Silver- and gold-catalyzed intramolecular rearrangement of propargylic alcohols tethered with methylenecyclopropanes: Stereoselective synthesis of allenylcyclobutanols and 1-vinyl-3-oxabicyclo[3.2.1]octan-8-one derivatives

Article abstract of DOI:10.1021/jo902261r

(Chemical Equation Presented) Ag(I)-catalyzed intramolecular reaction of monoarylmethylenecyclopropanes (MCPs) tethered with 1,1,3-triarylprop-2-yn-1-ols provides diastereoselective access to polysubstituted allenylcyclobutanols and the obtained allenylcy

Full text of DOI:10.1021/jo902261r

pubs.acs.org/joc
Silver- and Gold-Catalyzed Intramolecular Rearrangement of
Propargylic Alcohols Tethered with Methylenecyclopropanes:
Stereoselective Synthesis of Allenylcyclobutanols and
1-Vinyl-3-oxabicyclo[3.2.1]octan-8-one Derivatives
Liang-Feng Yao,† Yin Wei,‡ and Min Shi*,†,‡
†School of Chemistry & Molecular Engineering, East China University of Science and Technology, 130 Mei
Long Lu, Shanghai 200237, China, and ‡State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai, China, 200032
mshi@mail.sioc.ac.cn
Received October 21, 2009
Ag(I)-catalyzed intramolecular reaction of monoarylmethylenecyclopropanes (MCPs) tethered with
1,1,3-triarylprop-2-yn-1-ols provides diastereoselective access to polysubstituted allenylcyclobuta-
nols and the obtained allenylcyclobutanols catalyzed by Au(I) furnish a wide range of bridged
bicyclic compounds with a vinyl-substituted quaternary stereogenic center stereoselectively.
Introduction
blocks for the synthesis of 2,5-dihydrofurans,3 vinylic
epoxides,4 unsaturated ketones,5 and numerous other valu-
able compounds.6 However, only a few examples of ring
expansion of allenylcyclopropanols or allenylcyclobutanols
catalyzed by gold or palladium via a Wagner-Meerwein
shift have been reported.7 Hence, a much more appealing
strategy for examining the reaction of allenylcyclopropanols
or allenylcyclobutanols is, therefore, highly desirable.
The use of gold compounds as homogeneous catalysts for
the conversion of many organic substrates is one of the
fastest growing areas in organic chemistry today.1 Among
these transformations, the cyclization of 2,3-allenols is play-
ing a major role because 2,3-allenols2 are versatile building
*To whom correspondence should be addressed. Fax: 86-21-64166128.
(1) (a) Dyker, G. Angew. Chem., Int. Ed. 2000, 39, 4237. (b) Hashmi,
A. S. K. Gold Bull. 2003, 36, 3. (c) Hashmi, A. S. K. Gold Bull. 2004, 37, 51. (d)
Results and Discussion
€
Krause, N.; Hoffmann-Roder, A. Org. Biomol. Chem. 2005, 3, 387. (e)
We have previously reported that the intermolecular
reaction of monoarylmethylenecyclopropanes (MCPs) with
Hashmi, A. S. K. Angew. Chem., Int. Ed. 2005, 44, 6990. (f) Hashmi,
A. S. K.; Hutchings, G. Angew. Chem., Int. Ed. 2006, 45, 7896. (g) Hashmi,
A. S. K. Chem. Rev. 2007, 107, 3180. (h) Furstner, A.; Davies, P. W. Angew.
€
Chem., Int. Ed. 2007, 46, 3410. (i) Shen, C. H. Tetrahedron 2008, 64, 3885. (j)
Skouta, R.; Li, C.-J. Tetrahedron 2008, 64, 4917. (k) Muzart, J. Tetrahedron
2008, 64, 5815. (l) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239. (m)
Arcadi, A. Chem. Rev. 2008, 108, 3266.
(2) For general reviews, see: (a) Ma, S. Acc. Chem. Res. 2003, 36, 701. (b)
Ma, S. Chem. Rev. 2005, 105, 2829. (c) Deng, Y. Q.; Gu, Z. H.; Ma, S. Chin. J.
