Platinum-catalyzed cycloisomerization reaction of 1,6-enyne coupling with rearrangement of propargylic esters

Article abstract of DOI:10.1021/jo802043z

(Chemical Equation Presented) A platinum-catalyzed cycloisomerization of 1,6-enyne coupling with the rearrangement chemistry of propargylic ester has been developed. Most probably, under platinum catalysis, propargylic ester undergoes the 1,3-acyloxy migr

Full text of DOI:10.1021/jo802043z

SCHEME 1
Platinum-Catalyzed Cycloisomerization Reaction
of 1,6-Enyne Coupling with Rearrangement of
Propargylic Esters
Li Lu, Xue-Yuan Liu, Xing-Zhong Shu, Ke Yang,
Ke-Gong Ji, and Yong-Min Liang*
State Key Laboratory of Applied Organic Chemistry, Lanzhou
UniVersity, Lanzhou 730000, People’s Republic of China
liangym@lzu.edu.cn
ReceiVed September 16, 2008
reactions to afford desired products.4 The mechanism was
proposed via the rearrangement of the intermediate vinylcyclo-
propyl metal carbenes XI. Consequently, further studies on the
reaction diversity of enynes governed by different functional
groups are still attractive.
On the other hand, platinum- and gold-catalyzed transfor-
mations of readily available propargylic esters have received
much attention in recent years.8 The metal allene complexes
are considered as common intermediates, which further react
with various functional groups to give astonishingly diverse
products (Scheme 2). What we are interested in is the effect
of this functional group when introduced into the cycloi-
somerization of enynes. On the basis of previous efforts in
this area,9 we envision that 1,6-enyne A with the propargylic
A platinum-catalyzed cycloisomerization of 1,6-enyne cou-
pling with the rearrangement chemistry of propargylic ester
has been developed. Most probably, under platinum catalysis,
propargylic ester undergoes the 1,3-acyloxy migration to
afford metal allene intermediate, which is followed by the
Diels-Alder-type reaction. 1,3-Acyloxy migration is the key
step during the transformation.
In the last decades, platinum and gold complexes have
emerged as powerful carbophilic π-acids for the activation of
alkynes toward a variety of nucleophiles.1 This strategy has been
well applied in the cycloisomerization reactions of 1,n-enynes,
which are attractive processes due to the high demands for atom
economy in newly developed reactions.2–7 Particularly intriguing
of this transformation is the diversity and complexity generated
by both the skeleton rearrangement and the influence of
functional groups. In this content, aromatic groups,3 alkenes,3,4
silyl ethers,5 alcohols,6 aldehydes,7 epoxides,7 and ethers7 are
excellent partners in the cycloisomerization of 1,6-enynes.
However, in most cases, these functional groups follow the same
path in nucleophilic attack to promote the ring-opening of the
intermediate cyclopropyl metal carbenes (Scheme 1). A limited
exception was reported recently by Fu¨rstner and co-workers.4
It was found that the 1,6-enynes bearing another alkene group
in the alkene position undergo formal intramolecular Diels-Alder
(2) (a) For selected reviews on metal-catalyzed isomerizations of enynes,
see: (a) Ref 1a,d,h,i. (b) Ma, S.; Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006,
45, 200–203. (c) Bruneau, C. Angew. Chem., Int. Ed. 2005, 44, 2328–2334. (d)
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C.; Buisine, O.; Malacria, M. Chem. ReV. 2002, 102, 813–834, For selected
examples, see. (h) Toullec, P. Y.; Genin, E.; Leseurre, L.; Genet, J.-P.; Michelet,
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(1) For selected reviews on Au and/or Pt catalysis, see (a) Jime`nez-Nu`n˜ez,
E.; Echavarren, A. M. Chem. ReV 2008, 108, 3326–3350. (b) Li, Z.; Brouwer,
C.; He, C. Chem. ReV. 2008, 108, 3239–3265. (c) Muzart, J. Tetrahedron 2008,
64, 5815–5849. (d) Michelet, V.; Toullec, P. Y.; Gene´t, J.-P. Angew. Chem.,
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Eur. J. 2006, 12, 5916–5923. (i) Zhang, L.; Sun, J.; Kozmin, S. A. AdV. Synth.
