Opening the Way to Catalytic Aminopalladation/Proxicyclic Dehydropalladation: Access to Methylidene γ-Lactams

Article abstract of DOI:10.1021/acs.orglett.6b00143

A new aerobic intramolecular palladium(II)-based catalytic system that triggers aminopalladation/dehydropalladation of N-sulfonylalkenylamides to give the corresponding methylidene γ-lactams has been identified. Use of triphenylphosphine and chloride anio

Full text of DOI:10.1021/acs.orglett.6b00143

Letter
pubs.acs.org/OrgLett
Opening the Way to Catalytic Aminopalladation/Proxicyclic
Dehydropalladation: Access to Methylidene γ‑Lactams
Melanie M. Lorion,† Filipe J. S. Duarte,‡ Maria Jose Calhorda,‡ Julie Oble,*,† and Giovanni Poli*,†
́
́
†Sorbonne Universites
75252 Paris Cedex 05, France
́
, UPMC Univ Paris 06, Institut Parisien de Chimie Molec
́
ulaire, UMR CNRS 8232, Case 229, 4 Place Jussieu,
‡Centro de Química e Bioquímica, DQB, Faculdade de Cien
̂
cias, Universidade de Lisboa, 1749-016 Lisboa, Portugal
S
* Supporting Information
ABSTRACT: A new aerobic intramolecular palladium(II)-based catalytic
system that triggers aminopalladation/dehydropalladation of N-sulfonyl-
alkenylamides to give the corresponding methylidene γ-lactams has been
identified. Use of triphenylphosphine and chloride anion as ligands is
mandatory for optimal yields, and molecular oxygen can be used as the
sole terminal oxidant. Scope and limitations of the methods are described.
A mechanism is proposed on the basis of experimental results as well as
density functional theory calculations.
Scheme 1. Possible Pathways for Pd(II)-Catalyzed Cyclization
of N-Ts-carboxamides
alladium-catalyzed oxidative alkene heterocyclization repre-
Psents a widespread, atom-economical approach toward the
synthesis of oxygen- or nitrogen-containing cyclic scaffolds.1
However, starting from the same type of substrates and reaction
conditions, two kinds of reactivities can be operative: allylic C−H
activation2 or nucleopalladation3 (aminopalladation or oxy-
palladation).4,5 We have recently investigated in detail the
interplay of these mechanisms in intramolecular Pd(II)-catalyzed
aminations6 and oxylations7 for various unsaturated N-sulfonyl
carbamates, N-sulfonyl carboxamides, and carboxylic acids. The
optimized reaction conditions found in these studies were as
follows: 10 mol % of Pd(OAc)2, 15 mol % of PhS(O)
(CH2)2S(O)Ph as the ligand, and 1.07 equiv of phenyl-
benzoquinone (PhBQ) as oxidant in AcOH for nitrogen-based
nucleophiles and in CH2Cl2 with 1 equiv of NaOAc for oxygen-
based nucleophiles. The results of these studies suggest the
involvement of an initial rapid equilibrium between the PdX2−
substrate complex and a cyclic nucleopalladated intermediate
(NuPI).8 In particular, when the cyclic NuPI carries a H atom in a
distocyclic9 position (substrate with internal double bond), it can
evolve via a rapid β-H elimination (Scheme 1, top, for N-Ts
carboxamide). On the contrary, when the only β-H atom
available in the cyclic NuPI is in a proxicyclic9 position (substrate
with terminal double bond), β-H elimination is totally or partially
forbidden (Scheme 1, middle, product A), the cyclic NuPIs
remaining in an unproductive equilibrium with the starting
substrates.10,11 In this case, alternative reactivities, such as the
allylic C−H activation of the olefinic substrate, can take place
(Scheme 1, bottom line, product B).
dehydropalladation, the proxicyclic hydrogen atom being too
electron-depleted to interact with the palladium atom. Moreover,
an intramolecular interaction between the Pd atom and an
oxygen atom of the sulfonyl moiety could prevent the
synperiplanar H−C−C−Pd arrangement needed for the
dehydropalladation process (Figure 1, left). In this paper, we
disclose new conditions that allow evolution of the AmPI (Figure
1, right).
