Branched/linear selectivity in palladium-catalyzed allyl-allyl cross-couplings: the role of ligands

Article abstract of DOI:10.1016/j.tet.2015.05.015

Abstract While Pd-catalyzed allyl-allyl cross-couplings in the presence of small-bite-angle bidentate ligands reliably furnish the branched regioisomer with high levels of selectivity, cross-couplings in the presence of large-bite-angle bidentate ligands

Full text of DOI:10.1016/j.tet.2015.05.015

Tetrahedron 71 (2015) 6409e6413
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Branched/linear selectivity in palladium-catalyzed allyl-allyl
q
cross-couplings: the role of ligands
Michael J. Ardolino, James P. Morken *
Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
While Pd-catalyzed allyl-allyl cross-couplings in the presence of small-bite-angle bidentate ligands re-
liably furnish the branched regioisomer with high levels of selectivity, cross-couplings in the presence of
large-bite-angle bidentate ligands give varying, often unpredictable, levels of selectivity. In a combined
computational and experimental study, we probe the underlying features that govern the regioselectivity
in these metal-catalyzed cross-couplings.
Received 12 March 2015
Received in revised form 1 May 2015
Accepted 5 May 2015
Available online 15 May 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Bite angle
Cross-coupling
Allylation
Pd catalysis
1. Introduction
The transition metal-catalyzed coupling of two allylic fragments
has the power to generate synthetically useful 1,5-dienes from an
1
allylic electrophile and allylic nucleophile (Scheme 1). Under pal-
ladium catalysis, the allyl-allyl coupling reaction has been known for
some time and typically yields linear, achiral dienes of type A with
2
monodentate phosphine ligands (Eq 1). Recently, our group has
disclosed a number of methods that employ chiral, small-bite-angle
bidentate phosphine ligands to reverse the regioselectivity of these
couplings to give branched 1,5-dienes of type C with excellent regio-
Scheme 1. Linear/branched selectivity in allyl-allyl coupling.
3
and enantioselectivity (Eq 2). Recent mechanistic and computa-
4
3
Table 1 and in line with previous studies, use of PPh as the ligand
tional studies have supported previous proposals that the reaction
3
0
5
in the Pd-catalyzed coupling of cinnamyl t-butyl carbonate 1 and
allyl B(pin) 2 (entry 1) gives high selectivity for the linear 1,5-diene
. Ligands with smaller bite-angles (entries 2e4) gave high
is operative through an inner-sphere 3,3 -reductive elimination, in
which coupling at carbons 3 and 3 through the conformation as
0
4
shown in B leads to the branched isomer. These studies are in line
branched selectivity, however, selectivity became unpredictable as
with computational studies on the preferred reductive elimination
6
5
a
the bite-angle increased (entries 6e8). Unable to explain the
pathways for unsubstituted allylic systems by Eschavarren and
Espinet,5 which also found the 3,3 -reductive elimination to be
c
0
source of such disparate regioselectivity in systems containing
either monodentate or wide-bite-angle bidentate ligands, we un-
dertook additional mechanistic and computational studies to probe
0
preferred over direct coupling at the 1 and 1 carbons.
Although our previous study provided a deeper understanding
of the origins of branched regioselectivity for small-bite-angle
bidentate phosphine ligands, it did not explain trends in regiose-
lectivity that we have observed with other ligands.3 As seen in
7
the origins of linear selectivity.
a
2. Results and discussion
2.1. Monodentate ligands
q
This article is submitted with a hearty congratulations to Professor Tsuji on
receipt of the 2014 Tetrahedron Prize for Creativity in Organic Chemistry!
To explore the source of high linear regioselectivity in
Pd-catalyzed allyl-allyl couplings with monodentate ligands,
*
Corresponding author. Tel.: þ1 627 552 6290; e-mail address: morken@bc.edu
(
J.P. Morken).
http://dx.doi.org/10.1016/j.tet.2015.05.015
040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
0

6410
M.J. Ardolino, J.P. Morken / Tetrahedron 71 (2015) 6409e6413
Table 1
a
Impact of ligand structure on cross coupling selectivity
ꢀ
Entry
Ligand
PPh
dppbenzene
dppe
dppp
dppf
dppb
DPEphos
Xantphos
B
n
( )
Yield (%)
b:l (3:4)
1
2
3
4
5
6
7
8
3
d
96
70
77
80
43
77
58
1:>20
97:3
98:2
97:3
94:6
38:62
72:28
53:47
83
85
91
96
98
102
109
>95% conv.
a
Data in entries 1e7 from ref. 3a.
