Platinum(IV)-catalyzed regioselective synthesis of highly substituted 4H-cyclopenta[b]furans via cascade heterocyclization of 2-(1-alkynyl)-3-aryl-2- propenals with arylet

Article abstract of DOI:10.1002/adsc.201200597

A platinum-catalyzed cascade heterocyclization and formal [3+2] cycloaddition reaction of 2-(1-alkynyl)-3-aryl-2-propenals and arylethenes has been developed. This cyclization reaction shows excellent regioselectivity to obtain highly substituted 4H-cyclo

Full text of DOI:10.1002/adsc.201200597

COMMUNICATIONS
DOI: 10.1002/adsc.201200597
Platinum(IV)-Catalyzed Regioselective Synthesis of Highly
Substituted 4H-Cyclopenta[b]furans via Cascade Hetero-
cyclization of 2-(1-Alkynyl)-3-aryl-2-propenals with Arylethenes
a
a
a
a
a
Ting He, Pin Gao, Shu-Chun Zhao, You-Di Shi, Xue-Yuan Liu,
a,
and Yong-Min Liang *
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, Peopleꢀs Republic of China
a
Fax : (+86)-931-891-2582; phone: (+86)-931-891-2596; e-mail: liangym@lzu.edu.cn
Received: July 9, 2012; Revised: November 13, 2012; Published online: January 29, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200597.
Abstract: A platinum-catalyzed cascade heterocycli-
zation and formal [3+2]cycloaddition reaction of
bonds have proven to be effective and powerful meth-
[1]
odologies for the synthesis of cyclic structures. Re-
cently, the formation of polycyclics via transition
metal-catalyzed processes has drawn much attention
2-(1-alkynyl)-3-aryl-2-propenals and arylethenes has
been developed. This cyclization reaction shows ex-
cellent regioselectivity to obtain highly substituted
[
2]
[3]
of chemists as well as our group, due to the mild-
ness of the reaction conditions and the high regio-
and stereoselectivities.
4H-cyclopenta[b]furans in moderate to excellent
yields.
Among many heterocycles, the substituted furans
are one of the most common structural units in natu-
ral products. In particular, cycloalka[b]furan is an
Keywords: cascade reactions; cyclization; platinum;
regioselectivity; transition metal catalysts
[
4]
important intermediate for the synthesis of pharma-
[
5,6]
ceuticals and bioactive natural molecules.
Typical approaches to cycloalka[b]furans, which in-
volved the cyclization of alkene-, alkyne- and cyclo-
Transition metal-catalyzed cascade reactions for the propane-containing carbonyl compounds, have been
[
7–11]
construction of carbon-carbon and carbon-heteroatom reported (Scheme 1).
Although these methods
Scheme 1. Typical methods for synthesis of cycloalka[b]furans.
Adv. Synth. Catal. 2013, 355, 365 – 369
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365

Ting He et al.
COMMUNICATIONS
[a]
Table 1. Optimization of platinum-catalyzed cascade reaction of 1a and 2a.
[b]
Entry
[Pt]/
A
H
U
G
R
N
U
G
Solvent
1a:2a
Atmosphere
Yield [%]
1
2
3
4
5
6
7
8
9
PtCl (10)
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
1,4-dioxane
DMF
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:1
1:2
1:2
1:2
air
28
46
54
53
2
PtCl (10)
CO
CO
CO
CO
CO
CO
CO
CO
CO
CO
2
PtCl (10)
4
Pt
A
H
U
G
R
N
U
G
2
2
PtI (10)
60
2
PtI (10)
84 [
4
c]
K PtCl (10)
n.r.
2
4
PtI (10)
75
73
4
PtI (5)
4
1
1
0
1
PtI (10)
36 [
4
c]
PtI (10)
n.r.
4
[
[
[
a]
The reaction was carried out with 1a (0.2 mmol), 2a and Pt catalysts in solvent (2 mL) at 608C for 2 h.
Yield of the isolated product.