We decided to search for new reaction conditions able to
unlock the proxicyclic β-H elimination step, expected to give rise
to alkylidene lactams (see product A, Scheme 1).14 In line with
the above reasoning, we surmised thatthe presence of a base and a
coordinating ligand such as a phosphine15 could remove the
constraints, thereby allowing the β-H elimination process to take
Puzzled by the forbidden (or strongly inhibited)12 elimination
of the cyclic NuPI proxicyclic β-H atoms, we decided to
undertake further studies on this issue.13 In the particular case of
N-Ts carbamates and N-Ts carboxamides, we thought that under
the acidic reaction conditions the nitrogen atom of the cyclic
AmPI8 is likely to be protonated which would, in turn, inhibit
Received: January 15, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b00143
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
palladium source, the oxidant, or the base resulted in drastic yield
drops (entries 12 and 13) or in the total recovery of the unreacted
substrate (entry 14).
With our optimal conditions in hand [PdCl2(PPh3)2] (10 mol
%), NaOAc (1.5 equiv), O2 (1 atm), THF, reflux, 1 h, we
proceeded to explore the scope of the reaction (Scheme 2).17 The
Figure 1. Dormant vs evolving AmPIs from N-Ts carboxamide 1a.
a
Scheme 2. Scope of the Pd(II)-Catalyzed Aerobic Amination
place. Furthermore, in order todevelop agreen process, the use of
molecular oxygen as the sole oxidant was considered.16
We chose as model substrate pent-4-enoic acid N-tosyl amide
1a,17 which gave rise only to degradation under the previously
used acidic conditions (see Scheme 1). The influence of
palladium catalyst, and the base, as well as of the ligand, was
investigated, and the results are presented in Table 1.
Table 1. Optimization of the Pd(II)-Catalyzed Aerobic
a
Amination
b
entry
Pd cat
phosphine (mol %)
base
yield (%)
c
1
Pd(OAc)2
PPh3 (20)
XPhos (20)
Binap (10)
dppe (10)
PPh3 (10)
PPh3 (30)
PPh3 (20)
PPh3 (20)
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
K2CO3
NEt3
65
2
Pd(OAc)2
20
c
3
Pd(OAc)2
30
4
Pd(OAc)2
0
5
Pd(OAc)2
41
c
6
Pd(OAc)2
5
a
7
Pd(OAc)2
0
Reaction conditions: 1a−t (1 equiv), [PdCl2(PPh3)2] (10 mol %),
c
8
Pd(OAc)2
20
NaOAc (1.5 equiv) O2 (1 atm), THF (0.2 M), isolated yields.
b
c
9
PdCl2(PPh3)2
PdCl2(PPh3)2
Pd(OAc)2
NaOAc
NaOAc
NaOAc
NaOAc
92
Nonreproducible result. Structure was confirmed by single-crystal X-
d
10
11
12
13
14
92
ray diffraction analysis.
d
d
d
,
e
f
PPh3 (20)
92
12
26
,
PdCl2(PPh3)2
PdCl2(PPh3)2
effect of the substitution on the sulfonyl moiety was investigated
first. Electron-donating substituents (1a−d) on the aryl ring were
well tolerated. Electron-withdrawing para-substitution, such as
nitro (1e) or trifluoromethyl groups (1j), chlorine atoms (1g), or
fluorine atoms (1i) also led to the corresponding alkylidene γ-
lactams in good yields. On the other hand, electron-withdrawing
ortho-substitution (o-NO2, o-Br) (1f, 1h) was not compatible.
The bicyclic and heterocyclic naphthyl- (1k) and thiophene-yl-
substituted (1l) amides performed well. A mesyl substitution led
to the target alkylidene γ-lactams (2m) with a good yield too,
indicating that the scope is not limited to aromatic sulfonyl
derivatives. However, the triflyl derivative (1n) did not afford the
desired product. Nonsulfonyl groups such as benzyl, aryl,
benzoyl, tert-butoxycarbonyl (BOC), or tert-butylsulfinyl sub-
stituents were found to be unpromising (see the Supporting
Information). The acidity of the N−H in the N-protected
carboxamides seems to be crucial. Indeed, the lack of reactivity of
the triflyl, alkyl, and acyl derivatives suggests that the ideal pKa for
the substrates is around 4−5. Substituents on the tether were
then tested (Scheme 2). Alkyl and allyl substituents (1o, 1r)
afforded the desired products with good yields. Phenyl
substitution (1p−q,s−t) did also work, albeit with a slight yield
erosion.
d
NaOAc
0
a
b
Reaction conditions: 1a (1 equiv), THF (0.2 M). Spectroscopic (1H
c
NMR) yields using an internal standard (butadiene sulfone). Traces
of oxidation product 3a were observed. Reaction time: 1 h. LiCl (20
mol %) was added. Without oxidant.
