Tandem Remote Csp3-H Activation/Csp3-Csp3 Cleavage in Unstrained Aliphatic Chains Assisted by Palladium(II)

Article abstract of DOI:10.1021/acs.organomet.8b00920

We report here a proof-of-concept for the cleavage of unstrained remote Csp³-Csp³ bonds at room temperature assisted by a directing group, opening up new possibilities to use aliphatic carboxylic acids as suitable alkenyl coupling partners. This strategy involves the Pd-mediated Csp³-H activation directed by a tethered 8-aminoquinoline group, followed by a concerted asynchronous carbene insertion into the Pd-C bond, and an unexpected β-carbon-carbon bond splitting. The insertion of a coupling partner into a Pd-C bond is a novel route to promote C-C bond cleavage, which in contrast to most common methodologies does not rely on the use of strained carbocycles.

Full text of DOI:10.1021/acs.organomet.8b00920

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Tandem Remote Csp3−H Activation/Csp3−Csp3 Cleavage in
Unstrained Aliphatic Chains Assisted by Palladium(II)
†,#
Marta Perez-Gomez, Hamid Azizollahi,†,‡,# Ivan Franzoni,§ Egor M. Larin,§ Mark Lautens,*,§
́
́
,†
́
́
and Jose-Antonio García-Lopez*
†
́
́
Grupo de Química Organometalica, Departamento de Química Inorganica, Universidad de Murcia, Murcia 30100, Spain
‡Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, 91775-1436 Mashhad, Iran
§Davenport Research Laboratories, Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada
S
* Supporting Information
ABSTRACT: We report here a proof-of-concept for the cleavage of
unstrained remote Csp3−Csp3 bonds at room temperature assisted by a
directing group, opening up new possibilities to use aliphatic carboxylic
acids as suitable alkenyl coupling partners. This strategy involves the Pd-
mediated Csp3−H activation directed by a tethered 8-aminoquinoline
group, followed by a concerted asynchronous carbene insertion into the
Pd−C bond, and an unexpected β-carbon−carbon bond splitting. The
insertion of a coupling partner into a Pd−C bond is a novel route to promote C−C bond cleavage, which in contrast to most
common methodologies does not rely on the use of strained carbocycles.
Scheme 1. Reported (a−c) and Novel (d) Routes for C−C
Bond Cleavage Assisted by Transition Metals
INTRODUCTION
■
The study of transition metal mediated reactions has boosted
the possibilities to functionalize unreactive C−H and C−C
bonds, allowing their consideration as suitable functional
groups when tackling complex molecular design challenges.1,2
While the activation of remote Csp2−H and Csp3−H moieties
has been made widely accessible with the help of directing
groups1,3 (such as 8-aminoquinoline),4 the cleavage of C−C
bonds is mainly restricted to (a) the oxidative addition of C−
CN groups5 or C−C bonds present in strained cycloalkyl
substrates6 to transition metals in low oxidation state (Scheme
1a); (b) chelation-assisted activation of unstrained C−Csp2
bonds5b,7 (Scheme 1b); (c) processes involving a β-carbon
elimination in systems bearing a strained cycloalkyl group6
(Scheme 1c); or (d) decarboxylation or decarbonylation
reactions.2j The methods dealing with unstrained Csp3−Csp3
cleavage are less common,2j,8−10 and they are related to specific
moieties which, upon splitting of the Csp3−Csp3 bond, lead to
cyclopentadienyl rings9 or substrates where at least one of the
Csp3 atoms is bound to either a heteroatom or two carbonyl
groups. Moreover, although some β-carbon elimination
reactions in unstrained Csp3−Csp3 systems have been
reported, they involve σ-alkyl complexes of early transition
metals such as Lu, Sc, Zr, or Ti, among others.10 Nevertheless,
in spite of the impressive developments achieved in the
activation of C−H and C−C bonds, the synthetic methods
merging the functionalization of both types of bond are still in
their infancy.8i,11−14 Significantly, most of them rely on
intramolecular processes taking place on conveniently designed
substrates, which typically include a strained cycloalkyl moiety
in order to promote the C−C cleavage step.13 With the
exception of decarboxylative or decarbonylative methods, the
limited examples of intermolecular reactions encompassing C−
H/C−C activations also involve the use of a strained
Received: December 17, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.8b00920
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
cycloalkane as a coupling partner.14 Recently, Engle and co-
workers found a catalytic procedure for unstrained Csp3−H/
Csp3−Csp3 cleavage where one of the Csp3 forms part of a 1,3-
dicarbonyl leaving group.8i Hence, further development of
strategies merging Csp3−H and Csp3−Csp3 bond activations
in ubiquitous unstrained aliphatic moieties remains a
challenging and appealing goal. In the course of our
investigations devoted to the use of Pd in organic synthesis,15
we uncovered a new path to promote the Csp3−Csp3 bond
cleavage based on the Csp3−H palladation of acyclic alkyl
chains, followed by the insertion of an unstrained molecule, a
carbene in this case (Scheme 1d).
yield of alkene 6a was obtained, which corresponded to a
stoichiometric transformation.
The likely reason underlying the inability of Pd to restart the
catalytic cycle relies on the nature of the proposed Pd species
5, generated upon the C−C bond cleavage. We have isolated
the Pd species arising from the stoichiometric reaction, finding
that it did not further react with ligands such as PPh3, picoline,
t-BuNC, phenanthroline, or diphenylphosphinoethane
(DPPE). Solid 5 was partially soluble in common organic
solvents, and its 1H NMR spectrum in CDCl3 showed multiple
overlapped signals in the aromatic region (see the Supporting
Information). The spectrum did not change in more polar
solvents such as d6-DMSO. The mass spectrometry + ESI of a
sample of 5 in CH2Cl2 showed a broad range of peaks up to
more than 1000 m/z ratio. The spectrum showed an intense
peak at 145.070 m/z, which could correspond to the 8-
aminoquinoline moiety (M + H+ = 145.076) generated upon
fragmentation of species 5. The IR spectrum of 5 showed an
intense band at 1733 cm−1, presumably corresponding to the
stretching of the CO bond present in the amide moiety
attached to the quinoline ring. With these data in hand, we
tentatively propose that the solid 5 might be composed by a
mixture of Pd-coordination oligomers containing N-(quinolin-
8-yl) acetamide units.