Fig. 2. Calculated activation free energy barriers (
B3LYP-PCM(THF)/LANL2DZ(Pd)-6-31G**(C,H,P) (333.15 K). All energies include free
PPh to align with those shown in Fig. 1.
DG) in kcal/mol relative to GS
A
(
3
computational studies utilizing density functional theory (DFT)
were carried out.8 These studies considered possible pathways
leading to linear and branched isomers of phenyl-substituted 1,5-
branched compound 3 (TS
only 8.4 kcal/mol. The activation energy for 1,1 -reductive elimi-
nation to give linear product (TS
D
, Fig. 2) was found to have a barrier of
0
diene products of type 3 and 4 (Table 1), and began from the bis-
E
) was calculated to be 18.2 kcal/
1
ligated, bis(
ies,
h
-allyl) complex GS
A
(Fig. 1). Based on previous stud-
0
mol, now almost 10 kcal higher in energy than the 3,3 (TS
D
). This
5
a,c
the two lowest energy routes for bond formation from GS
should be through coupling at the either 3 and 3 (TS
A
0
result suggests that the 1,1 -pathway remains an improbable source
of linear product for the three-coordinate system as well. Searching
for an alternate explanation, we found the benzylic ground state
0
0
A
) or 1 and 1
0
carbons (TS
B
). The 3,3 -pathway to give the branched isomer 3 (TS
A
)
was calculated to have an activation free energy barrier of 14.6 kcal/
E
(GS ) to be far less disfavored with only one ligand on the palla-
0
mol. The alternate 1,1 -coupling to give linear product (TS
B
), lies
10
dium, now only 1.5 kcal/mol higher in energy than GS
from this ground-state formation of linear product 4 via 3,3 -re-
ductive elimination through TS
C
.
Excitingly,
5
.5 kcal/mol higher in energy, making it an unlikely source of 4. An
0
0
alternate route to this linear product could be 3,3 reductive elim-
ination from a complex in which the palladium sits at the benzylic
F
was found to have a barrier of only
0
4.3 kcal/mol. Presumably by allowing the favored 3,3 -elimination
B
carbon of the allyl fragment (GS ). This more highly-strained
to occur between two unsubstituted carbons, this activation free
energy lies lower than any of the other barriers calculated for for-
mation of either isomer of diene. Reaction through TS could rep-
F
resent the dominant source of the linear product in allyl-allyl
couplings with monodentate ligands, and its low barrier compared
ground state was calculated to be 15.3 kcal/mol higher in energy
9
than GS
considered that instead of bond-formation, complex GS
dissociate one PPh ligand to form three-coordinate palladium
complex GS . This ground state lies almost 22 kcal/mol lower in
energy than GS , and the barrier for its formation (TS ) is only
.7 kcal/mol. These energies suggest that formation of complex GS
A
, making it an improbable species in the reaction. It was
A
might
3
C
to TS
observed experimentally with PPh
Although systems containing only one phosphine ligand should
favor linear product formation (TS , Fig. 2), the calculations also
suggest that the branched product should be favored (TS , Fig. 1)
would explain why such high linear to branched ratios are
D
11
A
C
.
3
3
C
A
from GS should be both rapid and thermodynamically favored,
presumably driven by a loss of strain.
