F+ Reagent-Promoted Pd-Catalyzed C7-H Arylation of 1-Naphthamides

Article abstract of DOI:10.1021/acscatal.9b04352

The development of a strategy for remote C7-H functionalizations of the naphthalene rings is greatly challenging. Disclosed herein is an example of direct and regioselective arylation of the naphthalene rings at the C7 position that is promoted by F⁺ reagents. This protocol features good tolerance of reactive functional groups, mild reaction conditions, and simple reaction system. By control experiments, a kinetic isotope effect (KIE) experiment, and NMR experiments, the mechanistic pathway involving a carbopalladation/aryl migration has been illustrated clearly. Beyond the simple directing function, the sterically hindered N-(t-butyl)amide plays an important role in the regioselectivity control via a carbopalladation/aryl migration.

Full text of DOI:10.1021/acscatal.9b04352

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Letter
F+ Reagent-Promoted Pd-Catalyzed C7-H Arylation of 1-Naphthamides
Min Zhang, Anping Luo, Yang Shi, Rongchuan Su, Yudong Yang, and Jingsong You
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b04352 • Publication Date (Web): 21 Nov 2019
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Page 1 of 7
ACS Catalysis
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F+ Reagent-Promoted Pd-Catalyzed C7−H Arylation of 1-
Naphthamides
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Min Zhang, Anping Luo, Yang Shi, Rongchuan Su, Yudong Yang* and Jingsong You*
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan
University, 29 Wangjiang Road, Chengdu 610064, P. R. China
ABSTRACT: The development of a strategy for remote C7–H functionalizations of the naphthalene rings is greatly challenging.
Disclosed herein is an example of direct and regioselective arylation of the naphthalene rings at the C7 position promoted by F+
reagents. This protocol features good tolerance of reactive functional groups, mild reaction conditions and simple reaction
system. By control experiments, kinetic isotope effect (KIE) experiment, and NMR experiments, the mechanistic pathway involving
a carbopalladation/aryl migration has been illustrated clearly. Beyond the simple directing function, the sterically hindered N-
(t-butyl)amide plays an important role in the regioselectivity control via a carbopalladation/aryl migration.
KEYWORDS: palladium catalysis, C7-arylation, naphthalene, F+ reagent, regioselectivity
(a) Classic electrophilic substitution reaction of naphthalene rings
Naphthalenes are very important bicyclic aromatic
EWG
EDG
compounds frequently found in natural products, drugs,
agrochemicals and organic functional materials. Thus, the
highly regioselective functionalization of the naphthalene rings
has been an extremely attractive research topic for a long time.
However, controlling site-selectivity on the substituted
naphthalenes is challenging due to seven subtly different C−H
bonds that may all be functionalized. Electrophilic aromatic
substitutions of mono-substituted naphthalenes are classic
approaches to synthesize disubstituted naphthalenes, but
usually deliver lower yields because of the regioselectivity
problem (Scheme 1a).1 The naphthalenes bearing an electron-
donating group (EDG) at C1 typically undergo C4
functionalization, while those with an electron-withdrawing
group (EWG) give the C5 and/or C8-subsitutued products.
With the development of C–H functionalization of simple
aromatics, transition metal-catalyzed site-selective C–H
functionalizations of naphthalenes have gradually been
illustrated along with the generality of aromatic substrates
(Scheme 1b). Various directing groups (DGs) have been
demonstrated to control ortho-selectivity in diverse
functionaliztions of naphthalenes.2 Several strategies for meta-
C−H functionalzation of simple aromatics have been applied to
C3 functionalization of naphthalenes, including directed
remote C–H functionalization3,4 and use of norbornene as a
transient mediator.5 Electron-rich 1-naphthylamines have
special reactivity at remote C4 position via single electron
transfer (SET).6 Transition metal-catalyzed directed peri-C–H
functionalization of 1-substituted naphthalenes has been
developed for the synthesis of 1,8-disubstituted
naphthalenes.1c,7 Recently, in the investigation of para-
selective alkylation of benzamides, the alkylations of N,N-
diethyl-1-naphthamide have been found to exhibit C6-
selectivity.8 However, there are not any examples on the
selective remote C7–H functionalizations, clearly illustrating
the challenge of achieving C7 selectivity of naphthalenes.
