Palladium-catalyzed cross-coupling reactions in one-pot multicatalytic processes

Article abstract of DOI:10.1021/ja0733235

Palladium-catalyzed cross-coupling reactions have been investigated in multicatalytic processes to synthesize disubstituted alkenes and alkanes from carbonyl derivatives. The use of copper-catalyzed methylenation reactions is the key starting reaction to produce terminal alkenes which are not isolated, but submitted to further structure elongation. Not only is the isolation of the alkene intermediate unnecessary, but also the copper catalyst is a beneficial cocatalyst in the palladium-catalyzed cross-coupling reactions. The desired products are thus typically obtained in higher yields using this one-pot approach. We have used these processes to synthesize hydroxylated (E)-stilbenoids, which are known chemopreventive and chemotherapeutic agents, odorant-substituted indanes, and non-natural amino acids, such as homophenylalanine.

Full text of DOI:10.1021/ja0733235

Published on Web 10/06/2007
Palladium-Catalyzed Cross-Coupling Reactions in One-Pot
Multicatalytic Processes
He´le`ne Lebel,* Chehla Ladjel, and Lise Bre´thous
Contribution from the De´partement de Chimie, UniVersite´ de Montre´al, C.P. 6128, Succursale
Centre-Ville, Montre´al, Que´bec, Canada H3C 3J7
Received May 10, 2007; E-mail: helene.lebel@umontreal.ca
Abstract: Palladium-catalyzed cross-coupling reactions have been investigated in multicatalytic processes
to synthesize disubstituted alkenes and alkanes from carbonyl derivatives. The use of copper-catalyzed
methylenation reactions is the key starting reaction to produce terminal alkenes which are not isolated, but
submitted to further structure elongation. Not only is the isolation of the alkene intermediate unnecessary,
but also the copper catalyst is a beneficial cocatalyst in the palladium-catalyzed cross-coupling reactions.
The desired products are thus typically obtained in higher yields using this one-pot approach. We have
used these processes to synthesize hydroxylated (E)-stilbenoids, which are known chemopreventive and
chemotherapeutic agents, odorant-substituted indanes, and non-natural amino acids, such as homophe-
nylalanine.
Introduction
importance, because of the predominance of these bonds in
organic molecules.
One-pot strategies are well-known in organic synthesis as
efficient processes to access complex molecules without isolat-
ing intermediates.1 More recently, the use of transition-metal-
catalyzed reactions has further improved these processes.2,3 For
instance, one metal complex can be used to catalyze more than
one reaction, or various metal complexes could be added
concomitantly or sequentially to achieve various transformations,
without isolation of intermediate species. These types of
processes have been called tandem catalysis,2e pseudodomino
strategies,2f or multicatalytic cascades.4 In any case, all of these
processes eliminate intermediate recovery steps, thereby con-
siderably decreasing the amount of generated waste.5 Moreover,
it has been shown in many cases that the overall yields for one-
pot procedures are higher than those obtained with step-by-
step procedures. Among the one-pot processes, the ones that
allow the formation of multiple C-C bonds are of great
Recently, our group has disclosed novel one-pot procedures
based on the transition-metal-catalyzed methylenation of car-
bonyl compounds. Both rhodium(I) and copper(I) complexes
catalyzed the formation of methylenetriphenylphosphorane in
the presence of (trimethylsilyl)diazomethane, 2-propanol, and
triphenylphosphine.6 This reagent performed the methylenation
of aldehyde and ketone substrates to produce the corresponding
terminal alkenes in high yields and chemoselectivity. We have
(3) Selected examples: (a) Murelli, R. P.; Snapper, M. L. Org. Lett. 2007, 9,
1749-1752. (b) Poe, S. L.; Kobaslija, M.; McQuade, D. T. J. Am. Chem.