While calculations on the bis-ligated systems failed to indicate
a potential origin for the experimentally observed linear product,
C
they did point to complex GS as a reasonable intermediate. As
a result, we considered potential pathways for bond-formation
from this complex (Fig. 2). In line with the studies by Espinet,5c
barriers for diene formation from this three-coordinate system
F
A
when two ligands are bound to Pd. If the mono- and bis-ligated
complexes indeed give opposite regioselectivity, it appeared tena-
ble that branched to linear ratios should be dependent on the
equilibrium between these two complexes. To explore this idea
experimentally, the Pd-catalyzed allyl-allyl coupling of cinnamyl
carbonate 1 and allylB(pin) 2 was carried out with increasing
equivalents of triphenylphosphine (Scheme 2). While the linear
isomer 4 remained favored in all cases, entries 3 and 4 show that
the amount of branched product 3 increased with higher equiva-
lents of triphenylphosphine relative to Pd. In line with the com-
were found to be lower overall than those found for the bis-ligated
0
system (Fig. 1). From GS
C
, 3,3 -reductive elimination to give the
putations suggesting that three-coordinate GS
C
lay far below four-
coordinate GS , a large excess (10 equiv) of ligand was required to
A
exceed even a 10:1 ratio of linear to branched product (entry 4).
This experiment supports the idea that the linear isomer arises
Fig. 1. Calculated activation free energy barriers (
DG) in kcal/mol relative to GS
A
(
B3LYP-PCM(THF)/LANL2DZ(Pd)-6-31G**(C,H,P) (333.15 K).
3
Scheme 2. Effect of added PPh on allyl-allyl coupling.

M.J. Ardolino, J.P. Morken / Tetrahedron 71 (2015) 6409e6413
6411
from a three-coordinate complex, while the branched isomer might
arise from a complex involving two phosphine ligands.
96:4). Assuming that Dt-BPF is able to act as a hemilabile ligand in
this reaction as well, these results suggest that the lowered regio-
selectivity could arise from a competition between palladium
complexes in which one or both of the phosphines of the bidentate
ligand are coordinated.
2
.2. Bidentate ligands
Having established a tenable explanation for the linear selectivity
observed with monodentate ligands, the effect of bidentate ligand
bite-angle on regioselectivity was explored. We had originally pro-
posed that small-bite-angle bidentate ligands gave high branched
0
selectivity by separating the 1 and 1 carbons, effectively slowing the
0
0
1
,1 -elimination pathway and allowing the 3,3 -path to prevail. In
contrast, a larger bite-angle ligand might increase the proximity of
0
0
the1 and1 carbons, allowingthe1,1 -reductive elimination toensue.
To probe this hypothesis computationally, the activation free energy
Scheme 3. Effect of Bis(phosphino)ferrocene ligand on allyl-allyl coupling.
0
0
barriers for both the 3,3 - and 1,1 -reductive elimination pathways
were calculated for four of the ligands shown inTable 1. Interestingly,
the calculations provide little correlation between elimination bar-
riers and ligand bite-angle (Fig. 3). Each of the ligands showed DD
values favoring the 3,3 -pathway by >11 kcal/mol relative to the
,1 -path. These results fail to provide a link between ligand bite-
angle and the variability in regioselectivity observed experimen-
tally, and suggest that an alternate explanation is required.
Considering other pathways that could lead to the linear cou-
pling product, we considered whether large-bite-angle ligands
might allow reaction through three coordinate ‘arm off’ complexes
To explore computationally the ability of larger-bite-angle li-
gands to act as hemilabile ligands (Fig. 4), xantphos (53:47 b:l,
entry 8, Table 1) was chosen as a model ligand due to its structural
rigidity and nonselectivity in coupling reactions. Overall, these
computations indicated that xantphos may be able to access
z
G
0
0
1
a similar pathway leading to linear diene formation as that pro-
1
posed for triphenylphosphine. Starting from bis-ligated, bis(
h
-al-
0
lyl) GS
F
, 3,3 -reductive elimination through TS
H
to give branched
product occurs with an activation free energy barrier of 12.6 kcal/
0
mol. The 1,1 -pathway (TS
I
) is almost 15 kcal/mol higher in energy,
and remains an improbable source of linear product. As an alternate
to bond formation, GS can instead dissociate one arm of the
phosphine ligand to give mono-ligated GSG, which lies only
F
akin to TS as proposed for monodentate ligands. In this context,
factors other than bite-angle such as ligand flexibility could also
play a role in regiocontrol. As flexibility is often unrelated to ligand
bite-angle,6 this feature might explain the nonlinear correlation
between bite-angles and branched to linear ratios (e.g., entries 5e8,
Table 1). To examine this effect, the experiment shown in Scheme 3
was carried out.13 While structurally similar to bidentate dppf, di-
tert-butylphenylferrocene (Dt-BPF) has been shown to act as
a hemilabile or monodentate ligand in Pd-catalyzed cross-cou-
plings.14 Accordingly, when employed in the allyl-allyl coupling of
cinnamyl electrophiles and allylB(pin) (Scheme 3), Dt-BPF gives
a nearly opposite branched to linear ratio relative to dppf (15:85 vs
F
,12
3
.4 kcal/mol higher in energy. From this three-coordinate complex,
0
z
3,3 -reductive elimination through TS
also furnish the branched diene product.
