Au/Ag-catalyzed intramolecular ring-opening of vinylidene-cyclopropanes (VDCPs): An easy access to functional tetrahydropyrans

Article abstract of DOI:10.1021/ol902832s

Chemical Equation Presentation An intramolecular ring-opening of vinylidenecyclopropanes (VDCPs) tethered with alcohol chains has been established. A serles of transition metal catalysts and their combinations have been screened under mild conditions, and

Full text of DOI:10.1021/ol902832s

ORGANIC
LETTERS
2010
Vol. 12, No. 5
920-923
Au/Ag-Catalyzed Intramolecular
Ring-Opening of Vinylidene-cyclopropanes
(VDCPs): An Easy Access to Functional
Tetrahydropyrans
Wei Li,† Wei Yuan,† Surech Pindi,‡ Min Shi,*,† and Guigen Li*,‡
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032 China,
and Department of Chemistry and Biochemistry, Texas Tech UniVersity, Lubbock,
Texas 79409-1061
mshi@mail.sioc.ac.cn; guigen.li@ttu.edu
Received December 8, 2009
ABSTRACT
An intramolecular ring-opening of vinylidenecyclopropanes (VDCPs) tethered with alcohol chains has been established. A series of transition
metal catalysts and their combinations have been screened under mild conditions, and a cocatalyst system consisting of [(Ph3PAu)3O]BF4 (4
mol %) and AgOTf (4 mol %) was found to catalyze the reaction to completion within 10-30 min in 1,4-dioxane at 60 °C to give allene-
functionalized tetrahydropyrans.
Tetrahydropyrans widely exist in naturally occurring and
biologically active products, which inspired the development
of creative synthetic approaches to their derivatives.1,2
Meanwhile, relevant catalytic reactions using gold complexes
have been studied actively,3 which includes gold catalyzed-
activation of alkynes,4 allenes,5 and alkenes.6 However, the
Au-catalyzed opening reactions of highly strained small rings
have not been well documented so far.7
In the past several years, we and others have been engaging
in chemical transformations of vinylidenecyclopropanes
(VDCPs). These compounds were found to be thermally
stable and adequately reactive for many important reactions
in the presence of various transition metal catalysts.8 For
example, the catalytic intramolecular ring-opening/cycload-
dition of VDCPs for the formation of carbocyclic or
heterocyclic compounds9 and Au-catalyzed addition of
nucleophiles to unsaturated carbon-carbon bonds4-6 have
been successfully developed. During our ongoing study of
VDCPs chemistry, we now design and synthesize a series
of vinylidenecyclopropanes tethered with alcohol chains and
explore their intramolecular ring-opening reaction. In this
communication, we report the preliminary results of this
(2) (a) Elliot, M. C.; Williams, E. J. Chem. Soc., Perkin Trans. 1 2001,
2303–2340. (b) Clarke, P. A.; Santos, S. Eur. J. Org. Chem. 2006, 9, 2045–
2053.
† Chinese Academy of Sciences.
(3) (a) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395–403. (b) Fu¨rstner,
A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410–3449. (c) Zhang,
L.; Sun, J.; Kozmin, S. A. AdV. Synth. Catal. 2006, 348, 2271–2296. (d)
Peng, Y.; Li, C.; Zhang, G. Z.; Zhang, L. M. J. Am. Chem. Soc. 2009, 131,
5061–5063. (e) Hoffmann-Ro¨der, A.; Krause, N. Org. Biomol. Chem. 2005,
3, 387–391. (f) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chem., Int. Ed.
2006, 45, 7896–7936. (g) Marion, N.; Nolan, S. P. Angew. Chem., Int. Ed.
2007, 46, 2750–2752.
‡ Texas Tech University.
(1) (a) Smith, A. B., III.; Safonov, I. G.; Corbett, R. M. J. Am. Chem.
Soc. 2001, 123, 12426–12427. (b) Smith, A. B., III.; Safonov, I. G. Org.
Lett. 2002, 4, 635–638. (c) Trost, B. M.; Gutierrez, A. C.; Livingston, R. C.
Org. Lett. 2009, 11, 2539–2542. (d) Chavre, S. N.; Choo, H.; Lee, J. K.;
Pae, A. N.; Kim, Y.; Cho, Y. S. J. Org. Chem. 2008, 73, 7467–7471. (e)
Hu, X.-H.; Liu, F.; Loh, T.-P. Org. Lett. 2009, 11, 1741–1743
.
10.1021/ol902832s  2010 American Chemical Society
Published on Web 02/08/2010

