Novel platinum-catalyzed tandem reaction: An efficient approach to construct naphtho[l,2-b]furan

Article abstract of DOI:10.1021/jo802645s

An efficient approach to synthesize naphtho[1,2-b]furan has been developed via platinum-catalyzed tandem reaction. This new tandem catalysis induces a cycloisomerization of allenyl ketone, followed by a 6Π-electrocyclization- type reaction of carbene intermediate. The metal carbene proved to be an effective intermediate in the 6π-electrocyclization-type reaction.

Full text of DOI:10.1021/jo802645s

SCHEME 1. Proposed Tandem Reaction
Novel Platinum-Catalyzed Tandem Reaction: An
Efficient Approach to Construct
Naphtho[1,2-b]furan
Hao Wei,† Hongbin Zhai,†,‡ and Peng-Fei Xu*,†
State Key Laboratory of Applied Organic Chemistry,
College of Chemistry and Chemical Engineering,
Lanzhou UniVersity, Lanzhou 730000,
People’s Republic of China, and Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, People’s Republic of China
SCHEME 2. Synthesis of Precursors
xupf@lzu.edu.cn
ReceiVed December 2, 2008
Ag-, Cu-, and Pt-catalyzed cycloisomerizations of allenyl
ketones have also been reported by Gevorgyan.4b The carbonyl
oxygen atom served as an intramolecular nucleophile and the
carbene intermediate B finally delivered the product C. We
envisioned that the 1,3-dien-5-yne intermediate D with an
alkynyl group at the ortho-position would undergo a 6π-
electrocyclization-type reaction to afford naphtho[1,2-b]furan.5
Naphtho[1,2-b]furan is widely identified as a key structural
subunit in numerous natural products. Although a number of
synthetic methods have appeared for the preparation of this class
of heterocycle, further development of novel expeditious
methods is still desired.6
An efficient approach to synthesize naphtho[1,2-b]furan has
been developed via platinum-catalyzed tandem reaction. This
new tandem catalysis induces a cycloisomerization of allenyl
ketone, followed by a 6π-electrocyclization-type reaction of
carbene intermediate. The metal carbene proved to be an
effective intermediate in the 6π-electrocyclization-type reaction.
The starting materials were prepared in three steps as shown
in Scheme 2. Aldehyde 2 was obtained by a Sonogashira cross-
coupling of 2-iodobenzaldehyde 1 with a terminal alkyne.7
Treatment of 2 with propargyl magnesium bromide in the
presence of a catalytic amount of HgCl2 in Et2O gave the alcohol
3.8 This was then oxidized to 4 by using the Dess-Martin
reagent.9 This step included a subsequent isomerization of the
propargyl function to the allenyl ketone during the workup.10
Initially, we started our investigation by using the substrate
4a (Table 1). The desired transformation was examined by using
Modern synthetic research has been directed toward the
development of new methodologies that provide synthetic
efficiency and atom economy.1 One of the ways to fulfill this
goal is to develop and use tandem reactions. Tandem reactions
serve as a powerful tool for the rapid and efficient assembly of
complex structures from simple starting materials with minimal
production of waste.2 Development of catalytic tandem reactions
has proven to be a challenging task. There has been tremendous
development in gold and platinum catalysis, which has led to
new synthetic methods as well as versatile applications in the
total synthesis of natural products. Both gold and platinum
catalysts are superior reagents in activating alkynes, allenes, and
alkene functionalities under mild conditions and at low catalyst
loading. They offer an attractive alternative means for highly
efficient tandem reactions.3
(3) (a) Fru¨stner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410.
(b) Bongers, N.; Krause, N. Angew. Chem., Int. Ed. 2008, 47, 2178. (c) Gorin,
D. J.; Toste, F. D. Nature 2007, 446, 395. (d) Jime´nez, N. E.; Echavarren, A. M.
Chem. Commun. 2007, 333. (e) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chem.,
Int. Ed. 2006, 45, 7896.
(4) (a) Hashimi, A. S. K.; Schwarz, L.; Choi, J.-H.; Frost, T. M. Angew.
