A New Insight into the Stereoelectronic Control of the Pd0-Catalyzed Allylic Substitution: Application for the Synthesis of Multisubstituted Pyran-2-ones via an Unusual 1,3-Transposition

Article abstract of DOI:10.1002/chem.201900323

Pyran-2-ones 3 undergo a novel Pd⁰-catalyzed 1,3-rearrangement to afford isomers 6. The reaction proceeds via an η²-Pd complex, the pyramidalization of which (confirmed by quantum chemistry calculations) offers a favorable antiperiplanar alignment of the Pd?C and allylic C?O bonds (C), thus allowing the formation of an η³-Pd intermediate. Subsequent rotation and rate-limiting recombination with the carboxylate arm then gives isomeric pyran-2-ones 6. The calculated free energies reproduce the observed kinetics semi-quantitatively.

Full text of DOI:10.1002/chem.201900323

A Journal of
Accepted Article
Title: A New Insight into the Stereoelectronic Control of the Pd(0)-
Catalyzed Allylic Substitution: Application for the Synthesis of
Multisubstituted Pyran-2-ones via an Unusual 1,3-Transposition
Authors: Milan Pour, Zbyněk Brůža, Jiří Kratochvíl, Jeremy N. Harvey,
Lubomír Rulíšek, Lucie Nováková, Jana Maříková, Jiří Kuneš,
and Pavel Kočovský
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201900323
Link to VoR: http://dx.doi.org/10.1002/chem.201900323
Supported by

Chemistry - A European Journal
10.1002/chem.201900323
FULL PAPER
A New Insight into the Stereoelectronic Control of the Pd(0)-Catalyzed
Allylic Substitution: Application for the Synthesis of Multisubstituted
Pyran-2-ones via an Unusual 1,3-Transposition
[
a]
[a]
[b]
[c]
[d]
Zbyněk Brůža, Jiří Kratochvíl, Jeremy N. Harvey, Lubomír Rulíšek,* Lucie Nováková, Jana
Maříková, [a] Jiří Kuneš, Pavel Kočovský,*[a, e] and Milan Pour*[a]
[a]
2
Abstract: Pyran-2-ones 3 undergo a novel Pd(0)-catalyzed 1,3-
pyramidalization of the sp centers and the palladacyclic nature
of the η -intermediate.
2
2
rearrangement to afford isomers 6. The reaction proceeds via an η -
Pd complex, whose pyramidalization (confirmed by quantum
chemistry calculations) offers a favorable antiperiplanar alignment of
the Pd-C and allylic C-O bonds (C), thus allowing the formation of an
3
η -Pd intermediate. Subsequent rotation and rate-limiting
recombination with the carboxylate arm then gives isomeric pyran-2-
ones 6. The calculated free energies reproduce the observed
kinetics semi-quantitatively.
Introduction
3
Chart 1. Stereoelectronic effects in the formation of η -complexes.
The classical Tsuji-Trost Pd(0)-catalyzed allylic substitution[1]
represents a robust, stereo- and regioselective methodology that
has been frequently utilized in organic synthesis as an Results and Discussion
3
indispensable tool. The reaction is known to proceed via η -
complexes[1] that are formed from allylic esters, typically with
inversion of configuration, where the Pd approaches the allylic
moiety from the side opposite to the leaving group
Construction of 4-Substituted-5-alkylidene Pyran-2-ones.
The pyran-2-one moiety, occurring in a number of natural
products, is known to be responsible for a wide range of
(
A in Chart 1).[2,3] Retention pathway for the formation of η3-
biological effects, such as antifungal, antibiotic, and cytotoxic.
[7]
complexes (B) has also been reported, especially in those
instances, where the leaving group can coordinate the
approaching palladium and thus steer its approach to the C=C
bond.[4,5] In all these reactions, good alignment of the -orbitals
of the double bond with the σ bond of the leaving group (X) has
been regarded as a prerequisite for the reaction to occur.[1-6] In
other words, the allylic leaving group should be positioned
perpendicularly to the plane of the C=C bond (A/B). Herein, we
show that this commonly accepted interpretation of the
It is, therefore, of little surprise that the past decade has
witnessed a considerable effort aiming at the development of an
efficient and modular construction of the pyran-2-one core.[
We have recently disclosed[10,11] a new method for rapid
assembly of novel 4-substituted-5-alkylidene pyran-2-ones 3
through a cross-coupling of 2-tributystannyl allyl alcohols 1 and
β-iodo acrylates 2, catalyzed by the ligand-free palladium black
(Scheme 1). Notably, this reaction did not proceed under
8,9]
4
homogeneous conditions with PdL , presumably due to the
stereoelectronic effect requires
a
modification, reflecting
enhanced stability of the ligated products of the initial oxidative
addition.[
11]
[
a]
Z. Brůža, Dr. J. Kratochvíl, Jana Maříková, Dr. J. Kuneš, Prof. P.
Kočovský, Prof. M. Pour,
Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy,
Charles University, Hradec Králové 500 05, Czech Republic,
e-mail: pour@faf.cuni.cz
[
b]
Prof. J. N. Harvey,Department of Chemistry, Katholieke Universiteit
Leuven, B-3001 Leuven, Belgium.
Dr. L. Rulíšek, Institute of Organic Chemistry and Biochemistry, Czech
[
c]
Academy of Sciences, 166 10 Prague 6, Czech Republic.
e-mail: rulisek@uochb.cas.cz
1
Scheme 1. Synthesis of 4-substituted-5-alkylidene pyran-2-ones (for R and
R see Table 2).
2
[
d]
Dr. L. Nováková, Department of Analytical Chemistry, Faculty of
Pharmacy, Charles University, Hradec Králové 500 05, Czech Republic.
[
e]
Prof. P. Kočovský, Department of Organic Chemistry, Faculty of Natural
Sciences, Charles University, 128 43 Prague 2, Czech Republic
e-mail: pavel.kocovsky@natur.cuni.cz
Palladium-Catalyzed 1,3-Rearrangement of 5-Alkylidene
Pyran-2-ones. While screening the reaction conditions for the
1
2
Supporting information for this article is given via a link at the end of the
document.
preparation of pyran-2-one 3a (R = Pr, R = Ph; see Table 2 for
R1 and R2), an unexpected formation of the isomeric 4,6-
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201900323
FULL PAPER
disubstituted-5-methylene pyran-2-one 6a as
a byproduct
(
≤11%) was observed (Scheme 2) in those cases, when the Pd
Table 1. Optimization of the Pd-catalyzed pyran-2-one isomerization 3d →
6d.