reaction for the synthesis of tetrahydropyran core structures
as represented in Scheme 1.
followed by the hydroboration-oxidation reaction.11 A series
of compound 2 have been successfully synthesized in
moderate to good yields under mild conditions as shown in
Scheme 2.
The initial experiment on the intramolecular ring-opening
of VDCPs 2 was performed by subjecting them to the
catalytic system consisting of AgOTf (10 mol %) as the
catalyst in 1,4-dioxane at 60 °C. There is no desired product
formed with nearly all starting materials 2a unconsumed after
the reaction was performed in 60 min (Table 1, entry 1).
However, when (Ph3P)AuCl (5 mol %) was added into the
catalytic system, the corresponding tetrahydropyran product
3a was obtained in 41% yield along with some unknown
byproduct (Table 1, entry 2). The use of AgNTf2 resulted in
the same yield of 41%, but AgBF4 and AgSbF6 only gave
the yields of 24% and 19%, respectively, under above
condition (Table 1, entries 3-5). Increasing the amount of
(Ph3P)AuCl and AgOTf did not improve the yields (Table
1, entry 6). Pleasantly, it was found that when
[(Ph3PAu)3O]BF4 (4 mol %)12 was used as the catalyst, 3a
can be obtained in 54% yield within a period of 90 min
(Table 1, entry 7). Furthermore, when AgOTf (4.0 mol %)
was used as cocatalyst together with [(Ph3PAu)3O]BF4 (4
mol %), the reaction was greatly accelerated and can be
finished within 10 min affording 3a in 59% yield (Table 1,
entry 8). Other conditions shown in Table 1 result in either
complex mixture or substantially decreased chemical yields.
Scheme 1
.
Au(I)-Catalyzed Intramolecular Addition/
Ring-Opening of VDCPs 2
Scheme 2. Synthesis of Hydroxyl Group-Attached VDCPs
This project started from the synthesis of the hydroxyl
chain-branched vinylidenecyclopropanes (VDCPs) 2 as the
substrates. Several known methods were utilized for this
synthesis and were confirmed to result in either no product
or in a trace ammount of product.10 The successful procedure
was realized by obtaining diarylvinylidenecyclopropanes 1
We next examined the scope of this reaction under the
optimal condition by employing the starting materials we
synthesized. As shown in Table 2, the present catalytic
intramolecular ring-opening/addition proceeded smoothly to
completion within 10 - 30 min for diphenylvinylidenecy-
Table 1. Condition Optimization Results
entrya
catalyst (x)
additive (y)
solvent
temp (°C)
time (min)
yield (%)b 3a
1
2
3
-
AgOTf (10)
AgOTf (10)
AgBF4 (10)
AgNTf2 (10)
AgSbF6 (10)
AgOTf (15)
-
AgOTf (4)
AgOTf (1)
AgOTf (4)
AgOTf (4)
AgOTf (4)
AgOTf (4)
AgOTf (4)
AgOTf (4)
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
toluene
60
60
60
60
60
60
60
60
60
60
60
60
60
20
80
60
20
40
60
480
60
90
10
1200
15
15
0
41
24
41
19
37
54
59
38
49
32
49
complex
trace
complex
(Ph3P)AuCl (5)
(Ph3P)AuCl (5)
(Ph3P)AuCl (5)
(Ph3P)AuCl (5)
4
5c
6
(Ph3P)AuCl (10)
7
8
9
10
11
12
13
14
15
[(Ph3PAu)3O]BF4 (4)
[(Ph3PAu)3O]BF4 (4)
[(Ph3PAu)3O]BF4 (1)
[(Ph3PAu)3O]BF4 (4)
[(Ph3PAu)3O]BF4 (4)
[(Ph3PAu)3O]BF4 (4)
[(Ph3PAu)3O]BF4 (4)
[(Ph3PAu)3O]BF4 (4)
[(Ph3PAu)3O]BF4 (4)
THF
THF
DCE
1,4-dioxane
600
5
120
1,4-dioxane
5
a Reaction conditions: VDCP 2a (0.1 mmol) and [(Ph3PAu)3O]BF4 (4 mol %) were dissolved in 1,4-dioxane (3.0 mL), and then AgOTf (4 mol %) was
added. The resulted mixtures were stirred for different time at 60 °C under argon atmosphere. b Isolated yield. c Thirty-one percent of 2a was recovered.
Org. Lett., Vol. 12, No. 5, 2010
921