d
e
f
A preliminary experiment using Pd(OAc)2 as the Pd source,
PPh3 as the ligand, and NaOAc as the base, in THF at reflux,
under O2 (1 atm) afforded over 24 h the desired alkylidene γ-
lactam 2a in 65% yield along with traces of the Saegusa
overoxidation product 3a18 (Table 1, entry 1). Replacement of
PPh3 for another monophosphine such as XPhos (entry 2) or a
diphosphine such as Binap or dppe (entries 3 and 4), as well as
changing of the phosphine loading, did not improve the outcome
(entries 5 and 6).19 The use of K2CO3 or NEt3 as base completely
or severely inhibited the reaction (entries 7 and 8). Other
oxidants such as PhBQ and 2,6-dimethylbenzoquinone (2,6-
DMBQ) did not lead to better results (see the Supporting
Information). Gratifyingly, use of [PdCl2(PPh3)2] as the Pd
source afforded 2a as the sole product in 92% NMR yield (entry
9). Furthermore, with this palladium catalyst the reaction time
could be reduced to 1 h (entry 10). The same result could be
obtained using Pd(OAc)2, PPh3, and NaOAc and by addition of
20 mol % of LiCl, which confirmed the crucial role of the chloride
anion (entry 11). Furthermore, one by one omission of the
Finally, this method was extended to the more challenging hex-
5-enoic acid N-tosylamide 4a, which in the previously developed
acidic conditions led to an inseparable mixture (71:29) of the
vinylpyrrolidone 6a (from the C−H activation path, product B, n
B
DOI: 10.1021/acs.orglett.6b00143
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
= 2, Scheme 1) and the methylidene piperidone 5a (from an
aminopalladation/dehydropalladation sequence, product A, n =
2, Scheme 1). In the event, treatment of carboxamide 4a with the
new reaction conditions again gave a mixture of 6a and 5a, though
in a modified 1:1 ratio. However, replacing molecular oxygen for
2,6-DMBQ increased both the yield and, more importantly, the
amount of alkylidene lactam 5a (83:17) (Scheme 3).
Scheme 5. Proposed Mechanism of the Catalytic Cycle
Scheme 3. Pd(II)-Catalyzed Amination 5-Enoic Acid N-
Tosylamide
Finally, to unveil the stereochemistry of the process, the
selectively deuterium-labeled N-tosylamide (Z)-D1 was synthe-
sized and tested for cyclization. Indeed, assuming that the
dehydropalladation is a stereospecific syn process,20 a syn-
aminopalladation should afford a (Z)-lactam, while an anti-
aminopalladation is expected to lead to the (E)-isomer.
Submission of (Z)-D1a to our reaction conditions provided the
γ-lactam (E)-D2a, which unequivocally disclosed an anti-
aminopalladation process (Scheme 4). A small amount of (Z)-
D2awas also observed, which could come from a competitive syn-
aminopalladation or from an anti-aminopalladation followed by
an anti-dehydropalladation.
favoring the anti-aminopalladation process and allowing the
synperiplanar H−C−C−Pd arrangement needed for the
subsequent dehydropalladation step. On the other hand, k2 PP
(chelating) diphosphines such as Binap or dppe (see Table 1,
entries 3 and 4), which do not change easily to monocoordination
with palladium, halt, or strongly inhibit, dehydropalladation.
Worthy of note, too, this protocol calls for the presence of
chloride anions (compare Table 1, entries 1 and 11). This fact
may be rationalized on the basis of the higher electron-
withdrawing power of chlorine, as compared to bromine,
iodine,24 or acetate, which maximizes the electrophilic character
of the coordinated alkene.25 Furthermore, according to Jutand’s
studies,23 we can predict that one chloride ligand is likely to stay
bound to palladium throughout the catalytic cycle, which implies
the involvement of an anionic Pd(II)−peroxo intermediate
during the reoxidation step. Finally, acetate anion behaves as
proton shuttle in two points of the catalytic cycle: the
aminopalladation and the reductive elimination step.