a
black catalyst used was generated from Pd(PPh
3
)
4
via an air
oxidation of the phosphine ligand.[11] Subsequently,
b
isomerization of 3b, labeled at the 6-position with 13C, was found
entry
catalyst
solvent
Ratio 3d : 6d
to proceed under homogeneous conditions with Pd(PPh
3
)
4
(3
7
0 °C
45 °C
4 : 96
5 : 95
68 : 32
68 : 32
-
35 °C
-
o
mol%) in DMF at 120 C for 60 min, which afforded 3b and 6b in
11]
3
0% and 64% yield, respectively.[ Since the label moved from
1
2
3
4
5
6
7
a
Pd(TFP)
Pd(TFP)
4
4
CH
2
Cl
2
4 : 96
C(6) to the exo-methylene, the latter reaction can be assumed to
MeOH
5 : 95
6 : 94
-
3
proceed via the η -Pd complex 5 that undergoes a partial
rotation about the C(4)-C(5) bond with ensuing attack by the
Pd(TFP)4
Pd(TFP)
Pd(PPh
Pd(diphos)
Pd (dba) /(-)-DIOP
2
Me CO
7 : 93
liberated carboxylate. Replacement of Pd(PPh
[
3
)
4
with Pd(TFP)
TFP = tris(2-furyl)phosphine][12] allowed to obtain the same
4
4
MeCN
MeOH
MeOH
9 : 91
-
o
3b/6b mixture (31% and 65%, respectively) at 90 C within 210
3
)
4
-
-
-
7 : 93
5 : 95
3 : 97
min and the reaction mixture turned out to be cleaner.
2
-
2
3
CH
2
Cl
2
-
The reaction was carried out on a 0.2 mmol scale in 0.5 mL of solvent with 3
mol% of PdL
over the period of 4 h. bDetermined by 1H NMR spectroscopy;
n
no other products or impurities were detected.
Subsequently, a series of lactones 3c-3u was prepared
(
see the SI) and subjected to the optimized conditions with
Pd(TFP) Cl (1:1) mixture,
at 35 oC in MeOH or a MeOH-CH
depending on the solubility (Table 2).
4
2
2
Table 2 shows broad applicability of the reaction. The
presence of the hydroxymethyl group as the R1 substituent is
clearly beneficial, as documented by high yields and short
reaction times for substrates 3c-3h (entries 3-8); only for the
thienyl derivative 3i the yield dropped slightly (entry 9). Notably,
among the rearranged products, 6h is of particular interest,
since this compound represents a substituted [3]dendralene,
where two of its double bonds constitute part of the rigid
pyranone ring.
Bulky R2 substituents (aryl and Pr) also support the
conversion (entries 11, 12, and 16); on the other hand, with
small groups in that position (R2 = H or Me), the reaction
proceeds less efficiently (entries 10, 13, and 14). More complex
substitution pattern, as in 3o and 3p, proved to be well tolerated
Scheme 2. Pd-Catalyzed allylic 1,3-rearrangement.
A logical question then arose as to whether this side
reaction can be enforced to proceed to completion and whether
theoretical analysis can rationalize this rather anomalous
behavior. Herein, we report on the development of this
isomerization into a practical synthetic protocol to obtain yet
another, very unusual pyran-2-one substitution pattern via a
simple switch from heterogeneous to homogeneous Pd-catalysis. (entries 15 and 16), although in the latter instance the reaction
became rather slow. With R2 = CH
outcome copied that observed for other CH
OH (3q, entry 17), the
First elucidated was the temperature and solvent effect,
2
employing 3d[ as a model compound (Table 1): MeOH and
11]
2
OH derivatives
2 2
CH Cl were found to be suitable solvents for reaching good
(entries 3-8).
o
o
conversions at 70 C and even at 45 and 35 C (Table 1, entries
The ortho-condensed derivatives 3r and 3s behaved in a
similar way, giving 6r and 6s in high yields, though after a longer
period of time. By contrast, the C(4)-unsubstituted pyran-2-ones
3t and 3u did not undergo the reaction. Hence, the steric
o
1
and 2); only at 28 C the reaction proved to be rather slow,
2 2
giving 17:83 (CH Cl ) and 19:81 (MeOH) ratios, respectively,
over 20 h. The isomerization also proceeded in Me
2
CO and
o
2
MeCN but only at 70 C (entries 3 and 4), whereas DMF, THF,
and toluene turned out to be unsuitable at this temperature.
Screening of other homogeneous catalysts at 35 °C
congestion, exercised by the C(4)-substituent R , can be
regarded as the driving force for the allylic transposition to occur.
In its absence, the reaction either becomes very slow (3j, entry
10) or does not proceed at all (3t and 3u).
revealed that only the Pd0L
promoting the isomerization. With TFP, Ph
MeOH and DIOP[13] in CH
Cl , the 3d:6d ratio was found to be in
type complexes were capable of
P, and diphos in
4
3
2
2
the range of 7:93 to 3:97 within 4 h (entries 5-7). Other ligands,
such as PEPSI-iPr, oxazolines, and MeCN, proved ineffective
(
see also Table S2 in Supporting Information). The two isomers
are at a dynamic equilibrium, since ca 5 % of 3d was detected
1
by H NMR within 4 hrs following the exposure of pure 6d to the
optimized reaction conditions (vide infra).
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201900323
FULL PAPER
A
closer look at the reaction, which starts with
2
η -coordination (4), suggests that the stereoelectronic
considerations should be modified to reflect the actual geometry
Table 2. Scope of the Pd-catalyzed pyran-2-one isomerization 3 → 6.a
2
R1
R2
of the η -complex and its palladacyclic nature. It is well known
entry substrate product
Time Yield
h) (%)b
2
(
that η -complexes are partly pyramidalized at the carbons of the
original C=C bond. Thus, the Zeisse salt K[PtCl
3
(C
2
H
4
)] is
1
2
3
3a
3bc
3c
6a
6bd
6c
Pr
Ph
Ph
Ph
4
54
65e
90
°
pyramidalized at each carbon atom by 17 , according to neutron
diffraction.[ In the rhodium complex CpRh(C
15]
H
4
)(C
F
) the CH
2
2
2
°
2
°
C
5
H
11
3.5
4
and CF
2
groups are bent away from planarity by 21 and 37 ,
respectively,[ while the η -nickel-complex of (NC)
16]
2
C=C(CN)
2
2
CH
2
OH
o
exhibits deviation of 38 , close to the corresponding epoxide
(32°).[
17]
4
5
3d
6d
6e
CH
CH
2
OH
OH
Pr
4
4
91f
84
Taking into account the Chatt-Dewar-Duncanson model,[18] it
can be argued that, since the η2 → η3 conversion features a
3eg
4-(MeO)-C
2
6 4
H
“
nucleophilic” expulsion of the nucleofuge, it is the back-donation
6
7
8
3f
3g
3h
6f
6g
6h
CH
CH
CH
2
2
2
OH
OH
OH
4-(NO
2
)-C
6
H
4
4
4
85
86
from Pd (C in Chart 2) rather than donation (A in Chart 1) that
should play the key role. Therefore, geometry C, featuring
donation from the d-orbital[19] to the σ*-orbital of the leaving
group C-X bond, can be regarded as a more appropriate model.
