Stable cyclic (alkyl)(amino)carbenes as rigid or flexible, bulky, electron-rich ligands for transition-metal catalysts: A quaternary carbon atom makes the difference

Article abstract of DOI:10.1002/anie.200501841

(Chemical Equation Presented) Like NHCs? Not quite: Cyclic (alkyl)-(amino)carbenes (CAACs) are strong σ-donors and have steric environments that differ dramatically from those of bulky, electron-rich phosphines (A) and cyclic diaminocarbenes (B). These re

Full text of DOI:10.1002/anie.200501841

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of bulky, electron-rich, phosphines A and cyclic diaminocar-
benes (N-heterocyclic carbenes (NHCs)) B (Figure 1).[2]
These ligands stabilize the active catalytic species, and
accelerate the important catalytic steps, namely oxidative
Figure 1. Schematic view of ligands A–C showing their different steric
demands.
addition, transmetallation, and reductive elimination. On the
other hand, excessive steric hindrance can present some
drawbacks for the coupling of bulky reactants.[3] To overcome
this problem Glorius and co-workers have successfully
developed ligands with “flexible steric bulk” using the
conformational flexibility of cyclohexane.[4]
Herein we report the synthesis of stable cyclic (alkyl)-
(amino)carbenes (CAACs) C (Figure 1). The replacement of
one of the electronegative amino substituents of NHCs B by a
strong s-donor alkyl group makes the CAAC ligands C even
more electron-rich than A and B. Moreover, owing to the
presence of a quaternary carbon atom in a position a to the
carbene center, carbenes C feature steric environments that
differentiate them dramatically from both ligands A and B
(Figure 1), and amplifies flexible steric bulk effect. We show
that the peculiar electronic and steric properties of carbenes C
allow for the synthesis of CAAC-palladium complexes that
are highly efficient for the catalytic a-arylation of carbonyl
compounds.
Homogeneous Catalysis
DOI: 10.1002/anie.200501841
Stable Cyclic (Alkyl)(Amino)Carbenes as Rigid
or Flexible, Bulky, Electron-Rich Ligands for
Transition-Metal Catalysts: A Quaternary Carbon
Atom Makes the Difference**
Vincent Lavallo, Yves Canac, Carsten Präsang,
Bruno Donnadieu, and Guy Bertrand*
Direct detection of singlet alkyl carbene compounds
usually requires matrix-isolation conditions or nanosecond
time-resolved laser flash photolysis techniques.[5] However,
last year we reported that, provided a tertiary alkyl group is
bonded to the carbene center, acyclic (alkyl)(amino)carbenes
are isolable and, importantly, behave as strong s-donors
toward transition-metal centers.[6] NHCs B are more robust
and give rise to more active catalysts, when used as ligands for
transition metals, than their acyclic counterparts.[7] Therefore
it was reasonable to believe that CAACs C would also be
more stable than their acyclic variants, and would have
interesting ligand properties.
The method used to prepare the precursor of acyclic
(alkyl)(amino)carbenes, namely the alkylation of the corre-
sponding enamines, is very limited in its scope. Therefore, we
have designed a new synthetic approach, which is very
versatile (Scheme 1). The choice of R, R1, and R2 substituents
The availability of catalysts to perform specific transforma-
tions is critical for both industry and academia. Over the
years, the success of homogeneous catalysis can be attributed
largely to the development of a diverse range of ligand
frameworks that have been used to tune the behavior of a
variety of metal-containing systems. Advances in ligand
design have allowed not only for improvements of known
processes in terms of scope, mildness, and catalyst loadings,
but also for the discovery of new selective reactions. A good
illustration is given by palladium-catalyzed coupling reac-
tions, which are applied to a wide area of endeavors ranging
from synthetic organic chemistry to materials science.[1] For
these catalytic processes, which represent some of the most
powerful and versatile tools available for synthetic chemists,
major advances have recently been reported thanks to the use
[*] V. Lavallo, Dr. Y. Canac, Dr. C. Präsang, B. Donnadieu, Dr. G. Bertrand
UCR-CNRS Joint Research Chemistry Laboratory (UMR 2282)
Department of Chemistry
University of California
Riverside, CA 92521-0403 (USA)
Fax: (+1)951-827-2725
E-mail: gbertran@mail.ucr.edu
[**] We are grateful to the NIH (R01 GM 68825) and RHODIA for
financial support of this work, and to the Alexander von Humboldt
Foundation (C.P.).