Chem., Int. Ed. 2000, 39, 2285. (b) Schwier, T.; Gevorgyan, V. J. Am. Chem.
Soc. 2007, 129, 9868.
Recently, Hashimi reported that the cycloisomerization of
(5) (a) Tantillo, D. J. Annu. Rep. Prog. Chem., Sect. B: Org. Chem. 2006,
102, 269. (b) Beaudry, C. M.; Malerich, J. P.; Trauner, D. Chem. ReV. 2005,
105, 4757.
allenyl ketones was catalyzed by cationic AuCl3 (Scheme 1).4a
(6) See e.g.: (a) van Otterlo, W. A. L.; Morgans, G. L.; Madeley, L. G.;
Kuzvidza, S.; Moleele, S. S.; Thornton, N.; de Koning, C. B. Tetrahedron 2005,
61, 7746. (b) Maertens, F.; Toppet, S.; Compernolle, F.; Hoornaert, G. J. Eur.
J. Org. Chem. 2004, 12, 2707. (c) Mart´ın-Matute, B.; Nevado, C.; Ca´rdenas,
D. J.; Echavarren, A. M. J. Am. Chem. Soc. 2003, 125, 5757. (d) Arrault, A.;
Merour, J.-Y.; Leger, J.-M.; Jarry, C.; Guillaumet, G. HelV. Chim. Acta 2001,
84, 2198. (e) Duperrouzel, P.; Lee-Ruff, E. Can. J. Chem. 1980, 58, 51.
(7) Hamze, A.; Provot, O.; Alami, M.; Brion, J.-D. Org. Lett. 2005, 7, 5625.
(8) Albert, P.; August, R.; Mahrokh, T.; Tadamichi, F. J. Am. Chem. Soc.
1983, 105, 933.
† Lanzhou University.
‡ Chinese Academy of Sciences.
(1) Trost, B. M. Science 1991, 254, 1471.
(2) For recent review of tandem reactions, see: (a) Guo, H.-C.; Ma, J.-A.
Angew. Chem., Int. Ed. 2006, 45, 354. (b) Nicolaou, K. C.; Edmonds, D. J.;
Bulger, P. G. Angew. Chem., Int. Ed. 2006, 45, 7134. (c) Pellissier, H.
Tetrahedron 2006, 62, 2143. (d) Tietze, L. F.; Rackelmann, N. Pure Appl. Chem.
2004, 76, 1967. (e) Nicolaou, K. C.; Montagnon, T.; Snyder, S. A. Chem.
Commun. 2003, 551.
2224 J. Org. Chem. 2009, 74, 2224–2226
10.1021/jo802645s CCC: $40.75 2009 American Chemical Society
Published on Web 02/09/2009

TABLE 1. Optimization of Reaction Conditionsa
TABLE 2. Platium-Catalyzed Synthesis of Naphtho[1,2-b]furana
entry
catalyst (mol %)
solution
t (°C)
time (h)
yield
1
2
3
4
5
6
7
8
Au(PPh3)Cl (5)
AuCl (5)
DCM
DCM
DCM
DCM
DCM
DCM
DCE
CH3CN
toluene
toluene
toluene
toluene
40
40
40
40
40
40
60
60
60
80
rt
24
24
24
24
24
5
6
6
5
5
NRb
NR
trace
NR
AuCl3 (5)
AgBF4 (5)
AgOTf (5)
PtCl2 (10)
PtCl2 (10)
PtCl2 (10)
PtCl2 (10)
PtCl2 (10)
PtCl2 (10)
PtCl2 (10)
NR
51%
42%
14%
69%
72%
11%
62%
9
10
11
12
24
5
100
a Reactions were conducted with 0.4 mmol of 4a in 3 mL of solvent.
b No reaction.
a variety of transition metal complexes in CH2Cl2 at 40 °C.11
In the presence of Au(PPh3)Cl and AuCl, the formation of
naphtha[1,2-b]furan 5a was not observed (Table 1, entries 1
and 2). Treatment of compound 4a with 5 mol % of AuCl3 only
produced a small amount of 5a, and the reaction did not proceed
to completion even after 24 h (Table 1, entry 3). In the absence
of transition metal salts, the reaction did not take place at all.