J
(DG ¼10.0 kcal/mol) would
C E G
As seen with triphenylphosphine (GS to GS , Fig. 2), GS can
I
alternately isomerize to give GS , which lies 3.1 kcal/mol higher in
energy than GS , presumably due to increased steric interactions
G
between the adjacent phenyl substituent and the dissociated arm
0
of the ligand. From this complex, 3,3 -reductive elimination (TS
K
) to
form linear product showed a relatively small barrier of only
z
4
.4 kcal/mol, giving DDG values of ꢁ1.7 and ꢁ2.5 kcal/mol relative
to TS
Curtin-Hammett control, these calculations point to reaction
through the mono-ligated TS as not only possible, but preferred. It
H J
and TS , respectively. Assuming that the reaction is under
K
should be noted that the relative calculated energies predict a much
lower branched to linear ratio than is observed experimentally;
however, the actual product ratio values are likely within the error
H J K
of the calculated energy values, as TS , TS and TS all lie within
2.5 kcal/mol of one another. These calculations serve as qualitative
evidence that large-bite-angle, flexible ligands may behave as
hemilabile structures and allow reaction through three-coordinate
complexes. This proposal could also explain why dppb, a flexible
ꢀ
ligand with a bite-angle (98 ) smaller than that of the more-rigid
ꢀ
ꢀ
DPEphos or xantphos (102 and 109 , respectively) furnishes less
branched product (entries 6e8, Table 1).
3. Conclusion
Overall, this study provides insight into how ligands control
regioselectivity in allyl-allyl couplings. Although previous pro-
posals considered small-bite-angle bidentate ligands to promote
0
0
high branched selectivity by controlling rates of 3,3 - versus 1,1 -
reductive elimination, the present study provides evidence of an
alternate pathway. We now propose that the linear diene product
0
is instead formed through a 3,3 -reductive elimination from
a mono-ligated complex (F, Scheme 4) in which Pd sits at the
substituted carbon of the allyl fragment. This explanation accounts
for the high linear selectivity observed with monodentate ligands,
and also provides a rationale for why large-bite-angle bidentate
2
Fig. 3. Calculated reductive elimination selectivity from L Pd(allyl)(cinammyl) com-
plexes with varied ligand bite-angle.

6412
M.J. Ardolino, J.P. Morken / Tetrahedron 71 (2015) 6409e6413
F
Fig. 4. Calculated activation free energy barriers (DG) in kcal/mol relative to GS (B3LYP-PCM(THF)/LANL2DZ(Pd)-6-31G**(C,H,P) (333.15 K).
bisphosphine ligands show inconsistent results. It is clear that li-
gand flexibility may play a significant role in controlling regiose-
lectivity in allyl-allyl couplings, and may be an overlooked factor in
related transition-metal catalyzed processes as well.
in 5 mL of THF under a nitrogen atmosphere was added dropwise at
ꢀ
ꢀ
ꢁ78 C, and the solution was warmed to 0 C for 2 h followed by
gradual warming to room temperature overnight. The reaction was
ꢀ
re-cooled to 0 C and quenched with diethyl ether and ice water
(100 mL of a 3:2 mixture), poured into a separatory funnel and
extracted into diethyl ether (3ꢂ100 mL). The combined organics
were dried over magnesium sulfate, filtered, and concentrated in
vacuo. The crude reaction mixture was purified on silica gel (10:1
pentane:diethyl ether) to afford a clear, colorless oil (1.78 g, 76%
yield). R
f
¼0.60 (10:1 pentane:diethyl ether, stain in KMnO
4
) Spec-
tral data are in accordance with the literature.
