Diastereoselective Nickel-Catalyzed Carboiodination Generating Six-Membered Nitrogen-Based Heterocycles

Article abstract of DOI:10.1021/acs.orglett.9b02797

A scalable, diastereoselective nickel-catalyzed carboiodination reaction is reported that avoids metal-based reducing agents. Novel anti-dihydroquinolones and previously unreported tetrahydroquinolines are now readily prepared. The generation of anti-dihydroquinolones is noteworthy, as this selectivity is opposite to that of the Pd variant. Mechanistic insight into the nature of the nickel-catalyzed carboiodination reaction was derived experimentally, suggesting a catalyst-controlled cyclization and stereoretentive reductive elimination.

Full text of DOI:10.1021/acs.orglett.9b02797

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Diastereoselective Nickel-Catalyzed Carboiodination Generating
Six-Membered Nitrogen-Based Heterocycles
Austin D. Marchese, Louise Kersting, and Mark Lautens*
Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada
M5S 3H6
S
* Supporting Information
ABSTRACT: A scalable, diastereoselective nickel-catalyzed carboiodination reaction is reported that avoids metal-based
reducing agents. Novel anti-dihydroquinolones and previously unreported tetrahydroquinolines are now readily prepared. The
generation of anti-dihydroquinolones is noteworthy, as this selectivity is opposite to that of the Pd variant. Mechanistic insight
into the nature of the nickel-catalyzed carboiodination reaction was derived experimentally, suggesting a catalyst-controlled
cyclization and stereoretentive reductive elimination.
Scheme 1. Ni-Catalyzed Carboiodination Cyclizations
ver the past decade, carboiodination has emerged as a
Onew strategy to build complex heterocyclic scaffolds
containing a reactive C−I bond.1−3 Typically, palladium has
been used to perform this reaction, but the use of air-sensitive
catalysts as well as high-molecular-weight and expensive
ligands is often required.2 Among the various reactions we
have reported, palladium was shown to form iodinated
dihydroisoquinolones (DHIQs) with high selectivity for the
syn diastereomer.3e
Recently we discovered a nickel-catalyzed carboiodination
reaction that employs simple phosphines or phosphites as
ligands (Scheme 1).2a,c To date this methodology has been
applied to make five-membered heterocycles and shown
promise in generating enantioenriched products.
During our investigations of the diastereoselectivity of
nickel-catalyzed carboiodination reactions, we observed an
interesting phenomenon: Ni and Pd form opposite diaster-
eomers of the DHIQ scaffold, each with moderate to high
selectivity.
Utilizing a Ni−phosphite catalyst generated in the absence
of a metal reductant, we can selectively obtain the anti
diastereomer of DHIQs in moderate to excellent yields. These
conditions also enabled the synthesis of iodotetrahydroquino-
lines (iodo-THQs), a scaffold that has not been reported in
carboiodination chemistry. Again, high yields and excellent
diastereoselectivity favoring the anti isomers were observed.
We also identified a method for the synthesis of enantioen-
riched products via enantioenriched starting materials as well
as key mechanistic insight for the general nickel-catalyzed
carboiodination reaction.
make up the core of known EP1 receptor ligands.5 The iodide
handle provides a simple route to study the structure−activity
relationship of some analogues that cannot be easily prepared
under the previously reported route of synthesis.
The optimized conditions leading to efficient carboiodina-
tion were NiI2 (10 mol %) and P(OiPr)3 (40 mol %) in
2-Substituted THQs are an interesting scaffold in their own
Received: August 7, 2019
right, as they are known to be AMPK activators4 as well as to
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02797
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
toluene (1 mL) at 80 °C for 18 h, which provided the product
2a in 85% isolated yield as a single diastereomer (88:12 d.r. for
the crude reaction). Changing the ligand to P(OEt)3 gave the
product in 78% yield with 83.5:16.5 d.r. (Table 1). Other
Scheme 2. Ni-Catalyzed Carboiodination Generating
Dihydroisoquinolones
Table 1. Optimization of Ni-Catalyzed Carboiodination
a
entry
variation from standard conditions
yield (%)
d.r.