Org. Chem. 2006, 26, 1468.
(5) Shimizu, I.; Sugiura, T.; Tsuji, J. J. Org. Chem. 1985, 50, 537.
(6) (a) Friesen, R. W.; Blouin, M. J. Org. Chem. 1996, 61, 7202. (b)
Uemura, K.; Shiraishi, D.; Noziri, M.; Inoue, Y. Bull. Chem. Soc. Jpn. 1999,
72, 1063. (c) Mao, S. L.; Probst, D.; Werner, S.; Chen, J. Z.; Xie, X. Q.;
Brummond, K. M. J. Comb. Chem. 2008, 10, 235. (d) Shi, M.; Lu, J. M.
Chem.;Eur. J. 2009, 15, 6065.
(3) (a) Gelin, R.; Gelin, S.; Albrand, M. Bull. Soc. Chim. Fr. 1972, 1946.
(b) Olsson, L. I.; Claesson, A. Synthesis 1979, 743.
(4) (a) Kang, S.-K.; Yamaguchi, T.; Pyun, S.-J.; Lee, Y.-T.; Bail, T.-G.
Tetrahedron Lett. 1998, 39, 2127. (b) Ma, S.; Zhao, S. J. Am. Chem. Soc.
1999, 121, 7943.
(7) (a) Trost, B. M.; Xie, J. J. Am. Chem. Soc. 2006, 128, 6044. (b) Trost,
B. M.; Xie, J. J. Am. Chem. Soc. 2008, 130, 6231. (c) Kleinbeck, F.; Toste,
F. D. J. Am. Chem. Soc. 2009, 131, 9178. (d) Yeom, H. S.; Yoon, S. J.; Shin, S.
Tetrahedron Lett. 2007, 48, 4817. (e) Trost, B. M.; Yasukata, T. J. Am. Chem.
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9466 J. Org. Chem. 2009, 74, 9466–9469
Published on Web 11/16/2009
DOI: 10.1021/jo902261r
r
2009 American Chemical Society

Yao et al.
JOCArticle
1,1,3-triarylprop-2-yn-1-ols in the presence of BF3 OEt2
TABLE 1. AgOTf-Promoted Intramolecular Rearrangement of 1 to 2
3
afforded allenylcyclobutanols in good yields. We have
proposed this reaction to proceed via a BF3-induced
Meyer-Schuster rearrangement generating an allene-catio-
nic intermediate that then reacts with MCPs.8 We antici-
pated that the allene-cationic intermediate, readily generated
from propargylic alcohol in the presence of Lewis acid, might
undergo similar Lewis acid-catalyzed intramolecular re-
arrangement, leading to polysubstituted allenylcyclobutanols.
On the basis of this hypothesis, treatment of 1a with 5 mol %
of Sc(OTf)3 produced the desired polysubstituted allenyl-
cyclobutanol 2a in 26% yield as a single stereoisomer. Next,
we screened a wide array of Lewis acids and solvents to
determine the optimal reaction conditions. The results of
these experiments are summarized in Table SI-1 (see the
Supporting Information). The examination of Lewis acids
revealed that AgOTf was the best catalyst for this transfor-
mation among all tested Lewis acids including Sc(OTf)3,
Zn(NTf2)2, Nd(NTf2)3, Bi(OTf)2Cl, La(OTf)3, Cu(OTf)2,
Yb(OTf)3, Sn(OTf)2, and TMSOTf as well as Brønsted acid
trifluoromethanesulfonic acid CF3SO3H (TfOH) and transi-
tion metal PtCl2. Meanwhile, we also found that dichlor-
omethane (DCM) was the most suitable solvent in this
reaction. Moreover, the yield of the rearrangement was
improved by employing 50 mol % of H2O as the additive
(see Table SI-2 in the Supporting Information). Therefore,
the optimized reaction conditions were determined to be the
following: 1.0 equiv of 1a as the substrate in the presence of
0.5 equiv of H2O with AgOTf (5 mol %) in DCM at room
temperature.