RESULTS AND DISCUSSION
■
We were interested in the reactivity of palladacycle 2a, arising
from the Csp3−H activation of alkyl-substituted 8-amino-
quinoline 1a, toward carbene precursors such as diazo
compound 3a (Scheme 2).16 Thus, we started our study by
Scheme 2. Reactivity of Palladacycles 2a and 2b toward
Diazocompound 3a
In addition, we performed the reaction of species 5 with CO
in MeOH at 70 °C for 16 h (Scheme 3) and observed the
Scheme 3. Reactivity of Species 5 toward CO
reacting complex 2a with compound 3a in toluene at 90 °C
under inert atmosphere. The reaction was repeated in MeCN
at 80 °C and in CH2Cl2 at room temperature finding similar
results. To our surprise, no alkenylated derivative arising from
a possible β-hydrogen elimination (Scheme 1d) was detected
in the reaction mixture. Instead, terminal alkene 6a (Scheme
2) was the main produced product. Apparently, plausible
intermediate 4a, arising from the carbene insertion into the
Pd−C bond present in palladacycle 2a, did not evolve through
the expected β-hydrogen but through a β-carbon elimination,
affording alkene 6a. To further confirm the origin of the
coupled moieties in this transformation, we performed the
reaction of palladacycle 2b, bearing a methyl group on the
palladated carbon. Indeed, the reaction generated a mixture of
E/Z isomers of alkenes 6b in a 7:1 ratio (Scheme 2).
The unexpected coupling of alkyl substituted 8-aminoquino-
line amides 1 with the diazocompound 3 represents a novel
entry to the synthesis of alkenes. Furthermore, this process
encompasses a) a remote Csp3−H activation, and b) a carbene
insertion and Csp3−Csp3 cleavage at room temperature. In
contrast to other approaches merging C−H and C−C bond
cleavage reported to date,13 none of the coupling partners bear
a strained cycloalkyl moiety to promote the C−C bond
splitting step.
formation of palladium black. From the crude reaction mixture
we could isolate and characterize the methyl ester 10, likely
arising form methoxycarbonylation of the 8-amidoquinoline-
Pd unit contained in 5, along with N-(quinolin-8-yl)acetamide
11, formed upon protodepalladation of the Pd−CH2 bond in
that unit.
It is likely that the stability of species 5 prevents the
coordination of a new molecule of substrate 1a, a key step to
allow the catalytic cycle to proceed. We decided to continue
investigating this novel transformation since the Csp3−Csp3
cleavage is an underexplored research area, where stoichio-
metric organometallic chemistry can shed light and set the
basis for future catalytic developments. In addition, stoichio-
metric organometallic studies have made possible challenging
coupling reactions, finding applications in the synthesis of
natural products and pharmaceuticals.17
We then performed the reaction of substrate 1a with diazo
compound 3a in a one-pot, two-step procedure, thus avoiding
the isolation of the palladacycle intermediate. No significant
differences were found in the yield (Scheme 4). With these
conditions in hand, we explored the scope of the reaction.
First, we tested several diazo compounds with different
substitution patterns. We found that aryl substituted α-
diazocarbonyl compounds were well-tolerated, providing
good yields (measured by NMR) for aryl rings containing
either electron-withdrawing or -donating groups (6c and 6d,
Scheme 4). When a more stabilized diazocompound bearing
We tried to perform the coupling reaction of amide 1a and
diazo compound 3a in a catalytic fashion by using a 10 mol %
of a Pd(II) source under a wide range of conditions (see the
Supporting Information). Unfortunately, a maximum of 10%
B
DOI: 10.1021/acs.organomet.8b00920
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
sensitive to the bulkiness of the ester group, as observed by
comparison of the outcome of the reactions of substrate 1b
and methyl- or benzyl-diazocarbonyl esters (E/Z ratio, 7:1 and
9:1 respectively, for products 6b and 6h, Scheme 5). The
reactions of standard phenyl diazocarbonyl ester 3a with
substrates 1f and 1g, bearing a phenyl group either in the 3- or
4-position of the alkyl chain, gave none or traces of the
expected coupling products, even when the second step of the
reaction was carried out in MeCN at 80 °C. Nevertheless,
these substrates did produce coupling products 6k and 6l when
they reacted with the less sterically hindered ethyl 2-
diazoacetate. Curiously, in these reactions only the E isomer
could be detected in the crude reaction mixture. The behavior
of substrate 1h, containing a phenyl substituent in C5-position
of the alkyl chain, was similar to simple alkyl substituted
substrates 1b−e, affording the alkene 6m in 52% isolated yield,
although only the E isomer could be observed in the crude
reaction mixture. When the Ph group was located at remote
positions there was no influence in the outcome of the
reaction, with 1i giving a 57% isolated yield of product 6n as a
E/Z mixture in a ratio >95:5 (Scheme 5).
Scheme 4. Scope of the Coupling Reaction of 1a with
Different Diazocompounds
two ester groups was used, the reaction afforded a poor yield of
the alkene (6e, 23% NMR yield, Scheme 3). The use of the
monosubstituted ethyl 2-diazoacetate rendered a 60% yield of
corresponding ethyl acrylate 6f. Diphenyl diazomethane
proved unproductive under these reaction conditions,
rendering intermediate complex 2a as the main reaction
product.
Aliphatic carboxylic acids are important moieties present in
natural products, such as fatty acids, and biologically active
compounds and pharmaceuticals, like biotin, ibuprofen, or
gemfibrozil to name a few. Hence, we extended our study to 8-
aminoquinoline amide derivatives of oleic and linoleic acids 1j
and 1k. The reactions of these starting materials with the
diazocarbonyl coupling partner 3a led to the expected diene 6o
and triene 6p, respectively, in good isolated yields (Scheme 6).
Next, we moved to evaluate the Csp3−Csp3 cleavage of 8-
aminoquinoline amides containing longer alkyl chains (Scheme
5). We observed that the reaction proceeded smoothly with
Scheme 5. Scope of Substrates 1 and Diazocompounds
Scheme 6. Use of Oleic and Linoleic Acid Derivatives
To evaluate the factors governing this transformation, we
performed the reaction of pivalic acid derivative 1c and found
that α-disubstitution on the amide hampered the reaction,
giving a 34% yield of 6a (Scheme 5). We also tested the
reaction of diazocompound 3a and other σ-alkyl palladacycles
arising from other ligands such as 2-pivaloylpyridine or 8-
methylquinoline. In those cases, no alkene 6a was produced.