1
2
3
4
5
6
7
8
9
P(OEt)3 instead of P(OiPr)3 at 100 °C
30 mol % ligand
50 mol % ligand
100 °C instead of 80 °C
120 °C instead of 80 °C
60 °C instead of 80 °C
0.4 M instead of 0.1 M
0.2 M instead of 0.1 M
0.4 equiv of NEt3 added
78
88
88
88
83
25
88
88
88
83.5:16.5
88:12
88:12
88:12
83.5:16.5
88:12
88:12
88:12
88:12
a
Yields of the major diastereomer as determined by 1H NMR analysis
using 1,3,5-trimethoxybenzene as an internal standard.
phosphites were studied but yielded only trace amounts, or
less, of product.6 The use of phosphines in this reaction
showed no reactivity whatsoever.7 Changing the amount of
ligand to 30 or 50 mol % led to no further improvement, and
incomplete conversion was observed at <30 mol % ligand.
Thus, 40 mol % ligand was chosen as the optimal conditions
for subsequent experiments. Increasing the temperature to 100
°C showed no significant change in the reaction. However,
when the temperature was reduced to 60 °C, incomplete
conversion was observed. Changing the concentration to 0.4 or
0.1 M did not affect the reaction, and neither did introducing
amine additives.8
a
b
Isolated yield of the major diastereomer. Combined isolated yield
of the inseparable mixture of diastereomers. The value in parentheses
c
is the yield of the major diastereomer. 20% catalyst was employed.
d
Enantiomerically enriched starting material was used.
We began exploring the scope of the reaction by first altering
the substituents on the pendent aromatic ring (Scheme 2).
Under the standard conditions, product 2a was obtained in
85% yield with 88:12 d.r. The reaction was scaled up to 1
mmol, giving product 2a in 78% yield with 87:13 d.r. A Cl
moiety at the para position had no effect on the yield or
diastereoselectivity of the reaction, and the product was
obtained with 98.5:1.5 e.r. when enantioenriched starting
material was employed. A crystal structure of rac-2b was
obtained, displaying an anti configuration of the pendent aryl
ring and CH2I moiety, which confirmed that Ni indeed shows
diastereoselectivity opposite to that of Pd. Moving the chlorine
to the meta position had little effect on the yield and
diastereoselectivity of the reaction (2c). The enantiomerically
enriched bis(methoxy) moiety was also well-tolerated, giving
the product 2d in 69% yield with 86:14 d.r. and 99:1 e.r.
Introducing an electron-withdrawing CF3 moiety at the ortho
position significantly affected the diastereoselectivity, as 2e was
obtained with 69:31 d.r., while still maintaining good reactivity,
giving the product in a combined yield of 98%. The observed
decrease in diastereoselectivity is likely due to a steric
interaction with the ortho CF3 rather than an electronic bias
arising from the electron -withdrawing nature of this group.
An electron-donating methyl group para to the iodide
modestly reduced both the yield and diastereoselectivity (2f).
An electron-withdrawing Cl meta to the aryl iodide moiety had
little effect on the yield and d.r., and the product (2g) was
obtained with 84:16 d.r. while maintaining an 98.5:1.5 e.r. The
tetramethoxy-substituted product 2h was formed with a
reduced d.r of 75:25, but the product was still obtained in
good yield with >99:1 e.r. This starting material showed
reduced reactivity and required double the catalyst loading to
achieve complete conversion. Employing a substrate with two
dioxolane moieties severely decreased the reactivity and
required double the catalyst loading. The d.r. was 1:1, giving
the anti diastereomer in 40% isolated yield (2i). The decrease
in d.r. is likely due to a combination of the electron-donating
para-dioxolane as well as the steric hindrance of the ortho
substitution. In 2014, our group published the formal synthesis
of (+)-corynoline featuring the Pd-catalyzed carboiodination
reaction, starting from compound 1i. Although there is no
diastereoselectivity, the ability to isolate product 2i as a single
diastereomer in moderate yield is noteworthy, as it represents a
precursor to the natural product epi-corynoline, which was
unattainable using the palladium methodology.