With these results in hand, we probed the scope of this
reaction using the optimized conditions. As shown in Table 1, a
wide range of polysubstituted allenylcyclobutanols were acces-
sible in synthetic modest yields ranging from 20% to 56%.
Substrates possessing electron-rich aromatic substituents were
generally tolerated (Table 1, entries 4-7); however, substrates
1b and 1c with the electron-poor substituents afforded slightly
lower yields (Table 1, entries 2 and 3). The geometric isomer
Z-1a furnished the corresponding 2a in 38% yield, which
presumably results from the sterically hindered factor
(Table 1, entry 8). In the case of 1i, 1j, and1k, the corresponding
2i, 2j, and 2k were obtained in moderate yields and the
substituents on the aromatic R2 of 1 did not significantly affect
the reaction outcomes (Table 1, entries 10-12). Using 1h as the
substrate led to 2h in 20% yield along with a novel compound
3h in 18% yield (Table 1, entry 9). Alkyl-substituent compound
1l was also a suitable substrate for this reaction, giving 2l in
32% yield (Table 1, entry 13). The structure of 2e has been
further confirmed by X-ray diffraction and its ORTEP drawing
is indicated in Figure 1 and the CIF data have been presented in
the Supporting Information.9 It should be emphasized here
that when R1 = alkenyl or alkynyl group, the corresponding
entrya
R1/R2
C6H5/C6H5, 1a
4-ClC6H4/C6H5, 1b
4-FC6H4/C6H5, 1c
4-MeC6H4/C6H5, 1d
4-MeOC6H4/C6H5, 1e
3,4,5-(MeO)3C6H2/C6H5, 1f
3-BnOC6H4/C6H5, 1g
C6H5/C6H5, Z-1a
C6H5/4-MeC6H4, 1h
C6H5/4-ClC6H4, 1i
C6H5/4-FC6H4, 1j
yield of 2 [%]b
1
2
3
4
5
6
7
8
9
10
11
12
13
2a, 50
2b, 44
2c, 44
2d, 53
2e, 56 X-ray
2f, 53
2g, 40
2a, 38
2h, 20c
2i, 34
2j, 44
2k, 40
2l, 32
C6H5/4-MeOC6H4, 1k
C7H15/C6H5, E and Z-1l
aReaction conditions: 1 (0.2 mmol), H2O (0.1 mmol), and AgOTf
(5 mol %) in DCM (2 mL) at rt. bIsolated yield. cAnother product 3h was
formed in 18% yield.
substrate 1 cannot be prepared under the previously reported
conditions.
To enrich the diversity of the reaction for allenylcyclobu-
tanols, we initially examined the ring expansion reaction of
2a in the presence of Au(I) catalyst. When allenylcyclobuta-
nol 2a was treated with Ph3PAuCl (5 mol %) and AgOTf (5
mol %) in DCM at 40 °C, a novel bridged compound 3a was
exclusively delivered in 65% yield as a single stereoisomer
(Scheme 1, eq 1). Notably, if 1a was employed as the
substrate under identical conditions (5 mol % Ph3PAuCl
and 5 mol % AgOTf) in DCM through a one-pot reaction, 3a
was also obtained in 43% yield (Scheme 1, eq 2). After many
attempts, we identified the optimized reaction conditions
that were to carry out the reaction using Ph3PAuCl (5 mol
%) and AgOTf (5 mol %) in DCM at 40 °C (conditions A)
(see Table SI-3 in the Supporting Information).
(8) Yao, L.-F.; Shi, M. Org. Lett. 2007, 9, 5187.