These results point to the strong chelation of the 8-
aminoquinoline as a key factor that enables the C−C bond
splitting to proceed smoothly. When the reaction of pallada-
cycle 2a with 3a was carried out in the presence of PMe3, the
replacement of MeCN by the PMe3 ligand in 2a took place
leading to complex 2c (see the Supporting Information),
avoiding the formation of 6a, which may discard outersphere
mechanisms in the reaction with the diazocompound.
We monitored the reaction of complex 2a with an excess of
diazocompound 3a in an NMR tube under nitrogen
atmosphere (Figure 1) to check the possible existence of
intermediate 4a. Nevertheless, although we could observe the
progressive conversion of starting materials 2a and 3a into
alkene 6a, we detected only the signals corresponding to these
species. Noteworthy, the reaction starts immediately upon
mixture of the reagents, reaching a 30% conversion of 2a in the
derivatives arising from butyric, caproic, and capric carboxylic
acids, yielding corresponding alkenes 6b, 6i, and 6j in good
yields. The E/Z ratio of the products increased with the length
of the alkyl chain, rising form 7:1 to >95:5 (measured by H
NMR) when passing from 4 to 9 carbons in the aliphatic
1
moiety of the starting materials. The E/Z ratio was also slightly
C
DOI: 10.1021/acs.organomet.8b00920
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Figure 1. 1H NMR monitoring of the reaction of 2a and 3a in an NMR tube under N2 atmosphere at 20 °C. Species are marked with color dots as
follows: complex 2a (red); diazocompound 3a (blue); alkene 6a (green); free MeCN (black).
Figure 2. Key modeled structures and computed concerted asynchronous mechanism for the formation of 6a.
first 2 min. This experiment suggests that either intermediate
4a has a very short lifetime or that the reaction proceeds in a
concerted asynchronous fashion where there is no such an
intermediate, as pointed out by DFT calculations (see below).
Furthermore, we observed that the excess of diazocompound
3a was fully consumed after 8 h, with the appearance of a range
of multiple peaks in the 3.5−4.0 ppm region, attributed to the
methoxy group in a plausible polymeric material formed by
reaction of the excess of diazocompound with the Pd-
acetamide fragment present in the reaction mixture. Moreover,
when a second batch of diazocompound 3a was added to the
NMR tube, it was also consumed (see the monitoring data in
the Supporting Information), explaining in part why no clear
signals can be identified in the NMR spectra of species 5 and
why some excess of the diazocompound is necessary to reach
the full conversion of starting complex 2a into alkene 6a.
In order to gain a better understanding of the underlying
mechanism for this transformation, a computational study was
carried out.18 We first studied the reactivity of postulated
palladacycle intermediate 4a toward either β-hydride or
-carbon elimination processes (Scheme 1d). The first
mechanism is precluded by an unfavorable Pd−C1−C2−H
dihedral angle (63−83°) and by a poor orientation of the
orbitals imposed by the cyclic nature of this intermediate. The
same structural features were also at the origin of the
unrealistic activation energies computed for the β-carbon
elimination process (Figure 1, TS_4a_8a, ΔG⧧ = 49.5 kcal
mol−1).
D
DOI: 10.1021/acs.organomet.8b00920
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
For full experimental procedures and characterization data of
starting materials 1a−k, palladacycles 2a−c, and alkenes 6a−p, see
the Supporting Information.
We next studied the reactivity of the thermodynamically
favored intermediate generated by reaction of palladacycle 2
with diazocompound 3a, namely, 7a (Figure 2). Our attempts
to locate the transition state for the carbene insertion process
connecting 2a to 4a were unsuccessful. Relaxed scans analysis
of the potential energy surface by shortening of the distance
between C1 (red) and C2 (blue) in 7a suggest a highly
concerted asynchronous insertion/elimination process leading
to olefin 6a without the intermediacy of 4a. The corresponding
transition state models the formation of the C1C2 and the
Pd−C3 bonds while breaking the C2−C3 bond (Figure 2).
The computed activation energy for this concerted asynchro-
nous mechanism is 17.5 kcal mol−1, a value consistent with a
reaction carried out at room temperature.
Corresponding product 8a undergoes ligand exchange to
release the final product and the palladacycle 9. This
intermediate may represent unidentified unreactive species 5
or (one of) its precursor(s). Extension of this mechanism in
the case of methyl-substituted intermediate 7b was considered.
Comparison of the activation energies for the two possible
pathways leading to either E or Z isomer of 6b provides a
theoretical ratio of 8:1 in favor of the former (ΔΔG⧧ = 1.2 kcal
mol−1). This result is in remarkable agreement with the
experimental 7:1 E/Z ratio obtained in the reaction between
palladacycle 2b and diazocompound 3a, thus lending support
for our mechanistic model for this transformation. Unfortu-
nately, for the reasons explained above, we were unable to fully
characterize proposed species 5 or 9, which would have further
supported experimentally the plausible mechanism found by
DFT. Hence alternative stepwise reaction pathways can not be
discarded for this process, for instance involving bimetallic
intermediates.
Representative Procedure A: Synthesis of Starting Material
1a. Propionyl chloride (1.5 mL, 16.8 mmol) was added to a solution
of 8-aminoquinoline 1 (2.0 g, 14.0 mmol) and triethylamine (2 mL)
in dry CH2Cl2 (30 mL) under N2 atmosphere. The mixture was
stirred at room temperature overnight. The reaction mixture was
diluted with CH2Cl2 (25 mL) and washed with Na2CO3 aq. (2 × 40
mL). The organic layer was dried over MgSO4 and filtered. The
solvent was removed to dryness. The crude was purified by column
chromatography (silica-gel, petroleum ether/EtOAc, gradient from 0
to 15% EtOAc) to afford 1a as a dense yellow oil that solidified slowly
(2150 mg, 10.7 mmol, 76% yield). Mp: 30 °C. IR (cm−1) υ (CO)
1
1690 (s). H NMR (400 MHz, CDCl3) δ = 9.82 (br s, 1 H), 8.78−
8.80 (m, 2 H), 8.15 (dd, J = 8.4, 1.7 Hz, 1 H), 7.43−7.55 (m, 3 H),
2.60 (q, J = 7.6 Hz, 2 H), 1.34 (t, J = 7.2 Hz, 3 H). 13C NMR (75
MHz, CDCl3) δ = 172.4 (s, Cq), 148.0 (s, CH), 138.2 (s, Cq), 136.2
(s, CH), 134.5 (s, Cq), 127.8 (s, Cq), 127.3 (s, CH), 121.5 (s, CH),
121.2 (s, CH), 116.2 (s, CH), 31.1 (s, CH2), 9.7 (s, CH3). HR-MS
(+ESI) m/z calcd for C12H13N2O [M + H]+ 201.1022, found
201.1030. These data are in agreement with the data reported in the
literature.4b
Representative Procedure B: Synthesis of Complex 2a.