Naturally, some degree of deviation (θ) from ideal collinearity
4-(MeO
2
C)-C
6 4
H
(E)-
4.5
78h
2
CH=CHCO Me
(
D/E) should be allowed in analogy with Wagner-Meerwein
9
3i
3j
6i
6j
CH
2
OH
2-thienyl
H
3.5
11
69
rearrangements that are known to tolerate up to 30°
distortion.[20-22]
10
1-hydroxycyclohexan-
-yl
53i
1
11
3k
6k
1-hydroxycyclohexan-
-yl
3,4-Cl
2
C
6
H
3
4
89i
1
12
13
14
15
16
3l
3m
3n
3o
3p
6l
6m
6n
6o
6p
CH
2
N
3
Pr
Me
Me
4.5
18.5
10
74
74
33
53
60
Cl-CH CH
2
2
CH
2
Me
BocNH-CH
Chart 2. A new interpretation of the stereoelectronic effects in the formation of
η -complexes: Collinearity of the C-Pd and C-X bonds in the  -complex. For
computed orbitals, see the SI (Figure S2).
3
2
2
CH
2
CH
2
3,4-Cl
2
C
6
H
3
6
Ph
19
Quantum Chemical Calculations. To gain credence for the
qualitative orbital considerations and to elucidate the mechanism
in detail, assess the validity of the stereoelectronic arguments,
and characterize the intermediates and transition states,
quantum chemical calculations were carried out for three
representative cases, namely a facile vs. less efficient reaction
(3d → 6d vs. 3j → 6j) and absence of reactivity (3u → 6u). A
computational approach similar to that employed by us
previously,[23] was used (see the computational details section
below) with the difference that we obtained electronic energies
1
7
3q
6q
PhCH
2
CH
2
OH
4
75j
a
The reaction was carried out on a 0.5 mmol scale in MeOH (2.0 mL) at 35 o
C
b
with Pd(TFP)
4
(3 mol%). The 3:6 ratios in the crude product were ≤5:95
1
(
unless stated otherwise) according to H NMR; no other discrete products
were isolated. Labeled with 13C in the CH
c
d
13
2
O group. Labeled with C in the
e
o
exo-methylene (ref 11). Carried out in DMF at 90 C over 120 min; the 3b:6b
ratio was 31:65 (ref 11). fCarried out on a gram scale. g(E)-isomer. The
product undergoes decomposition and was characterized only by NMR
spectroscopy. Carried out in a 1:1 MeOH-CH
mixture of 3q and 6q (13:87).
h
i
mixture. jAn inseparable
2
Cl
2
(
Eel(QM) in eq. 1) of the stationary points employing both
“
calibration quality” coupled cluster (DLPNO-CCSD(T)/CBS-est)
Stereoelectronic Effects in the Palladium-Catalyzed 1,3-
Rearrangement of 5-Alkylidene Pyran-2-ones.
method and by “standard” DFT methods (BP-86-D3, B3LYP-D3
and TPSSh-D3). Notably, the coupled cluster and DFT-D3
values were fairly similar to each other. Thus, general
conclusions are, to a large extent, independent on the method
used (c.f. Figure S2 in SI for the TPSSh-D3/COSMO-RS
[
14]
Stereoelectronic control of this 1,3-transposition requires that
the allylic leaving group be positioned more or less
perpendicularly to the plane of the C=C bond (A in Chart 1).
Therefore, the isomerization 3 → 6 emerged as a surprise, since
lactones 3 are nearly planar molecules, which should preclude
the reaction. The X-ray structure of 3c actually shows that the
allylic C-O bond is far from any alignment with the π-system in
both conformations present in the crystal; here the dihedral
reaction profiles) – with the exception of the Pd(TFP) /Pd(TFP)4
3
pre-equilibrium discussed below and to a smaller extent binding
of the reactant to the Pd(TFP)3 catalyst. To unambiguously
identify reaction coordinates, a thorough conformational search
was carried out to identify the lowest-energy conformers for all
species involved in the reaction.[24]
°
angles deviate from the plane of the C=C bond by mere 9 and
4
2°, respectively, i.e., far away from the postulated ideal of 90°
First, computations have clearly shown that the reaction,
carried out in MeOH, should be slightly exergonic, with GDLPNO-
(
see the SI).
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201900323
FULL PAPER
CCSD(T)/COSMO-RS = -1.9, -4.0, -1.9 kcal mol-1 for the 3d/6d, 3j/6j,
and 3u/6u reactant/product pairs, respectively. Less clear is the
involved in the rate-determining step (RDS), the RDS in the 3u
→ 6u conversion is represented by TS .
1
solution form of the Pd(TFP)
dissociation is known to occur in toluene almost quantitatively to
yield Pd(PPh
as the most stable species.[25] Reproducing this
n
3 4
catalyst: for Pd(PPh ) , ligand
3 3
)
experimental observation computationally is not trivial,
considering the large contributions from dispersion and
solvation,[
26]
yet our B3-LYP/COSMO-RS protocol yielded
3 4
G ) →
B3LYP-D3/COSMO-RS = -1.8 kcal mol-1 for the Pd(PPh
3 3 3
Pd(PPh ) + PPh
reaction in toluene (-0.2 kcal mol-1 in MeOH),
which is in agreement with the experimental observations. The
same approach suggests a less favorable dissociation process
for Pd(TFP)
energy change is sensitive to the method used. Therefore, our
mechanistic analysis starts with Pd(TFP)
The isomerization commences with the replacement of the
coordinated TFP ligand in Pd(TFP) by the reactant 3 to form the
4
but the precise prediction of the associated free
3
.
3
initial reactant complex 4 and/or 4_Rot (depicted for the reaction
of 3d in Figure 1). This step presumably occurs through an
associative mechanism with an intermediate or TS [Pd(TFP) (3)]
3
and is slightly exergonic with GDLPNO-CCSD(T)/COSMO-RS = -2.2, -3.6,
and -1.3 kcal.mol-1 for 3d, 3j, and 3u, respectively (Figure 2).
Figure 2. Reaction coordinates for the 3d → 6d, 3j → 6j, and 3u → 6u
reactions. The (formal) addition of reactants and loses of TFP in the initial
steps are omitted for clarity.