The nature of the protecting group was examined and found
to have a strong impact. A benzyl moiety gave the product in a
combined yield of 91% with 1.5:1 d.r. (2j). A substrate lacking
B
DOI: 10.1021/acs.orglett.9b02797
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Letter
the pendent aromatic ring was also reactive, and the
unsubstituted dihydroisoquinoline 2k was formed in 98% yield.
Next, we wanted to explore the viability of using the
carboiodination reaction to generate iodo-THQs (Scheme 3).
impacted the reaction, providing the product 2p in 82% yield
as a single diastereomer.
Substituting the pendent aromatic ring at the para position
with Me and F substituents gave the products 2q and 2f in
excellent yields as single diastereomers. Having a 2,4-
dichlorophenyl ring hindered the reactivity of the starting
material, giving the product 2s in only 48% isolated yield even
when 20 mol % catalyst was used at 120 °C. This result is likely
due to increased steric hindrance at the ortho position. A PMB-
protected alcohol on the α-carbon of the acetyl group required
elevated temperatures of 120 °C but was otherwise well-
tolerated, giving the product 2t in 70% yield as a single
diastereomer.
Scheme 3. Ni-Catalyzed Carboiodination Generating
Tetrahydroquinolines
To probe the influence of the ligand versus the substrate,
cyclization of a racemic mixture of 1a was explored with a
chiral nickel catalyst (Scheme 4). When an (R)-BINOL-
Scheme 4. Catalyst-Controlled Enantioselective Migratory
Insertion
derived N,N-diisopropyl phosphoramidite ligand was mixed
with NiI2 in toluene in the presence of manganese, the product
was obtained in ∼70:30 d.r. Each diastereomer was
enantiomerically enriched with the opposite stereochemistry
of the pendent Ph group. This suggests that each enantiomer
of the starting material reacted on the same face of the olefin in
a parallel resolution process. In both cases, the R stereocenter
was obtained at the newly formed quaternary carbon,
suggesting a catalyst-controlled migratory insertion. This result
supports a classic two-electron migratory insertion cyclization
rather than a radical pathway and is consistent with our
previous findings with phosphines.2c It also aligns with what
has been reported on the palladium-catalyzed carboiodination
reaction employing aryl halides.3j
To investigate the nature of the carbon−iodine bond-
forming step, we undertook a deuterium labeling study (Table
2). Both phosphines and phosphites promote the Ni-catalyzed
carboiodination reaction to form THQs, oxindoles, and
indolines.2c The N-Ts starting material 1u is more readily
prepared than the N-Ac analogue. Additionally, the Ni−
phosphite system failed to catalyze the reaction of substrate 1u,
so PPh3 was used as the ligand in this study. At 10 h, the
reaction showed high diastereoselectivity, giving indoline 2u
with a diasteromeric ratio of 29.5:1. This result is indicative of
a stereoretentive reductive elimination, analogous to what was
reported by Tong in 2011, who employed palladium as a
catalyst.3j
a
b
The reaction was run at 120 °C. 20 mol % catalyst was employed.
We investigated both Ni and Pd9 catalysis and observed that
both catalysts generated the same diastereomer of product 2l.