Pd(OAc)2 (448 mg, 2 mmol) and K2CO3 (553 mg, 4 mmol) were
added to a solution of 1a (400 mg, 2 mmol) in CH3CN (15 mL). The
resulting suspension was stirred at reflux for 16 h. The suspension was
filtered through a Celite pad, the filtrate concentrated to ca. 2 mL, and
Et2O (15 mL) added. The resulting suspension was filtered, and the
solid was washed with Et2O (2 × 5 mL) and air-dried to give complex
2a as a yellow solid (618 mg, 2.03 mmol, 89% yield). Dec. point: 170
°C. IR (Nujol, cm−1) υ (CO) 1722 (s). 1H NMR (400.9 MHz,
CDCl3) δ = 9.02 (dd, J = 8.0, 1.2 Hz, 1 H), 8.27 (dd, J = 4.5, 1.6 Hz, 1
H), 8.13 (dd, J = 8.6, 1.6 Hz, 1 H), 7.47 (t, J = 8.0 Hz, 1 H), 7.33−
7.17 (m, 2 H), 2.79 (t, J = 7.3 Hz, 2 H), 2.35 (s, 3 H), 1.77 (t, J = 7.3
Hz, 2 H). 13C NMR (100.1 MHz, CDCl3) δ = 187.0 (s, Cq), 146.7 (s,
Cq), 145.7 (s, CH), 145.0 (s, Cq), 137.7 (s, CH), 129.7 (s, Cq),
129.0 (s, CH), 120.4 (s, 2 × CH), 118.3 (s, Cq), 118.1 (s, CH), 43.1
(s, CH2), 4.1 (s, CH2), 3.5 (s, CH3). Elemental analysis calcd (%) for
C14H13N3OPd: C: 48.64, H: 3.79, N: 12.15. Found: C: 48.55, H:
3.74, N: 12.03.
Synthesis of Complex 2b. Prepared according to the procedure B
from substrates N-(quinolin-8-yl)butyramide (400 mg, 1.87 mmol)
and Pd(OAc)2 (419 mg, 1.87 mmol). Data for compound 2b: yellow
solid (481 mg, 1.34 mmol, 72% yield). Mp: 200 °C. IR (Nujol, cm−1)
υ (CO) 1722 (s). 1H NMR (300 MHz, CDCl3) δ = 9.02 (dd, J = 7.9,
1.2 Hz, 1 H), 8.29 (dd, J = 4.7, 1.6 Hz, 1 H), 8.13 (dd, J = 8.4, 1.7 Hz,
1 H), 7.46 (d, J = 8.0 Hz, 1 H), 7.35−7.15 (m, 2 H), 2.97−2.82 (m, 1
H), 2.61−2.45 (m, 2 H), 2.34 (s, 3 H), 1.10 (d, J = 6.7 Hz, 3 H). 13C
NMR (100 MHz, CDCl3) δ = 185.2 (s, Cq), 146.5 (s, Cq), 145.8 (s,
CH), 144.5 (s, Cq), 137.5 (s, CH), 129.5 (s, Cq), 128.8 (s, CH),
120.4 (s, CH), 119.9 (s, CH), 118.1 (s, CH), 117.8 (s, Cq), 52.8 (s,
CH2), 24.9 (s, CH3), 19.3 (s, CH), 3.3 (s, CH3). Elemental analysis
calcd (%) for C15H15N3OPd·1/2 H2O: C: 48.80, H: 4.37, N: 11.40.
Found: C: 48.74, H: 4.13, N: 11.16.
CONCLUSION
■
In summary, we have discovered a new path to promote the
cleavage of Csp3−Csp3 bonds present in unstrained alkyl
chains by exploiting several reactivity modes of Pd(II):
directed Csp3−H activation, concerted migratory insertion of
a carbene moiety, and β-carbon−carbon bond cleavage. This
route allows the use of aliphatic carboxylic acids as alkenyl
synthons and represents a new case of study for directed C−C
activation. This work may serve as a proof of concept to inspire
future catalytic developments. Further studies on the reaction
mechanism will be necessary to gain a deeper understanding
on this transformation.
EXPERIMENTAL SECTION
■
General Considerations, Materials, and Instrumentation.
Infrared spectra were recorded on a PerkinElmer spectrum 100
spectrophotometer. High-resolution ESI mass spectra were recorded
on an Agilent 6220 Accurate Mass TOF LC/MS spectrometer.
Melting points were determined using a Reichert apparatus and are
uncorrected. Nuclear magnetic resonance (NMR) spectra were
recorded on a 300 or 400 MHz Bruker NMR spectrometers in
CDCl3 at 298 K (unless stated otherwise). All chemical shift values
are reported in parts per million (ppm) with coupling constant (J)
Representative Procedure C: Synthesis of Alkene 6a from
Palladacycle 2a. A 50 mL Schlenck was charged with 2a (50 mg,
0.15 mmol) and dry dichloromethane (5 mL) under N2 atmosphere,
and 3a (51 μL, 0.33 mmol) was added. The reaction mixture was
stirred at room temperature for 16 h. After this period, the reaction
mixture was diluted with dichloromethane (10 mL) and filtered
through a Celite pad. Diethyl ether (15 mL) was added. The resulting
suspension was filtered and the brown solid was air-dried to give the
solid 5, containing unidentified Pd-species (see the Supporting
Information). The filtrate was concentrated to dryness. The crude
contained a 95% yield determined from the 1H NMR spectrum of the
crude reaction mixture using 1,3,5-trimethoxycarbonyl benzene as
standard. The crude was purified by preparative TLC (silica gel, 10:1
petroleum ether/EtOAc), affording compound 6a as an oil (18 mg,
1
values reported in Hz. All spectra were referenced to TMS for H
NMR and the CDCl3 solvent peak for 13C{1H} NMR. Anhydrous
MeCN, CH2Cl2 and toluene were purchased from commercial
sources and used as received. TLC tests were run on TLC Alugram Sil
G plates and visualized under UV light at 254 nm. Chromatography:
Separations were carried out on silica gel or neutral alumina. For
those compounds where no elemental analysis is provided, clean
NMR spectra are provided as a proof of bulk purity.