No reaction
b]
c]
have proven to be availiable, the search to design new
With the optimized conditions in hand, we surveyed
methods with good functional group tolerance, more the cascade cyclization of various enyne aldehydes
easily accessible materials and excellent regioselectivi- 1 with 2a to clarify the scope of this reaction
[
12,13]
ty is still of current interest.
a highly regioselective Pt-catalyzed cascade heterocy- donating aromatic groups in substituent R gave the
clization/[3+2]cycloaddition of 2-(1-alkynyl)-3-aryl-2- desired highly substituted 4H-cyclopenta[b]furans in
propenals with arylethenes to construct polysubstitut- good to excellent yields (3aa–ga, ia). The structure of
ed 4H-cyclopenta[b]furans. 3fa was also confirmed by an X-ray crystal struture
Herein, we report (Scheme 2). Both electron-withdrawing and electron-
1
ACHTUNGTRENNUNG
[
15]
Initial research was focused on the reaction of 2- analysis (Figure 1). To our delight, a substrate with
benzylidene-4-phenylbut-3-ynal 1a and ethene-1,1- an aliphatic alkyne substituent also afforded the de-
diyldibenzene 2a (2.0 equiv.) in the presence of PtCl2 sired product 3ha in 54% yield. Other substituents
1
(
10 mol%) in toluene at 60 8C (Table 1, entry 1). We Ar (3ja and 3ka) have also proved to be successful
were pleased to find that the reaction resulted in and gave the corresponding products (yields: 95%
a 28% yield of the desired product, 2,4,6,6-tetraphen- and 78%). Comparing 3ja with 3ka, the electron-with-
yl-5,6-dihydro-4H-cyclopenta[b]furan 3aa. Further ex- drawing aromatic group showed a higher yield than
periments showed that carbon monoxide, which plays the electron-rich group in this cascade cyclization re-
[
14]
a role of coordination with Pt catalysts,
cient for improving the yield of 3aa (Table 1, entry 2).
Other Pt catalysts, such as PtCl , Pt(cod) Cl (cod= zation of 2-benzylidene-4-phenylbut-3-ynal 1a and
was effi- action.
We next investigated the scope of the cascade cycli-
AHCTUNGTRENNUNG
4
2
2
1
,5-cyclooctadiene), and PtI could also afford the de- arylethenes
2
under the optimized conditions
sired product in moderate yields (Table 1, entries 3– (Scheme 3). The reaction proceeded smoothly with
), but PtI was found to be the most effective to give various substituted diphenylethylenes. Both electron-
2
5
4
the furan product in 84% yield. Additionally, using rich and electron-deficient substituent groups such as
K PtCl as catalyst, the reaction did not occur at all methyl, methoxy, fluoro- and chloro- were well toler-
2
4
(
Table 1, entry 7). Decreasing the amount of PtI and ated in this reaction (3ab–ae). It is noteworthy that
4
the ratio between 2a and 1a both reduced the yields asymmetrical alkenes such as 1-methyl-4-(1-phenylvi-
of the furan products (Table 1, entries 8 and 9). In nyl)benzene and styrene could also be employed to
a further survey, polar aprotic solvents such as 1,4-di- obtain the desired furans (3af, 3ag) in the yields of
oxane also provided the desired product with low 75% and 64%, respectively. Substituted styrenes such
yield, whereas no reactions occurred in DMF as p-methylstyrene and p-methoxystyrene also afford-
(
Table 1, entries 10 and 11). Herein, the optimum re- ed the desired products (3ah, 3ai) in moderate yields.
action conditions for 3aa were found to be 1.0 equiv. However, other alkenes such as 1,2-diphenylethene,
of 1a, 2.0 equiv, of 2a and 10 mol % of PtI in toluene enols and vinyl ether cannot afford the desired prod-
4
at 60 8C under CO.
ucts, respectively.
366
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Adv. Synth. Catal. 2013, 355, 365 – 369

Platinum(IV)-Catalyzed Regioselective Synthesis of Highly Substituted 4H-Cyclopenta[b]furans
Scheme 3. Platinum-catalyzed cascade [3+2]cyclization of
aldehyde 1a with various arylethenes 2.
Scheme 2. Platinum-catalyzed cascade reaction of various
adehydes 1 and 1,1-diphenylethylene 2a.
To our surprise, when 2-benzylidene-1,4-diphenyl-
but-3-yn-1-one 1l and ethene-1,1-diyldibenzene 2a
were employed in the above [3+2]cycloaddtion, the
desired product was not detected but instead a trisub-
Scheme 4.
stituted furan 4la was obtained in 92% yield
(
Scheme 4), which may be the result of the steric
effect of the phenyl group at the C-1 position of 4la.