Kinetic modeling. To make quantitative comparison with the
experimental reaction times (Table 2), the DLPNO-
CCSD(T)/COSMO-RS and B3LYP-D3 reaction coordinates were
subjected to kinetic modeling. At first sight, the standard free
energies computed here are difficult to reconcile with the
observed reactivity, whereby the reactants reach equilibrium
with the products within a few hours. For example, analysis of
2
4
entry 4 in Table 2 gives an apparent half-life of 10 - 10 s for 3d,
which corresponds to an apparent standard free energy barrier
-1
of 21-24 kcal mol . However, the calculated standard free
energy difference between Pd(TFP) + reactant and rate-limiting
TS is much larger, namely at +36.2 (DLPNO-CCSD(T)) and
4
2
Figure 1. The reaction mechanism for the Pd(0)-catalyzed allylic isomerization
+32.2 kcal mol-1 (B3LYP-D3). Clearly, the difference from
experiment is larger than the expected error margin.
3d → 6d.
A
closer kinetic analysis, taking into account the
experimental concentrations rather than the standard conditions,
indicates that the calculated free energies are in fact in
agreement with experiment, at least within the expected error
margin. Qualitatively, this can be explained by noting that given
In the next step, the C-O bond is cleaved (RC-O = 2.2 Å in
the transition state TS ) and the η -complex 5 is formed; the
1
3
computed activation free energies associated with this process
≠
-1
are ΔG DLPNO-CCSD(T)/COSMO-RS = 19.8, 18.5, and 22.9 kcal mol for
4
the unfavorable dissociation equilibrium for Pd(TFP) , the
3
d → 5d, 3j → 5j, and 3u → 5u, respectively. Both TS
1
and the
steady-state concentration of TFP will be well below the
standard state 1 M, so that the further loss of TFP and substrate
binding equilibrium to form 4d will be much more favorable than
those expected, given the computed standard free energies.
Quantitative insight was obtained from kinetic simulations
using the Tenua program,[27] with rate constants calculated from
3
ensuing intermediate 5 (formally an η -allyl zwitterionic complex)
are stabilized by hydrogen bonding between the departed
carboxylate and the CH
energy difference between the most stable reactant structure 4
with a hydrogen bond between the hydroxyl and the oxygen of
2
OH group. It can be noticed that the free
(
the furyl group) and the conformer 4_rot (with the re-orientated
the ab initio data. Using the raw calculated free energies, the
modelled half-life of reaction for 3d in MeOH at 35 °C, with
Pd(TFP) at 0.0075 M and substrate 0.25 M, comes out at 5000
4
h, and thereby about 103 times slower than is observed
hydroxyl that is now hydrogen-bonded to the lactone oxygen of
-1
the reactant) is almost negligible (~1 kcal mol ; Figure S3 in the
SI). Fairly stable η3-intermediates
(with free energies
comparable to 4, c.f. Figure 2) convert via the TS (overall
activation energies of 21.4, 23.9, and 22.0 kcal mol-1 for 5d →
d, 5j → 6j, and 5u → 6u, respectively) to the final product
complexes 6pc, which are, again, energetically close to the
5
2
experimentally. This large difference in rate can be interpreted in
terms of an error in the apparent free energy of activation of
6
about 4 kcal mol-1 – significant, but smaller than the error of 8-15
kcal mol-1 estimated above, based simply upon the standard free
-1
reactant complexes 4 (~1 kcal mol ). This implies that the final
energies. This error could reflect overestimating the free energy
dissociation of the product is quite close to being isoergic.
for dissociation of Pd(TFP)
4
1 2
, or for TS and TS , or for both.
2
Interestingly, while for 3d → 6d and 3j → 6j reactions the TS is
Indeed, B3LYP-D3 suggests
a
smaller free energy of
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201900323
FULL PAPER
(+9.4 kcal mol-1 instead of +14.7), but
in the η -complex 4d has been calculated to be by mere 18 ,
which can be regarded as being comfortably within the tolerable
range. Awareness of these effects can be expected to change
the philosophy of strategic planning in organic synthesis, since
our findings broaden the scope of the π-allyl chemistry to the
substrates previously regarded as unlikely to react.
2
°
dissociation to Pd(TFP)
3
using this modified value only leads to a decrease in the half-life
by a factor of thirteen: the greater degree of dissociation
corresponds to a higher steady-state concentration of TFP,
which inhibits further reaction, as discussed above. If, instead,
we assume that theory over-predicts the free energy of TS
1
and
, and they are decreased by 4.5 kcal mol , this leads to
predicted kinetics broadly in line with experiment, with a half-life
of 3.7 h. We note that the whole region between TS and TS
-1
TS
2
1
2
Experimental Section
involves zwitterions that are presumably stabilized by hydrogen-
bonding to solvent, an effect which is only partly described by
the continuum approach used here.
Representative procedure for the preparation of pyran-2-
one 6d. Commercial Pd black (25 mg, 0.02 equiv) was added to
a solution of (Z)-methyl-3-iodo-3-propyl acrylate (3.000 g, 11.8
mmol) and (E)-2-tributylstannyl but-2-en-1,4-diol (5.570 g, 14.2
mmol, 1.2 equiv)11 in DMF (12 mL). The flask was placed into a
Obtaining
straightforward than obtaining absolute reactivity. Indeed, in the
present case, with barriers TS and TS
lowered by 4 kcal mol-1
reactivity
trends
is
somewhat
more
1
2
relative to reactants, the predicted rates for substrates 3d, 3j,
and 3u are in relation 200:8:1 to one another, i.e. 3j is much less
reactive than 3d, and 3u somewhat less reactive still,
qualitatively consistent with the experimentally observed
diminished reactivity for 3j and the lack of reactivity for 3u. Once
again, even for relative reactivity, accuracy by greater than a
factor of 1-2 kcal mol-1 remains hard to achieve, so the
qualitative agreement found here is quite satisfactory.
pre-heated oil bath at 70 °C and the mixture was stirred at this
temperature until TLC showed complete consumption of the iodo
acrylate. The reaction mixture was then diluted with EtOAc, and
the solution was washed with saturated aqueous NH
aqueous NaF. The precipitate was filtered off and the organic
phase was dried over anhydrous Na SO . Chromatography on
4
Cl and 4%
2
4
silica gel (hexanes:EtOAc 7:3) furnished pyran-2-one 3d (1.460
g, 8 mmol, 68%) as a yellow oil.[11]
Compound 3d (1.449 g, 8.23 mmol) and Pd(TFP) (256 mg, 0.25
4
The calculations have also corroborated the initial orbital
and
stereoelectronic
considerations.