1
0.11 mmol, 73% isolated yield). IR (cm−1) υ (CO) 1721 (s). H
E
DOI: 10.1021/acs.organomet.8b00920
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
NMR (300 MHz, CDCl3) δ = 7.43−7.38 (m, 2 H), 7.37−7.32 (m, 3
H), 6.35 (d, J = 1.2 Hz, 1 H), 5.88 (d, J = 1.2 Hz, 1 H), 3.82 (s, 3 H).
13C NMR (75 MHz, CDCl3) δ = 167.3 (s, Cq), 141.3 (s, Cq), 136.7
(s, Cq), 128.3 (s, CH), 128.2 (s, CH), 128.1 (s, CH), 126.9 (s, CH2),
52.2 (s, CH3). GC-MS (+EI) m/z calcd for C10H10O2, 162.07. Found,
162.10. These data are in agreement with the data reported in the
literature.19
Representative Procedure D: One-Pot Two-Step Synthesis
of Alkene 6a from 8-Aminoquinolin amide 1a and Diazo-
compounds 3a. Step 1: A Schlenck tube was charged with
corresponding substrate N-(quinolin-8-yl)propionamide 1a (100
mg, 0.5 mmol), Pd(OAc)2 (112 mg, 0.5 mmol), and K2CO3 (138
mg, 1 mmol) in MeCN (7 mL). The suspension was stirred at reflux
for 16 h. Step 2: The solvent of the suspension was taken to dryness.
The tube was set under nitrogen atmosphere, dry CH2Cl2 (5 mL)
added, and diazocompond 3a (176 μL, 1.1 mmol) added to the
reaction mixture. The mixture was stirred at room temperature for 16
h. The crude was diluted with CH2Cl2 (15 mL) and filtered through a
Celite pad. The filtrate was concentrated to dryness and the crude was
purified by preparative TLC (silica gel, petroleum ether/EtOAc
(9:1)) to afford product 6a. Yield: 62 mg, 0.38 mmol, 76% isolated
yield.
rapid construction and late-stage diversification of functional
molecules. Nat. Chem. 2013, 5, 369−375. (c) Yang, L.; Huang, H.
Transition-Metal-Catalyzed Direct Addition of Unactivated C−H
Bonds to Polar Unsaturated Bonds. Chem. Rev. 2015, 115, 3468−
3517. (d) Hartwig, J. F. Evolution of C−H Bond Functionalization
from Methane to Methodology. J. Am. Chem. Soc. 2016, 138, 2−24.
(e) Gensch, T.; Hopkinson, M. N.; Glorius, F.; Wencel-Delord, J.
Mild metal-catalyzed C−H activation: examples and concepts. Chem.
Soc. Rev. 2016, 45, 2900−2936. (f) Della Ca’, N.; Fontana, M.; Motti,
E.; Catellani, M. Pd/Norbornene: A Winning Combination for
Selective Aromatic Functionalization via C−H Bond Activation. Acc.
Chem. Res. 2016, 49, 1389−1400. (g) He, J.; Wasa, M.; Chan, K. S. L.;
Shao, Q.; Yu, J.-Q. Palladium-Catalyzed Transformations of Alkyl C−
H Bonds. Chem. Rev. 2017, 117, 8754−8786. (h) Sambiagio, C.;
̈
Schonbauer, D.; Blieck, R.; Dao-Huy, T.; Pototschnig, G.; Schaaf, P.;
Wiesinger, T.; Zia, M. F.; Wencel-Delord, J.; Besset, T.; Maes, B. U.
W.; Schnurch, M. A comprehensive overview of directing groups
̈
applied in metal-catalysed C−H functionalisation chemistry. Chem.
Soc. Rev. 2018, 47, 6603−6743.
(2) For reviews on C−C activation: (a) Jun, C.-H. Transition metal-
catalyzed carbon−carbon bond activation. Chem. Soc. Rev. 2004, 33,
610−618. (b) Murakami, M.; Matsuda, T. Metal-catalysed cleavage of
carbon−carbon bonds. Chem. Commun. 2011, 47, 1100−1105.
(c) Seiser, T.; Saget, T.; Tran, D. N.; Cramer, N. Cyclobutanes in
Catalysis. Angew. Chem., Int. Ed. 2011, 50, 7740−7752. (d) Ruhland,
K. Transition-Metal-Mediated Cleavage and Activation of C−C
Single Bonds. Eur. J. Org. Chem. 2012, 2012, 2683−2706. (e) Xu, T.;
Dermenci, A.; Dong, G. Transition Metal-Catalyzed C−C Bond
Activation of Four-Membered Cyclic Ketones. Top. Curr. Chem. 2014,
346, 233−257. (f) Liu, H.; Feng, M.; Jiang, X. Unstrained carbon-
carbon bond cleavage. Chem. - Asian J. 2014, 9, 3360−3389.
(g) Souillart, L.; Cramer, N. Catalytic C−C Bond Activations via
Oxidative Addition to Transition Metals. Chem. Rev. 2015, 115,
9410−9464. (h) Kondo, T. Ruthenium- and Rhodium-Catalyzed
Strain-Driven Cleavage and Reconstruction of the C−C Bond. Eur. J.
Org. Chem. 2016, 2016, 1232−1242. (i) Murakami, M.; Ishida, N.
Potential of Metal-Catalyzed C−C Single Bond Cleavage for Organic
Synthesis. J. Am. Chem. Soc. 2016, 138, 13759−13769. (j) Song, F.;
Gou, T.; Wang, B.-Q.; Shi, Z.-J. Catalytic activations of unstrained C-
C bond involving organometallic intermediates. Chem. Soc. Rev. 2018,
47, 7078−7115.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.8b00920.
■
S
Full experimental procedures, spectral data, DFT energy
profiles (PDF)
Cartesian coordinates of the optimized structures (XYZ)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: joangalo@um.es.
*E-mail: mlautens@chem.utoronto.ca.