Scheme 3. Mechanisms of Au(I)-Catalyzed Intramolecular Addition/Ring-Opening of VDCPs
aromatic rings of Ar1 and Ar2 also afforded the corresponding
tetrahydropyran derivatives 3h and 3j in moderate to good
yields, but in the case of 2i bearing a strong electron-donating
group (MeO) on Ar1 and Ar2 rings, products of complex
mixtures were formed (Table 2, entries 7-9). For unsym-
metrical diarylvinylidenecyclopropane 2k, the corresponding
tetrahydropyran derivative 3k was obtained as a pair of
diastereoisomers with the ratio of 1:1 (Table 2, entry 10).
Obviously, the present gold-catalyzed reaction should be
further imporved in future so as to minimize the formation
of unidentified byproducts (see the Supporting Information).
A mechanism hypothesis was proposed as shown in
Scheme 3. At the beginning, Au(I) complex is oxidized to
L-Au+ species by cocatalyst AgOTf prior to attacking
starting material 2. The addition/ring-opening can occur
through two possible pathways: gold cation works as a Lewis
acid to activate the allene functionality, affording intermedi-
ate A (path 1);5 Au(I) catalyzes the ring-opening via
formation of cationic intermediate B (path 2). The intramo-
lecular nucleophilic addition by the hydroxyl group onto
electrophilic carbon centers in intermediate A or B gives the
same intermediate C, which produces the corresponding
tetrahydropyran derivative 3 followed by protonation along
with the regeneration of Au(I) catalytic species for the
catalytic cycles.
Table 2. [(Ph3PAu)3O]BF4/AgOTf Co-Catalyzed Intramolecular
Addition/Ring-Opening
time
entrya
Ar1/Ar2/Ar3
C6H5/C6H5/C6H4, 2b
C6H5/C6H5/p-CH3C6H4, 2b
C6H5/C6H5/p-CH3OC6H4, 2c
C6H5/C6H5/p-FC6H4, 2d
C6H5/C6H5/p-CIC6H4, 2e
C6H5/C6H5/p-BrC6H4, 2f
C6H5/C6H5/m-BrC6H4, 2g
p-CH3C6H4/p-CH3C6H4/C6H5, 2h
(min) yield (%)b
3
1
2
3
4
5
6
7
8
10
30
30
10
15
15
30
15
3a, 59
3b, 62
3c, 69
3d, 56
3e, 45
3f, 55
3g, 60
3h, 55
complex
products
3j, 60
9
10
11
p-CH3OC6H4/p-CH3OC6H4/C6H5, 2i
p-CIC6H4/p-CIC6H4/C6H5, 2j
p-CIC6H4/C6H5/C6H5, 2k
10
20
20
3k, 45c
a Reaction conditions: VDCP 2 (0.1 mmol) and [(Ph3PAu)3O]BF4 (4
mol %), AgOTf (4 mol %) were dissolved in 1,4-dioxane (3.0 mL), and
then the mixtures were stirred for different time at 60 °C. b Isolated yield.
c 3k was obtained as a pair of diastereoisomer (1:1). d It could not be cleanly
isolated from some other compounds by column chromatography.
In conclusion, a new intramolecular tandem addition/ring-
opening of diarylvinylidenecyclopropanes (VDCPs) has been
clopropanes 2b-2g that bear both electron-withdrawing and
electron-donating groups on their rings of Ar3. The corre-
sponding tetrahydropyran derivatives 3b-3g were generated
in moderate to good yields (Table 2, entries 1-6). Similarly,
introducing moderate electron-donating or electron-with-
drawing groups (Me and Cl for 2h and 2i, respectively) onto
(6) (a) Rosenfeld, D. C.; Shekhar, S.; Takemiya, A.; Utsunomiya, M.;
Hartwig, J. F. Org. Lett. 2006, 8, 4179–4182. (b) Skouta, R.; Li, C.-J. Angew.
Chem., Int. Ed. 2007, 46, 1117–1119. (c) Zhou, C.-Y.; Che, C.-M. J. Am.
Chem. Soc. 2007, 129, 5828–5829.