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(3) (a) Nieto-Oberhuber, C.; Pe´rez-Gala´n, P.; Herrero-Go´mez, E.; Lauterbach,
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A. M. J. Am. Chem. Soc. 2008, 130, 269–279. (b) Nieto-Oberhuber, C.; Lo´pez,
S.; Echavarren, A. M. J. Am. Chem. Soc. 2005, 127, 6178–6179. (c) Fu¨rstner,
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474 J. Org. Chem. 2009, 74, 474–477
10.1021/jo802043z CCC: $40.75 2009 American Chemical Society
Published on Web 11/18/2008

TABLE 2. Scope Study of Platinum-Catalyzed Cyclization of
Enynesa
SCHEME 2
TABLE 1. Optimization of Reaction Conditionsa
entry
catalyst (mol %)
solution t, °C time, h yield, %
1
2
3
4
5
6
7
8
PtCl2 (10), CO (1 atm) toluene
PtCl2 (10), CO (1 atm) CH3CN
PtCl2 (10), CO (1 atm) Dioxane
PtCl2 (10), CO (1 atm) DCE
80
80
80
80
80
80
rt
rt
rt
rt
rt
24
24
24
24
24
36
3
3
3
3
3
65
NRb
NR
83
PtCl2 (10), COD (40)
PtCl2 (10)
DCE
DCE
DCE
DCE
DCE
DCE
DCE
46
41
Au(PPh3)BF4 (5)
Au(PPh3)SbF6 (5)
Au(PPh3)OTf (5)
AuCl3 (5)
6c
11c
tracec
8c
9
10
11
AuCl (5)
tracec
a Reactions were conducted with 0.4 mmol of 1a in 3 mL of solvent.
b No reaction. c Most of the material was decomposed.
ester in its alkene position might undergo Diels-Alder
reaction after 1,3-migration of the acetate group, where the
intermediate vinylcyclopropyl metal carbenes C might be
involved (Scheme 2).4 Herein, we report a platinum-catalyzed
cycloisomerization of 1,6-enyne coupling with migration
chemistry of propargylic esters.
Optimization studies of this transformation started with the
use of enyne 1a as the model substrate (Table 1). To our delight,
the concept works nicely. Treatment of 1a in the presence of
10 mol % of PtCl2 under CO (1 atm)10 afforded the desired
aryl ketone 2a in 65% yield after the reaction mixture was stirred
in toluene (3 mL) at 80 °C for 24 h (entry 1). The nature of the
solvent had a substantial effect on the efficiency of the reaction.
No reaction was observed in either CH3CN or dioxane, whereas
1,2-dichloroethane (DCE) gave the best result (entries 1-4).
a All reactions were carried out with 1 (0.4 mmol) with 10 mol % of
PtCl2 under CO (1 atm) in DCE (3 mL) at 80 °C for 24 h. b No
reaction.
(6) (a) Nieto-Oberhuber, C.; Mun˜oz, M. P.; Lo´pez, S.; Jime´nez-Nu´n˜ez, E.;
Nevado, C.; Herrero-Go´mez, E.; Raducan, M.; Echavarren, A. M. Chem. Eur.
J. 2006, 12, 1677–1693. (b) Me´ndez, M.; Mun˜oz, M. P.; Echavarren, A. M.
J. Am. Chem. Soc. 2000, 122, 11549–11550.
(7) Jime´nez-Nu´n˜ez, E.; Claverie, C. K.; Nieto-Oberhuber, C.; Echavarren,
A. M. Angew. Chem., Int. Ed. 2006, 45, 5452–5455.
(8) (a) Correa, A.; Marion, N.; Fensterbank, L.; Malacria, M.; Nolan, S. P.;
Cavallo, L. Angew. Chem., Int. Ed. 2008, 47, 718–721. (b) Fu¨rstner, A.; Davies,
P. W. Angew. Chem., Int. Ed. 2007, 46, 3410–3449. (c) Marion, N.; Nolan,
S. P. Angew. Chem., Int. Ed. 2007, 46, 2750–2752. (d) Marco-Contelles, J.;
Soriano, E Chem. Eur. J. 2007, 13, 1350–1357. (e) Valentin, R. J. Org. Chem.
