Rhodium-catalyzed vinylcyclopropanation/cyelopentenation of strained alkenes via a sequential carborhodation process

Article abstract of DOI:10.1021/jo900039g

A rhodium-catalyzed reaction of dienylboronate esters with alkenes is described. Strained bicyclic alkenes show the highest reactivity toward the rhodium-catalyzed addition of the dienylboronate esters. Depending on the substitution pattern of dienylboron

Full text of DOI:10.1021/jo900039g

Rhodium-Catalyzed Vinylcyclopropanation/Cyclopentenation of
Strained Alkenes via a Sequential Carborhodation Process
Nai-Wen Tseng and Mark Lautens*
DaVenport Research Laboratories, Department of Chemistry, UniVersity of Toronto, Toronto,
Ontario, Canada M5S 3H6
mlautens@chem.utoronto.ca
ReceiVed January 8, 2009
A rhodium-catalyzed reaction of dienylboronate esters with alkenes is described. Strained bicyclic
alkenes show the highest reactivity toward the rhodium-catalyzed addition of the dienylboronate
esters. Depending on the substitution pattern of dienylboronate esters, an intramolecular 1,6- or
1,4-addition mechanism may be operative, affording carbocycles containing a vinylcyclopropane or
cyclopentene moiety.
SCHEME 1. Rhodium-Catalyzed Cascade Addition/
Cyclization Process
Introduction
The development of the rhodium-catalyzed addition of
organoboron reagents to unsaturated molecules has attracted a
significant amount of attention in the past decade.1 It has been
demonstrated to be a powerful method to construct structurally
complex molecules. In addition, this method has been extended
toward the formation of carbocycles via a sequential carbor-
hodation process, which provides a rapid and efficient synthetic
route from simple starting materials.2 We have previously
employed this strategy with ortho-functionalized arylboronate
esters for the synthesis of indanes3 and indenes.4 This process
is triggered by the addition of an arylrhodium intermediate to
alkene or alkyne coupling partners. The annulated products were
obtained after intramolecular carborhodation of the organor-
hodium intermediate to the tethered Michael acceptor (Scheme
1). This approach has also been extended to a wide variety of
the functional groups to form different carbocycles as demon-
strated by other research groups.3
Our interest in using the dienylboronate ester 1 for the cascade
addition/cyclization reaction arose from our previous studies.3,4
The initial goal was to replace the aromatic system with a simple
olefin group in the boronate ester starting material to give the
corresponding carbocycles containing substituted cyclopentene
moieties. However, when we subjected the dienylboronate ester
1 to previously reported conditions, an unexpected vinylcyclo-
propane product was obtained,5 presumably via a rare 1,6-
additition of an organorhodium species.7 Further studies revealed
that this reaction is a substrate-controlled process, as substituted
dienylboronate esters afforded cyclopenetene products under the
same reaction conditions. Herein, we disclose our full results
on the scope of this rhodium-catalyzed addition of dienylbor-
onate esters to bicyclic alkenes, as well as our latest insights
into the reaction mechanism.
(1) (a) Hayashi, T. Synlett 2001, 879. (b) Fagnou, K.; Lautens, M. Chem.
ReV. 2003, 103, 169. (c) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829.
(d) Hayashi, T. Bull. Chem. Soc. Jpn. 2004, 77, 13. (e) Modern Rhodium-
Catalyzed Organic Reactions; Evans, P. A., Ed.; Wiley-VCH: Weinheim,
Germany, 2005.
(2) For a recent review, see: Miura, T.; Murakami, M. Chem. Commun. 2007,
217.
(3) (a) Lautens, M.; Mancuso, J. Org. Lett. 2002, 4, 2105. (b) Lautens, M.;
Mancuso, J. J. Org. Chem. 2004, 69, 3478.
(4) Lautens, M.; Marquardt, T. J. Org. Chem. 2004, 69, 4607.