4.3. Cross-coupling in Table 1 with PPh
3
An oven-dried two-dram vial equipped with magnetic stir bar
was charged with Pd (dba) (1.1 mg, 1.25 mol), triphenylphos-
phine (PPh ) (1.3, 5.2, 10.4 or 26.2 mg; 5.0, 20, 40.0 or 100 mol),
2
3
m
Scheme 4. Lowest energy paths to linear and branched products.
3
m
and THF (0.2 mL) in a dry-box under argon atmosphere. The vial
was capped and stirred for five minutes, then tert-butyl cinnamyl
carbonate (23.4 mg, 0.100 mmol) was added, followed by allyl-
boronic acid pinacol ester (20.2 mg, 0.120 mmol). The vial was
sealed, removed from the dry-box, and allowed to stir at 60 C for
12 h. After this time, the reaction mixture was diluted with diethyl
4
4
. Experimental
.1. General
ꢀ
1H NMR spectra were recorded on a Varian Unity Inova 500
(
(
500 MHz). Liquid Chromatography was performed using forced flow
flash chromatography) on silicagel (SiO
, 230ꢂ450 Mesh) purchased
ether, filtered through a plug of silica gel and concentrated in vacuo.
1
2
The branched:linear product was determined by H NMR, spectral
3
a
16
from Silicycle. Thin Layer Chromatography was performed on 25
silicagel plates purchased from Silicycle. Visualizationwasperformed
usingultravioletlight(254nm), potassiumpermanganate (KMnO )in
mm
data for the branched and linear products (3 and 4) are in accord
with the literature.
4
water. All reactionswere conducted inoven-dried glassware underan
inert atmosphere of argon. Tetrahydrofuran (THF) was purified using
a Pure Solv MD-4 solvent purification system from Innovative Tech-
nology Inc. by passing through two activated alumina columns after
being purged with argon. Tris(dibenzylideneacetone) dipalladium(0)
4
.4. Computational details
All calculations were performed using Gaussian 09 with all ge-
ometry optimizations, energies and frequencies calculated at the
DFT level utilizing the B3LYP hybrid functional.
17,18
The 6-31G**
[
9
Pd
2
(dba)
3
], tripheylphosphine (PPh
3
), 4,5-Bis(diphenylphosphino)-
basis set was used for the elements C, H, P, B, F and O in conjunction
with the LANL2DZ relativistic pseudopotential for Pd and Fe. All
free energies were calculated at 333.15 K or 273.15 K. The PCM
model was used to estimate the effect of solvation (THF). The
frequency calculations for transition states demonstrated one
imaginary frequency each, and each general transition state was
found to connected with the correct ground states through IRC
calculations. NBO analysis was carried out with Gaussian NBO
0
,9-dimethylxanthene (Xantphos), and 1,1 -bis(ditertbutylphos-
phino)ferrocene(Dt-BPF), were purchasedfromStremChemicals, Inc.
All other reagents were purchased from either Fisher or Aldrich and
used without further purification.
19
4
.2. Preparation of 1a15
2
0
A flame-dried round-bottomed flask equipped with a magnetic
stir bar was charged with THF (30.0 mL) and cinnamyl alcohol
version 3.1. The three-dimensional structures presented in the
figures were visualized utilizing CYLview.
21
(
1.34 g, 10.0 mmol) under a nitrogen atmosphere. The solution was
ꢀ
cooled to ꢁ78 C, and n-butyl lithium (10 mmol, 4.8 mL of a 2.1 M
Acknowledgements
solution) was added dropwise over a period of 10 min, and the
ꢀ
solution was stirred at ꢁ78 C for 30 min. A separately prepared
Frontier Scientific is acknowledged for generous donations of
allylB(pin). The NIH (GM-64451) is acknowledged for financial
solution of di-tert-butyl dicarbonate (2.18 g, 10.0 mmol) dissolved

M.J. Ardolino, J.P. Morken / Tetrahedron 71 (2015) 6409e6413
6413
support. MJA acknowledges support in the form of fellowships from
the American Chemical Society (DOC) and AstraZeneca.