■
ORCID
Ivan Franzoni: 0000-0001-8110-6218
Mark Lautens: 0000-0002-0179-2914
(3) (a) Topczewski, J. T.; Cabrera, P. J.; Saper, N. I.; Sanford, M. S.
Palladium-catalysed transannular C−H functionalization of alicyclic
amines. Nature 2016, 531, 220−224. (b) Chen, G.; Gong, W.;
Zhuang, Z.; Andra, M. S.; Chen, Y.-Q.; Hong, X.; Yang, Y.-F.; Liu, T.;
Houk, K. N.; Yu, J.-Q. Ligand-accelerated enantioselective methylene
C(sp3)-H bond activation. Science 2016, 353, 1023−1027. (c) Liu, Y.;
Ge, H. Site-selective C−H arylation of primary aliphatic amines
enabled by a catalytic transient directing group. Nat. Chem. 2017, 9,
1037−1038. (d) Xu, Y.; Dong, G. sp3 C−H activation via exo-type
directing groups. Chem. Sci. 2018, 9, 1424−1432.
́
́
Jose-Antonio García-Lopez: 0000-0002-8143-7081
Author Contributions
#M.P.-G. and H.A. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Financial support from MINECO (grant CTQ2015-69568-P)
■
́
́
and Fundacion Seneca (grant 19890/GERM/15) is gratefully
acknowledged. M.L. thanks the University of Toronto, Alphora
Research Inc., and the Natural Sciences and Engineering
Research Council (NSERC) for financial support. E.M.L
thanks NSERC for a postgraduate scholarship (CGS-D). I.F.
thanks the Collaborative Research and Training Experience
(Create ChemNET) program for a postdoctoral fellowship.
H.A. thanks Ministry of Science, Research and Technology of
Iran for a Ph.D. stay fellowship. The computational studies
reported herein were carried out at the Centre for Advanced
Computing (https://cac.queensu.ca).
(4) (a) Zaitsev, V. G.; Shabashov, D.; Daugulis, O. Highly
Regioselective Arylation of sp3 C−H Bonds Catalyzed by Palladium
Acetate. J. Am. Chem. Soc. 2005, 127, 13154−13155. (b) Shabashov,
D.; Daugulis, O. Auxiliary-Assisted Palladium-Catalyzed Arylation and
Alkylation of sp2 and sp3 Carbon−Hydrogen Bonds. J. Am. Chem. Soc.
2010, 132, 3965−3972. (c) Daugulis, O.; Roane, J.; Tran, L. D.
Bidentate, Monoanionic Auxiliary-Directed Functionalization of
Carbon−Hydrogen Bonds. Acc. Chem. Res. 2015, 48, 1053−1064.
(5) (a) Tobisu, M.; Chatani, N. Catalytic reactions involving the
cleavage of carbon−cyano and carbon−carbon triple bonds. Chem.
Soc. Rev. 2008, 37, 300−307. (b) Chen, F.; Wang, T.; Jiao, N. Recent
Advances in Transition-Metal-Catalyzed Functionalization of Un-
strained Carbon−Carbon Bonds. Chem. Rev. 2014, 114, 8613−8661.
(c) Xia, Y.; Wang, J.; Dong, G. Suzuki−Miyaura Coupling of Simple
Ketones via Activation of Unstrained Carbon−Carbon Bonds. J. Am.
Chem. Soc. 2018, 140, 5347−5351.
REFERENCES
■
(1) For reviews on C−H activation: (a) Alberico, D.; Scott, M. E.;
Lautens, M. Aryl−Aryl Bond Formation by Transition-Metal-
Catalyzed Direct Arylation. Chem. Rev. 2007, 107, 174−238.
(b) Wencel-Delord, J.; Glorius, F. C-H Bond Activation enables the
(6) (a) Fumagalli, G.; Stanton, S.; Bower, J. F. Recent Method-
ologies That Exploit C−C Single-Bond Cleavage of Strained Ring
F
DOI: 10.1021/acs.organomet.8b00920
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Systems by Transition Metal Complexes. Chem. Rev. 2017, 117,
9404−9432. (b) Chen, P.-H.; Billett, B. A.; Tsukamoto, T.; Dong, G.
Cut and Sew” Transformations via Transition-Metal-Catalyzed
Carbon−Carbon Bond Activation. ACS Catal. 2017, 7, 1340−1360.
(c) For an alternative example of C−C cleavage driven by strain, see
Fawcett, A.; Biberger, T.; Aggarwal, V. K. Carbopalladation of C−C
σ-bonds enabled by strained boronate complexes. Nat. Chem. 2019,
11, 117.
(7) (a) Suggs, J. W.; Jun, C.-H. Directed cleavage of carbon-carbon
bonds by transition metals: the α-bonds of ketones. J. Am. Chem. Soc.
1984, 106, 3054. (b) Jun, C.-H.; Lee, H. Catalytic Carbon−Carbon
Bond Activation of Unstrained Ketone by Soluble Transition-Metal
Complex. J. Am. Chem. Soc. 1999, 121, 880. (c) Xia, Y.; Wang, J.;
Dong, G. Suzuki−Miyaura Coupling of Simple Ketones via Activation
of Unstrained Carbon−Carbon Bonds. J. Am. Chem. Soc. 2018, 140,
5347−5351. (d) Just-Baringo, X.; Larrosa, I. Ketone C−C Bond
Activation Meets the Suzuki-Miyaura Cross-coupling. Chem. 2018, 4,
1203. (e) Zhu, J.; Wang, J.; Dong, G. Catalytic activation of
unstrained C(aryl)−C(aryl) bonds in 2,2′-biphenols. Nat. Chem.
2019, 11, 45−51.
(8) (a) Kondo, T.; Kodoi, K.; Nishinaga, E.; Okada, T.; Morisaki, Y.;
Watanabe, Y.; Mitsudo, T.-A. Ruthenium-Catalyzed β-Allyl Elimi-
nation Leading to Selective Cleavage of a Carbon−Carbon Bond in
Homoallyl Alcohols. J. Am. Chem. Soc. 1998, 120, 5587−5588.
(b) Niwa, T.; Yorimitsu, H.; Oshima, K. Palladium-Catalyzed 2-
Pyridylmethyl Transfer from 2-(2-Pyridyl)-ethanol Derivatives to
Organic Halides by Chelation-Assisted Cleavage of Unstrained Csp3-
Csp3 Bonds. Angew. Chem., Int. Ed. 2007, 46, 2643−2645. (c) Li, H.;
Li, W.; Liu, W.; He, Z.; Li, Z. An Efficient and General Iron-Catalyzed
C-C Bond Activation with 1,3-Dicarbonyl Units as a Leaving Groups.