1984, 49, 950–952. (f) Mainetti, E.; Mourie`s, V.; Fensterbank, L.; Malacria,
M.; Marco-Contelles, J. Angew. Chem., Int. Ed. 2002, 41, 2132–2135. (g) Harrak,
Y.; Blaszykowski, C.; Bernard, M.; Cariou, K.; Mainetti, E.; Mouries, V.;
Dhimane, A.-L.; Fensterbank, L.; Malacria, M. J. Am. Chem. Soc. 2004, 126,
8656–8657. (h) Mamane, V.; Gress, T.; Krause, H.; Fu¨rstner, A. J. Am. Chem.
Soc. 2004, 126, 8654–8655.
Other platinum catalyst systems did not lead to an increase in
yield (entries 5 and 6). Gold catalysts also catalyzed this
cyclization, but in poor yields (entries 7-11). Thus, the use of
PtCl2 (10 mol %) and CO (1 atm) in DCE (3 mL) at 80 °C was
found to be the most efficient and was subsequently used as
the standard condition.
Under the optimized reaction conditions, various O-tethered
enynes were investigated, as shown in Table 2. In most cases, the
desired cyclized products were generated in good to high yields.
The electronic properties of the substituent on the aryl group11
attached to the alkyne affected the reaction. Electron-rich substit-
uents gave results superior to those obtained from electron-
J. Org. Chem. Vol. 74, No. 1, 2009 475

SCHEME 3. Proposed Mechanism
to afford the complex B. Formal Diels-Alder-type reaction of
compound B generated the adducts E, which underwent further
isomerization and aromatization14 to give the desired product
2. The nature of the Diels-Alder-type reaction from B to E
might be consistent with that reported by Fu¨rstner and co-
workers recently.4 Electrophilic metal carbene C, generated from
the attack of the alkene moiety to the platinum-activated triple
bond, might have cyclized to the six-membered-ring cation D,
which could have released cycloadduct E and regenerated the
catalyst.
In conclusion, we have reported a platinum-catalyzed tandem
reaction of propargylic ester isomerization and subsequent
cyclizations with 1,6-enyne. The allene metal intermediate
generated from 1,3-acyloxy migration of propargylic ester was
proved to be an excellent candidate in the Diels-Alder-type
reaction. Platinum catalyst, regenerated from the migration
process, efficiently participated in the activation of another triple
bond, which might have been a crucial factor for this
transformation.
withdrawing ones (entries 2 and 3 vs 4 and 5). When an aromatic
substituent was exchanged with an alkyl group, the desired aryl
ketone 2f was also obtained in high yield (entry 6). However,
terminal alkyne 1g did not afford any cyclized product, with most
of the starting material recovered after 24 h. This might be due to
the fact that the propargylic ester with the terminal triple bond
normally undergoes 1,2-acyloxy migration without generating an
allene intermediate (entry 7).11 Substrates with a phenyl or methyl
group at the position adjacent to the oxygen atom reacted
smoothly12 to afford the respective products 2h and 2i in good
yields (entries 8 and 9). Furthermore, a substituent at the propargylic
position was also tolerated (entry 10).
Experimental Section
General Procedure for the Platinum-Catalyzed Cycloisomer-
ization of 1,6-Enynes. To a stirred solution of enyne 1 (0.4 mmol)
in DCE (3.0 mL) was added 10.6 mg (10 mol %) of PtCl2 under
CO atmosphere (1 atm). When the mixture was stirred at 80 °C
for 24 h, ethyl acetate (30 mL) was added. The mixture was
evaporated under reduced pressure. The residue was purified by
chromatography on silica gel to afford corresponding products
2.