FG EWG
EDG/EWG
2
8
1
7
+
3
6
5
4
FG = functional group.
FG
FG
(b) Transition metal-catalyzed C-H functionalization of naphthalene rings
ref. 1c,7
H
8
DG
ref. 2
undisclosed
C7-H functionalization
1
2
7
H
H
H
H
6
3
ref. 3-5
ref. 8
ref. 6
4
H
5
(c) This work: the first selective C7-H arylation
O
electron-rich ring O
R
R
O
R
Pd
anti--H
elimination
H
[ArPdIV +
]
Ar
H
Ar
H
B
A
electron-deficient ring
carbopalladation/aryl migration
C7 selectivity control
more electron-deficient
A ring than B ring
sterically hindered
directing group
+ 1.2 kcal/mol
cationic [PdIV] species
C
D
(calculated) in DCM
(calculated) in DCM
unfavorable
X-ray structure
favorable
Scheme 1. C–H functionalizations of naphthalene rings
Transition metal-catalyzed C–H arylation via the
carbopalladation/aryl migration has been documented to
enable meta-C–H arylation of (hetero)aromatic ring.9 Inspired
by these works, we envisioned that the C7–H arylation of
naphthalenes could occur via such a palladation/aryl migration
pathway with the assistance of a directing group at C1-position
(Scheme 1c). The key yet challenging problem encountered in
this proposed path is selectivity control, ie, how to reach high
selectivity at C7. The N-(t-butyl)amide as a sterically hindered
directing group has been extensively used in the directed C–H
functionalizations. Beyond the simple directing function, we
herein attempt to use such
regioselectivity issue. Firstly, the installation of the N-(t-
a strategy to address the
butyl)amide at C1 may promote palladation at C2 or C8. X-ray
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single crystal structure shows that the carbonyl O-atom is
that DCE (1,2-dichloroethane), HFIP (hexafluoroisopropanol)
and o-DCB (1,2-dichlorobenzene) were superior to DCM,
providing approximately 60% yield (Table S4). When the
reaction was operated in the presence of 1.25 equiv of NFSI and
2a, the desired product 3a was obtained in 68% yield along
with the C8–arylated byproduct 3a' in 4% yield (3a/3a'= 17:1)
and 1,1'-biphenyl in 13% yield (Table S6, entry 5). In addition,
2.0 equiv of other oxidants (e.g., Ag2O, Cu(OAc)2, DTBP (di-t-
butyl peroxide), mCPBA (m-chlorobenzoperoxoic acid), K2S2O8,
PhI(OAc)2, and DDQ (2,3-dicyano-5,6-dichlorobenzoquinone))
instead of NFSI did not afford 3a or only gave a trace amount of
3a, indicating the unique effect of F+ reagents (Table S7, entries
1-8). The replacement of PhB(OH)2 with iodobenzene (PhI) did
not afford any desired product (Table S7, entry 10).
Furthermore, no arylation was detected in the reaction of 1a,
phenyl bromide and PivOK in N,N-dimethylacetamide in the
absence of NFSI (Table S7, entry 11).
located to allow the cyclometallation at C8 rather than C2.10
The DFT calculation further indicates that the C conformation
is slightly higher in energy than D in solution state. Secondly,
the N-(t-butyl)amide at C1 makes the A ring more electron-
deficient than the B ring. Thus, the electrophilic catalytic
system enables the preferential cyclometallation at C8 (B ring).
Thirdly, the complexation of the palladium center with a DG is
kinetically favourable for the carbopalladation11 and is
beneficial to restrain the deprotonation and re-aromatization
at C8.
1
2
3
4
5
6
7
8
9
Pd(OAc)2
(
)
10
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12
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O
NHtBu
B(OH)2
O
NHtBu
cationic PdII species
Ph
+
Pd(TFA)2 ( yield: 32%)
3a
2a
1a
cationic PdIV species
(
)
Table 1: Scope of 1-naphthamides and aryl boronic acidsa
Pd(OAc)2/NFSI (yield: 60%)
O
NR1R2
O
NR1R2
aReaction conditions: 1a (0.10 mmol), 2a (0.15 mmol) and [Pd]
(1.0 equiv) in 1 mL of dichloromethane (DCM) at 80 °C for 12 h
under N2.