Angew. Chem., Int. Ed. 2011, 50, 2975−2978. (d) Liu, Z.-Q.; Zhao, L.;
Shang, X.; Cui, Z. Unexpected Copper-Catalyzed Aerobic Oxidative
Cleavage of C(sp3)−C(sp3) Bond of Glycol Ethers. Org. Lett. 2012,
14, 3218−3221. (e) Cooke, H. A.; Peck, S. C.; Evans, B. S.; van der
Donk, W. A. Mechanistic Investigation of Methylphosphonate
Synthase, a Non-Heme Iron-Dependent Oxygenase. J. Am. Chem.
Soc. 2012, 134, 15660−15663. (f) Zhao, Y.; Cai, S.; Li, J.; Wang, D. Z.
Visible-light photo-catalytic C−C bond cleavages: preparations of
N,N-dialkylformamides from 1,2-vicinal diamines. Tetrahedron 2013,
69, 8129−8131. (g) Chen, Y.-C.; Zhu, M.-K.; Loh, T.-P. Csp3−Csp3
Bond Cleavage in the Palladium-Catalyzed Aminohydroxylation of
Allylic Hydrazones Using Atmospheric Oxygen as the Sole Oxidant.
Org. Lett. 2015, 17, 2712−2715. (h) Wang, D.; Mao, J.; Zhu, C.
Visible light-promoted ring-opening functionalization of unstrained
cycloalkanols via inert C−C bond scission. Chem. Sci. 2018, 9, 5805−
5809. (i) Tran, V. T.; Gurak, J. J. A.; Yang, K. S.; Engle, K. M.
Activation of diverse carbon−heteroatom and carbon−carbon bonds
via palladium(II)-catalysed β-X elimination. Nat. Chem. 2018, 10,
1126−1133.
(9) (a) Benfield, F. W. S.; Green, M. L. H. Alkyl, alkynyl, and olefin
complexes of bis(π-cyclopentadienyl)-molybdenum or -tungsten: a
reversible metal-to-ring transfer of an ethyl group. J. Chem. Soc.,
Dalton Trans. 1974, 1324−1331. (b) Eilbracht, P.; Dahler, P. Die
Spaltung nichtgespannter CC-Einfachbindungen in Tricarbonyleisen-
komplexen 5,5-dialkylsubstituierter Cyclopentadiene. Chem. Ber.
1980, 113, 542−554. (c) Hemond, R. C.; Hughes, R. P.; Locker,
H. B. Competitive C-H and C-C Activation In the Reaction of
Pentamethylcyclopentadiene with Decacarbonyldimanganese. Organo-
metallics 1986, 5, 2391−2392. (d) Jones, W. D.; Maguire, J. A.
Preparation, dynamic behavior, and C-H and C-C cleavage reactions
of (.eta.4-C5H6)Re(PPh3)2H3. Structures of (.eta.4-C5H6)Re-
(PPh3)2H3, CpRe(PPh3)2H2, and CpRe(PPh3)H4. Organometallics
1987, 6, 1301−1311. (e) Crabtree, R. H.; Dion, R. P.; Gibboni, D. J.;
McGrath, D. V.; Holt, E. M. Carbon-carbon bond cleavage in
hydrocarbons by iridium complexes. J. Am. Chem. Soc. 1986, 108,
7222−7227. (f) Crabtree, R. H.; Dion, R. P. Selective alkane C−C
bond cleavage via prior dehydrogenation by a transition metal
complex. J. Chem. Soc., Chem. Commun. 1984, 1260−1261.
(10) (a) Watson, P. L.; Roe, D. C. beta.-Alkyl transfer in a
lanthanide model for chain termination. J. Am. Chem. Soc. 1982, 104,
6471−6473. (b) Hajela, S.; Bercaw, J. E. Competitive Chain Transfer
by.beta.-Hydrogen and.beta.-Methyl Elimination for a Model Ziegler-
Natta Olefin Polymerization System [Me2Si(.eta.5-C5Me4)2]Sc-
{CH2CH(CH3)2}(PMe3). Organometallics 1994, 13, 1147−1154.
(c) Horton, A. D. Direct Observation of β-Methyl Elimination in
Cationic Neopentyl Complexes: Ligand Effects on the Reversible
Elimination of Isobutene. Organometallics 1996, 15, 2675−2677.
(d) O’Reilly, M. E.; Dutta, S.; Veige, A. S. β-Alkyl Elimination:
Fundamental Principles and Some Applications. Chem. Rev. 2016,
116, 8105−8145.
(11) (a) Nairoukh, Z.; Cormier, M.; Marek, I. Merging C−H and
C−C bond cleavage in organic synthesis. Nat. Rev. Chem. 2017, 1,
0035. (b) Ye, J.; Shi, Z.; Sperger, T.; Yasukawa, Y.; Kingston, C.;
Schoenebeck, F.; Lautens, M. Remote C−H alkylation and C−C
bond cleavage enabled by an in situ generated palladacycle. Nat. Chem.
2017, 9, 361−368.
(12) Schwarz, H. Remote functionalization of C-H and C-C bonds
by ″naked″ transition-metal ions (Cosi Fan Tutte). Acc. Chem. Res.
1989, 22, 282−287.
(13) (a) Aïssa, C.; Furstner, A. A Rhodium-Catalyzed C−H
̈
Activation/Cycloisomerization Tandem. J. Am. Chem. Soc. 2007,
129, 14836−14837. (b) Seiser, T.; Roth, O. A.; Cramer, N.
Enantioselective Synthesis of Indanols from tert-Cyclobutanols
Using a Rhodium-Catalyzed C-C/C-H Activation Sequence. Angew.
́
Chem., Int. Ed. 2009, 48, 6320−6323. (c) Crepin, D.; Tugny, C.;
Murray, J.-H.; Aïssa, C. Facile and chemoselective rhodium-catalysed
intramolecular hydroacylation of α,α-disubstituted 4-alkylidenecyclo-
propanals. Chem. Commun. 2011, 47, 10957−10959. (d) Masarwa, A.;
Didier, D.; Zabrodski, T.; Schinkel, M.; Ackermann, L.; Marek, I.