Scheme 1. Retrosynthetic analysis for the preparation of CAACs.
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is virtually unlimited (except that R1 and R2 cannot be H) and
the ring skeleton can be modified at will.
This synthetic strategy was first tested with imine 1a
(Scheme 2) prepared from 2,6-diisopropylaniline and the
simplest aldehyde featuring a secondary alkyl substituent, 2-
methylpropanal. Deprotonation of 1a with lithium diiso-
propylamide (LDA) afforded the aza-allyl anion, which
readily induces the ring opening of 1,2-epoxy-2-methylpro-
pane leading to the corresponding alkoxide 2a. Subsequent
treatment with triflic anhydride (TfOTf) at À788C gives rise
to the triflate derivative, which upon warming to room
temperature affords the aldiminium salt 3a in 58% yield
(based on the imine). Lastly, deprotonation with LDA
Scheme 4. Stereoselective synthesis of CAAC Cc. 1) Dimethyloxirane;
2) TfOTf; 3) LDA; Ar=2,6-diisopropylphenyl.
oxirane is completely diastereoselective (Scheme 4). It leads
to the diastereomer affording the best protection for the
carbene and the ensuing metal center to which it is bound.
Moreover, in contrast with Cb, the chair conformation is
locked. Indeed, the other chair conformation would put
both the iso-propyl and methyl groups in unfavorable
axial positions (even a boat conformation would be
highly adverse). It is apparent from the molecular
structure, obtained by a single-crystal X-ray diffraction
study (Figure 2)[8] that the steric environment of this
quantitatively affords carbene Ca as
a white solid
(Scheme 2). CAAC Ca is perfectly stable at room temper-
ature in the solid state and in solution, for at least two weeks.
Scheme 2. Synthesis of CAAC Ca. Ar=2,6-diisopropylphenyl.
The presence of the tertiary carbon center next to the
carbene center offers the possibility of constructing ligands
featuring different types of steric environment. Spiro-CAAC
Cb, readily prepared in a manner similar to that used for Ca,
but using cyclohexyl carbaldehyde, illustrates how the con-
cept of flexible steric bulk can be incorporated into this ligand
family. In fact, compared to the NHCs B developed by
Glorius and co-workers,[4] the cyclohexane ring of Cb is closer
to the carbene and to an ensuing metal center, and therefore
the effects of the “flexible wing” should be amplified
(Scheme 3).
Figure 2. Molecular view of the crystal structure of Cc. Selected bond
lengths [Š] and angles [8]: N1-C1 1.315(3), C1-C2 1.516(3); N1-C1-C2
106.54(18).
CAAC is very different from that of phosphines (described as
a cone) and NHCs (defined as fan-like):[9] the locked
cyclohexane moiety constitutes a “wall of protection” not
only for the carbene center, but also for a metal if Cc is being
used as a ligand (Figure 2). It is noteworthy that Cc is
enantiomerically pure and has been prepared without time-
consuming enantio- or diastereoselective separation.
The carbonyl stretching frequencies of cis-[IrCl(CO)2(L)]
complexes are recognized as an excellent measure of the s-
donor and p-acceptor properties of the ligand L.[10] Addition
of half an equivalent of [{IrCl(cod)}2](cod = 1,5-cycloocta-
diene) to a THF solution of carbene Cc led to the formation of
[IrCl(cod)(Cc)], which upon treatment with CO at room
temperature afforded cis-[IrCl(CO)2(Cc)]( 4c) in high yield.
The average value of the carbonyl stretching frequencies for
complex 4c (nav(CO) = 2013 cmÀ1) indicates that the donor
power of Cc is higher than that of electron-rich phosphines
(PCy3: nav(CO) = 2028 cmÀ1) and even NHC ligands (2017–
Scheme 3. Flexible steric bulk for a) NHCs (B) and b) CAACs (Cb).