(9) The crystal data of 2e have been deposited in CCDC with number
732287. Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Fax þ44-1223/336-033;
E-mail deposit@ccdc.cam.ac.uk). Empirical formula C28H26O3; formula
weight 410.49; crystal size 0.217 ꢀ 0.216 ꢀ 0.041; crystal color colorless,
crystal habit prismatic; crystal system monoclinic; lattice type primitive;
˚
˚
˚
lattice parameters a = 13.5410(18) A, b = 16.611(2) A, c = 10.4723(14) A,
˚
3
R = 90°, β = 108.179(3)°, γ = 90°, V = 2237.9(5) A ; space group P2(1)/c;
Z = 4; Dcalc = 1.218 g/cm3; F000 = 872; R1 = 0.0474, wR2 = 0.0913;
diffractometer Rigaku AFC7R.
J. Org. Chem. Vol. 74, No. 24, 2009 9467

Yao et al.
JOCArticle
TABLE 2. Gold-Catalyzed Reaction of 2 To Construct Bridged Bicyclic
Compound 3
entry
R1/R2
C6H5/C6H5, 2a
4-ClC6H4/C6H5, 2b
4-FC6H4/C6H5, 2c
4-MeC6H4/C6H5, 2d
4-MeOC6H4/C6H5, 2e
3,4,5-(MeO)3C6H2/C6H5, 2f
3-BnOC6H4/C6H5, 2g
C6H5/4-MeC6H4, 2h
C6H5/4-ClC6H4, 2i
C6H5/4-FC6H4, 2j
conditionsa
yield of 3 [%]b
1
2
3
4
5
6
7
8
9
A
B
B
3a, 65, X-ray
3b, 64
3c, 75
3d, 74
3e, 80
3f, 70
3g, 60
3h, 63
3i, 77
A
A
A
A
A
A
A
A
A
10
11
12
3j, 70
3k, 85
3l, 52
C6H5/4-MeOC6H4, 2k
C7H15/C6H5, 2l
aConditions A: The reactions were carried out with 2 (0.2 mmol),
Au(Ph3P)Cl (5 mol %), and AgOTf (5 mol %) in DCM (2 mL) at 40 °C.
Conditions B: The reactions were carried out with 2 (0.2 mmol),
Au(Ph3P)Cl (5 mol %), and AgOTf (5 mol %) in DCE (2 mL) at
60 °C. bIsolated yield.
FIGURE 1. ORTEP drawing of 2e.
SCHEME 1. The Transformation of 2a
The scope of this reaction was then probed by using the
optimal protocol shown in eq 1 (Scheme 1). As can be seen in
Table 2, the reaction of substrates 2 proceeded smoothly under
the optimal reaction conditions. The electronic nature of the
substituents on the aromatic rings of 2 has a small influence on
the reaction outcomes. The reaction of 2b-g with either
electron-donating or electron-withdrawing substituents on the
aromatic rings R1 gave rise to 3b-g in moderate to excellent
yields (as for electron-withdrawing substituents on the aromatic
rings R1, the reaction should be carried out at 60 °C: conditions
B) (Table 2, entries 2-7). Similarly, compounds 2h-k posses-
sing various substituents on the R2 aromatic rings afforded the
corresponding products 3h-k in 63-85% yields (Table 2,
entries 8-11). To our delight, when R2 is an aliphatic group,
the formation of 3l was observed in 52% yield (Table 2, entry
12). The structure of 3a has been further confirmed by X-ray
diffraction (Figure 2) and its CIF data have been presented in
the Supporting Information.10 It should be noted that when R2
is an alkyl group such as Me (substrate 1m), the reaction is
sluggish under the standard conditions, affording the hydroxyl
group migrated product 4a in 12% yield along with the recovery
of 1m in 85% yield (Scheme 2).
FIGURE 2. ORTEP drawing of 3a.
SCHEME 2. Gold and Silver Co-catalyzed Reaction of 1m
(10) The crystal data of 3a have been deposited in CCDC with number
704726. Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (Fax þ44-1223/336-033;
E-mail deposit@ccdc.cam.ac.uk). Empirical formula C27H24O2; formula
weight 380.46; crystal size 0.412 ꢀ 0.201 ꢀ 0.075; crystal color colorless,
crystal habit prismatic; crystal system orthorhombic; lattice type primitive;
˚
˚
˚
lattice parameters a = 11.3164(12) A, b = 17.6548(19) A, c = 20.537(2) A,
˚
3
R = 90°, β = 90°, γ = 90°, V = 4103.0(8) A ; space group Pcab; Z = 8;
Dcalc = 1.232 g/cm3; F000 = 1616; R1 = 0.0777, wR2 = 0.1888; diffracto-
meter Rigaku AFC7R.