Soc. 2006, 128, 15586-15587. (c) Onodera, G.; Nishibayashi, Y.; Uemura,
S. Angew. Chem., Int. Ed. 2006, 45, 3819-3822. (d) Leclerc, J. P.; Andre,
M.; Fagnou, K. J. Org. Chem. 2006, 71, 1711-1714. (e) Ackermann, L.;
Althammer, A. Synlett 2006, 3125-3129. (f) Lofberg, C.; Grigg, R.; Keep,
A.; Derrick, A.; Sridharan, V.; Kilner, C. Chem. Commun. 2006, 5000-
5002. (g) Guo, R. W.; Morris, R. H.; Song, D. J. Am. Chem. Soc. 2005,
127, 516-517. (h) Guo, R. W.; Morris, R. H.; Song, D. J. Am. Chem. Soc.
2005, 127, 516-517. (i) Deng, L.; Giessert, A. J.; Gerlitz, O. O.; Dai, X.;
Diver, S. T.; Davies, H. M. L. J. Am. Chem. Soc. 2005, 127, 1342-1343.
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Y.; Yoshikawa, M.; Inada, Y.; Milton, M. D.; Hidai, M.; Uemura, S. Angew.
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(4) These terms have been essentially defined to address mechanistic implica-
tions of these various one-pot processeses; for additional discussions, see:
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9
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J. AM. CHEM. SOC. 2007, 129, 13321-13326
13321

A R T I C L E S
Scheme 1
Lebel et al.
opportunities to develop new efficient one-pot multicatalytic
processes are rich. In this paper, we report the use of copper-
catalyzed methylenation reactions in one-pot procedures to
access disubstituted alkenes via a palladium-catalyzed Heck
reaction and alkanes using a hydroboration-palladium-catalyzed
Suzuki reaction.
Results and Discussion
One-Pot Methylenation-Heck Cross-Coupling Reac-
tions: Access to (E)-Stilbenoid Derivatives. A number of
stilbenes have been isolated from natural sources. Among them,
hydroxylated (E)-stilbenoids,11 such as resveratrol (3,4,5-
trihydroxystilbene, a phytoalexin found in grapes and other food
products), have attracted considerable attention because of their
potential therapeutic value as chemopreventive and chemo-
therapeutic agents.12,13 Various synthetic routes have been
developed, including a number based on Heck technologies.14
Recently, cross-metathesis reactions have also been successfully
used to prepare hydroxylated (E)-stilbenoids.15 However, in all
cases, it is required to have a styrene derivative as the substrate.
Although some are commercially available, most styrenes need
to be prepared from the corresponding benzaldehyde or benzylic
alcohol. Using a multicatalytic strategy combining a methyl-
enation reaction with a coupling reaction avoids the need for
isolating the styrene intermediate (which can potentially poly-
merize), thereby decreasing the amount of required reagents and
solvents (for workup and purification procedures), while
producing less waste. At the outset, we envisioned developing
a rhodium-catalyzed methylenation-ruthenium-catalyzed cross-
metathesis to address this issue. However, our preliminary results
with this multicatalytic process showed limitations, as 5 equiv
of the alkene moiety was required (eq 1).16
Scheme 2
also reported multicatalytic processes for the synthesis of
alkenes, using an oxidation-methylenation procedure and a
methylenation-metathesis procedure with the sequential addi-
tion of various palladium, rhodium, and ruthenium complexes
(Scheme 1).7 Furthermore, we have shown that we could take
advantage of the dual activity of Wilkinson’s catalyst with both
carbonyl derivatives and alkene derivatives. Indeed, one-pot
procedures involving rhodium-catalyzed methylenation-hy-
droboration reactions8 and rhodium-catalyzed methylenation-
hydrogenation9 reactions have been described (Scheme 2).
The one-pot processes that we have reported thus far are based
on the rhodium-catalyzed methylenation reaction. Given the
recently developed copper-catalyzed methylenation reaction,6h
and the known ability of copper complexes to serve as
cocatalysts in palladium-catalyzed cross-coupling reactions,10
To overcome these problems, we changed the strategy to
explore the combination of the rhodium- or copper-catalyzed
methylenation reaction with a palladium-catalyzed Heck cross-
coupling reaction. The challenge was to find cross-coupling
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limited to acrylate derivatives.