Ar=2,6-diisopropylphenyl.
In contrast to Cb, carbene Cc (Scheme 4) exemplifies the
rigidity and extreme steric bulk that CAACs can provide to
metal centers to which they are bound. As a starting material,
we chose the imine 1c derived from (À)-menthone. The key
step of the synthesis is based on the propensity of relatively
bulky reactants to approach the cyclohexane moiety from the
equatorial direction. This effect is reinforced by the presence
of the iso-propyl group, and therefore the reaction with the
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2020 cmÀ1); only the abnormal C5-bound NHCs are stronger
donors (2003 cmÀ1).[10]
substrate for the palladium-catalyzed a-arylation of
ketones.[11–14] With nonhindered aryl chlorides the superior
catalytic activity of CAAC complex 5c over 5a,b is demon-
strated (entries 1–8). A turn over number (TON) of up to
7200 has been obtained at room temperature. This compares
extremely favorably with the best TON reported to date: 4200
at 1208C.[14c] When a di-ortho-substituted aryl chloride is used
(entries 9–14), no catalytic activity has been observed with 5a
and 5c, but in marked contrast 5b is active, even at room
temperature. Entries 11 and 13 indicate the thermal stability
of the catalyst.
The steric and electronic properties of CAACs should
benefit the numerous catalytic processes which require bulky
electron-rich ligands at the metal center. As an example of
such a process, we chose to study the palladium-catalyzed a-
arylation of ketones, discovered concurrently in 1997 by the
groups of Buchwald,[11] Hartwig,[12] and Miura.[13] This reac-
tion has not yet been achieved at room temperature with non-
activated aryl chlorides; moreover there are no examples with
sterically hindered di-ortho-substituted aryl chlorides. The
use of CAAC ligands C, indeed, overcomes these limitations.
The [PdCl(allyl)(CAAC)]complexes 5a–c (Figure 3) were
readily prepared in high yields by addition of [{Pd-
(allyl)(Cl)}2]to the corresponding carbenes Ca–c, and isolated
as air stable colorless crystals; they can even be purified by
column chromatography on silica gel.
The dramatic differences observed in the catalytic activity
of complexes 5a–c can be rationalized by the different steric
environments created by ligands Ca, Cb, and Cc. Carbene Ca
is not sterically hindered enough to favor reductive elimi-
nation at room temperature. This step is easily promoted, for
relatively small substrates, by the very rigid and bulky Cc
ligand. However, entry 14 shows that Cc gives rise to a
catalyst very sensitive to excessive steric hindrance. The
molecular structures shown in Figure 3 clearly show that the
steric environment around the metal is very similar for 5a and
5b, and therefore cannot explain the superior catalytic
activity of 5b. However, in solution, the cyclohexane moiety
of 5b can easily undergo a ring flip, which leads to a steric
environment similar to that of 5c.[15] This flexibility also
explains the superiority of 5b over 5c in accommodating
sterically demanding substrates in the coupling process.
Although the a-arylation of carbonyl compounds has a
broad scope of application,[16] very little success has been
reported with aldehydes,[17] mostly because of the competing
aldol condensation. It was reasonable to believe that this side
reaction could be reduced by taking advantage of the mild
conditions allowed by CAAC palladium complexes. Indeed,
2-chlorotoluene is coupled with isobutanal with high effi-
ciency at ambient temperature. Using 1 mol% of 5c, the
desired product was obtained after 16 h in 98% yield, and no
evidence of aldol condensation products was observed. This is
the first example of a-arylation of an aldehyde with an aryl
chloride.