7. Portions of this work have been published in the thesis of MJA. See: Ardolino,
M. J. Synthesis of Enantioenriched 1,5- Dienes and 1,5-Enynes by a Palladium-
catalyzed 3,3-Reductive Elimination: Methodology Development and Mechanistic
Studies Ph.D. Dissertation; Boston College: Chestnut Hill, MA, 2014.
Supplementary data
8. For references detailing the use of DFT for distinguishing between transition
states leading to regio- and stereoisomers in related allylic substitutions, see:
(
a) Keith, J. A.; Behenna, D. C.; Mohr, J. T.; Ma, S.; Marinescu, S. C.; Oxgaard, J.;
Experimental and computational procedures and data are in-
cluded as Supplementary data. Supplementary data associated
with this manuscript can be found in the online version. Supple-
mentary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.05.015.
Stoltz, B. M.; Goddard, W. A., III. J. Am. Chem. Soc. 2007, 129, 11876; (b) Keith, J.
A.; Behenna, D. C.; Sheridan, N.; Mohr, J. T.; Ma, S.; Marinescu, S. C.; Nielsen, R.
J.; Oxgaard, J.; Stoltz, B. M.; Goddard, W. A., III. J. Am. Chem. Soc. 2012, 134,
1
9050; (c) Yamamoto, Y.; Takada, S.; Miyaura, N. Organometallics 2009, 28, 152.
0
0
9
. The 3,3 and 1,1 -pathways from this complex were considered, however,
calculations failed to converge.
0. NBO analysis of GS also shows some donation of electron density from the
E
1
adjacent arene into unfilled orbital of the Pd, suggesting that such an in-
References and notes
teraction might also help to stabilize this more-hindered ground state.
0
0
1
1. In addition to the pathways discussed that are operative through 3,3 - or 1,1 -
couplings, there exists an additional
3
1
1. Negishi, E.-I.; Liao, B. In Handbook of Organopalladium Chemistry for Organic
h -h pathway that might also account for
Synthesis; Negishi, E.-I., de Meijere, A., Eds.; Wiley-Interscience: West Lafayette,
IN, 2002; Vol. 1, pp 591e596.
the linear selectivity. The activation barriers for these couplings were calculated
0
0
- or 1,1 - barriers discussed. See
to be substantially higher than the 3,3
Supplementary data.
2
. For nonselective or linear selective allyl-allyl couplings, see: (a) Trost, B. M.;
Keinan, E. Tetrahedron Lett. 1980, 21, 2595; (b) Godschalx, J.; Stille, J. K. Tetra-
hedron Lett. 1980, 21, 2599; (c) van Heerden, F. R.; Huyser, J. J.; Williams, D. B. G.;
Holzapfel, C. W. Tetrahedron Lett. 1998, 39, 5281; (d) Nakamura, H.; Bao, M.;
Yamamoto, Y. Angew. Chem., Int. Ed. 2001, 40, 3208; (e) Flegeau, E. F.; Schneider,
U.; Kobayashi, S. Chem.dEur. J. 2009, 15, 12247; (f) Jim eꢀ nez-Aquino, A.; Flegeau,
12. Casey, C. P.; Whittaker, G. T. Isr. J. Chem. 1990, 30, 299.
13. It was necessary to use cinnamyl chloride as the electrophile in the coupling
with Dt-BPF due to a significant amount of background reaction with the
t-butoxide produced from carbonate 1.
14. Kawatsura, M.; Hartwig, J. H. J. Am. Chem. Soc. 1999, 121, 1473.
15. Adapted from: Trost, B. M.; Fraisse, P. L.; Ball, Z. T. Angew. Chem., Int. Ed. 2002, 41,
1059.
E. F.; Schneider, U.; Kobayashi, S. Chem. Commun. 2011, 9456 For intramolecular
allyl-allyl couplings, see: (g) Trost, B. M.; Pietrusiewicz, K. M. Tetrahedron Lett.