With 5% of AgBF4 or AgOTf as a catalyst, the starting material
4a was rapidly consumed, but TLC monitoring did not indicate
that any trace of 5a was formed (Table 1, entries 4 and 5).
Fortunately, naphtha[1,2-b]furan 5a was obtained by using PtCl2
(10 mol %) as a catalyst (Table 1, entry 6). On the other hand,
the effect of the solvent was investigated and the use of toluene
afforded comparable results. Employing 1,2-dichloroethane and
MeCN resulted in diminished yields (Table 1, entries 7 and 8).
Finally, upon increasing the temperature to 80 °C, a yield of
72% was obtained (Table 1, entry 10). Thus, the use of PtCl2
(10 mol %) at 80 °C in toluene was found to be the most
efficient conditions.
With the optimized reaction conditions in hand, we next
explored the scope of this process by studying a wide variety
of substrates (Table 2). Substrates 4b, 4c, and 4d, which have
alkenyl, cycloalkyl, and aryl substituents, afforded the desired
products 5b, 5c, and 5d in moderate to good yields. Substrates
4e, 4f, 4g, and 4h, which bear methyl and benzyl ethers or
trimethylsilyl substituent, gave the corresponding naphtho[1,2-
b]furans 5e, 5f, 5g, and 5h in good yields. The reactions of 4i,
4j, and 4k, which have an electron-rich group or an electron-
deficient group on the aromatic ring, also furnished the desired
products 5i, 5j, and 5k in good yields. However, the substrate
a All reactions were carried out with 4 (0.4 mmol) with 10 mol % of
PtCl2 in toluene (3 mL) at 80 °C. b No reaction.
4l did not provide desired benzofuran 5l even with high catalyst
loading (15 mol %) and a prolonged reaction time at an elevated
temperature.
(9) (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4156. (b) Frigerio,
M.; Santagostino, M.; Sputore, S. J. Org. Chem. 1999, 64, 4537. (c) Ireland,
R. E.; Liu, L. J. Org. Chem. 1993, 58, 2899. (d) Meyer, S. D.; Schreiber, S. L.
J. Org. Chem. 1994, 59, 7549.
(10) Hashmi, A. S. K.; Bats, J. W.; Choi, J.-H.; Schwarz, L. Tetrahedron
Lett. 1998, 39, 7491.
(11) For recent examples on transition metal catalysis, including reactions
of allenes, see e.g.: (a) Chianese, A. R.; Lee, S. J.; Gagne´, M. R. Angew. Chem.
2007, 119, 4118; Angew. Chem., Int. Ed. 2007, 46, 4042. (b) Marion, N.; Nolan,
S. P. Angew. Chem. 2007, 119, 2806; Angew. Chem., Int. Ed. 2007, 46, 2750.
(c) Hashmi, A. S. K. Chem. ReV. 2007, 107, 3180. (d) Widenhoefer, R. A.;
Han, X. Eur. J. Org. Chem. 2006, 20, 4555. (e) Zhang, L.; Sun, J.; Kozmin,
S. A. AdV. Synth. Catal. 2006, 348, 2271. (f) Hoffmann-Ro¨der, A.; Krause, N.
Org. Biomol. Chem. 2005, 3, 387.
Two mechanistic pathways for this reaction are proposed in
Scheme 3. The intermediate 6, generated from compound 4 with
PtCl2, is converted into R,ꢀ-unsaturated carbene complex 8
through intramolecular nucleophilic attack of the oxygen atom
on the PtCl2-π-complexed allenic double bond.12 In path a,
platinum carbene 8 converts into 9 through a 6π-electrocycliza-
tion-type reaction, and the intermediate 9 then undergoes a 1,3-
hydrogen shift and loss of the proton to give the intermediate
J. Org. Chem. Vol. 74, No. 5, 2009 2225

SCHEME 3. Proposed Mechanism
In conclusion, we have developed an efficient method for
constructing various substituted naphtho[1,2-b]furan via the Pt-
catalyzed tandem cycloisomerization and 6π-electrocycliztion-
type reaction. The deuterium-labeling experiment shows the
metal carbene intermediate generated from cycloisomerization
of allenyl ketones may be an effective functionality in the 6π-
electrocyclization-type reaction.