Table 1 summarizes the results obtained using complexes
5a–c for the a-arylation of propiophenone, the classical
Table 1: Palladium-mediated a-arylation of propiophenone with aryl
chlorides.[a]
Entry
Aryl
chloride
Catalyst
([mol%])
T
[8C]
t
[h]
Yield
[%][b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
PhCl
PhCl
PhCl
PhCl
5a (0.5)
5b (0.5)
5c (0.5)
5c (0.1)
5c (0.01)
5a (0.5)
5b (0.5)
5c (0.5)
5a (0.5)
5b (0.5)
5b (0.5)
5b (1)
23
23
23
23
23
23
23
23
23
23
70
23
50
50
70
70
1
22
29
100
83
72
0
10
82
0
32
56
61
81
0
1
PhCl
38
70
36
36
70
36
4
16
20
20
2-MePhCl
2-MePhCl
2-MePhCl
2,6-Me2PhCl
2,6-Me2PhCl
2,6-Me2PhCl
2,6-Me2PhCl
2,6-Me2PhCl
2,6-Me2PhCl
5b (1)
5c (0.5)
In recent years, several different types of stable carbene
compounds have been prepared,[18] but only the “pure” s-
donor NHCs, when used as ligands, have led to highly active
and robust catalysts,[19] which compete or even surpass their
[a] Conditions: THF (1 mL), NaOtBu (1.1 mmol), propiophenone
(1.0 mmol), aryl chloride (1.0 mmol); all reactants (Aldrich) were used
as received. [b] Yields as determined by NMRspectroscopy.
Figure 3. Molecular view of the crystal structures of 5a–c. Selected lengths [Š] and angles [8]: 5a: N-C1 1.3133(11), C1-C2 1.5298(12), C1-Pd
2.0246(9); N-C1-C2 108.51(8). 5b: N-C1 1.310(4), C1-C2 1.526(4), C1-Pd 2.020(3); N-C1-C2 108.7(2). 5c: N-C1 1.315(5), C1-C2 1.543(5), C1-Pd
2.045(4); N-C1-C2 108.8(3).
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3H, CHCH3, J = 6.5 Hz), 0.83 ppm (d, 3H, CHCH3, J = 6.5 Hz);
13C NMR (CDCl3, 258C, 125 MHz): d = 192.64 (CH), 144.7, 144.5,
131.7, 129.0, 125.6, 125.1, 120.6 (q, J = 321.6 Hz), 81.6, 58.5, 52.2, 51.0,
45.4, 34.7, 29.9, 29.5, 29.2, 28.1, 27.1, 26.7, 25.5, 22.8, 22.7, 22.3, 22.2,
22.1, 18.7 ppm.
bulky, electron-rich phosphine counterparts. It is generally
believed that in contrast to NHCs, Fischer-type carbenes
would not survive the standard conditions of organometallic
catalysis, because of the cleavage of the metal–carbon
bond;[20,21] moreover they are regarded as weak s-donors
and good p-acceptors. Our work demonstrates that the
readily available CAACs are strong s-donors, weak p-
acceptors, and form highly catalytically active “cyclic Fischer
carbene complexes”. Their unique steric and electronic
properties, in addition to the broad range of structural
features possible, which arise as a result of the presence of a
tertiary carbon in a position a to the carbene center, makes
these carbenes highly desirable as ligands for various catalytic
processes, including asymmetric variants.
Ca–Cc: A 1/1 mixture of LDA and iminium salt 3 (5.0 mmol) was
cooled to À788C and THF was added (30 mL). The suspension was
warmed to room temperature and stirred for 30 min. After evapo-
ration of the solvent under vacuum, a solid residue containing the
corresponding carbene C and LiOTf was obtained and used for the
complexation reaction without further purification, except for Cc. In
this case, the solid residue was extracted with hexane (30 mL), and
after evaporation of the solvent under vacuum, Cc was obtained as a
white microcrystalline solid. Ca: 13C NMR ([D8]THF, 258C,
125 MHz): d = 304.2 (C), 145.8, 137.5, 128.0, 123.8, 82.5, 57.7, 50.3,
29.1, 28.9, 27.5, 21.7 ppm. Cb: 13C NMR ([D8]THF, 258C, 125 MHz):
d = 309.4 (C), 145.8, 137.8, 127.9, 123.6, 81.2, 63.3, 47.7, 35.8, 29.3, 29.1,
26.4, 23.0, 21.5 ppm. Cc: 92%, m.p. 1158C; [a]2D3 = + 1138 (hexane);
1H NMR (C6D6, 258C, 500 MHz): d = 7.13–7.25 (m, 3H, Har), 3.18
(sept, 2H, CHCH3, J = 6.9 Hz), 2.54–2.78 (m, 2H), 2.11 (m, 1H),
1.72–1.97 (m, 4H), 1.41 (dd, 1H, J = 12.3 and J = 3.3 Hz), 1.11–1.27
(m, 21H), 1.06 (d, 3H, CHCH3, J = 6.9 Hz), 1.02 (d, 3H, CHCH3, J =
6.9 Hz), 0.96 ppm (3H, CHCH3, J = 6.6 Hz); 13C NMR ([D8]THF,
258C, 125 MHz): d = 319.0 (C), 146.6, 145.7, 138.1, 127.6, 123.8, 123.3,
79.7, 69.4, 53.1, 52.0, 48.0, 36.9, 30.2, 29.8, 29.1, 29.0, 28.6, 27.7, 27.0,
25.4, 24.1, 23.6, 22.8, 21.9, 21.2, 18.7 ppm.