A proposed mechanism for the formation of allenylcyclo-
butanols and sequential gold(I)-catalyzed ring expansion of
9468 J. Org. Chem. Vol. 74, No. 24, 2009

Yao et al.
JOCArticle
SCHEME 3. Proposed Reaction Mechanism
Experimental Section
General Procedure for the Reaction of 1a in the Presence of
AgOTf and H2O. (E)-4-((2-Benzylidenecyclopropyl)methoxy)-1,1-
diphenylbut-2-yn-1-ol (1a) (76 mg, 0.2 mmol) and silver triflate (3
mg, 5 mol %) were dissolved in DCM (2.0 mL), then H2O (1.8 mg,
0.1 mmol) was added to this mixture by a 25 μL microsyringe. The
mixture was stirred for 6 h at room temperature (25 °C). The solvent
was removed in vacuo and the residue was purified by flash column
chromatography on silica gel with petroleum ether-EtOAc (4:1) as
an eluent to give 2a as a light yellow oil (38 mg, 50%).
Compound 2a: brown oil; 1H NMR (CDCl3, 300 MHz, TMS)
δ 1.99 (dd, 1H, J = 8.7, 18.6 Hz, CH2), 2.18 (dd, 1H, J = 10.5,
21.3 Hz, CH2), 2.38-2.44 (m, 1H, CH), 2.47 (s, 1H, OH), 3.61
(dd, 1H, J = 9.0, 11.1 Hz, CH), 3.77 (dd, 1H, J = 3.0, 12.0 Hz,
CH2), 3.86 (d, 1H, J = 12.0 Hz, CH2), 4.11 (d, 1H, J = 12.6 Hz,
CH2), 4.21 (d, 1H, J = 12.6 Hz, CH2), 6.73-6.78 (m, 3H, Ar),
6.86-6.88 (m, 2H, Ar), 7.06-7.31 (m, 10H, Ar); 13C NMR
(CDCl3, 75 MHz, TMS) δ 17.8, 40.4, 51.4, 66.1, 67.3, 75.1,
102.1, 112.7, 126.4, 127.07, 127.12, 127.4, 127.5, 127.6, 128.3,
128.7, 129.0, 135.3, 136.6, 138.5, 203.0; IR (CH2Cl2) ν 3420,
3081, 3058, 3027, 2975, 2945, 2844, 1941, 1728, 1598, 1493, 1453,
1373, 1334, 1265, 1195, 1160, 1078, 1031, 984, 904, 883, 867, 767,
736, 700, 633, 606, 563 cm-1; MS (%) m/z 380 (M•þ, 13), 105
(100), 77 (74), 165 (59), 91 (56), 167 (49), 215 (40), 202 (37), 115
(33); HRMS (EI) calcd for C27H24O2 380.1776, found 380.1773.
Representative Procedure for the Gold(I)-Catalyzed Reaction
of 2a. 5-(2,2-Diphenylvinylidene)-7-phenyl-3-oxa-bicyclo[4.2.0]-
octan-6-ol (2a) (76 mg, 0.2 mmol) was added to a stirring suspen-
sion of gold triphenylphosphine chloride (5 mg, 5 mol %) and
silver triflate (3 mg, 5 mol %) in dichloromethane (2 mL) then the
mixture was stirred for 8 h at 40 °C. After removal of the solvent
under reduced pressure, silica gel flash chromatography eluting
with 10% ethyl acetate in petroleum ether afforded 3a as a colorless
crystal solid (50 mg, 65%).