Ar
Pd(OAc)2, NFSI
DCE or o-DCB, 80 C, N2
R3
+
ArB(OH)2
R3
1
2
3 4
,
Scope of 1-naphthamides (in DCE)
Scheme 2. Evaluation of stoichiometric reaction systemsa
O
NiPr2
O
NHR
Following the above proposal,9b,9c we began our
investigation by the reaction of 1-naphthamide (1a) and
PhB(OH)2 (2a) in the presence of stoichiometric palladium
species (Scheme 2). Unfortunately, Pd(OAc)2 did not deliver the
arylated naphthalene 3a. However, the replacement of
Pd(OAc)2 with the cationic Pd(TFA)2 afforded 3a in 32% yield.
We envisioned a more electrophilic high-valent cationic PdIV
species might further promote the C7−H arylation. As well-
known, a cationic PdIV species can be formed with electrophilic
R = tBu, 68%, 59%b
R = Cy, 58%
Ph
Ph
3a,
3b,
3c,
Ph
R = Me, 14%
3d,
73%
NHtBu
NHtBu
R
O
O
O
c
3g,
R = Me, 81%
Ph
c
c
3e,
3f,
R = Me, 69%
3h,
3i,
R = OMe, 56%
R = Ph, 73%, 58%b
R = OMe, 47%c
R
NHtBu
NHtBu
NHtBu
O
O
Ph
Ph
Ph
X = Br, 48%d
X = F, 61%c, 50%b,c
3j,
reagents12
and
N-fluoro-N-
d
3l,
46%
fluorination
3k,
(phenylsulfonyl)benzenesulfonamide (NFSI) can react with
PdII and arylation reagents to form Ar–PdIV species.13 Thus, the
reaction of 1a with 2a was performed in the presence of
Pd(OAc)2 and NFSI, affording 3a in 60% yield (Scheme 2). This
X
CHO
NHtBu
O
NHtBu
O
N
Ph
Ph
reaction could also be extended to
a catalytic version,
COOMe
O
O
delivering 3a in 51% yield along with 5% yield of the C8–
arylated byproduct 3a' (Scheme 3). Other electrophilic
fluorination reagents showed less efficiencies partly owing to
the unfavourable coordination of the tertiary amine or pyridyl
moiety to the palladium center.13 The yields were improved
with the increase of the steric hindrance around pyridyl
e
3n,
38%
e
3o,
32%
3m,
42%
Scope of aryl boronic acids (in o-DCB)
O
NHtBu
O
NHtBu
Me
O
NHtBu
Me
Me
moiety, which might inhibit the coordination (F+2, F+3, F+ and
4
f
4b,
76%
4c,
48%
4a
, 81%
O
F+5). Considering the high price of NFTMPT, NFSI was selected
as the oxidant for the following investigation.
RO
O
NHtBu
4g,
X
NHtBu
R = Ph, 54%
4d,
4e,
4f,
X = F, 80%
b
O
NHtBu
NHtBu
NHtBu
4h,
R = CF3, 73%, 57%
O
O
b
X = Cl, 68%, 63%
X = Br, 49%
B(OH)2
Ph
Pd(OAc)2 (10 mol%)
F+ reagent (2.0 equiv)
H
Ph
+
+
R
O
NHtBu
4l, R = SO2Me, 46%c
4m
ROC
O
NHtBu
NHtBu
DCM (1 mL), 80 °C, N2, 12 h
1a
2a
4i,
4j,
4k,
R = H, 41%
3a
3a'
R = OEt, 52%
R = Me, 56%, 40%
, R = NO2, 47%
b
Cl
O
S
O
S
N
N
NHtBu
O
O
NHtBu
O
N
F
2BF4
Ph
N
F
Ph
N
F
Cl
N
F
Cl
OTf
N
F
O
O
F
OTf
BF4
OTf
Ph
MeO
F+1 (NFSI)
F+2 (NFTMPT)
F+
F+
F+
5
F+6 (selectfluor)
3
4
f
4n
, 78%
4o
4p
, 56%
, 49%
3a 51%
3a' 5%
53%
37%
21%
15%
ND
NR
NR
trace
trace
trace
aReaction conditions: 1 (0.10 mmol), 2 (0.125 mmol), Pd(OAc)2
(10 mol%), and NFSI (0.125 mmol) in 1 mL of DCE or o-DCB at
80 °C for 12 h under N2. b3 mol% of Pd(CF3COO)2 instead of 10
aReaction conditions: 1a (0.10 mmol), 2a (0.15 mmol),
Pd(OAc)2 (10 mol%) and F+ reagent (2.0 equiv) in 1 mL of DCM.
c
d
mol% of Pd(OAc)2, 36 h. at 100 °C. NFTMPT instead of NFSI.