Experimental Section
General Procedure for Substituted Naphtha[1,2-b]furan 5
from the Tandem Reaction of Compound 4. To a solution of
substrate 4 (0.40 mmol) in toluene (3.0 mL) was added 10.0 mg
(0.04 mmol, 10 mol %) of PtCl2 under air at 80 °C. When the
reaction was complete as determined by TLC analysis, the reaction
mixture was diluted with diethyl ether (40 mL). The mixture was
washed with water and brine. The organic layer was separated, dried
over anhydrous Na2SO4, and evaporated under reduced pressure.
The residue was purified by flash column chromatography on silica
gel to afford the corresponding naphtho[1,2-b]furan 5.
Trimethyl(naphtho[1,2-b]furan-4-yl)silane (5h). 5b was pre-
pared according to the above procedure in 68% yield as an oil: 1H
NMR (400 MHz, CDCl3) δ 7.87-7.85 (d, J ) 8.0 Hz, 1 H),
7.58-7.55 (dd, J ) 1.6, 8.8 Hz, 1 H), 7.50 (s, 1H), 7.44-7.43 (d,
J ) 3.6 Hz, 1 H), 7.40-7.36 (m, 1 H), 7.22-7.18 (td, J ) 1.2, 8.0
Hz, 1 H), 6.54-6.52 (q, J ) 1.6 Hz, 1 H), 0.32 (s, 9 H); 13C NMR
(100 MHz, CDCl3) δ 151.9, 141.8, 134.2, 132.0, 128.8, 126.5,
125.3, 118.0, 111.5, 109.7, 105.2, 99.5, 0.19. IR (KBr, cm-1) 2958,
2154, 1479, 1250, 862, 759; HRMS (EI) (calcd for C15H15OSi)
240.0965, found 240.0960 [M+].
SCHEME 4. Proof of the Proposed Mechanism
SCHEME 5. Deuterium Labeling Experiment
Acknowledgment. We are grateful for the financial support
of the National Natural Science Foundation of China (NSFC,
20772051) and the Program for program “111” and NCET-05-
0880 from the Chinese Ministry of Education of the People’s
Republic of China.
11, which ultimately leads to the observed product 5. Alterna-
tively, platinum carbene 8 undergoes a 1,2-hydrogen shift first
to give the intermediate 12. Then, 6-endocyclization of 12 leads
to the product 5 (path b).
To uncover the reaction mechanism, we investigated the
reaction of compound 12h (R ) TMS) in the presence of 10
mol % of PtCl2 in toluene at 80 °C (Scheme 4). The reaction
did not occur to give the product 5h6c and we concluded that
the reaction could not occur through path b. Furthermore, we
carried out the deuterium-labeling experiment (Scheme 5). When
D2O (1.5 equiv) was added to the reaction mixture, the product
5h with the deuterium-labeling at the C-2 position (56% D
incorporation) was obtained in 66% yield. The result was
consistent with the mechanism of path a.
Supporting Information Available: Experimental details and
characterization data for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
JO802645S
(12) For platinum-carbene intermediates, see, e.g.: (a) Chatani, N.; Furukawa,
N.; Sakurai, H.; Murai, S. Organometallic 1996, 15, 901. (b) Mamane, V.; Gress,
T.; Krause, H.; Fu¨rstner, A. J. Am. Chem. Soc. 2004, 126, 8654. (c) Funami, H.;
Kusama, H.; Iwasawa, N. Angew. Chem., Int. Ed. 2007, 46, 909. (d) Fru¨stner,
A.; Szillat, H. J. Am. Chem. Soc. 1998, 120, 8305. (e) Fru¨stner, A.; Stelzer, F.;
Szillat, H. J. Am. Chem. Soc. 2001, 123, 12863.
2226 J. Org. Chem. Vol. 74, No. 5, 2009