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Pd-Catalyzed Cross-Coupling Reactions
A R T I C L E S
Table 1. One-Pot Transition-Metal-Catalyzed Methylenation-Heck
Cross-Coupling Process: Optimization of the Reaction Conditions
Table 2. One-Pot Copper-Catalyzed-Methylenation-Heck
Cross-Coupling Process
a Isolated yields. b Step-by-step process.
reaction conditions which would be compatible with residues
and the solvent (THF) of the methylenation reaction. We first
studied the synthesis of stilbene 1 from p-anisaldehyde, testing
both methylenation reactions with either Wilkinson’s complex
or copper(I) chloride and a variety of reaction conditions for
the cross-coupling reactions (Table 1). In none of the cases,
the corresponding styrene derivative was isolated. Overall, better
yields of stilbene 1 were observed when copper(I) chloride was
used as the methylenation catalyst rather than Wilkinson’s
complex. These results suggest that copper(I) chloride serves
as a cocatalyst and/or that Wilkinson’s catalyst inhibits the Heck
cross-coupling reaction. The use of palladium tetrakis(triph-
enylphosphine)17 (entry 1) or palladium bis(triphenylphosphine)
dichloride under Jeffery reaction conditions18 (entry 2) led to
the desired product in low yield, whereas moderate yields were
observed under Fu’s reaction conditions19 (entry 3).
These reaction conditions were used with 3,5-dimethoxyben-
zaldehyde to give in 73% yield the methylated resveratrol 10,
known to be as biologically active as the resveratrol itself.
The best yield for the one-pot process was obtained by
performing a copper-catalyzed methylenation reaction, followed
by a Heck cross-coupling with palladium diacetate and tri-o-
tolylphosphine in triethylamine (entry 4).20 The desired (E)-
stilbene 1 was isolated directly from p-anisaldehyde as a single
diastereomer in 88% yield, without isolation of the styrene
intermediate.21 In comparison, a 56% yield was obtained for
the formation of 1 when the step-by-step process was performed,
in which the alkene intermediate was isolated. Table 2 shows
the scope of this one-pot process focusing on the synthesis of
hydroxylated (E)-stilbenoids. The use of electron-rich aryl
halides led to moderate yields (Table 2, entry 2 vs entries 1-3),
whereas the use of electron-rich aldehydes produced typically
the desired stilbene in good yields (Table 2, entries 4 and
6-9).22
One-Pot Methylenation-Intramolecular Heck Cross-
Coupling Reactions: Access to Odorant Indane Precursors.
Intramolecular Heck reactions are popular for the synthesis of
heterocyclic and carbocyclic moieties.23 We became interested
in the synthesis of substituted indanes, known as odorant
products (Figure 1).24 We envisioned synthesizing these products
(17) Akita, Y.; Noguchi, T.; Sugimoto, M.; Ohta, A. J. Heterocycl. Chem. 1986,
23, 1481-1485.
(21) Surprisingly, the use of the more reactive 4-iodotoluene as a coupling agent
did not produce the desired product in a better yield. Only 45% was obtained
to produce 1 using CuCl and the Heck reaction conditions described in
Table 1, entry 4.
(18) Jeffery, T. Chem. Commun. 1984, 1287-1289.
(19) (a) Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989-7000. (b)
Netherton, M. R.; Fu, G. C. Org. Lett. 2001, 3, 4295-4298.
(20) Patel, B. A.; Ziegler, C. B.; Cortese, N. A.; Plevyak, J. E.; Zebovitz, T. C.;
Terpko, M.; Heck, R. F. J. Org. Chem. 1977, 42, 3903-3907.
(22) The 1,1-disubstituted alkene was also isolated (5-10%) in some cases and
accounted for some of the lower yields.