(5) Tseng, N. W.; Mancuso, J.; Lautens, M. J. Am. Chem. Soc. 2006, 128,
5338.
10.1021/jo900039g CCC: $40.75
Published on Web 02/25/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 2521–2526 2521

Tseng and Lautens
SCHEME 2. Synthesis of Dienylboronate Ester 1
TABLE 1. Reaction with Norbornene Derivativesa
SCHEME 3. Proposed Reaction Mechanism
potassium fluoride as base,11 with heating at 80 °C in dioxane/
H2O12 for 3 h. With norbornene as a coupling partner, product
3 was obtained in 84% yield (Table 1, entry 1). The structures
of the products 3 and 15 were determined unambiguously by
X-ray crystallography, which also confirmed the Z-olefin
geometry.5
We believe this unexpected rhodium-catalyzed vinylcyclo-
propanation reaction follows the mechanism proposed in Scheme
3. The active catalyst LnRh(I)OH I,13 formed in situ, trans-
(6) For examples using aldehydes, ketones and esters, see: (a) Shintani, R.;
Okamoto, K.; Hayashi, T. Chem. Lett. 2005, 34, 1294. (b) Matsuda, T.; Makino,
M.; Murakami, M. Chem. Lett. 2005, 34, 1416. (c) Matsuda, T.; Shigeno, M.;
Makino, M.; Murakami, M. Org. Lett. 2006, 8, 3379. (d) Shintani, R.; Okamoto,
K.; Otomaru, Y.; Ueyama, K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54. (e)
Miura, T.; Shimada, M.; Murakami, M. Synlett 2005, 667. (f) Miura, T.; Shimada,
M.; Murakami, M. Angew. Chem., Int. Ed. 2005, 44, 7598. (g) Miura, T.;
Shimada, M.; Murakami, M. Tetrahedron 2007, 63, 6131. (h) Miura, T.; Sasaki,
T.; Nakazawa, H.; Murakami, M. J. Am. Chem. Soc. 2005, 127, 1390. For nitriles,
see: (i) Miura, T.; Nakazawa, H.; Murakami, M. Chem. Commun. 2005, 2855.
(j) Miura, T.; Murakami, M. Org. Lett. 2005, 7, 3339. For R,ꢀ-unsaturated
carbonyl compounds, see: (k) Shintani, R.; Tsurusaki, A.; Okamoto, K.; Hayashi,
T. Angew. Chem., Int. Ed. 2005, 44, 3909. (l) Kurahashi, T.; Shinokubo, H.;
Osuka, A. Angew. Chem., Int. Ed. 2006, 45, 6336. For ethers, see: (m) Miura,
T.; Shimada, M.; Murakami, M. J. Am. Chem. Soc. 2005, 127, 1094. (n) Miura,
T.; Sasaki, T.; Harumashi, T.; Murakami, M. J. Am. Chem. Soc. 2006, 128,
2516. For bromides, see: (o) Harada, Y.; Nakanishi, J.; Fujihara, H.; Tobisu,
M.; Fukumoto, Y.; Chatani, N. J. Am. Chem. Soc. 2007, 129, 5766. For iodides,
see: (p) Shintani, R.; Yamagami, T.; Hayashi, T. Org. Lett. 2006, 8, 4799. For
isocynates, see: (q) Miura, T.; Takahashi, Y.; Murakami, M. Org. Lett. 2007, 9,
5075. For benzyl chlorides, see: (r) Miyamoto, M.; Harada, Y.; Tobisu, M.;
Chatani, N. Org. Lett. 2008, 10, 2975 For allenes, see: (s) Miura, T.; Ueda, K.;
Takahashi, Y.; Murakami, M. Chem. Commun. 2008, 5366.
(7) (a) de la Herran, G.; Murcia, C.; Csaky, A. G. Org. Lett. 2005, 7, 5629.