In addition, it is not possible that the phenyl group in
the C-1 position could be eliminated as a phenyl
cation in the process of forming the cyclopenta[b]fur-
an.
Although the accurate mechanism of the reaction
remains unclear, a plausible mechanism is proposed
in Scheme 5. In this process, the oxygen of the car-
bonyl group as a nucleophile attacks the platinum co-
ordinated alkynes A to form an oxonium ion inter-
[
8]
mediate, which subsequently isomerizes to a furan
carbocation B. Then, the nucleophilic attack of elec-
tron-rich olefins to the carbocation B might result in
Figure 1. X-ray structure of 3fa.
Adv. Synth. Catal. 2013, 355, 365 – 369
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asc.wiley-vch.de
367

Ting He et al.
COMMUNICATIONS
[16–20]
Typical Procedure for the Preparation of 1l
To a solution of phenylmagnesium bromide (1.99 g, 11
mmol) in THF was added enal 1a (2.32 g, 10 mmol). When
the reaction was complete as monitored by TLC, the reac-
tion mixture was quenched with saturated aqueous NH Cl,
4
extracted with ethyl acetate, dried with MgSO and concen-
4
trated under reduced pressure. The residue was purified by
chromatography on silica gel using 10:1 hexane/EtOAc to
afford the alcohol. Then, the alcohol was dissolved in
CH Cl and treated with 20 equiv. of MnO for 12 h. The
2
2
2
residue obtained upon filtration and evaporation of the sol-
vent was purified by chromatography on silica gel using 20:1
hexane/EtOAc to afford 1l.
Typical Procedure for the Preparation of 3
To a solution of PtI (14.0 mg, 0.02 mmol) in 2.0 mL of anhy-
4
drous toluene under carbon monoxide were added 1 (0.2
mmol) and 2 (0.4 mmol). The mixture was stirred at 608C.
When the reaction was complete as monitored by TLC, the
reaction mixture was evaporated under vacuum. The residue
was purified by chromatography on silica gel using 100:1
hexane/EtOAc to afford the corresponding polysubstituted
4
H-cyclopenta[b]furan 3.
Scheme 5. Plausible mechanism.
the formation of C. The [3+2]cyclization of inter-
mediate C leads to the structure D, which undergoes
deprotonation to obtain compound E, followed by
metal protonation to generate the desired products 3.
In summary, we have developed an effecient ap-
proach for the synthesis of highly substituted 4H-cy-
clopenta[b]furans via platinum-catalyzed cascade in-
voling heterocyclization and formal [3+2]cycloaddi-
tion of 2-(1-alkynyl)-3-aryl-2-propenals and aryle-
thenes. The reaction shows good to excellent yields.
Acknowledgements
The authors gratefully acknowledge National Basic Research
Program of China (973 program) and “111” program of
MOE. We thank the NSF (NSF-21072080, NSF-20732002)
and the Fundamental Research Funds for the Central Univer-
sities (lzujbky-2010-223) for financial support.
The high chemo- and regioselectivity is also disclosed. References
A plausible mechanism is proposed and further re-
search of this reaction is underway in our group.
[1] a) N. Chatani, Directed Metallation, in: Topics in Or-
ganometallic Chemistry; Springer, Berlin, 2007;
b) Handbook of CÀH Transformations, (Ed.: G.
Dyker), Wiley-VCH, Weinheim, 2005; c) N. T. Patil, Y.
Yamamoto, Chem. Rev. 2008, 108, 3395–3442; d) I. Na-
kamura, Y. Yamamoto, Chem. Rev. 2004, 104, 2127–
Experimental Section
[16–18]
Typical Procedure for the Preparation of 1a
2
198; e) V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev.
2
002, 102, 1731–1769; f) M. Rubin, A. W. Sromek, V.
To a round-bottom flask, (Z)-2-iodo-3-phenylacrylaldehyde
2.58 g, 10 mmol), Pd(PPh ) Cl (140.4 mg, 0.2 mmol) and
CuI (19.1 mg, 0.1 mmol) were added, the flask was flushed
Gevorgyan, Synlett 2003, 2265–2291; g) F. Kakiuchi, S.
Murai, Acc. Chem. Res. 2002, 35, 826–834.