(23) Gibson, S. E.; Middleton, R. J. Contemp. Org. Synth. 1996, 3, 447-471.
9
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A R T I C L E S
Lebel et al.
Table 3. One-Pot Transition-Metal-Catalyzed
Methylenation-Hydroboration-Suzuki Cross-Coupling Process:
Optimization of the Reaction Conditions
Figure 1. Structure of odorant indanes.
via a one-pot methylenation-intramolecular Heck cross-
coupling sequence, starting from aldehyde 11 and ketone 13
(eqs 3 and 4).25,26
a Isolated yields. b In parentheses, isolated yields for the step-by-step
process.
Table 4. One-Pot Transition-Metal-Catalyzed
Methylenation-Hydroboration-Suzuki Cross-Coupling Process
Using Garner’s Aldehyde
The intramolecular Heck reaction was very efficient, as
cyclopentene 12 was isolated in 90% yield starting from
aldehyde 11. The exo-alkene was initially formed, but the double
bond quickly isomerized to the internal position to produce
cyclopentene 12. The corresponding dimethylindane product 14
was obtained in 63% yield, using palladium tetrakis(triph-
enylphosphine) and sodium formate in DMF: the organopal-
ladium intermediate (which cannot â-eliminate) was thus
reduced in situ, to regenerate the catalyst.27
One-Pot Methylenation-Suzuki Cross-Coupling Reac-
tions: Access to Non-Natural Amino Acids. Non-natural
amino acids not only display interesting biological properties,
but also have been widely used as synthetic building blocks.28
Homophenylalanine derivatives showed pharmacologic poten-
tial, and thus, considerable attention has been devoted to their
syntheses.29 Elongation of unsaturated amino acid derivatives,
particularly serine-derived starting material, has been used as a
strategy to access homophenylalanine analogues. Indeed, non-
natural amino acid derivatives have been produced from the
methylenated Garner aldehyde via a hydroboration-Suzuki
cross-coupling reaction sequence.29c,d As we have previously
established that organoboranes could be produced from alde-
hydes via a one-pot rhodium-catalyzed methylenation-hydrobo-
ration process,8 we envisioned combining this approach with a
Suzuki cross-coupling reaction. One of the key points was to
find the suitable hydroborating agent to generate the requisite
a Isolated yields. b PdCl2(dppf) as the Suzuki catalyst.
aliphatic organoborane for the Suzuki cross-coupling reaction.
Our initial results showed that it was not possible to use an
organoborane derived from catecholborane, the hydroborating
agent initially used in the rhodium-catalyzed methylenation-
hydroboration cascade. Indeed, to perform Suzuki couplings with
an aliphatic organoborane, 9-borabicyclo(3.3.1)nonane (9-BBN)
was required as the hydroborating reagent. In preliminary
studies, both the rhodium- and the copper-catalyzed methyl-
enation reactions of Garner’s aldehyde30 were tested, followed
(24) Kraft, P.; Eichenberger, W. Eur. J. Org. Chem. 2003, 3735-3743.
(25) Aldehyde 11 is readily available in five steps from commercially available
3,4-dimethoxybenzaldehyde. See the Supporting Information for details.
(26) Ketone 13 is readily available in four steps from known 4-(hydroxymethyl)-
2-methoxyphenyl acetate. See the Supporting Information for details.
(27) (a) Banerjee, M.; Mukhopadhyay, R.; Achari, B.; Banerjee, A. K. Org.
Lett. 2003, 5, 3931-3933. (b) Burns, B.; Grigg, R.; Ratananukul, P.;
Sridharan, V.; Stevenson, P.; Worakun, T. Tetrahedron Lett. 1988, 29,
4329-4332.
(28) (a) Sardina, F. J.; Rapoport, H. Chem. ReV. 1996, 96, 1825-1872. (b)
Moloney, M. G. Nat. Prod. Rep. 2002, 19, 597-616.