(b) Hayashi, T.; Tokunaga, N.; Inoue, K. Org. Lett. 2004, 6, 305. (c) Hayashi,
T.; Yamamoto, S.; Tokunaga, N. Angew. Chem., Int. Ed. 2005, 44, 4224. For a
similar 1,6-addition using iridium catalyst, see: (d) Nishimura, T.; Yasuhara,
Y.; Hayashi, T. Angew. Chem., Int. Ed. 2006, 45, 5164.
(8) (a) Piers, E.; Wong, T.; Coish, P. D.; Rogers, C. Can. J. Chem. 1994,
72, 1816. (b) Marek, I.; Meyer, C.; Normant, J.-F. Org. Synth. 1997, 74, 194.
(9) Li, W.; Nelson, D. P.; Jensen, M. S.; Hoerrner, R. S.; Cai, D.; Larsen,
R. D.; Reider, P. J. J. Org. Chem. 2002, 67, 5394.
(10) Netherton, M. R.; Fu, G. C. Org. Lett. 2001, 3, 4295.
(11) Wright, S. W.; Hageman, D. L.; McClure, L. D. J. Org. Chem. 1994,
59, 6095.
(12) For recent reviews on organic reactions in aqueous media, see: (a) Li,
C.-J. Chem. ReV. 2005, 105, 3095. (b) Li, C.-J.; Chen, L. Chem. Soc. ReV. 2006,
35, 68.
a All reactions were run under the following conditions: 1 (0.20
mmol, 1 equiv), alkene (0.20-0.22 mmol, 1.0-1.1 equiv), [Rh(cod)Cl]2
-
(0.006 mmol, 3 mol %), t-Bu3PH+BF4 (0.012 mmol, 6 mol %), and KF
(0.40 mmol, 2 equiv) in 3.0 mL of dioxane and 0.3 mL of H2O.
b Isolated by column chromatography. c Yield obtained by using
-
[Rh(cod)Cl]2 (0.012 mmol, 6 mol %) and t-Bu3PH+BF4 (0.024 mmol,
12 mol %).
Results and Discussions
Dienylboronate ester 1 was synthesized from readily available
ethyl (Z)-ꢀ-iodoacrylate,8 which was reduced with DIBAL,
followed by Wittig olefination to generate the dienyl iodide.
Conversion of the iodide to boronate ester 1 was accomplished
via an in situ trapping of the vinyllithium intermediate with
triisopropylborate,9 which was then esterified with pinacol.
We initiated the investigations on this rhodium-catalyzed
vinylcyclopropanation reaction by screening for optimal reaction
conditions. The phosphine ligand was found to play a crucial
role for this transformation as monodentate bulky phosphine
ligands showed superior reactivity over bidentate phosphine
ligands. Optimal reaction conditions were found using
10
-
[Rh(cod)Cl]2 as the rhodium source with t-Bu3PH+BF4
,
2522 J. Org. Chem. Vol. 74, No. 6, 2009

Rhodium-Catalyzed Reactions of Strained Alkenes
TABLE 2. Reaction with Aza- and Oxabicyclic Alkenesa
TABLE 3. Reaction with Nonbicyclic Alkenesa
a All reactions were run under the following conditions: 1 (0.20 mmol, 1
equiv), alkene (0.21-0.24 mmol, 1.05-1.20 equiv), [Rh(cod)Cl]2 (0.006
-
mmol, 3 mol %), t-Bu3PH+BF4 (0.012 mmol, 6 mol %), and KF (0.40
mmol, 2 equiv) in 3.0 mL of dioxane and 0.3 mL of H2O. b Isolated by
column chromatography.