Scheme 4. Assessment of the Stereochemistry of the
Aminopalladation
In conclusion, in the framework of our ongoing long-term
research program dedicated to the mechanistic study of
transition-metal-catalyzed nucleophilic additions to alkenes, we
have now developed a new aerobic Pd-catalyzed protocol
providing access to a diverse array of alkylidene γ-lactams from
N-sulfonylalkenylamides. From a mechanistic viewpoint, this
new procedure opens the way to aminopalladation/proxicyclic β-
dehydropalladation, a sequence hitherto regarded as forbidden
for these substrates. A thorough optimization established that
triphenylphosphine and chloride anions are central to promote
the cyclization, and ad hoc experiments unequivocally demon-
strated that the aminopalladation step occurs via anti stereo-
chemistry. Finally, with the help of DFT calculations, a plausible
catalytic cycle is put forward. Studies are in progress to intercept
the transient AmPI through alternative ways.
The mechanism of this transformation was studied using DFT
calculations,21 leading to the proposal of a catalytic cycle (Scheme
5). The substrate 1a coordinates to Pd(II) by dissociative
substitution of one phosphine from the [PdCl2(PPh3)2]
precatalyst, affording Int-I. This substitution is endergonic by
52.2 kJ mol−1. Int-I undergoes acetate anion assisted anti-
aminopalladation, which brings about chloride release with an
energy barrier of 11.3 kJ mol−1 (TS-1, 63.5 kJ mol−1),22 leading to
the corresponding AmPI II (41.5 kJ/mol). The subsequent
proxicyclic β-H elimination involves a high energy intermediate
(AmPI-II′, ΔG = 80 kJ mol−1), followed by the highest energy
transition state (TS-2, 80.1 kJ mol−1), and generates Int-III.
Alkene decoordination releases product 2a and [PdCl(H)-
(PPh3)], which undergoes acetate anion assisted reductive
elimination to give an anionic Pd(0) species.23 Finally,
reoxidation by O2 regenerates the competent catalyst (see also
section IX in the SI).
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b00143.
X-ray crystallographic data for compound 2i (CIF)
Experimental procedures, compound characterization,
computational details, coordinates, structures and energies
of all intermediates and transition states, and reaction
energy profile (PDF)
In this catalytic cycle, triphenylphosphine is expected to
prevent coordination between a sulfonyl oxygen and palladium,
C
DOI: 10.1021/acs.orglett.6b00143
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Jones, G. C.; Booker-Milburn, K. I. J. Am. Chem. Soc. 2005, 127, 7308.
(f) Timokhin, V. I.; Stahl, S. S. J. Am. Chem. Soc. 2005, 127, 17888.
(g) Cucciolito, M. E.; D’Amor, A.; Vitagliano, A. Organometallics 2005,
24, 3359. (h) Hahn, C.; Morvillo, P.; Herdtweck, E.; Vitagliano, A.
Organometallics 2002, 21, 1807. (i) Hahn, C.; Morvillo, P.; Vitagliano, A.
Eur. J. Inorg. Chem. 2001, 2001, 419.
(11) When only a proxicyclic H position is available, activation of the
cyclic NuPI by a strong oxidant like PhI(OAc)2 allows the formation of
acetoxylated products. This oxidation turns out to be much faster than
the C−H activation reactivity; see: (a) Chen, S.; Wu, T.; Liu, G.; Zhen, X.
Synlett 2011, 2011, 891. (b) Hovelmann, C. H.; Streuff, J.; Brelot, L.;
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: julie.oble@upmc.fr.
*E-mail: giovanni.poli@upmc.fr.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank Camille Huynh (UPMC) for her contribution in
preliminary experiments, Geoffrey Gontard (UPMC) for X-ray
crystallographic analyses, and Omar Khaled (UPMC) for HRMS
analyses. CNRS, UPMC, and Labex Michem are acknowledged
for financial support. Support through CMST COST Action,
CM1205 (CARISMA), is also gratefully acknowledged. M.J.C.
Muniz, K. Chem. Commun. 2008, 2334. (c) Li, Y.; Song, D.; Dong, V. M.
̃
J. Am. Chem. Soc. 2008, 130, 2962. (d) Alexanian, E. J.; Lee, C.; Sorensen,
E. J. J. Am. Chem. Soc. 2005, 127, 7690.
(12) Under these acidic conditions, a small extent of proxicyclic β-H
elimination was observed only when starting from hex-5-enoic acid N-
tosylamide.
and F.J.S.D. thank the Fundaca̧ o para Ciencia e Tecnologia for
̂
̃
(13) For an example of a blocked proxicyclic dehydropalladation
process from a cyclic AmPI, see: Balaz
́ ́
s, A.; Hetenyi, A.; Szakonyi, Z.;
financial support (UID/MULTI/00612/2013) and a fellowship
Sillanpaa, R.; Fulop, F. Chem. - Eur. J. 2009, 15, 7376.