9
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Pd-Catalyzed Cross-Coupling Reactions
A R T I C L E S
Table 5. One-Pot Transition-Metal-Catalyzed
Methylenation-Hydroboration-Suzuki Cross-Coupling Process
with Various Aldehydes
this one-pot process to obtain the corresponding alkane in 64%
yield (entry 9).
The homophenylalanine hydrochloride salt (24) was easily
synthesized from product 16 via a Jones oxidation, followed
by a trifluoroacetic acid cleavage of the Boc protecting group
(eq 5).29e
It was also possible to transform other aldehydes using this
multicatalytic one-pot procedure. Indeed, piperonal was reacted
to form product 25 after the Suzuki cross-coupling with
4-bromoanisole (eq 6).
a Isolated yields.
by the addition of 9-BBN and the palladium-catalyzed Suzuki
cross-coupling with 4-bromoanisole using various palladium
complexes (Table 3). Neither the alkene nor the organoborane
intermediates were isolated. The best result was obtained with
copper chloride as the methylenation catalyst and tetrakis-
(triphenylphosphine) as the Suzuki cross-coupling catalyst,
leading to product 15 in 83% isolated yield (entry 3). Higher
yields are obtained for the one-pot procedure compared to the
step-by-step process, in which the alkene intermediate was
isolated.
A variety of other electrophiles (typically aryl bromides) were
tested under these reaction conditions (Table 4). Higher yields
were obtained when the copper-catalyzed methylenation reaction
was used in the one-pot process. Electron-rich aryl bromides
were reacted in good yields (entries 2-5), as well as electron-
poor aryl bromides (entries 6-8). It is not necessary to protect
the ketone (entry 6), and in the presence of PdCl2(dppf)2, the
coupling product with o-nitrophenyl bromide was produced in
78% yield (entry 7). It is also possible to use methyl iodide in
A variety of aldehydes were tested in the one-pot process
using 2-methylpropenyl bromide as the coupling partner in the
Suzuki reaction (Table 5). Copper catalysts were used with
Garner’s aldehyde and aromatic and unsaturated aldehydes.
After the hydroboration and Suzuki cross-coupling, products
26-28 were isolated in 62-80% overall yield (entries 1-3).
No workup or purification procedure is required between each
step. When other aliphatic aldehydes were reacted, either
IMesCuCl31 or RhCl(PPh3)3 was used to catalyze the methyl-
enation reaction, as copper chloride or iodide led to lower yields
(entries 4-6). The one-pot process tolerated unprotected ketone-
containing aldehyde substrate, as both the methylenation and
the hydroboration reactions were chemoselective, and compound
31 was isolated in 49% yield (entry 6).
Conclusion
In conclusion, we have developed a series of efficient one-
pot procedures to produce substituted alkenes and alkanes in
good yields, while minimizing the number of manipulations.
Furthermore, these one-pot processes led to products having
important biological properties. Finally, synergic effects have
been observed, as the copper-catalyzed methylenation reactions
proved superior in these one-pot processes, suggesting that
copper(I) complexes served as a cocatalyst in cross-coupling
reactions.
(29) (a) De Frutos, M. P.; Dolores Fernandez, M.; Fernandez-Alvarez, E.;
Bernabe, M. Tetrahedron Lett. 1991, 32, 541-2. (b) Reginato, G.; Mordini,
A.; Caracciolo, M. J. Org. Chem. 1997, 62, 6187-6192. (c) Campbell, A.
D.; Raynham, T. M.; Taylor, R. J. K. Tetrahedron Lett. 1999, 40, 5263-
5266. (d) Sabat, M.; Johnson, C. R. Org. Lett. 2000, 2, 1089-1092. (e)
Collier, P. N.; Campbell, A. D.; Patel, I.; Raynham, T. M.; Taylor, R. J.
