)-protected alkynes can be well
accounted. The reaction of terminal alkynes with Ag(I) salts would lead
to the formation of silver acetylide, thereby hampering the cyclization.
See: Yao, X.; Li, C.-J. Org. Lett. 2005, 7, 4395-4398. However, in the
TMS-protected alkynes, steric hindrance created by three methyl
groups might hamper the cyclization.
(11) The intramolecular 5-exo-dig/6-endo-dig cyclization of oxygen
nucleophiles to alkynes has been reported. See, for instance: (a)
Sashida, H.; Kawamukai, A. Synthesis 1999, 1145-1148. (b) Bellina,
F.; Ciucci, D.; Vergamini, P.; Rossi, R. Tetrahedron 2000, 56, 2533-
2545. (c) Gabriele, B.; Salerno, G.; Fazio, A.; Pittelli, R. Tetrahedron
2003, 59, 6251-6259.
Quite astonishingly, the substrate 1f (R ) COOEt)
gave 4 upon treatment with 5% AgSbF6 under the
J. Org. Chem, Vol. 70, No. 24, 2005 10097

SCHEME 1. Plausible Mechanism for Cyclization
Reaction
of two acetylenic carbons and the shift of the carbonyl
carbon in the presence of AgSbF6 clearly indicate the
involvement of such a cationic intermediate.15
Silver-catalyzed cascade cyclization reaction of
alkynones with alcohols described herein represents a
general and versatile approach to the 1-allenyl chromenes.
The mild reaction conditions, simple procedure, easily
available starting materials, and reasonable yields make
the method attractive. The allenyl moiety can be easily
introduced in the heterocycle by using this procedure,
which on further functionalization may give access to
highly substituted heterocycles.
Experimental Section
The preparation of 3a is representative. 1a (0.050 g, 0.1838
mmol), MeOH (0.012 g, 0.3676 mmol), AgSbF6 (5 mol %), and
CH2Cl2 (2 mL) were stirred at 35 °C in a screw-capped vial for
16 h. Water (10 mL) was added, and the resulting reaction
mixture was extracted with ethyl acetate. The extracts were
concentrated to give a thick residue. The resulting residue was
purified by column chromatography with use of silica gel as a
solid phase and 9:1 hexanes-ethyl acetate as an eluent to afford
pure 3a (0.053 g, 95%).
which would be formed by the nucleophilic attack of
carbonyl oxygen to the silver coordinated alkyne.12 The
benzopyrylium ion formed in this way would undergo
subsequent trapping with alcohols. The protonation and
regeneration of the Ag(I) catalyst produce the annulation
products. Another conceivable pathway is that silver salts
act as a catalysts13 for Michael reaction forming the
intermediate II, which would then cyclize with the
proximal alkyne activated by the Ag(I) coordination.
However, the fact that 1-benzoyl pentyne14 does not
undergo the reaction under the present catalytic system
might exclude the possibility. To support the formation
of benzopyrylium cation in the present reaction, 13C NMR
studies of a 1:1 mixture of 1a and AgSbF6 in CD2Cl2 at
room temperature (1 h) were carried out. Disappearance
Acknowledgment. N.T.P. thanks the Japan Society
for the Promotion of Science (JSPS) for a postdoctoral
research fellowship.
Supporting Information Available: Experimental de-
tails, synthetic method for starting material preparation,
1
characterization data, and H NMR spectra of newly synthe-
sized compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
JO051524Q
(14) The reaction of 1-benzoyl pentyne (0.2 mmol), MeOH (2 equiv),
AgSbF6 (5 mol %) in CH2Cl2 was carried out at 35 °C in a screw-capped
vial for 16 h. However, no Michael addition product was noticed; slight
decomposition of starting material was observed by the TLC and 1H
NMR analysis.
(12) Such type of transition metal-catalyzed benzopyrylium cation
formation is known in the case of the compounds containing alkynes
tethered with carbonyl groups. See: (a) Asao, N.; Takahashi, K.; Lee,
S.; Kasahara, T.; Yamamoto, Y. J. Am. Chem. Soc. 2002, 124, 12650-
12651. (b) Asao, N.; Aikawa, H.; Yamamoto, Y. J. Am. Chem. Soc. 2004,
126, 7458-7459. (c) Sato, K.; Yudha, S. S.; Asao, N.; Yamamoto, Y.
Synthesis 2004, 9, 1409-1412. (d) Asao, N.; Nogami, T.; Lee, S.;
Yamamoto Y. J. Am. Chem. Soc. 2003, 125, 10921-10925. (e) Kusama,
H.; Funami, H.; Shido, M.; Hara, Y.; Takaya, J.; Iwasawa, N. J. Am.
Chem. Soc. 2005, 127, 2709-2716. (f) Patil, N. T.; Wu, H.; Yamamoto,
Y. J. Org. Chem. 2005, 70, 4531-4534. (g) Zhu, J.; Germain, A. R.;
Porco, J. A., Jr. Angew. Chem., Int. Ed. 2004, 43, 1239-1239.
(13) Aza-Michael reaction of enones catalyzed by transition metal
salts are known. See: Kobayashi, S.; Kakumoto, K.; Sugiura, M. Org.
Lett. 2002, 4, 1319-1322.
(15) See Supporting Information for the 13C NMR spectra (1a and
1a + AgSbF6).
10098 J. Org. Chem., Vol. 70, No. 24, 2005