Indeed,
in
the
mmol, 3 mol%) were transferred into a dry, Ar-filled flask. The
flask was evacuated and flushed with Ar (3×). Anhydrous MeOH
2
η -intermediates 4d and 4j (4/4_rot) the alignment of the
Pd-C(5) and C(6)-O bonds deviates from collinearity by mere
(
30 mL) was added, and the flask was placed into an oil-bath
°
°
+
18 and +16 (E), respectively, which is well within the 30°
heated at 35 °C and the mixture was stirred at this temperature.
When TLC analysis indicated no further change (4 h), the
solvent was evaporated and the residue was purified by column
chromatography (hexanes: EtOAc 8:2) to afford 6d (1.365 g;
9
4
2
1
tolerance[
20-22]
proposed
for
the
Wagner-Meerwein
rearrangements (vide supra).[28] On the contrary, the same
deviation for 4u is as large as +49° which provides an elegant
and intuitive stereoelectronic explanation for the lack of reactivity
of the compound.
f
1%) as a yellow oil (R = 0.41 in hexanes: EtOAc 3:7).
-Propyl-5-methylidene-6-hydroxymethyl-5,6-dihydro-2H-pyran-
1
-one (6d). H NMR (500 MHz, CDCl
3
) δ 5.84 (s, 1H), 5.60 (s,
H), 5.41 (s, 1H), 5.05 (t, J = 6.0 Hz, 1H), 3.92 – 3.72 (m, 2H),
Conclusions
2.44 – 2.31 (m, 2H), 1.65 – 1.52 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H).
13C NMR (126 MHz, CDCl
) δ 163.5, 154.2, 136.2, 116.6, 116.1,
81.4, 65.6, 33.5, 20.8, 13.8. IR (ATR) max 3367, 2962, 2962,
3
In summary, the Pd0L
originally observed as a side reaction during the coupling 1 + 2
3, was nurtured into a synthetically useful protocol for the
-catalyzed allylic isomerization 3 → 6,
4
-1
2934, 2874, 1675, 1407, 1363, 1247, 1080,1068 cm . LRMS
+
+
→
(RIC) m/z (rel. intensity) 205.1 [M+Na] (100); 183.1 [M+1] (19);
preparation of pyran-2-ones with an unusual structural pattern.
The latter reaction represents a [1,3] rearrangement that would
normally be symmetry-allowed only in the excited state.[29] In a
broader perspective, the present study demonstrates that
structurally different products can be obtained from the same
173.1 (49); 165.2 (15); 157.7 (12); 133.8 (24). HRMS (TOF-ESI)
+
m/z cal for. C10
H
14
O
3
183.1016; found 183.1024.
Computational details
All DFT calculations were carried out using the Turbomole 7.2
starting materials by marginal modification of reaction conditions. program.[30] Geometries of all structures (minima and saddle
This principle, in its own right, opens interesting new
opportunities, e.g., in the realm of multisubstituted heterocycles,
where it is not unusual that each substitution pattern at the
heterocyclic core requires its own synthetic strategy.[42]
points) were optimized employing the dispersion-corrected B-
P86 functional [BP86-D3(BJ)][
31,32]
and the def-TZVP basis set
(for Pd, this basis set includes the Stuttgart-Dresden effective
core potentials) in an implicit solvent with the dielectric constant
[33]
Substrates 3 are rather flat, which may seem to preclude
of 
solvation model
r
= 32.6 corresponding to methanol - using the COSMO
3
[34]
the formation of the required η -intermediate from the initially
as implemented in Turbomole 7.2 program.
2
generated η -complex (3 → 4 → 5). However, a more detailed
Subsequent vibrational frequency calculations were performed
at the same level of theory for all calculated structures, also in
an implicit solvent with ε = 32.6 (methanol). All transition states
r
analysis of the stereoelectronic effects, based on the back
2
donation in the η -complex as the decisive factor, suggests that
it is the alignment of the Pd-C bond with the allylic C-O bond (C)
that should be considered, rather than the currently accepted
alignment of the C=C bond π-system with the allylic bond of the
substrate (A). High-level quantum chemistry calculations have
fully confirmed this new analysis: the deviation (θ) from the
antiperiplanar arrangement of the key Pd-C and C-O bonds (E)
thus found possess exactly one negative Hessian eigenvalue,
while all other stationary points were confirmed to be genuine
minima on the potential energy surface (PES). By marginal
displacement of the transition state geometry towards initial and
final state, it was verified that the TS connects the desired
structures.
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201900323
FULL PAPER
The free energy value corresponding to a particular structure
can be conveniently expressed as:
Trost, Acc. Chem. Res. 1996, 29, 355. (d) J. Tsuji, Overview of the
Pd-Catalyzed Carbon-Carbon Bond Formation via π-Allylpalladium
and Propargylpalladium Intermediates in: Organopalladium
Chemistry for Organic Synthesis, (E. Negishi, Ed.); J. Wiley &
Sons: New York, 2002, p 1669.
G
S
= Eel + Gsolv + EZPVE - RTln(qtrans
q
rot
q
vib) + pV
(eq 1),
[
[
[
2] The anti-mechanism has been well established for Pd catalysts:
where Eel is the electrostatic potential energy of the molecule in
vacuo (gas-phase molecular energy), ΔGsolv is the solvation
energy, EZPVE is the zero-point vibrational energy whereas
(a) B. M. Trost, P. E. Strege, J. Am. Chem. Soc. 1975, 97, 2534.
(b) B. M. Trost, T. R. Verhoeven, J. Org. Chem. 1976, 41, 3215. (c)
T. Hayashi, T. Hagihara, M. Konishi, M. Kumada, J. Am. Chem.
Soc. 1983, 105, 7767.
rot
RTln(qtransq qvib) are the entropic terms obtained from the rigid-
3] Other metal catalysts, in particular Ir, Ru, Rh, and Fe, also seem to
prefer the anti-pathway but may differ from Pd in regioselectivity.
For a brief overview, see the reference section in: J. Štambaský, V.
Kapras, M. Štefko, M. Hocek, A. V. Malkov, P. Kočovský, J. Org.
Chem. 2011, 76, 7781.
rotor/harmonic oscillator (RRHO) approximation in which a free
rotor model was applied for low-lying vibrational modes under
-1
1
00 cm with a smoothing function applied (sometimes denoted
as quasi-RRHO, or RRFRHO approximation).
Electronic energies were obtained by performing single
point calculations employing the BP-86-D3(BJ), B3-LYP-
4] The syn-mechanism has been reported for Pd and Ni: (a) I. Starý,
P. Kočovský, J. Am. Chem. Soc. 1989, 111, 4981. (b) I. Starý, J.
Zajíček, P. Kočovský, Tetrahedron 1992, 48, 7229. (c) H.