allenylcyclobutanols is outlined in Scheme 3. Initially, the
reaction of 1a with AgOTf generates the intermediate A,
which can undergo intramolecular electrophilic attack to
furnish intermediate B. Intermediate B via 1,2-migration
results in ring expansion intermediate C. The nucleophilic
attack of H2O to intermediate C affords the product
2a. Subsequently, coordination of the cationic gold(I)
catalyst to the internal double bond of the allene moiety
in 2a triggers a ring expansion by a Wagner-Meerwein
shift,7b,11 producing vinylgold intermediate D. A sub-
sequent protodemetalation liberates the catalyst and
releases the product 3a.7c
In conclusion, a AgOTf-catalyzed intramolecular reaction
of monoarylmethylenecyclopropanes (MCPs) tethered with
1,1,3-triarylprop-2-yn-1-ols has been developed, providing
diastereoselective access to polysubstituted allenylcyclo-
butanols. The obtained allenylcyclobutanols catalyzed by
gold(I) furnish a wide range of 1-vinyl-3-oxabicyclo[3.2.1]-
octan-8-one derivatives with a vinyl-substituted quaternary
stereogenic center. Moreover, this method constitutes the
first report of synthesizing a polysubstituted bridged bicyclic
compound. Further efforts are in progress regarding the
scope and mechanistic details.
Compound 3a: white solid, mp 120-122 °C; 1H NMR (CDCl3,
300 MHz, TMS) δ 2.37 (dd, 2H, J = 4.2, 9.6 Hz, CH2), 2.57-2.61
(m, 1H, CH), 3.25-3.40 (m, 3H, CH and CH2), 3.87 (d, 1H, J =
10.2 Hz, CH2), 4.09-4.13 (m, 1H, CH2), 5.82(s, 1H, dCH), 6.60(d,
2H, J=6.9Hz,Ar),7.04-7.14 (m, 2H, Ar), 7.15-7.26 (m, 6H, Ar),
7.35-7.40 (m, 3H, Ar), 7.50-7.53 (m, 2H, Ar); 13C NMR (CDCl3,
75 MHz, TMS) δ 28.6, 46.2, 48.6, 61.3, 75.2, 77.1, 124.0, 127.1,
127.21, 127.23, 127.3, 127.7, 128.0, 128.5, 129.4, 129.8, 139.0, 139.6,
143.2, 145.8, 216.0; IR (CH2Cl2) ν 3056, 3026, 2959, 2852, 1746,
1598, 1493, 1456, 1445, 1217, 1162, 1068, 967, 809, 761, 737, 700,
616, 506 cm-1; MS (%) m/z 380 (M•þ, 100), 205 (90), 91 (57), 203
(53), 232 (52), 204 (47), 246 (45), 202 (44); HRMS (EI) calcd for
C27H24O2 380.1776, found 380.1783.
Acknowledgment. We thank the Shanghai Municipal Com-
mittee of Science and Technology (08dj1400100-2), National
Basic Research Program of China (973)-2009CB825300, and
the National Natural Science Foundation of China for
financial support (20872162, 20672127, 20872162, 20821002,
and 20732008) and Mr. Jie Sun for performing X-ray diffraction
experiments.
(11) (a) Colombo, M. I.; Bohn, M. L.; Ruveda, E. A. J. Chem. Educ. 2002,
79, 484. (b) Roman, L. U.; Cerda-Garcia-Rojas, C. M.; Guzman, R.;
Armenta, C.; Hernandez, J. D.; Joseph-Nathan, P. J. Nat. Products 2002,
65, 1540. (c) Garcia Martinez, A.; Teso Vilar, E.; Garcia Fraile, A.; Martinez-
Ruiz, P. Tetrahedron 2003, 59, 1565. (d) Guizzardi, B.; Mella, M.; Fagnoni,
M.; Albini, A. J. Org. Chem. 2003, 68, 1067.
Supporting Information Available: 13Cand1H NMR spectro-
scopic and analytic data for 1a-1l, 2a-2l, and 3a-3l as well as
X-ray crystal data of 2e and 3a. This material is available free of
charge via the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 74, No. 24, 2009 9469