(
ACHTUNGTRENNUNG
3
2
2
[
2] a) Metal-Catalyzed Cross-Coupling Reactions, (Eds.: F.
with nitrogen and Et N was added via syringe into the flask,
3
Diederich, P. J. Stang), Wiley-VCH, New York, 1998;
b) Metal Catalyzed Cross-Coupling Reactions, 2 edn.,
Vols. 1 and 2 (Eds: A. Meijere, F. Diederich), Wiley-
VCH, Chichester, 2004; c) M. Malacria, Chem. Rev.
followed by phenylacetylene (1.12 g, 11 mmol). The mixture
was stirred at room temperature. When the reaction was
complete as monitored by TLC, the reaction mixture was
quenched with water, extracted with CH Cl , dried with
nd
2
2
1
996, 96, 289–306; d) M. Victor, H. D. Peter, F. Alosis,
MgSO and concentrated under reduced pressure. The resi-
4
Chem. Eur. J. 2004, 10, 4556–4575; e) M. Yoshida, Y.
due was purified by chromatography on silica gel using 20:1
hexane/EtOAc to afford 1a.
Morishta, M. Fujita, M. Ihara, Tetrahedron 2005, 61,
4
381–4393; f) P. A. Inglesby, P. A. Evans, Chem. Soc.
Rev. 2010, 39, 2791–2805; g) T. Mark, Y.-H. Du, G. O.
Samuel, S. Vishaka, W. Kathryne, T. Lin, S. Michal, L.
Pu, J. Am. Chem. Soc. 2011, 133, 11780–11794.
368
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 365 – 369

Platinum(IV)-Catalyzed Regioselective Synthesis of Highly Substituted 4H-Cyclopenta[b]furans
[
3] a) R.-L. Yan, H. Yan, C. Ma, Z.-Y. Ren, X.-A. Gao, G.-
[6] a) W. Skuballa, Angew. Chem. 1981, 93, 1080–1081;
Angew. Chem. Int. Ed. Engl. 1981, 20, 1046–1048;
b) R. C. Nickolson, Tetrahedron Lett. 1983, 24, 47–50.
[7] J. Zhang, H. G. Schmalz, Angew. Chem. 2006, 118,
6856–6859; Angew. Chem. Int. Ed. 2006, 45, 6704–6707.
[8] a) T.-L. Yao, X.-X. Zhang, R. C. Larock, J. Am. Chem.
Soc. 2004, 126, 11164–11165; b) T.-L. Yao, X.-X.
Zhang, R. C. Larock, J. Org. Chem. 2005, 70, 7679–
S. Huang, Y.-M. Liang, J. Org. Chem. 2012, 77, 2024–
2
028; b) X.-C. Wang, R.-L. Yan, M.-J. Zhong, Y.-M.
Liang, J. Org. Chem. 2012, 77, 2064–2068; c) L.-N. Guo,
X.-H. Duan, Y.-M. Liang, Acc. Chem. Res. 2011, 44,
1
11–122; d) X.-F. Xia, X.-Z. Shu, K.-G. Ji, A. Shaukat,
X.-Y. Liu, Y.-M. Liang, J. Org. Chem. 2011, 76, 342–
45; e) R.-L. Yan, J. Luo, X.-C. Wang, C.-W. Ma, G.-S.
Huang, Y.-M. Liang, J. Org. Chem. 2010, 75, 5395–
397; f) X.-F. Xia, X.-Z. Shu, K.-G. Ji, Y.-F. Yang, A.
Shaukat, X.-Y. Liu, Y.-M. Liang, J. Org. Chem. 2010,
5, 2893–2902; g) L.-N. Guo, X.-H. Duan, X.-Y. Liu, J.
Hu, H.-P. Bi, Y.-M. Liang, Org. Lett. 2007, 9, 5425–
428.
3
7
685; c) N. T. Patil, H. Wu, Y. Yamamoto, J. Org.
Chem. 2005, 70, 4531–4534; d) N. T. Patil, Y. Yamamo-
to, ARKIVOC. 2007, 10, 121–141.
9] X. Huang, W.-J. Fu, M.-Z. Miao, Tetrahedron Lett.
5
[
7
2
008, 49, 2359–2362.
10] F. E. McDonald, C. C. Schultz, J. Am. Chem. Soc. 1994,
16, 9363–9364.
11] H. D. Scharf, E. Wolters, Chem. Ber. 1978, 111, 639–
60.