(1,3-Dihydroisobenzofuran-5-yl)(phenyl)methanone (2a). 2a
was prepared according to the above method in 83% yield as a
1
solid: mp 84-86 °C; H NMR (300 MHz, CDCl3) δ 7.80-7.69
To further explore the scope of application of this method,
the tether effect was further investigated. Various N-tethered
enynes reacted efficiently to afford the corresponding products
2k-m in good yields (eq 1). The results were similar to those
obtained from 1a-c. Moreover, this tandem transformation was
not limited to the heteroatom-tethered substrates. Enyne 1n gave
a superior result, affording the carbocyclic skeleton 2n in 87%
yield (eq 2).
(m, 4 H), 7.59-7.56 (m, 1 H), 7.51-7.45 (m, 2 H), 7.35-7.32
(m, 1 H), 5.16 (s, 4 H); 13C NMR (75 MHz, CDCl3) δ 196.3, 143.7,
139.4, 137.5, 137.0, 132.4, 129.8, 129.7, 128.2, 122.6, 120.7, 73.3,
73.1; IR (KBr, cm-1) 3060, 2926, 2857, 1768, 1658, 1616, 1315,
1281, 1048. Anal. Calcd for C15H12O2: C, 80.34; H, 5.39. Found:
C, 80.31; H, 5.45.
Phenyl(2-tosylisoindolin-5-yl)methanone (2k). 2k was prepared
according to the above method in 85% yield as a solid: mp 138-140
°C; 1H NMR(400 MHz, CDCl3) δ 7.79-7.56 (m, 7 H), 7.48-7.45
(m, 2 H), 7.34-7.26 (m, 3 H), 4.68 (s, 2 H), 4.66 (s, 2 H), 2.41 (s,
3 H); 13C NMR (100 MHz, CDCl3) δ 195.9, 143.8, 140.7, 137.5,
(9) (a) Ji, K.-G.; Shu, X.-Zh.; Chen, J.; Zhao, Sh.-Ch.; Zheng, Zh.-J.; Lu,
L.; Liu, X.-Y.; Liang, Y.-M Org. Lett. 2008, 10, 3919–3922. (b) Shu, X.-Zh.;
Liu, X.-Y.; Ji, K.-G.; Xiao, H.-Q.; Liang, Y.-M. Chem. Eur. J. 2008, 14, 5282–
5289. (c) Ji, K.-G.; Shen, Y.-W.; Shu, X.-Zh.; Xiao, H.-Q.; Bian, Y.-J.; Liang,
Y.-M. AdV. Synth. Catal 2008, 350, 1275–1280. (d) Shu, X.-Zh.; Liu, X.-Y.;
Xiao, H.-Q.; Ji, K.-G.; Guo, L.-N.; Liang, Y.-M. AdV. Synth. Catal 2008, 350,
243–248. (e) Shu, X.-Zh.; Liu, X.-Y.; Xiao, H.-Q.; Ji, K.-G.; Guo, L.-N.; Qi,
Ch.-Z.; Liang, Y.-M. AdV. Synth. Catal 2007, 349, 2493–2498.
(10) (a) Fu¨rstner, A.; Davies, P. W. J. Am. Chem. Soc. 2005, 127, 15024–
15025. (b) Fu¨rstner, A.; Davies, P. W.; Gress, T. J. Am. Chem. Soc. 2005, 127,
8244–8245. (c) Fu¨rstner, A.; Aissa, C. J. Am. Chem. Soc. 2006, 128, 6306–
6307. (d) Sohel, S. M. A.; Lin, S.-H.; Liu, R.-S. Synlett 2008, 745–750. (e) Das,
A.; Liao, H.-H.; Liu, R.-S. J. Org. Chem. 2007, 72, 9214–9218.