complex III,14 which preferentially undergoes intramolecular
1,6-addition, presumably due to the close proximity of the δ
carbon to the rhodium catalyst. Protodemetalation of the
resulting oxo-π-allylrhodium(I) IV gives the vinylcyclopropane
product and regenerates the catalyst LnRh(I)OH I. The Z-olefin
geometry in the product is believed to be formed as a
consequence of internal coordination of the carbonyl group in
oxo-π-allylrhodium(I) IV. The presence of the oxo-π-allylrhod-
ium(I) complex IV is supported by deuterium studies, which
shows >95% deuterium incorporation at the R carbon.5
We set out to explore the scope of this vinylcyclopropanation
reaction with a variety of alkenes. In general, norbornene and
norbornene derivatives gave the desired product in moderate
to good yield. Benzonorbornene 4 shows lower reactivity toward
this process; even after doubling the amount of the catalyst
loading, the corresponding product 5 was obtained in only 51%
yield (Table 1, entry 2). Norbornene derivatives 6 and 8
a All reactions were run under the following conditions: 1 (0.20 mmol, 1
equiv), alkene (0.08-0.22 mmol, 0.40-1.10 equiv), [Rh(cod)Cl]2 (0.006
mmol, 3 mol %), t-Bu3PH+BF4 (0.012 mmol, 6 mol %), and KF (0.40
-
mmol, 2 equiv) in 3.0 mL of dioxane and 0.3 mL of H2O. b Isolated by
column chromatography. c Yield obtained by using oxabicyclic alkene
(0.08 mmol, 0.40 equiv). d Yield obtained by using oxabicyclic alkene
(0.21 mmol, 1.05 equiv).
(13) (a) Brune, H.-A.; Unsin, J.; Hemmer, R.; Reichhardt, M. J. Organomet.
Chem. 1989, 369, 335. (b) Grushin, V. V.; Kuznetsov, V. F.; Bensimon, C.;
Alper, H. Organometallics 1995, 14, 3927. (c) Joo´, F.; Kova´cs, J.; Be´nyei, A. C.;
Na´dasdi, L.; Laurenczy, G. Chem.-Eur. J. 2001, 7, 193. (d) Hayashi, T.;
Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002, 124, 5052.
(14) Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J. Am. Chem. Soc. 2000,
122, 10464.
metalates with the boronate ester to give the dienylrhodium(I)
intermediate II and B(pin)OH. Subsequent carborhodation at
the exo face of norbornene affords the organorhodium(I)
J. Org. Chem. Vol. 74, No. 6, 2009 2523

Tseng and Lautens
TABLE 5. Reaction with Isomeric Dienylboronate Estersa
TABLE 4. Reaction with Different Boronate Estersa
a All reactions were run under the following conditions: boronate ester
(0.20 mmol, 1 equiv), norbornene (0.22 mmol, 1.1 equiv), [Rh(cod)Cl]2
-
(0.006 mmol, 3 mol %), t-Bu3PH+BF4 (0.012 mmol, 6 mol %), and KF
(0.40 mmol, 2 equiv) in 3.0 mL of dioxane and 0.3 mL of H2O.
b Isolated by column chromatography.
a All reactions were run under the following conditions: organoboron
reagent (0.20 mmol, 1 equiv), norbornene (0.22 mmol, 1.1 equiv),
-
[Rh(cod)Cl]2 (0.006 mmol, 3 mol %), t-Bu3PH+BF4 (0.012 mmol, 6
mol %), and KF (0.40 mmol, 2 equiv) in 3.0 mL of dioxane and 0.3 mL
of H2O. b Isolated by column chromatography.
FIGURE 1. Proposed conformation of intermediate III with bronoate
esters 1 and 41-43.
demonstrated the chemoselectivity of this transformation, as
vinylcyclopropanation occurred only at the strained and more
electron-rich olefins, giving the products in moderate to good
yields (entries 3 and 4). Reaction of bicyclo[2.2.2]oct-2-ene 10
gave the product 11 in low yield, suggesting that the reduced
strain energy of this substrate led to the lower reactivity of this
process (entry 5).
bridging nitrogen atom might strongly coordinate to the catalyst
and impede the catalytic cycle. However, we found that by
employing an azabicyclic alkene with the nitrogen atoms further
away from the alkene moiety, such as 24, affording an
interesting diamine product in low yield (entry 9).