1
985, 26, 4039; (h) Cuerva, J. M.; G oꢀ mez-Bengoa, E.; M eꢀ ndez, M.; Echavarren,
16. Radomkit, S.; Sarnpitak, P.; Tummatorn, J.; Batsomboon, P.; Ruchirawat, S.;
Ploypradith, P. Tetrahedron 2011, 67, 3904.
A. M. J. Org. Chem. 1997, 62, 7540 For related couplings, see: (i) Keinan, E.;
Peretz, M. J. Org. Chem. 1983, 48, 5302; (j) Keinan, E.; Bosch, E. J. Org. Chem. 1986,
17. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman,
J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Car-
icato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg,
J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Naka-
jima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J.
E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.;
Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S.
S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.;
Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.;
51, 4006.
3
. (a) Zhang, P.; Brozek, L. A.; Morken, J. P. J. Am. Chem. Soc. 2010, 132, 10686; (b)
Zhang, P.; Le, H.; Kyne, R. E.; Morken, J. P. J. Am. Chem. Soc. 2011, 133, 9716; (c)
Brozek, L. A.; Ardolino, M. J.; Morken, J. P. J. Am. Chem. Soc. 2011, 133, 16778; (d)
Le, H.; Kyne, R. E.; Brozek, L. A.; Morken, J. P. Org. Lett. 2013, 15, 1432 For related
allyl-allenyl couplings see: (e) Ardolino, M. J.; Morken, J. P. J. Am. Chem. Soc.
2
2
1
012, 134, 8770; (f) Ardolino, M. J.; Eno, M. S.; Morken, J. P. Adv. Synth. Catal.
013, 355, 3413 For related Ir- and Cu catalyzed couplings to furnish branched
,5-dienes, see: (g) Hornillos, V.; P eꢀ rez, M.; Fa n~ an aꢀ s-Mastral, M.; Feringa, B. L. J.
Am. Chem. Soc. 2013, 135, 2140; (h) Hamilton, J. Y.; Sarlah, D.; Carreira, E. M. J.
Am. Chem. Soc. 2014, 136, 3006; (i) Hamilton, J. Y.; Hauser, D.; Sarlah, D.; Car-
reira, E. M. Angew. Chem., Int. Ed. 2014, 53, 10759.
. Ardolino, M. J.; Morken, J. P. J. Am. Chem. Soc. 2014, 136, 7092.
. (a) M eꢀ ndez, M.; Cuerva, J. M.; G oꢀ mez-Bengoa, E.; C aꢀ rdenas, D. J.; Echavarren, A.
M. Chem.dEur. J. 2002, 8, 3620; (b) C ꢀa rdenas, D. J.; Echavarren, A. M. New J.
Chem. 2004, 28, 338; (c) Perez-Rodriguez, M.; Braga, A. A. C.; de Lera, A. R.;
Maseras, F.; Alvarez, R.; Espinet, P. Organometallics 2010, 29, 4983.
. The bite-angles as presented are the ‘natural bite-angles’ of the ligands, see: (a)
Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels,
A. D.; Farkas, O€ .; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09,
Revision A.02; Gaussian: Wallingford CT, 2009.
18. (a) Becke, A. D. Phys. Rev. A 1988, 38, 3098; (b) Lee, C.; Yang, W.; Parr, R. G. Phys.
Rev. B 1988, 37, 785.
4
5
19. (a) Miertus, S.; Scrocco, E.; Tomassi, J. Chem. Phys. 1981, 55, 117; (b) Barone, V.;
Cossi, M.; Tomassi, J. Chem. Phys. 1997, 107, 3210.
20. NBO Version 3.1. Glendening, E. D.; Reed, A. E.; Carpenter, J. E.; Weinhold, F..
21. Legault, C. Y. CYLview, 1.0b; Universit eꢀ de Sherbrooke, 2009; http://www.cyl-
6
van Leeuwen, P. W. N. M.; Kramer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. Rev.
view.org.
2000, 100, 2741; (b) van Leeuwen, P. W. N. M.; Kramer, P. C. J.; Reek, J. N. H. Pure
Appl. Chem. 1999, 71, 1443.