̈
̈
̈
̈
(SFRH/BPD/76878/2011, to F.J.S.D.).
(14) This type of sequence was observed from N-tosylamines: Fix, S.
R.; Brice, J. L.; Stahl, S. S. Angew. Chem., Int. Ed. 2002, 41, 164 From N-
tosylanthranilamides: see ref 4c. From hydrazones, see ref 4a,b.
REFERENCES
■
(1) For books on this topic, see: (a) Backvall, J.-E. In Modern Oxidation
̈
(15) For examples of Pd(II)-catalyzed oxidation of alkenes in presence
of phosphines, see: (a) Trost, B. M.; Donckele, E. J.; Thaisrivongs, D. A.;
Osipov, M.; Masters, J. T. J. Am. Chem. Soc. 2015, 137, 2776. (b) Trost, B.
M.; Thaisrivongs, D. A.; Donckele, E. J. Angew. Chem., Int. Ed. 2013, 52,
1523. (c) Li, L.; Chen, Q.-Y.; Guo, Y. Chem. Commun. 2013, 49, 8764.
(d) Trost, B. M.; Hansmann, M. M.; Thaisrivongs, D. A. Angew. Chem.,
Methods; Wiley-VCH: Weinheim, 2004. (b) Tsuji, J. In Palladium
Reagents and Catalysts, 2nd ed.; Wiley: New York, 2004. (c) Negishi, E -I.
In Handbook of Organopalladium Chemistry for Organic Synthesis; John
Wiley & Sons, Inc.: New York, 2002.
(2) For a selection of reviews on allylic C−H activation, see: (a) Liron,
F.; Oble, J.; Lorion, M. M.; Poli, G. Eur. J. Org. Chem. 2014, 20, 5863.
(b) Breder, A. Synlett 2014, 25, 899. (c) Ramirez, T. A.; Zhao, B.; Shi, Y.
Chem. Soc. Rev. 2012, 41, 931−942. (d) Engelin, C. J.; Fristrup, P.
Molecules 2011, 16, 951. (e) Jensen, T.; Fristrup, P. Chem. - Eur. J. 2009,
15, 9632.
Int. Ed. 2012, 51, 4950. (e) McMurry, J. E.; Koco
̌
vsky, P. Tetrahedron
Lett. 1984, 25, 4187.
(16) For reviews on Pd(II)-catalyzed oxidation reactions with oxygen
as oxidant, see: (a) Shi, Z.; Zhang, C.; Tang, C.; Jiao, N. Chem. Soc. Rev.
2012, 41, 3381. (b) Gligorich, K. H.; Sigman, M. S. Chem. Commun.
2009, 3854. (c) Muzart, J. Chem. - Asian J. 2006, 1, 508. (d) Stahl, S. S.
Angew. Chem., Int. Ed. 2004, 43, 3400.
(17) For synthesis and characterizations of all starting materials, see the
Supporting Information.
(18) For Pd-catalyzed Saegusa oxidation reactions, see: (a) Ito, Y.;
Hirao, T.; Saegusa, T. J. Org. Chem. 1978, 43, 1011. (b) Larock, R. C.;
Hightower, T. R.; Kraus, G. A.; Hahn, P.; Zheng, D. Tetrahedron Lett.
1995, 36, 2423.
(19) Use of triphenylphosphine oxide as the ligand provided 2a in 10%
NMR yield (see the Supporting Information) This suggests that under
our conditions triphenylphosphine is not oxidized by dioxygen (1H and
31P NMR analyses).
(20) For very rare examples of anti-β-H elimination with particular
substrates and/or conditions, see: (a) Takacs, J. M.; Lawson, E. C.;
Clement, F. J. Am. Chem. Soc. 1997, 119, 5956. (b) Maeda, K.;
Farrington, E. J.; Galardon, E.; John, B. D.; Brown, J. M. Adv. Synth. Catal.
2002, 344, 104. (c) Farina, V.; Azad Hossain, M. Tetrahedron Lett. 1996,
37, 6997−7000. (d) Lautens, M.; Fang, Y.-Q. Org. Lett. 2003, 5, 3679.
(e) Glover, B.; Harvey, K. A.; Liu, B.; Sharp, M. J.; Tymoschenko, M. Org.
Lett. 2003, 5, 301.
(21) All calculations were carried out with Gaussian09 at the
PBE1PBE/6-311+G(2d,2p)//PBE1PBE/6-31G(d,p) level in THF.
Details are given in the SI.