We also screened a variety of nonbicyclic alkenes under the
optimal reaction conditions. The unstrained 1,2-dihydronaph-
thalene 26 was found to undergo cyclopropanation, albeit in
low yield (Table 3, entry 1). Extension to an analogous alkene,
such as indene 28, did not afford any product (entry 2). Using
styrene 29 gave only the Heck-type product in low yield (entry
3).16 Reacting with 1-cyclohexenone 31 only afford the 1,4-
addition product in moderate yield (entry 4).17 Using other
strained alkenes, such as methylenecyclopropane 33 and cy-
clopropene 34,18 did not give any of the desired products (entries
5 and 6).
We next screened several boronate esters containing a similar
diene framework, but with different electron-withdrawing groups
and different groups on boron. Changing the tert-butyl ester to
tertiary amide gave 36 in low yield (Table 4, entry 1). Reacting
with boronate ester bearing a nitrile functional group afforded
the desired product 38 in moderate yield as a mixture of E/Z
isomers (entry 2). We speculate that the linear geometry of the
Aza- and oxabicyclic alkenes, which have been previously
used in transition metal catalyzed ring-opening reactions, were
also examined. Reacting with [3.2.1] oxabicyclic alkenes such
as 12 and 14 gave the desired product in good to excellent yield
(Table 2, entries 1 and 2). These results showed that ketone
and silyl ether groups are compatible under the reaction
conditions, as no 1,2-addition or desilylation were observed.
Surprisingly, [2.2.1] oxabicyclic alkene 16 gave 17 in low yield,
perhaps due to an interaction of the sulfone group with rhodium
catalyst (entry 3). Oxabicyclic alkene 18 did not give the
corresponding product, presumably due to a competitive acy-
lation reaction of an organorhodium intermediate with anhydride
functional groups, as previously reported by Frost and co-
workers (entry 4).15 Using less than 0.5 equiv of bisoxabicyclic
alkene 19 gave the double vinylcyclopropanation product in
good yield (entry 5). The monocyclized product could also be
obtained in moderate yield by controlling the amount of boronate
ester (entry 6). Extension of this method to nitrogen-containing
alkenes such as 22 and 23 proved to be problematic and gave
no desired product (entries 7 and 8). It is speculated that the
(16) Lautens, M.; Roy, A.; Fukuoka, K.; Fagnou, K.; Martin-Matute, B. J. Am.
Chem. Soc. 2001, 123, 5358.
(17) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16, 4229.
(18) Leong, P. Ph. D. thesis, University of Toronto (Canada), 2007.
(15) Frost, C. G.; Wadsworth, K. J. Chem. Commun. 2001, 2316.
2524 J. Org. Chem. Vol. 74, No. 6, 2009

Rhodium-Catalyzed Reactions of Strained Alkenes
TABLE 6. Reaction with Substituted Boronate Estersa
TABLE 7. Reaction with Substituted Boronate Esters with
Different Alkenesa
a All reactions were run under the following conditions: boronate ester
(0.20 mmol, 1 equiv), norbornene (0.22 mmol, 1.1 equiv), [Rh(cod)Cl]2
-
(0.006 mmol, 3 mol %), t-Bu3PH+BF4 (0.012 mmol, 6 mol %), and KF
(0.40 mmol, 2 equiv) in 3.0 mL of dioxane and 0.3 mL of H2O.
b Isolated by column chromatography. c Yield obtained by using
boronate ester 48 (1.00 mmol, 1 equiv), norbornene (1.10 mmol, 1.1
-
equiv), [Rh(cod)Cl]2 (0.03 mmol, 3 mol %), t-Bu3PH+BF4 (0.06 mmol,
6 mol %), and KF (2.00 mmol, 2 equiv) in 10 mL of dioxane and 1 mL
of H2O.
nitrile group has a weaker internal coordination as proposed in
intermediate IV, leading to a mixture of olefins. Changing the
pinacol boronate ester to potassium trifluoroborate 3919 gave
the corresponding product in lower yield (entry 3). Using
boronate ester 40, containing only one olefin group, did not
afford any product (entry 4), presumably due to the inability of
this substrate to form the double coordinated intermediate III.