K. J. Org. Chem. 2002, 67, 1802-1815. (f) Collier, P. N.; Campbell, A.
D.; Patel, I.; Taylor, R. J. K. Tetrahedron 2002, 58, 6117-6125. (g) Collier,
P. N.; Patel, I.; Taylor, R. J. K. Tetrahedron Lett. 2002, 43, 3401-3405.
(h) Pietruszka, J.; Witt, A.; Frey, W. Eur. J. Org. Chem. 2003, 3219-
3229. (i) Rodriguez, A.; Miller, D. D.; Jackson, R. F. W. Org. Biomol.
Chem. 2003, 1, 973-977. (j) Babu, I. R.; Hamill, E. K.; Kumar, K. J.
Org. Chem. 2004, 69, 5468-5470. (k) Harvey, J. E.; Kenworthy, M. N.;
Taylor, R. J. K. Tetrahedron Lett. 2004, 45, 2467-2471.
(31) IMesCuCl:
(30) (a) Garner, P.; Park, J. M. J. Org. Chem. 1987, 52, 2361-2364. (b) Garner,
P.; Park, J. M. J. Org. Chem. 1988, 53, 2979-2984. (c) Garner, P.; Park,
J. M.; Malecki, E. J. Org. Chem. 1988, 53, 4395-4398.
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A R T I C L E S
Lebel et al.
alkene was followed by TLC analysis. An aqueous solution of NaOH
(1.6 mmol, approximately 0.8 mL) was then added and thus quenched
the excess of 9-BBN. After the gas evolution was finished, Pd(PPh3)4
(0.028 g, 0.025 mmol) was added, followed by the corresponding alkyl
or aryl halide (0.750 mmol). Finally, tetrabutylammonium iodide
(TBAI) (0.12 mmol) was added, and the resulting mixture was stirred
under argon at 90 °C overnight. The reaction mixture was poured into
a separatory funnel and washed twice with ethyl acetate (2 × 10 mL).
The combined organic layers were washed with saturated aqueous NaCl
and then dried over MgSO4. The solvent was removed under reduced
pressure, and the residue was purified by flash chromatography using
the indicated solvent.
Procedure C: Copper-Catalyzed Methylenation-Suzuki Cross-
Coupling Process. To a solution of copper chloride (2.5 mg, 0.025
mmol) and triphenylphosphine (0.144 g, 0.550 mmol) in THF (3 mL)
was added 2-propanol (0.042 mL, 0.550 mmol) followed by the
aldehyde (0.500 mmol). To the resulting mixture was added (trimeth-
ylsilyl)diazomethane (0.700 mmol), and the reaction mixture was heated
to 60 °C. When the methylenation reaction was completed by TLC
analysis, toluene (3 mL) was added, followed by 9-BBN (0.122 g, 0.500
mmol). The mixture was then heated at 80 °C, and the disappearance
of the alkene was followed by TLC analysis. An aqueous solution of
NaOH (1.6 mmol, approximately 0.8 mL) was then added and thus
quenched the excess of 9-BBN. After the gas evolution was finished,
Pd(PPh3)4 (0.025 mmol, 0.028 g) was added followed by the corre-
sponding alkyl or aryl halide (0.750 mmol). Finally, TBAI (0.12 mL)
was added, and the resulting mixture was stirred under argon at 90 °C
overnight. The reaction mixture was poured into a separatory funnel
and washed twice with ethyl acetate (2 × 10 mL). The combined
organic layers were washed with saturated aqueous NaCl and then dried
over MgSO4. The solvent was removed under reduced pressure, and
the residue was purified by flash chromatography using the indicated
solvent.