(22) The deprotonation step might take place on the iminol tautomer.
Furthermore, the alternative allylic CH-activation is calculated to
proceed via a 161.1 kJ/mol TS. See the Supporting Information.
(23) Jutand, A. Eur. J. Inorg. Chem. 2003, 2003, 2017.
(24) Use of 20 mol % of LiBr, or LiI, in the presence of Pd(OAc)2, PPh3,
and NaOAc led to 2a in about 40% NMR yield, which confirmed the
crucial role of the chloride anion (Table 1, entry 11).
(3) For a selection of reviews on nucleopalladation, see: (a) Koco
̌
vsky,
́
P.; Backvall, J.-E. Chem. - Eur. J. 2015, 21, 36. (b) McDonald, R. I.; Liu,
̈
G.; Stahl, S. S. Chem. Rev. 2011, 111, 2981. (c) Keith, J. A.; Henry, P. M.
Angew. Chem., Int. Ed. 2009, 48, 9038. (d) Minatti, A.; Muniz, K. Chem.
̃
Soc. Rev. 2007, 36, 1142. (e) Beccalli, E. M.; Broggini, G.; Martinelli, M.;
Sottocornola, S. Chem. Rev. 2007, 107, 5318.
(4) For recent examples on these competing mechanisms, see:
(a) Mboyi, C. D.; Abdellah, I.; Duhayon, C.; Canac, Y.; Chauvin, R.
ChemCatChem 2013, 5, 3014. (b) Mboyi, C. D.; Duhayon, C.; Canac, Y.;
Chauvin, R. Tetrahedron 2014, 70, 4957. (c) Beccalli, E. M.; Broggini, G.;
Paladino, G.; Penoni, A.; Zoni, C. J. Org. Chem. 2004, 69, 5627.
(d) Zanoni, G.; Porta, A.; Meriggi, A.; Franzini, M.; Vidari, G. J. Org.
Chem. 2002, 67, 6064.
(5) For a recent reviews on palladium(II)-catalyzed oxidation of
alkenes on nucleopalladation and allylic C−H activation, see: Mann, S.
E.; Benhamou, L.; Sheppard, T. D. Synthesis 2015, 47, 3079.
(6) (a) Nahra, F.; Liron, F.; Prestat, G.; Mealli, C.; Messaoudi, A.; Poli,
G. Chem. - Eur. J. 2009, 15, 11078. (b) Rajabi, J.; Lorion, M. M.; Ly, V. L.;
Liron, F.; Oble, J.; Prestat, G.; Poli, G. Chem. - Eur. J. 2014, 20, 1539.
(c) Lorion, M. M.; Nahra, F.; Ly, V. L.; Mealli, C.; Mesaoudi, A.; Liron,
F.; Oble, J.; Poli, G. Chem. Today 2014, 32, 30. (d) Duarte, F. J. S.; Poli,
G.; Calhorda, M. J. ACS Catal. 2016, 1772.
(7) Louafi, F.; Lorion, M. M.; Oble, J.; Poli, G. Synlett 2015, 26, 2237.
See also: Zanoni, G.; Porta, A.; Meriggi, A.; Franzini, M.; Vidari, G. J. Org.
Chem. 2002, 67, 6064.
(8) We propose the acronym NuPI for a generic nucleopalladated
intermediate and AmPI and OxPI for the specific aminopalladated or
oxypalladated intermediates, respectively.
(9) We propose the terms distocyclic and proxicyclic to distinguish
between β-H eliminations involving a hydrogen atom on a linear
fragment or on a cyclic structure, respectively.
(10) For recent reports about the reversible aminopalladation, see:
(a) Zhu, H.; Chen, P.; Liu, G. Org. Lett. 2015, 17, 1485. (b) Wu, T.;
Cheng, J.;Chen, P.; Liu, G. Chem. Commun. 2013, 49, 8707. (c) White, P.
B.; Stahl, S. S. J. Am. Chem. Soc. 2011, 133, 18594. (d) Cochran, B. M.;
Michael, F. E. J. Am. Chem. Soc. 2008, 130, 2786. (e) Bar, G. L. J.; Lloyd-
(25) Fagnou, K.; Lautens, M. Angew. Chem., Int. Ed. 2002, 41, 26.
NOTE ADDED AFTER ASAP PUBLICATION
Paragraph discussing Scheme 5 was corrected February 23, 2016.
■
D
DOI: 10.1021/acs.orglett.6b00143
Org. Lett. XXXX, XXX, XXX−XXX