[
[
[
5
1
[
4] a) B. A. Keay, P. W. Dibble, in: Comprehensive Hetero-
cyclic Chemistry II, Vol. 2, (Eds: A. R. Katritzky, C. W.
Rees, E. F. V. Scriven), Pergamon Press, Oxford, 1996,
pp 395–436; b) D. M. X. Donnelly, M. J. Meegan, in:
Comprehensive Heterocyclic Chemistry, Vol. 4, (Eds.:
A. R. Katritzky, C. W. Rees), Pergamon, Oxford, 1984,
pp 657–712; c) M. V. Sargent, F. M. Dean, in: Compre-
hensive Heterocyclic Chemistry, Vol. 4, (Eds: A. R. Ka-
trizky, C. W. Rees), Pergamon Press, New York, 1984,
pp 599–656; d) H.-K. Lee, K.-F. Chan, C.-W. Hui, H. K.
Yim, X.-W. Wu, H. N. C. Wong, Pure Appl. Chem.
6
12] a) G.-Z. Zhang, X.-G. Huang, G.-T. Li, L.-M. Zhang, J.
Am. Chem. Soc. 2008, 130, 1814–1815; b) G.-T. Li, X.-
G. Huang, L.-M. Zhang, J. Am. Chem. Soc. 2008, 130,
6
944–6945.
[
13] a) H.-Y. Gao, J.-L. Zhang, Chem. Eur. J. 2012, 18,
2
1
777–2782; b) L.-F. Wang, R.-H. Fan, Org. Lett. 2012,
4, 3596–3599.
[
14] a) A. Fꢂrstner, C. Aissa, J. Am. Chem. Soc. 2006, 128,
306–6307; b) H.-K. Chang, S. Datta, A. Das, R.-S. Liu,
6
2
8
1
2
005, 77, 139–143; e) B. H. Lipshutz, Chem. Rev. 1986,
6, 795–819; f) G. Zeni, R. C. Larock, Chem. Rev. 2004,
04, 2285–2309; g) G. Zeni, R. C. Larock, Chem. Rev.
007, 107, 303–303.
Angew. Chem. 2007, 119, 4828–4831; Angew. Chem. Int.
Ed. 2007, 46, 4744–4747.
[
[
15] CCDC 887445 (3fa) contains the supplementary crys-
tallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
16] W. R. Bowman, C. F. Bridge, P. Brookes, M. O. Cloon-
an, D. C. Leach, J. Chem. Soc. Perkin Trans. 1 2002, 1,
58–68.
[17] A. S. K. Hashmi, I. Braun, M. Rudolph, F. Rominger,
Organometallics 2012, 31, 644–661.
[18] S.-F. Chen, J.-B. Wang, J. Org. Chem. 2007, 72, 4993–
4996.
[
5] a) A. F. Pozharskii, A. T. Soldatenkov, A. R. Katritzky,
in Heterocycles in Life and Society, Wiley, Chichester,
1
997; b) N. Toshiaki, N. Masako, N. Atsushi, J. Am.
Chem. Soc. 2003, 125, 7484–7485; c) S. Y. Ian, L. W.
Justin, A. K. Michael, Org. Lett. 2005, 7, 953–955;
d) S. Y. Ian, A. K. Michael, J. Am. Chem. Soc. 2007,
1
29, 1465–1469; e) H.-B. Deng, X.-B. Yang, Z.-L. Tong,
Z. Li, H.-B. Zhai, Org. Lett. 2008, 10, 1791–1793; f) J.
Pavol, M. C. Dane, J. D. Darren, J. Am. Chem. Soc.
2
009, 131, 16632–16633; g) I. Fuyuhiko, K. Masahiko,
M. Naoki, M. Chisato, Org. Lett. 2010, 12, 1800–1803;
h) B. Cheng, F.-F. Wu, X.-B. Yang, Y.-D. Zhou, X.-L.
Wan, H.-B. Zhai, Chem. Eur. J. 2011, 17, 12569–12572.
[19] M. J. Fuchter, J. N. Levy, Org. Lett. 2008, 10, 4919–
4922.
[20] J. N. Moorthy, S. Samanta, A. Koner, S. Saha, W. M.
Nau, J. Am. Chem. Soc. 2008, 130, 13608–13617.
Adv. Synth. Catal. 2013, 355, 365 – 369
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
369