Merging allylic carbon−hydrogen and selective carbon−carbon bond
activation. Nature 2014, 505, 199−203. (e) Masarwa, A.; Weber, M.;
Sarpong, R. Selective C−C and C−H Bond Activation/Cleavage of
Pinene Derivatives: Synthesis of Enantiopure Cyclohexenone
Scaffolds and Mechanistic Insights. J. Am. Chem. Soc. 2015, 137,
6327−6334. (f) Xia, Y.; Lu, G.; Liu, P.; Dong, G. Catalytic activation
of carbon−carbon bonds in cyclopentanones. Nature 2016, 539, 546−
550. (g) Wang, G.-W.; Bower, J. F. Modular Access to Azepines by
Directed Carbonylative C−C Bond Activation of Aminocyclopro-
panes. J. Am. Chem. Soc. 2018, 140, 2743−2747.
(14) (a) Cui, S.; Zhang, Y.; Wu, Q. Rh(III)-catalyzed C−H
activation/cycloaddition of benzamides and methylenecyclopropanes:
divergence in ring formation. Chem. Sci. 2013, 4, 3421−3426. (b) Wu,
J.-Q.; Qiu, Z.-P.; Zhang, S.-S.; Liu, J.−G.; Lao, Y.-X.; Gu, L.-Q.;
Huang, Z. S.; Li, J.; Wang, H. Rhodium(III)-catalyzed C−H/C−C
activation sequence: vinylcyclopropanes as versatile synthons in direct
C−H allylation reactions. Chem. Commun. 2015, 51, 77−80. (c) Zell,
D.; Bu, Q.; Feldt, M.; Ackermann, L. Mild C−H/C−C Activation by
Z-Selective Cobalt Catalysis. Angew. Chem., Int. Ed. 2016, 55, 7408−
7412. (d) Meyer, T. H.; Liu, W.; Feldt, M.; Wuttke, A.; Mata, R. A.;
Ackermann, L. Manganese(I)-Catalyzed Dispersion-Enabled C−H/
C−C Activation. Chem. - Eur. J. 2017, 23, 5443−5447. (e) Liang, Y.-
F.; Muller, V.; Liu, W.; Munch, A.; Stalke, D.; Ackermann, L.
̈ ̈
Methylenecyclopropane Annulation by Manganese(I)-Catalyzed
Stereoselective C-H/C-C Activation. Angew. Chem., Int. Ed. 2017,
56, 9415−9419. (f) Lu, Q.; Klauck, F. J. R.; Glorius, F. Manganese-
catalyzed allylation via sequential C−H and C−C/C−Het bond
activation. Chem. Sci. 2017, 8, 3379−3383. (g) Li, M.; Kwong, F. Y.
Cobalt-Catalyzed Tandem C−H Activation/C−C Cleavage/C−H
Cyclization of Aromatic Amides with Alkylidenecyclopropanes.
Angew. Chem., Int. Ed. 2018, 57, 6512−6516.
̈
(15) For recent works see (a) Yoon, H.; Rolz, M.; Landau, F.;
Lautens, M. Palladium-Catalyzed Spirocyclization through C-H
Activation and Regioselective Alkyne Insertion. Angew. Chem., Int.
́
́
́
Ed. 2017, 56, 10920−10923. (b) Perez-Gomez, M.; Hernandez-
́
Ponte, S.; Bautista, D.; García-Lopez, J.-A. Synthesis of spiro-
oxoindoles through Pd-catalyzed remote C−H alkylation using α-
diazocarbonyl compounds. Chem. Commun. 2017, 53, 2842−2845.
G
DOI: 10.1021/acs.organomet.8b00920
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
́
(c) Franzoni, I.; Yoon, H.; García-Lopez, J.-A.; Poblador-Bahamonde,
A. I.; Lautens, M. Exploring the mechanism of the Pd-catalyzed
spirocyclization reaction: a combined DFT and experimental study.
Chem. Sci. 2018, 9, 1496−1509.
(16) For migratory insertion of carbenes see Xia, J.; Qiu, D.; Wang,
J. Transition-Metal-Catalyzed Cross-Couplings through Carbene
Migratory Insertion. Chem. Rev. 2017, 117, 13810−13889.
(17) (a) Brown, J. M.; Gouverneur, V. Transition-Metal-Mediated
Reactions for C−F Bond Construction: The State of Play. Angew.
Chem., Int. Ed. 2009, 48, 8610−8614. (b) Trzupek, J. D.; Lee, D.;
Crowley, B. M.; Marathias, V. M.; Danishefsky, S. J. Total Synthesis of
Enantiopure Phalarine via a Stereospecific Pictet−Spengler Reaction:
Traceless Transfer of Chirality from l-Tryptophan. J. Am. Chem. Soc.
2010, 132, 8506−8512. (c) Kamlet, A. S.; Neumann, C. N.; Lee, E.;
Carlin, S. M.; Moseley, C. K.; Stephenson, N.; Hooker, J. M.; Ritter,
T. Application of Palladium-Mediated 18F-Fluorination to PET
Radiotracer Development: Overcoming Hurdles to Translation.
PLoS One 2013, 8, No. e59187. (d) Peacock, D. M.; Jiang, Q.;
Hanley, P. S.; Cundari, T. R.; Hartwig, J. F. Reductive Elimination
from Phosphine-Ligated Alkylpalladium(II) Amido Complexes To
Form sp3 Carbon−Nitrogen Bonds. J. Am. Chem. Soc. 2018, 140,
4893−4904. (e) Messina, M. S.; Stauber, J. M.; Waddington, M. A.;
Rheingold, A. L.; Maynard, H. D.; Spokoyny, A. M. Organometallic
Gold(III) Reagents for Cysteine Arylation. J. Am. Chem. Soc. 2018,
140, 7065−7069.
(18) The computational details and a more comprehensive
discussion on the theoretical results can be found in the Supporting
Information.
(19) Gualandi, A.; Mazzarella, D.; Ortega-Martínez, A.; Mengozzi,
L.; Calcinelli, F.; Matteucci, E.; Monti, F.; Armaroli, N.; Sambri, L.;
Cozzi, P. G. Photocatalytic Radical Alkylation of Electrophilic Olefins
by Benzylic and Alkylic Zinc-Sulfinates. ACS Catal. 2017, 7, 5357−
5362.
H
DOI: 10.1021/acs.organomet.8b00920
Organometallics XXXX, XXX, XXX−XXX