Experimental Section
Procedure A: Methylenation-Heck Cross-Coupling Process. To
a solution of CuCl (50 mg, 0.050 mmol) and triphenylphosphine (263
mg, 1.00 mmol) in dry THF (10 mL) at 25 °C was added 2-propanol
(0.0840 mL, 1.10 mmol) followed by the aldehyde (1.00 mmol). The
mixture was heated at 60 °C, and then (trimethylsilyl)diazomethane
(1.40 mmol) was added. The resulting yellow mixture was stirred at
60 °C. When the methylenation was completed by TLC analysis, THF
was concentrated and the mixture was diluted in triethylamine (2.00
mL). To this solution were added the aryl bromide (1.00 mmol), Pd-
(OAc)2 (0.011 g, 0.050 mmol), and P(o-tolyl)3 (0.030 g, 0.10 mmol).
The reaction mixture was stirred at 100 °C and was monitored by
following the disappearance of the styrene by TLC. After completion,
the reaction was quenched by adding water and extracted with ethyl
acetate. The combined organic layers were dried over MgSO4 and
concentrated under reduced pressure. The crude product was then
purified by flash chromatography, and stilbene was obtained as a white
solid.
5,6-Dimethoxy-1,1-dimethyl-2,3-dihydro-1H-indene (14).24 To a
solution of IMesCuCl (20 mg, 0.050 mmol) and triphenylphosphine
(315 mg, 1.20 mmol) in dry benzene (10 mL) at 25 °C was added
2-propanol (0.920 mL, 12.0 mmol) followed by 4-(2-bromo-4,5-
dimethoxyphenyl)butan-2-one (13)26 (1.00 mmol). The resulting mixture
was heated to 80 °C, and (trimethylsilyl)diazomethane (1.00 mmol)
was then added. After 4 h, an additional equivalent of (trimethylsilyl)-
diazomethane (1.00 mmol) was added. The resulting yellow mixture
was stirred at 80 °C for 12 h. Dry DMF (10 mL) was added, followed
by Pd(PPh3)4 (116 mg, 0.100 mmol). The reaction mixture was stirred
at 100 °C, and after an hour, sodium formate (2 mmol) was added.
After 24 h, the solvent was removed under reduced pressure and the
residue was purified by flash chromatography (5% EtOAc/hexanes).
The desired product 12 was obtained as a colorless liquid: Rf 0.56 (20%
EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) δ 6.74 (s, 1H), 6.67 (s,
1H), 3.88 (s, 3H), 3.85 (s, 3H), 2.83 (t, J ) 8 Hz, 2H), 1.93 (t, J ) 8
Hz, 2H), 1.24 (s, 6H); 13C NMR (400 MHz, CDCl3) δ 148.0, 147.8,
144.2, 134.0, 107.6, 105.4, 56.1, 55.9, 44.0, 41.7, 29.9, 28.7; IR (neat)
Acknowledgment. This research was supported by NSERC
(Canada), Boehringer Ingelheim (Canada) Lte´e, the Canadian
Foundation for Innovation, the Canada Research Chair Program,
and the Universite´ de Montre´al. Acknowledgment is also made
to the donors of the Petroleum Research Fund, administered
by the American Chemical Society, for partial support of this
research.
2948, 2858, 1765, 1606, 1497, 1464, 1303, 1212, 1067 cm-1
.
Procedure B: Rhodium-Catalyzed Methylenation-Suzuki Cross-
Coupling Process. To a solution of chlorotris(triphenylphosphine)-
rhodium (0.011 g, 0.012 mmol) and triphenylphosphine (0.144 g, 0.550
mmol) in THF (3 mL) was added 2-propanol (0.042 mL, 0.550 mmol)
followed by the aldehyde (0.500 mmol). To the resulting red mixture
was added (trimethylsilyl)diazomethane (0.700 mmol). Gas evolution
was observed, and the resulting mixture was stirred at room temperature.
When the methylenation reaction was completed by TLC analysis,
toluene (3 mL) was added, followed by 9-BBN (0.122 g, 0.500 mmol).
The mixture was then heated to 80 °C, and the disappearance of the
Supporting Information Available: Characterization data and
spectra (1H and 13C NMR) for new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
JA0733235
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13326 J. AM. CHEM. SOC. VOL. 129, NO. 43, 2007