Experimental Section
All manipulations were performed under an inert atmosphere of
argon using standard Schlenk techniques. Dry, oxygen-free solvents
1
were employed. H and 13C NMR spectra were recorded on Varian
Inova 300, 500, and Brucker Avance 300 spectrometers.
3a,b: A solution of LDA (4.66 g, 43.5 mmol) in Et2O (40 mL) was
added at 08C to a stirred solution of imine 1a or 1b (43.5 mmol) in
Et2O (40 mL). The solution was warmed to room temperature and
stirred for 2 h. After evaporation of the solvent under vacuum, the
residue was dissolved in Et2O (80 mL), and 1,2-epoxy-2-methylpro-
pane (4.06 mL, 45.7 mmol) was added dropwise. After stirring for
12 h at room temperature, trifluoromethane sulfonic anhydride
(7.68 mL, 45.7 mmol) was added at À788C. The solution was
warmed to room temperature and stirred for 1 h. After filtration,
the residue was washed with Et2O (80 mL). Extraction of the solid
with CH2Cl2 (40 mL) afforded 3a,b as white solids. 3a: 58%, m.p.
198–2008C; 1H NMR (CDCl3, 258C, 300 MHz): d = 9.48 (s, 1H, CH),
7.53 (m, 1H, Har), 7.34 (m, 2H, Har), 2.63 (sept, 2H, CHCH3, J =
6.9 Hz), 2.43 (s, 2H, CH2), 1.68 (s, 6H, CH3), 1.54 (s, 6H, CH3), 1.35
(d, 6H, CHCH3, J = 6.9 Hz), 1.17 ppm (d, 6H, CHCH3, J = 6.9 Hz);
13C NMR (CD3CN, 258C, 75 MHz): d = 192.2 (CH), 145.6, 133.1,
130.1, 126.6, 122.2 (q, J = 321.6 Hz), 85.8, 66.3, 48.8, 30.4, 28.5, 26.3,
4c: A solution of carbene Cc (0.34 g, 0.90 mmol) in THF (5 mL)
was added at À788C to a stirred THF solution (5 mL) of [{IrCl(cod)}2]
(0.27 g, 0.41 mmol). The solution was warmed to room temperature
and stirred for 3 h. After evaporation of the solvent under vacuum,
the residue was washed with hexane (15 mL), dissolved in THF
(5 mL), and carbon monoxide was bubbled through the solution
(45 min) at room temperature. After evaporation of the solvent under
vacuum, carbene complex 4c was obtained as a brown powder. 0.42 g,
71%; 1H NMR (CDCl3, 258C, 300 MHz): d = 7.55 (m, 1H, Har), 7.36
(m, 2H, Har), 2.61–2.76 (m, 3H), 2.38 (d, 1H, J = 14.4 Hz), 2.06–2.24
(m, 3H), 1.67–1.95 (m, 6H), 1.64 (s, 3H), 1.60 (s, 3H), 1.36 (d, 6H,
CHCH3, J = 6.6 Hz), 1.19–1.27 (m, 6H), 1.08 (d, 3H, CHCH3, J =
6.9 Hz), 0.97 (d, 3H, CHCH3, J = 5.4 Hz), 0.85 ppm (d, 3H, CHCH3,
J = 6.9 Hz); 13C NMR (CDCl3, 258C, 75 MHz): d = 191.3 (CO), 190.9
(C), 167.8 (CO), 144.8, 144.6, 132.3, 129.0, 126.1, 125.6, 82.4, 58.7, 58.6,
52.3, 51.1, 45.8, 34.6, 30.4, 30.1, 29.7, 28.6, 27.6, 27.4, 26.6, 23.3, 23.0,
1
26.2, 22.2 ppm. 3b: 48%, m.p. 268–2708C; H NMR (CD3CN, 258C,