Scheme 3. Survey of F+ reagentsa
eHFIP instead of DCE. fHFIP instead of o-DCB.
The reaction condition was further optimized (Tables S3-7).
Either higher or lower temperatures than 80 °C led to inferior
yields (Table S3, entries 1-5). Screening of solvents indicated
With the optimized conditions in hand, the scope of
naphthalenes was first explored. As shown in Table 1, various
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O
NHtBu
+
O
NHtBu
+
1-naphthamides successfully underwent the C7-arylation with
B(OH)2
1
2
3
4
5
6
7
8
PhB(OH)2. As we proposed, the steric effect of the amide group
seemed to have significant influence on the cross-coupling
reaction. Depending on the steric effect, the C7-arylated
products were obtained in the range of 14~73% yields (3a-
3d).10 No C2-arytlated product was detected. 1-Naphthamides
with both the electron-donating (e.g., methyl, and methoxy)
and electron-withdrawing (e.g., formyl, fluoro group and ester)
substituents smoothly underwent the arylation (3e-i, 3k-l and
3n). No or only trace amounts of the C8-arylated products were
detected. The very reactive bromo group could be retained and
no Suzuki-Miyaura coupling product was detected (3j).
Ph
Pd(OAc)2 (1.0 equiv)
DCE, 80 °C, N2, 12 h
(a)
(b)
Ph Ph
12%
2a
1a
(1.25 equiv)
B(OH)2
3a
(ND)
CONHtBu
H7/D7
Pd(OAc)2 (10 mol%)
NFSI (1.25 equiv)
DCE, 80 °C, N2
Me
CONHtBu
H6/D6
+
1.5 h - 3.0 h
kH/kD = 1.44
Me
4a 4a
/[D6]-
1a
1a
/[D7]-
2b
(1.25 equiv)
COOMe
+
B(OH)2
COOMe
+
Ph
COOMe
Pd(OAc)2 (10 mol%)
NFSI (1.25 equiv)
9
Ph
Ph
(c)
10
11
12
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N , 12 h
2
DCE, 80 °C,
Binaphthylamide was also
a suitable substrate (3m).
6b
6b'
7%
7%
2a
(1.25 equiv)
B(OH)2
Naphthalimide, an important organic photoelectric functional
skeleton, could deliver the π-extended product 3o under the
slightly modified reaction condition. Notably, even 3 mol% of
[Pd] species could efficiently promote the C7-arylation (3a, 3i
and 3k). No obvious decomposition of substrate 1 was detected
and the remaining substrates could be recovered, as
exemplified by 1f, 1j, 1n and 1o (see the supporting
information). In addition, the attempts of N-(t-butyl)-8-phenyl-
1-naphthamide 3a’ and N-(t-butyl)-7-phenyl-1-naphthamide
3a under the standard conditions led to a complex inseparable
mixture and no reaction, respectively.
Ph
Pd(OAc)2 (10 mol%)
NFSI (1.25 equiv)
+
+
N , 12 h
2
DCE, 80 °C,
(d)
3%
O
31%
2a
(1.25 equiv)
NHtBu
O
NHtBu
+
B(OH)2
Pd(OAc)2 (10 mol%)
NFSI (1.25 equiv)
Ph
(e)
CDCl3, rt, N2, 24 h
1a
2a
3a
(24%)
(1.25 equiv)
Scheme 5. Control experiments for the reaction
mechanism
To get some insights into the reaction mechanism, a series of
control experiments were conducted. First, the reaction of 1a
and 2a in the presence of stoichiometric Pd(OAc)2 could deliver
biphenyl in 12% yield along with the 95% recovery of 1a,
indicating that PdII could participate in the transmetalation of
phenylboronic acid (Scheme 5a).9b,13b Next, the parallel
competition reactions between p-tolylboronic acid 2b and N-
(tert-butyl)naphthamide 1a or [D7]-1a were carried out. A KIE
value of 1.44 suggests that a typical SEAr pathway for the C−H
bond activation is less likely in the C7-arylation because the
kH/kD value of a typical electrophilic palladation mechanism is
approximately 1.0.13a,14 This result also demonstrates that the
cleavage of the C7−H bond could not be included in rate-
determining step (Scheme 5b). Finally, methyl 1-naphthoate
and naphthalene instead of 1a were examined under the
standard conditions. The arylation of methyl 1-naphthoate
generated a mixture of C7-/C8-arylated product with a ratio of
1:1, and the reaction of naphthalene delivered 1-
phenylnaphthalene in 31% yield and 2-phenylnaphthalene in
3% yield,15 demonstrating the key role of the amide directing
group in the carbopalladation/aryl migration process (Scheme
5c and 5d).