(7) (a) Bauer, J. T.; Hadfield, M. S.; Lee, A.-L. Chem. Commun. 2008,
6405–6407. (b) Zhang, J.; Schmalz, H.-G. Angew. Chem., Int. Ed. 2006,
45, 6704–6707. (c) Shi, M.; Liu, L.-P.; Tang, J. Org. Lett. 2006, 8, 4043–
4046.
(8) (a) Maeda, H.; Mizuno, K. J. Synth. Org. Chem. Japan 2004, 62,
1014–1025. (b) Xu, G.-C.; Liu, L.-P.; Lu, J.-M.; Shi, M. J. Am. Chem.
Soc. 2005, 127, 14552–14553. (c) Li, W.; Shi, M. J. Org. Chem. 2008, 73,
4151–4154.
(4) (a) Zhang, G.; Peng, Y.; Cui, L.; Zhang, L. Angew. Chem., Int. Ed.
2009, 48, 3112–3115. (b) Liu, B.; De Brabander, J. K. Org. Lett. 2006, 8,
4907–4910. (c) Liu, Y.; Song, F.; Song, Z.; Liu, M.; Yan, B. Org. Lett.
2005, 7, 5409–5412. (d) Genin, E.; Toullec, P. Y.; Antoniotti, S.; Brancour,
C.; Genet, J.-P.; Michelet, V. J. Am. Chem. Soc. 2006, 128, 3112–3113.
(e) Robles-Machin, R.; Adrio, J.; Carretero, J. C. J. Org. Chem. 2006, 71,
5023–5026. (f) Kang, J.-E.; Kim, H.-B.; Lee, J.-W.; Shin, S. Org. Lett.
2006, 8, 3537–3540. (g) Li, W.; Yuan, W.; Shi, M.; Hernandez, E.; Li, G.
Org. Lett. 2010, 12, 64–67.
(9) Mizuno, K.; Sugita, H.; Kamada, T.; Otsuji, Y. Chem. Lett. 1994,
449–452.
(10) Sugita, H.; Mizuno, K.; Mori, T.; Isagawa, K.; Otsuji, Y. Angew.
Chem., Int. Ed. 1991, 30, 984–986.
(11) Morrill, T. C.; D’Souza, C. A.; Yang, L.; Sampognaro, A. J. J.
Org. Chem. 2002, 67, 2481–2484, and the references therein. As for the
detailed experimental procedures, please see the Supporting Information.
(12) (a) Nesmeyanov, A. N.; Perevalova, E. G.; Struchkov, Y. T.;
Antipin, M. Y.; Grandberg, K. I.; Dyadchenko, V. P. J. Organomet. Chem.
1980, 201, 343–349. (b) Yang, Y.; Ramamoorthy, V.; Sharp, P. R. Inorg.
Chem. 1993, 32, 1946–1950.
(5) (a) Hyland, C. T.; Hegedus, L. S. J. Org. Chem. 2006, 71, 8658–
8660. (b) Morita, N.; Krause, N. Angew. Chem., Int. Ed. 2006, 45, 1897–
1899. (c) Sromek, A. W.; Rubina, M.; Gevorgyan, V. J. Am. Chem. Soc.
2005, 127, 10500–10501. (d) Nishina, N.; Yamamoto, Y. Angew. Chem.,
Int. Ed. 2006, 45, 3314–3317.
922
Org. Lett., Vol. 12, No. 5, 2010

established for the synthesis of a variety of allene moieties
containing tetrahydropyran derivatives. An efficient cocata-
lyst system consisting of [(Ph3PAu)3O]BF4 (4 mol %) and
AgOTf (4 mol %) was found to catalyze this reaction to
completion within 10-30 min under mild conditions. The
reaction showed a good scope of substrates in modest to good
chemical yields and complete regioselectivity. A straight-
forward mechanism has been proposed for this new catalytic
reaction.
08dj1400100-2), Robert A. Welch Foundation (D-1361),
National Basic Research Program of China (973)-
2009CB825300, and the National Natural Science Founda-
tion of China (20929001, 20872162, 20672127, 20821002
and 20732008) for their generous support.
Supporting Information Available: Detailed description
1
of experimental procedures, 13C and H NMR spectra and
spectroscopic analytic data for all pure starting materials and
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. We thank the Shanghai Municipal
Committee of Science and Technology (06XD14005,
OL902832S
Org. Lett., Vol. 12, No. 5, 2010
923