(11) Li, G.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2008, 130, 3740–3741.
(12) (a) Barluenga, J.; Fernandez-Rodriguez, M. A.; Garcia-Garcia, P.;
Aguilar, E. J. Am. Chem. Soc. 2008, 130, 2764–2765. (b) Barluenga, J.; Riesgo,
L.; Vicente, R.; Lopez, L. A.; Tomas, M. J. Am. Chem. Soc. 2007, 129, 7772–
7773.
(13) For selected examples on [1,3]-OAc shift, see: (a) Zhang, G.; Catalano,
V. J.; Zhang, L. J. Am. Chem. Soc. 2007, 129, 11358–11359. (b) Marion, N.;
D´ıez-Gonza´lez, S.; Fre´montde, P.; Noble, A. R.; Nolan, S. P. Angew. Chem.,
Int. Ed. 2006, 45, 3647–3650. (c) Zhang, L.; Wang, S. J. Am. Chem. Soc. 2006,
128, 1442–1443. (d) Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804–16805.
(14) For examples of aromatization in the air, see: (a) Kadzimirsz, D.;
Hildebrandt, D.; Merz, K.; Dyker, G. Chem. Commun. 2006, 661–662. (b)
Abbiati, G.; Arcadi, A.; Bianchi, G.; Giuseppe, S. D.; Marinelli, F.; Rossi, E. J.
Org. Chem. 2003, 68, 6959–6966. (c) Also see ref 4.
The proposed mechanism of this transformation was shown
in Scheme 3. Platinum-promoted 1,3-acyloxy migration8,14 of
the propargylic ester led to the formation of the allene metal
intermediate A. This coordinated metal catalyst might have
efficiently participated in the activation of another triple bond
476 J. Org. Chem. Vol. 74, No. 1, 2009

137.3, 136.6, 135.1, 133.6, 132.6, 129.9, 128.3, 127.6, 125.0, 124.2,
122.5, 53.6, 53.4, 21.5; IR (KBr, cm-1) 2923, 2853, 2255, 1739,
1660, 1597, 1448, 1348, 1281, 1167, 1092, 911, 730. Anal. Calcd
for C22H19NO3S: C, 70.00; H, 5.07; N, 3.71. Found: C, 69.93; H,
4.89; N, 3.77.
2920, 2853, 1650, 1612, 1566, 1427, 1286, 1254, 1045, 904, 744.
Anal. Calcd for C22H22O5: C, 72.12; H, 6.05. Found: C, 72.03; H,
6.22.
Acknowledgment. We thank the NSF (NSF-20621091, NSF-
20672049) and the “Hundred Scientist Program” from the
Chinese Academy of Sciences for their financial support.
Diethyl 5-Benzoyl-1H-2,2(3H)-dicarboxylate (2n). 2n was
prepared according to the above method in 67% yield as an oil: 1H
NMR (300 MHz, CDCl3) δ 7.78-7.76 (d, J ) 8.1 Hz, 2 H),
7.66-7.55 (m, 3 H), 7.49-7.44 (m, 2 H), 7.31-7.28 (d, J ) 7.8
Hz, 1 H), 4.26-4.19 (q, J ) 6.9 Hz, 4 H), 3.66 (s, 2 H), 3.65 (s,
2 H), 1.29-1.24 (t, J ) 6.9 Hz, 6 H); 13C NMR (75 MHz, CDCl3)
δ 169.4, 171.2, 145.2, 140.4, 137.8, 136.6, 132.1, 129.8, 129.4,
Supporting Information Available: Detailed experimental
1
procedure and copies of H NMR and 13C NMR spectra of all
compounds as well as X-ray crystallography of 2d. This material
is available free of charge via the Internet at http://pubs.acs.org.
128.1, 125.8, 123.9, 61.8, 60.3, 40.4, 40.1, 13.9; IR (neat, cm-1
)
JO802043Z
J. Org. Chem. Vol. 74, No. 1, 2009 477