Kurosawa, S. Ogoshi, Y. Kawasaki, S. Murai, M. Miyoshi, I. Ikeda,
J. Am. Chem. Soc. 1990, 112, 2813. (d) H. Kurosawa, H. Kajimaru,
H. S. Ogoshi, H. Yoneda, K. Miki, N. Kasai, S. Murai, I. Ikeda, J.
Am. Chem. Soc. 1992, 114, 8417. (e) A. Vitagliano, B. Åkermark,
S. Hansson, Organometallics 1991, 10, 2592. (f) C. N. Farthing, P.
Kočovský, J. Am. Chem. Soc. 1998, 120, 6661. (g) P. Kočovský, A.
V. Malkov, Š. Vyskočil, G.-C. Lloyd-Jones, Pure Appl. Chem. 1999,
71, 1425. (h) C. Jonasson, M. Kritikos, J.-E. Bäckvall, K. J. Szabó,
Chem. Eur. J. 2000, 6, 432. (i) G. R. Cook, H. Yu, S.
Sankaranarayanan, P. S. Shanker, J. Am. Chem. Soc. 2003, 125,
5115. (j) K. Nehri, J. Franzén, J.-E. Bäckvall, Chem. Eur. J. 2005,
D3(BJ),[
31a,35]
and TPSSh-D3(BJ) and def2-TZVPD basis set,
[36]
in vacuum. The reference reaction and activation energies were
obtained using DLPNO-CCSD(T)/aug-cc-pVDZ calculations[37,38]
and ORCA 4.0 software.[39] By carrying out the MP2/aug-cc-
pVDZ and MP2/aug-cc-pVTZ calculations we were able to
obtain complete basis set estimates, DLPNO-CCSD(T)/CBS,
that have been used throughout. We used Truhlar’s
extrapolation scheme[40] to obtain E(MP2/CBS) to which the
ΔECC = E(DLPNO-CCSD(T)/aDZ) - E(MP2/aDZ) was added. The
ΔGsolv was obtained using Klamt’s conductor-like screening
model for realistic solvation method (COSMO-RS).[41] COSMO-
RS calculations were carried out using cosmotherm software
and the recommended protocol: BP86-D3(BJ)/def2-TZVPD
single point calculations in vacuo and in ideal conductor (e = ∞)
followed by the COSMO-RS calculations in the target solvent
11, 6937. (k) M. T. Oliviera, D. Audisio, S. Niyomchon, N. Maulide,
ChemCatChem. 2013, 5, 1239. (l) See also the related examples
of steering the Pd-approach to a C=C bond: A. V. Malkov, M.
Barłóg, L. Miller-Potucká, M. A. Kabeshov, L. J. Farrugia, P.
Kočovský, Chem. Eur. J. 2012, 18, 6873. (m) P. Kočovský, J.-E.
Bäckvall, Chem. Eur. J. 2015, 21, 36. For an overview of
stereodivergent catalysis, see: (n) I. P. Beletskaya, C. Nájera, M.
Yus, Chem. Rev. 2018, 118, 5080.
(
(
CH
3
OH). Finally,
a
correction of (1.9∙Δn) kcal.mol-1
corresponding to the difference between the concentration of
the ideal gas at 298 K and 1 atm and its 1 mol.L-1 concentration;
[
5] Retention pathway in the formation of π-allyl complexes appears to
be typical for Mo: (a) D. Dvořák, I. Starý, P. Kočovský, J. Am.
Chem. Soc. 1995, 117, 6130. (b) M. E. Krafft, A. M. Wilson, Z. Fu,
M. J. Procter, O. A. Dasse, J. Org. Chem. 1998, 63, 1748. (c) G. C.
Lloyd-Jones, S. W. Krska, D. L. Hughes, L. Gouriou, V. D. Bonnet,
K. Jack, Y. Sun, R. A. Reamer, J. Am. Chem. Soc. 2004, 126, 702.
(d) D. Hughes, G. C. Lloyd-Jones, S. W. Krska, L. Gouriou, V. D.
Bonnet, K. Jack, Y. Sun, R. A. Reamer, Proc. Nat. Acad. Sci.,
Δn is the change in number of moles in the reaction) has been
applied in order that the computed values refer to 1 mol.L-1
standard state.
Acknowledgements
2
004, 101, 5379. (e) A. V. Malkov, L. Gouriou, G. C. Lloyd-Jones, I.
Starý, V. Langer, P. Spoor, V. Vinader, P. Kočovský, Chem. Eur. J.
006, 12, 6910. With W catalysts, anti-pathway was assumed but
This work was supported by the Czech Science Foundation
(
project No. 18-17868S) and by the project EFSA-CDN (No.
2
CZ.02.1.01/0.0/0.0/16_019/0000841) co-funded by ERDF.
Graduate student (Z. B.) would like to acknowledge financial
support from Charles University (projects No. 1054216 and SVV
not rigorously proven: (f) B. M. Trost, M.-H. Hung, J. Am. Chem.
Soc. 1983, 105, 7757.
[6] The overall outcome of the metal-catalyzed allylic substitution is
also dependent on the nucleophile. Thus, stabilized enolates and
260 401). We also thank Prof. Jana Roithová for discussing the
3
related species typically attack the intermediate η -Pd complexes
computational details mentioned in ref (24).
from the face opposite to that occupied by the metal, i.e., with
inversion, as a result of a charge-controlled process. On the other
hand, syn-attack (i.e., retention) is typical for organometallics (due
to transmetalation), where orbital interactions (HOMO/LUMO) play
the key role. For a discussion of this dichotomy, observed for both
Conflicts of interest
2
3
η - and η -Pd complexes, see the following: a) J.-E. Bäckvall, E. E.
Björkman, L. Petersson, P. Siegbahn, J. Am. Chem. Soc. 1984,
The authors declare no competing financial interest.
1
06, 4369; b) J.-E. Bäckvall, E. E. Björkman, L. Petersson, P.
Keywords: allylic rearrangement • palladium • catalysis •
Siegbahn, J. Am. Chem. Soc. 1985, 107, 7265; c) P. Siegbahn, J.
3
stereoelectronic effects • quantum chemistry calculations
Am. Chem. Soc. 1995, 117, 5409. Reaction of η -Pd complexes
with carboxylates and other O-nucleophiles can be controlled from
highly selective syn-addition to almost pure anti-addition by
-
additives (e.g., Cl ). For anti-selective reactions of O-nucleophiles,
Notes and references
see the following: d) J.-E. Bäckvall, P. G. Andersson, J.-O.
Vågberg, Tetrahedron Lett. 1989, 30, 137; e) J.-E. Bäckvall, J.-O.
Vågberg, K. L. Granberg, Tetrahedron Lett. 1989, 30, 617; f) J.-E.
[
1] For reviews, see: (a) J. Tsuji, Tetrahedron 1986, 42, 4361. (b) B. M.
Trost, D. L. Van Vranken, Chem. Rev. 1996, 96, 395. (c) B. M.