Next, we tested the scope of arylboronic acids. Arylboronic
acids with various functional groups, such as methyl, fluoro,
chloro, bromo, aryl, trifluoromethoxy, formyl, ether, acyl,
methylsulfonyl, nitro and methoxy, at either para, meta, or
ortho position of the phenyl ring could react with 1-
naphthamide to afford the C7-arylated products in moderate to
high yields (4a-4p). In contrast to the para and meta-
substituent groups, the ortho-substituents led to diminishing
yields (4a-4c), suggesting that the increased steric congestion
could influence the reactivity.
CONHtBu
(A) H2SO4, H2O
1,4 -dioxane, 110 °C
COOR
CN
Ph
P2O5
Ph
Ph
toluene, 80 °C
93%
(B) H2SO4, MeOH, 110 °C
6a
A: , R = H, 92%
6b
B: , R = CH3, 90%
5
3a
Scheme 4. Transformations of 3a
To further illuminate the synthetic utility of this method, we
investigated the transformations of C7-arylated naphthalenes
(Scheme 4). For example, 3a was treated with P2O5 to afford 7-
phenyl-1-naphthonitrile 5 in 93% yield. Treatment of 3a with
dilute sulfuric acid in 1,4-dioxane and conc. H2SO4 in MeOH
gave 7-phenyl-1-naphthoic acid 6a and methyl 7-phenyl-1-
naphthoate 6b in 92% and 90% yields, respectively.
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Figure 1. a) 1H NMR spectra of 1a, 2a, [Pd] and NFSI in CDCl3. b) 19F NMR spectra of NFSI in CDCl3. c) 1H NMR spectra of the amide
proton of 1a in CDCl3
1
2
3
4
5
6
7
8
9
Considering that the C7-arylation could occur in CDCl3 at RT
(Scheme 5e), a series of 1H NMR spectra of the mixed reactants
(1a, 2a, Pd(OAc)2 and NFSI) in CDCl3 at RT in 8 hour period
were investigated. As shown in Figure 1a, only a combination
of 2a and Pd(OAc)2 leads to new proton signals, further
suggesting that the first step could be a transmetalation of
phenylboronic acid to form Ph–PdII.9b,13b A mixture of Pd(OAc)2
and NFSI did not gave rise to new peaks in the 19F NMR
spectrum, revealing that NFSI could not directly oxidize
Pd(OAc)2 to PdIV species (Figure 1b). Upon addition of 2a, a
mixture of 2a, Pd(OAc)2 and NFSI leads to a fresh 19F signal,
suggesting that NFSI takes part in the catalytic cycle after the
transmetalation of 2a and oxidizes Ph−PdII to produce
[F−PdIV−Ph] species.13b As illustrated in Figure 1c, the signal of
the amide proton of 1a shifts downfield from 5.85 to 5.99 ppm
only in the presence of all four reactants, indicating the
coordination of palladium center to the amide group in this
case. This result further implies that the oxygen atom of the
amide group coordinates to palladium center rather than the
nitrogen atom.
positions (Scheme 3 and Scheme 5d), further indicating the
pathway involving an aryl migration.