This result indicates that the diene framework plays a crucial
role in the vinylcyclopropanation process.
To probe the influence of olefin geometry on this vinylcy-
clopropanation reaction, various E,Z isomeric boronate esters
were tested. To our surprise, all olefin isomers gave the same
product as we obtained using 1, though in lower yield (Table
5, entries 1-3). The boronate ester 1, which has E,Z configu-
ration, gave the highest yield, presumably due to a more
favorable conformation in intermediate III compared to the other
isomers (Figure 1). In addition, the Z-olefin geometry in the
product was retained from different isomeric boronate esters,
which suggests the reaction mechanism must involve an olefin
isomerization step, possibly due to the presence of an equilib-
rium between (oxo-π-allyl)rhodium(I) IV and (oxo-π-pentadi-
enyl)rhodium(I) V.
We then examined substituent effects on the dienyl fragment.
When methyl-substituted boronate ester 44 was used, the
a All reactions were run under the following conditions: boronate ester
(0.20 mmol,
1 equiv), alkene (0.22-0.24 mmol, 1.1-1.2 equiv),
-
[Rh(cod)Cl]2 (0.006 mmol, 3 mol %), t-Bu3PH+BF4 (0.012 mmol, 6
mol %), and KF (0.40 mmol, 2 equiv) in 3.0 mL of dioxane and 0.3 mL
of H2O. b Isolated by column chromatography.
(19) For examples on rhodium-catalyzed 1,4-addition using potassium
organotrifluoroborates, see: (a) Batey, R. A.; Thadani, A. N.; Smil, D. V. Org.
Lett. 1999, 1, 1683. (b) Pucheault, M.; Darses, S.; Geneˆt, J.-P. Eur. J. Org.
Chem. 2002, 2002, 3552.
J. Org. Chem. Vol. 74, No. 6, 2009 2525

Tseng and Lautens
were added to the solution, which was stirred at 25 °C for 10 min.
To the bright yellow solution was added the alkene (0.09-0.24
mmol), followed by addition of the boronate ester (0.20 mmol),
and the reaction mixture was stirred at 80 °C for 3 h. The reaction
was quenched with brine, and the aqueous layer was extracted with
Et2O ( × 3). The combined organic layers were dried with MgSO4,
filtrated, and concentrated in vacuo. The crude material was then
purified by column chromatography on silica gel.
reductive Heck product 45 was obtained in low yield (Table 6,
entry 1). Reacting boronate ester 46 bearing a methyl substituent
ꢀ to the ester group gave the vinylcyclopropane product, though
in low yield (entry 2). In contrast, methyl-substituted boronate
ester 48 and 50 afforded the cyclopentene products in moderate
yield (entries 3 and 4). These results suggest that the rate of
intramolecular 1,4- versus 1,6-addition was strongly influenced
by the presence of substituents at δ or γ position. The structure
of the cyclopentene 49 was further confirmed by X-ray
crystallography of a derivative.20
We wanted to test the generality of this cyclopentenation
reaction by varying the substituents on the boronate esters and
the acceptor alkene. Reacting with boronate esters bearing
phenyl or isopropyl groups afforded the corresponding cyclo-
pentene products in moderate to good yield (Table 7, entries
1-3). Benzonorbornene and norbornene derivative gave the
products in moderate yield with methyl substituted boronate
esters (entries 4-7). More interestingly, using norbornadiene
as coupling partner only gave the monocyclized product, albeit
in unsatisfactory yield (entries 8 and 9).