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201900323
FULL PAPER
Bäckvall, P. G. Andersson, J. Org. Chem. 1991, 56, 2274; g) S. A.
[20] (a) A. Nickon, R. C. Weglein, J. Am. Chem. Soc. 1975, 97, 1271;
(b) A. B. Smith, B. A. Wexler, C.-Y. Tu, J. P. Konopelski, J. Am.
Chem. Soc. 1985, 107, 1308; (c) P. Kočovský, F. Tureček, V.
Langer, J. Podlahová, J. Podlaha, J. Org. Chem. 1986, 51, 4888
and refs. cited therein.
Stanton, S. W. Felman, S. W. Parkhurst, S. Godleski, S. J. Am.
Chem. Soc. 1983, 105, 1964; h) B. M. Trost, J. K. Lynch, S. R.
Angle, Tetrahedron Lett. 1987, 28, 375; i) B. M. Trost, S. R. Angle,
J. Am. Chem. Soc. 1985, 107, 6123. When the anti-face is
sterically hindered, attachment of the AcO- may become syn-
[21] (a) P. v R. Schleyer, L. K. M. Lam, D. J. Raber, J. L. Fry, M. A.
McKervey, J. R. Alford, B. D. Cuddy, V. G. Keizer, H. W. Geluk, J.
L. M. A. Schlatmann, J. Am. Chem. Soc. 1970, 92, 5246; (b) Z.
Majerski, P. v R. Schleyer, A. P. Wolf, J. Am. Chem. Soc. 1970, 92,
5731; (c) M. Saunders, J. Chandrasekhar, P. v R. Schleyer, P.
Rearrangements of Carbocations In Rearrangements in Ground
and Excited States (Ed. P. de Mayo); Academic: New York, 1980,
Vol 1, p 2434.
2
selective even for (π-allyl)PdCl/ complexes: j) C. A. Horiuchi, J. Y.
Satoh, J. Chem. Soc. Perkin Trans. I 1982, 2595. Reactions of Cl-,
N- and S-nucleophiles are usually anti-selective: for an overview,
see the reference section in ref 4b and 4g and review 4m.
[
7] For reviews on biological activity, see: (a) J. M. Dickinson, Nat.
Prod. Rep. 1993, 10, 71. (b) Z. S. Bhat, M. A. Rather, M. Maqbool,
H. U. Lah, S. K. Yousuf, Z. Ahmad, Biomed. Pharmacother. 2017,
9
1, 265. (c) Y.-Y. Qi, J. Su, Z.-J. Zhang, L.-W. Li, M. Fan, Y. Zhu,
[22] H. B. Bürgi, J. D. Dunitz, J.-M. Lehn, G. Wipff, Tetrahedron 1974,
30, 1563.
X.-D. Wu, G.-S. Zhao, Chem. Biodivers. 2018, 15, e1800043.
8] For reviews on synthetic methodology, see: (a) V. Eschenbrenner-
Lux, K. Kumar, H. Waldmann, Angew. Chem. Int. Ed. 2014, 53,
[
[
[23] (a) A. V. Malkov, M. Bell, P. Ramírez-López, L. Biedermannová, L.
Rulíšek, L. Dufková, M. Kotora, F. Zhu, P. Kočovský, J. Am. Chem.
Soc. 2008, 130, 5341; (b) A. V. Malkov, S. Stončius, M. Bell, F.
Castelluzzo, P. Ramírez-López, L. Biedermannová, L. Rulíšek, V.
Langer, P. Kočovský, Chem. Eur. J. 2013, 19, 9167; (c) M. A.
Kabeshov, O. Kysilka, L. Rulíšek, Y. V. Sulejmanov, M. Bella, A. V.
Malkov, P. Kočovský, Chem. Eur. J. 2015, 21, 12026.
11146. (b) M. Ghavre, M. Špulák, M. Pour, M. Tetrahedron Lett.
2017, 58, 263.
9] For recent examples, see: (a) Y. Mostinsky, R. Kotikalapudi, V.
Valerio, R. Nataf, D. Tsvelikhovsky, Adv. Synth. Catal. 2017, 359,
1
164. (b) S. Thimmarayaperumal, S. Shanmugam, ACS Omega
017, 2, 4900. (c) R. S. Pathare, S. Sharma, K. Gopal, D. M.
2
[24] Approximately 30 manually generated structures covering
plausible orientation of the furyl groups of the TFP ligands as well
as the Pd-coordinated reactant(s) were examined.
Sawant, R. T. Pardasani, R. T. Tetrahedron Lett. 2017, 58, 1387.
d) Y. Xiang, A. L. Rheingold, E. B. Pentzer, ACS Omega 2018, 3,
419.
10] J. Pavlík, I. Šnajdr, J. Kuneš, M. Špulák, M. Pour, J. Org. Chem.
009, 74, 703.
(
9
[25] B. E. Mann, A. Musco, A. J. Chem. Soc., Dalton Trans. 1975, 1673.
[26] a) C. L. McMullin, N. Fey, J. N. Harvey, Dalton Trans. 2014, 43,
13545; (b) S. Santoro, L. Deiana, G.-L. Zhao, S. Lin, F. Himo, A.
Córdova, ACS Catal. 2014, 4, 4474; (c) M. S. Ahlquist, P.-O.
Norrby, Angew. Chem., Int. Ed. 2011, 50, 11794.
[
[
[
2
11] J. Kratochvíl, Z. Novák, M. Ghavre, L. Nováková, A. Růžička, J.
Kuneš, M. Pour, Org. Lett. 2015, 17, 520.
12] For development of the Pd(TFP)
4
catalyst, see: (a) V. Farina, B.
[27] 27.
Tenua
2.1,
a
Java
kinetics
simulator,
see:
Krishnan, J. Am. Chem. Soc. 1991, 113, 9585. (b) V. Farina, S.
Kapadia, B. Krishnan, C. Wang, L. Liebeskind, J. Org. Chem. 1994,
http://bililite.com/tenua/. (a) L. E. Rush, P. G. Pringle, J. N. Harvey,
Angew. Chem., Int. Ed. 2014, 53, 8672; (b) M. Besora, F. Maseras,
59, 5905. (c) V. Farina, Pure Appl. Chem. 1996, 68, 73. For recent
WIREs
Comput.
Mol.
Sci.
2018,
in
press,
DOI:
synthetic applications, see, e.g.: (d) K. C. Nicolaou, P. G. Bulger, D.
Sarlah, Angew. Chem. Int. Ed. 2005, 44, 4442. (e) A. Steven, L. A.
Overman, L. A. Angew. Chem. Int. Ed. 2007, 46, 5488. (f) C. I.
Stathakis, S. Bernhardt, V. Quint, P. Knochel, Angew. Chem. Int.