300 MHz): d = 8.91 (s, 1H, CH), 7.67 (m, 1H, Har), 7.52 (m, 2H, Har),
2.78 (sept, 2H, CHCH3, J = 6.9 Hz), 2.53 (s, 2H, CH2), 1.19–2.11 (m,
10H, CH2), 1.59 (s, 6H, CH3), 1.40 (d, 6H, CHCH3, J = 6.9 Hz),
1.15 ppm (d, 6H, CHCH3, J = 6.9 Hz); 13C NMR (CD3CN, 258C): d =
191.3 (CH), 145.4, 132.9, 130.0, 126.4, 122.2 (q, J = 321.2 Hz), 85.0,
53.6, 45.9, 34.6, 30.2, 28.7, 26.1, 25.3, 22.1 ppm.
22.9, 22.5, 22.2, 19.4 ppm. IR (CH2Cl2): n˜ = 2055, 1971 (n(CO)) cmÀ1
.
5a–c: A solution of carbene C (5.2 mmol) in THF (15 mL) was
added at À788C to a stirred solution of [{Pd(allyl)(Cl)}2](0.95 g,
2.6 mmol) in THF (15 mL). The solution was warmed to room
temperature and stirred for 3 h. After evaporation of the solvent
under vacuum, the solid residue was washed with hexane (40 mL).
Extraction with CH2Cl2 (20 mL) afforded a gray solid, which was
recrystallized in THF (5a) or hexane (5b,c) at À208C. Carbene
complexes 5 were obtained as colorless crystals. 5a: 71%, m.p. 162–
1638C; 1H NMR (CDCl3, 258C, 300 MHz): d = 7.27–7.42 (m, 3H,
Har), 5.05 (m, 1H, Hallyl), 4.18 (d, 1H, Hallyl, J = 7.5 Hz), 3.19 (m, 3H,
CHCH3 and 2Hallyl), 3.01 (m, 1H, CHCH3), 2.02 (s, 3H, Hallyl, CH2),
1.64 (s, 6H, CH3), 1.23–1.40 ppm (m, 18H, CH3); 13C NMR (CDCl3,
258C, 75 MHz): d = 267.4 (C), 146.5, 135.8, 129.1, 125.1, 115.5, 81.5,
76.8, 57.5, 50.5, 48.6, 31.7, 30.6, 29.3, 28.6, 28.1, 27.5, 25.1 ppm. 5b:
3c: A solution of the lithium salt of dimethylamine (1.56 g,
30.5 mmol) in THF (40 mL) was added at 08C to a stirred solution of
imine 1c (10.00 g, 30.5 mmol) in THF (40 mL). The solution was
warmed to room temperature and stirred for 18 h. After evaporation
of the solvent and then heating under vacuum at about 2008C for
10 min, to remove the THF complexed to the lithium, the residue was
dissolved in toluene (100 mL). After adding dropwise 1,2-epoxy-2-
methylpropane (2.85 mL, 32.0 mmol), the solution was stirred for 12 h
at room temperature. Then Tf2O (5.39 mL, 32.0 mmol) was added at
À788C and the suspension was allowed to warm to room temperature
and stirred for 2 h. After filtration, the oily residue was washed with
boiling toluene (90 mL). Extraction of the residue with CH2Cl2
(60 mL) afforded 3c as a white solid, which was recrystallized in
CH2Cl2/Et2O at À208C. 6.65 g, 41%, m.p. 258–2608C; [a]2D3 = À388
1
74%, m.p. 176–1788C; H NMR (CDCl3, 258C, 300 MHz): d = 7.21–
7.63 (m, 3H, Har), 5.04 (m, 1H, Hallyl), 4.18 (d, 1H, Hallyl, J = 7.5 Hz),