In conclusion, we have accomplished the C7-selective
arylation of 1-naphthamides with aryl boronic acids through
the carbopalladation/aryl migration. This protocol avoids the
use of extra ligands and additives, and exhibits high catalytic
activity and good tolerance of reactive functional groups. The
electrophilic fluorination reagents are demonstrated as a
unique oxidant to enhance the reaction efficiencies of C7–H
arylation of naphthalenes. We believe that this work will give
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inspiration
for
other
types
of
C7-regioselective
functionalizations of naphthalene rings.
AUTHOR INFORMATION
Corresponding Author
*jsyou@scu.edu.cn
*yangyudong@scu.edu.cn
Author Contributions
O
NHtBu
X
Ph PdIV
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
X
Ph PdIV
F
O
NHtBu
F
H
H
C8-palladation
Path iii
IM3
aryl migration
O
NHtBu
H+
NHtBu
Funding Sources
This work was supported by grants from the National NSF of
China (Nos 21432005, 21672154 and 21502123).
IM2
O
X
Ph PdIV
F
F
NHtBu
coordination
O
X
PdIV
H
Ph
Notes
PhB(OH)2
Path i Path ii
H
reductive
The authors declare no competing financial interest.
elimination
transmetalation
IM4
+
Ph PdIVXF
O
NHtBu
Ph PdIVXF
Ph
reductive
elimination
PdIIX
Ph
ASSOCIATED CONTENT
Supporting Information.
IM1
anti--hydride
elimination
NFSI
Ph
oxidation
X
Experimental procedures, characterization of related
compounds, crystallographic data, and X-ray crystal structures
(CIF) of 1a (CCDC-1912345) and 3d (CCDC-1911106) are
available in the Supplementary Information. The Supporting
Information is available free of charge on the ACS Publications
website.
Ph Ph
O
NHtBu
+ HX
PhB(OH)2
Ph
PdIIX2
X = F, OAc, (PhSO2)2N
transmetalation
Scheme 6. Plausible mechanistic pathway.
Based on the above mechanistic studies and previous
literature,9,16 a plausible pathway is proposed (Scheme 6).
Firstly, the transmetalation of Pd(II) species with PhB(OH)2
(2a) generates a Ph−PdII species, which is subsequently
oxidized by NFSI to produce a reactive cationic [Ph−PdIV−F]
species IM1.12,13 Next, IM1 may undergo transmetalation to
afford the Ph2PdIVFX species and subsequent reductive
elimination to deliver 1,1'-biphenyl (path ii). Alternatively, IM1
coordinates with N-(tert-butyl)-1-naphthamide (1a) to
provide intermediate IM2 (path i). IM2 then goes through the
C8-palladation to form the cationic intermediate IM3.9 IM3
may experience a typical SEAr pathway to bring the C8-arylated
byproduct (path iii)13 or undergo the aryl migration from Pd
center to C7 to form intermediate IM4. The six-membered ring
structure enhanced the stability of cyclic palladium complex
IM3 and rendered the carbopalladation event (aryl migration)
kinetically favorable to give IM4.11 IM4 then undergoes an anti-
β-hydride elimination to deliver the C7-arylated naphthalene
and regenerate Pd(II) species. Additionally, a typical Heck-type
mechanism seems less favored because the deprotonation
process requires syn β-hydride elimination, in which the C−C
bond rotation of cyclometallic intermediate IM4 is prerequisite
but difficult.16 The arylation may occur at both the C7 and C8
ACKNOWLEDGMENT
The authors acknowledge the support from the Comprehensive
Training Platform of Specialized Laboratory, College of
Chemistry, Sichuan University.
ABBREVIATIONS
KIE, kinetic isotope effect; EDG, electron-donating group; EWG,
electron-withdrawing group; DGs, directing groups; NFSI, N-
fluoro-N-(phenylsulfonyl)benzenesulfonamide; NFTMPT, N-
fluoro-2,4,6-trimethylpyridinium
triflate;
DCE,
1,2-
dichloroethane; HFIP, hexafluoroisopropanol; o-DCB, 1,2-
dichlorobenzene; DTBP, di-t-butyl peroxide; mCPBA, m-
chlorobenzoperoxoic
dichlorobenzoquinone;
substitution.
acid;
SEAr,
DDQ,
electrophilic
2,3-dicyano-5,6-
aromatic
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O
O
R
R
O
R
Pd
H
Ar
H
1
ArB(OH)2
Ar
H
2
Pd(OAc)2/NFSI
3
carbopalladation/aryl migration
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