Ed. 2012, 51, 9428. (g) L. Klier, T. Bresser, T. A. Nigst, K.
Karaghiosoff, P. Knochel, J. Am. Chem. Soc. 2012, 134, 13584.
10.1002/wcms.1372.
[28] The allylic substrate i, featuring a seven-membered ring, also
seemingly rather flat, has been found to be readily converted into
the η3-complex iii (M. Meazza, M. Kamlar, L. Jašíková, B.
Formánek, A. Mazzanti, J. Roithová, J. Veselý, R. Rios, Chem. Sci.
2018, 9, 6368.). A thorough analysis of the published calculation
data shows that the alignment of the Pd-C and C-O bonds in the
η2-complex (ii) deviates from collinearity (model D) by θ = -23o and
θ = -21o for the anti and syn mechanism, respectively, which is in
line with our present findings.
(h) G. Vallot, C. S. Regens, D. P. O’Malley, E. Godineau, H.
Takikawa, A. Fürstner, Angew. Chem. Int. Ed. 2013, 52, 9534. (i) Y.
Yang, T. J. L. Mustard, P. H. Y. Cheong, S. L. Buchwald, Angew.
Chem. Int. Ed. 2013, 52, 14098. (j) D. Haas, J. M. Hammann, R.
Greiner, P. Knochel, ACS Catal. 2016, 6, 1540. (k) M. A. Miller, B.
Askevold, H. Mikula, R. H. Kohler, D. Pirovich, R. Weissleder,
Nature Commun. 2017, DOI: 10.1038/ncomms15906.
[
13] The development of an enantioselective version is currently in
progress. So far, no enantioselection was observed with 5%
2 3
Pd (dba) /12% (-)DIOP. On the other hand, with 5%
2 3
Pd (dba) /12% R,R-DACH (for the ligand, see: B. M. Trost, H. C.
Shen, L. Dong, J. P. Surivet, J. Am. Chem. Soc. 2003, 125, 9276)
in the presence of glacial AcOH (1 equiv), promising
enantioselectivity was attained (50 % ee, 30% overall yield).
[29] See
the
light-induced
verbenone
→
chrysanthenone
[
[
14] P. Kočovský, I. Starý, Rearrangements of Allylpalladium and
Related Derivatives, in: Organopalladium Chemistry for Organic
Synthesis, (E. Negishi, Ed.); J. Wiley & Sons: New York, 2002, p
rearrangement: (a) J. J. Hurst, J. J., G. H. Whitham, J. Chem. Soc.
1960, 2864; (b) W. F. Erman, J. Am. Chem. Soc. 1967, 89, 3828.
[30] TURBOMOLE V7.2 2017,
Karlsruhe and Forschungszentrum Karlsruhe GmbH, 1989-2007,
TURBOMOLE GmbH, since 2007; available from
http://www.turbomole.com.
a development of University of
2011.
15] A. R. Love, T. F. Koetzle, G. J. B. Williams, L. C. Andrews, R. Bau,
Inorg. Chem. 1975, 14, 2653.
[
[
16] L. J. Guggenberg, R. Cramer, J. Am. Chem. Soc. 1972, 94, 3779.
[31] (a) A. D. Becke, Phys. Rev. A 1988, 38, 3098; (b) S. H. Vosko, L.
Wilk, M. Nusair, Can. J. Phys. 1980, 58, 1200; (c) J. P. Perdew,
Phys. Rev. B 1986, 33, 8822.
17] C. Elschenbroich, A. Salzer, Organometallics:
A
Concise
Introduction, 2nd edition; VCH: Weinheim, 1992 p. 259.
[
[
18] (a) M. J. S. Dewar, Bull. Soc. Chim. Fr. 1951, 18, C79. (b) J. Chatt,
L. A. Duncanson, J. Chem. Soc. 1953, 586. (c) J. Chatt, L. A.
Duncanson, L. M. Venanzi, J. Chem. Soc. 1955, 4456.
[32] S. Grimme, Chem. Eur. J. 2012, 18, 9955-9964.
[33] F. Weigend, R. Ahlrichs, Phys. Chem. Chem. Phys. 2005, 7, 3297.
[34] A. Klamt, G. Schüürmann, J. Chem. Soc. Perkin Trans. 2, 1993,
799-805.
19] For the orbital analysis of pyramidalization, see, e.g.: T. A. Albright,
R. Hoffmann, J. C. Thibeault, D. L. Thorn, J. Am. Chem. Soc. 1979,
[35] C. Lee, W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785.
101, 3801.
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201900323
FULL PAPER
[
36] V. N. Staroverov, G. E. Scuseria, J. Tao, J. P. Perdew, J. Chem.
Phys. 2003, 119, 12129.
[
[
37] M. Sparta, F. Neese, Chem. Soc. Rev., 2014, 43, 5032.
38] D. G. Liakos, M. Sparta, M. K. Kesharwani, J. M. L. Martin, F.
Neese, J. Chem. Theory Comput. 2015, 11, 1525.
[
[
[
[
39] F. Neese,Wiley Interdiscip. Rev.-Comput. Mol. Sci. 2012, 2, 73.
40] D. G. Truhlar, Chem. Phys. Lett. 1998, 294, 45.
41] A. Klamt, J. Phys. Chem. 1995, 99, 2224.
42] A. Katritzky, C. Ramsden, J. Joule, V. Zhdankin, Handbook of
Heterocyclic Chemistry, 3rd Edition; Elsevier; Amsterdam, 2010.
This article is protected by copyright. All rights reserved.

Chemistry - A European Journal
10.1002/chem.201900323
FULL PAPER
Entry for the Table of Contents (Please choose one layout)
Layout 1:
FULL PAPER
Text for Table of Contents
Author(s), Corresponding Author(s)*
Page No. – Page No.
Title
((Insert TOC Graphic here: max.
width: 5.5 cm; max. height: 5.0 cm))
Layout 2:
FULL PAPER
Zbyněk Brůža, Dr. Jiří Kratochvíl, Prof.
Dr.Jeremy N. Harvey, Dr. Lubomír
Rulíšek, Dr. Lucie Nováková, Jana
Maříková, Dr. Jiří Kuneš, Prof. Dr. Pavel
Kočovský, Prof. Dr. Milan Pour
Page No. – Page No.
A new insight into Pd-catalyzed allylic isomerizations, exemplified by an unusual 1,3-
transposition leading to multisubstituted pyranones, is presented.
A New Insight into the
Stereoelectronic Control of the Pd(0)-
Catalyzed Allylic Substitution:
Application for the Synthesis of
Multisubstituted Pyran-2-ones via an
Unusual 1,3-Transposition
This article is protected by copyright. All rights reserved.