3.29 (m, 1H, CHCH3), 3.15 (m, 2H, Hallyl), 2.98 (m, 1H, CHCH3), 2.45
(m, 2H, CH2), 1.22–2.05 (m, 17H, Hallyl, CH2, CH3), 1.30 ppm (d, 12H,
CHCH3, J = 6.9 Hz); 13C NMR (CDCl3, 258C, 75 MHz): d = 267.8
(C), 146.5, 136.3, 129.0, 125.1, 115.6, 80.5, 77.0, 62.9, 48.3, 45.7, 38.8,
37.2, 31.3, 29.5, 28.6, 28.0, 27.0, 25.4, 25.3, 22.9, 22.4 ppm. 5c: 70%,
m.p. 157–1598C; [a]D23 = À18 (CHCl3); 1H NMR (CDCl3, 258C,
300 MHz): d = 7.20–7.38 (m, 3H, Har), 5.04 (m, 1H, Hallyl), 4.21 (d,
1H, Hallyl, J = 7.5 Hz), 3.70 (sept, 1H, CHCH3, J = 6.3 Hz), 3.15 (d,
1
(CHCl3); H NMR (CDCl3, 258C, 500 MHz): d = 9.73 (s, 1H, CH),
7.53 (m, 1H, Har), 7.34 (m, 2H, Har), 2.64 (m, 3H, CH), 2.20 (m, 2H),
2.04 (m, 2H), 1.90 (m, 2H), 1.78 (m, 2H), 1.59 (s, 3H, CH3), 1.55 (s,
3H, CH3), 1.35 (d, 3H, CHCH3, J = 7.0 Hz), 1.34 (d, 3H, CHCH3, J =
6.0 Hz), 1.21 (d, 3H, CHCH3, J = 6.5 Hz), 1.17 (d, 3H, CHCH3, J =
6.0 Hz), 1.06 (d, 3H, CHCH3, J = 7.0 Hz), 1.00–1.10 (m, 2H), 0.94 (d,
5708
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Angew. Chem. Int. Ed. 2005, 44, 5705 –5709

Angewandte
Chemie
1H, Hallyl, J = 14.1 Hz), 2.82–2.98 (m, 4H), 2.32 (m, 1H), 1.70–2.09 (m,
7H), 1.35–1.45 (m, 8H), 1.30 (d, 6H, CHCH3, J = 6.6 Hz), 1.29 (s,
3H), 1.20 (d, 3H, CHCH3, J = 6.9 Hz), 0.99 (t, 6H, CHCH3, J =
6.9 Hz), 0.93 ppm (d, 3H, CHCH3, J = 6.6 Hz); 13C NMR (CDCl3,
258C, 75 MHz): d = 272.0 (C), 148.3, 145.6, 137.5, 129.0, 126.4, 124.7,
114.9, 78.7, 78.0, 67.4, 54.2, 52.0, 51.2, 48.1, 33.7, 33.6, 30.7, 30.1, 29.2,
29.0, 28.6, 28.0, 27.2, 26.0, 25.7, 23.8, 22.4, 20.9 ppm.
a-Arylation procedure: Glass vials were charged under inert
atmosphere in the glovebox with NaOtBu (1.1 mmol) in THF
(0.5 mL). Then a mixture of the palladium catalyst (see Table 1 for
amounts), aryl halide (1.0 mmol) and propiophenone or isobutanal
(1.0 mmol) in THF (0.5 mL) was added at room temperature. Then
the reaction were stirred at the temperature for the period of time
indicated in Table 1. The reactions were quenched with aqueous
solution of NH4Cl and extracted with Et2O. The organic layer was
dried over MgSO4. All compounds were identified by 1H NMR
spectroscopy. The reported yields are determined by NMR spectros-
copy.
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Received: May 27, 2005
Published online: August 1, 2005
Keywords: arylation · carbenes ·
.
homogeneous catalysis · palladium
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Angew. Chem. Int. Ed. 2005, 44, 5705 –5709
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 5709