In summary, we have developed a vinylcyclopropane-forming
reaction via a rhodium-catalyzed cascade addition/cyclization
sequence. This process works best when strained bicyclic
alkenes were used. We also discovered that by using alkyl or
aryl substituted dienylboronate esters, the reaction will undergo
a different pathway to afford cyclopentene products. A wide
variety of polycyclic molecules containing vinylcyclopropane
or cyclopentene moieties can be synthesized via this convergent
rhodium-catalyzed, substrate-controlled process.
1
Vinylcyclopropane 3. (Table 1, entry 1) Yellow oil. H NMR
(400 MHz, CDCl3): δ 5.41 (dtd, J ) 10.6, 7.1, 0.7 Hz, 1H), 4.86
(dddd, J ) 10.5, 9.8, 1.6, 1.6 Hz, 1H), 3.09 (dd, J ) 7.1, 1.6 Hz,
2H), 2.32 (s, 2H), 1.46 (s, 9H), 1.45-1.41 (m, 3H), 1.27-1.21
(m, 2H), 1.03-0.97 (m, 1H), 0.75 (d, J ) 2.2 Hz, 2H), 0.66 (d, J
) 10.6 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 171.5, 134.5,
119.3, 80.4, 35.9, 34.7, 29.4, 28.4, 28.1, 24.6, 12.9; IR (neat): 2954,
2870, 1735, 1458, 1392, 1367, 1328, 1256, 1146, 1113, 956, 833,
702 cm-1. HRMS (ESI) calcd for C16H24NaO2 [M + Na+] 271.1668,
found 271.1672.
Cyclopentene 49. (Table 6, entry 3) Yellow oil. 1H NMR (400
MHz, CDCl3): δ 5.12 (d, J ) 1.6 Hz, 1H), 2.50-2.46 (m, 1H),
2.47 (dd, J ) 14.1, 4.3 Hz, 1H), 2.42-2.36 (m, 1H), 2.02-1.99
(m, 1H), 1.94-1.91 (m, 1H), 1.82 (dd, J ) 7.0, 3.1 Hz, 1H), 1.62
(dd, J ) 2.7, 1.6 Hz, 3H), 1.49-1.41 (m, 2H), 1.46 (s, 9H),
1.32-1.26 (m, 1H), 1.20-1.07 (m, 2H), 0.97-0.92 (m, 1H). 13C
NMR (100 MHz, CDCl3): δ 172.5, 142.9, 128.2, 80.1, 54.5, 52.2,
51.8, 42.9, 40.9, 40.4, 32.2, 29.0, 28.7, 28.1, 14.5; IR (neat): 2949,
2870, 1732, 1475, 1455, 1392, 1367, 1332, 1291, 1256, 1153, 1049,
954, 912, 867, 847, 830, 757 cm-1. HRMS (EI) calcd for C17H26O2
[M+] 262.1933, found 262.1931.
Acknowledgment. We gratefully acknowledge the financial
support of the Natural Sciences and Engineering Research
Council (NSERC) of Canada, the Merck Frosst Centre for
Therapeutic Research for an Industrial Research Chair, and the
University of Toronto. We also thank Dr. Alan J. Lough for
acquisition of X-ray crystallographic data.
Experimental Section
General Procedure for the Rhodium-Catalyzed Cascade
Addition/Cyclization Reactions. A solution of 0.3 mL of water
and 3 mL of dioxane in a 5-mL two-neck round-bottom flask was
purged with argon and stirred for 10 min at 25 °C. [Rh(cod)Cl]2
(3.0 mg, 0.006 mmol), tri-tert-butylphosphonium tetrafluoroborate
(3.5 mg, 0.012 mmol), and potassium fluoride (23.3 mg, 0.40 mmol)
Supporting Information Available: Experimental proce-
dures and crystallographic and spectroscopic characterization
data of all new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
(20) See Supporting Information.
JO900039G
2526 J. Org. Chem. Vol. 74, No. 6, 2009