Because of the simplicity, cost benefit, superior reactivity, and
diastereoselectivity of the Ni-catalyzed system, we focused on
using this catalyst. Under similar reaction conditions, N-
acylated tetrahydroquinolines were generated from the
corresponding alkylated 2-iodoaniline derivatives.10 Using
NiI2 (10 mol %) and P(OiPr)3 (40 mol %) in toluene
(0.133 M) at 100 °C afforded product 2l in 95% isolated yield
as a single diastereomer. The reaction also worked with NiI2
(10 mol %), PPh3 (20 mol %), and Mn (60 mol %) in toluene
(0.133 M) at 100 °C, giving product 2l in identical yield and
selectivity. This observation is noteworthy because the
phosphine system has been shown to be advantageous with
certain substituents2a and may be superior for different THQ
scaffolds than the ones explored in this study. The simplicity of
employing a phosphite lies in negating the need for
substoichiometric Mn, so all subsequent studies were
conducted using P(OiPr)3. A crystal structure of 2l was
obtained, confirming the anti configuration of the pendent aryl
group and the CH2I functionality. A Me or Cl moiety para to
the aryl iodide resulted in a slightly reduced yield, with
products 2m and 2n formed in 90% and 81% yield,
respectively, as single diastereomers. An electron-withdrawing
Cl atom meta to the aryl iodide had no effect on the reaction,
giving 2n in 98% yield as a single diastereomer. Changing the
halogen to a more electron-withdrawing fluorine modestly
This result along with the aforementioned observed parallel
resolution further support a catalyst-controlled migratory
insertion over single-electron alternatives.3j Over time, there
is a slight degradation in the diasteroselectivity (to ∼6:1). It is
possible that nickel may be able to reversibly oxidatively add
C
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Table 2. Deuterium Incorporation Study Indicative of a
Stereoretentive Reductive Elimination
Scheme 6. Derivatization of the C−I Bond
time (h) X (%D) Y (%D) total (% D)
d.r.
yield of 2u (%)
a
10
12
14
24
59
60
56
55
2
2
8
61
62
64
66
29.5:1
30:1
8:1
40
36
52
68
b
a
a
11
5.5:1
a
1
Yield determined by H NMR analysis using 1,3,5-trimethoxyben-
b
zene as an internal standard. Isolated yield of product 2u.
into the alkyl iodide bond, either through an SN2 pathway or a
single electron pathway, the former of which has been reported
in the palladium-catalyzed carboiodination methodology.3j
On the basis of these results, we propose the following
mechanism for the Ni-catalyzed carboiodination reaction
(Scheme 5). NiI2 is reduced to Ni0 by use of the alkyl
cyanation reaction is noteworthy, as it is the first step in the
previously reported synthesis of corynoline from epi-2i.
The softer nucleophile NaSPh gave the thiolated product 2x
in 80% yield. Utilizing Pd catalysis,13 we were able to reduce
the C−I bond in 79% yield (2y). This reaction is noteworthy,
as it shows the ability of Pd to oxidatively add into the C−I
bond and perform subsequent cross-coupling transformations.
In conclusion, we have identified a novel approach to
generate anti six-membered heterocycles via a simple metal-
reducing-agent-free Ni-catalyzed carboiodination reaction.
This report is complementary to the Pd methodology, as we
now have a way to generate each diastereomer of the DHIQ
products with high selectivity as well as a method to obtain
products with excellent e.r. The generation of these THQs is
also of interest, as these novel iodinated scaffolds closely
resemble important medicinally relevant compounds, with the
added alkyl iodide handle for further functionalization.
We have also conducted preliminary mechanistic experi-
ments suggesting that this reaction proceeds through an
oxidative addition−migratory insertion−reductive elimination
pathway. We are currently examining DFT to investigate the
origin of the change in diastereoselectivity for Ni and Pd
variants of the DHIQ synthesis.
Scheme 5. Potential Mechanism for the Ni-Catalyzed
Carboiodination Reaction
This methodology shows that nickel not only can perform
the carboiodination reaction on diverse scaffolds but also offers
unique selectivity compared with palladium. Its advantages
over palladium go beyond the basic economic and accessibility
arguments, as nickel can provide access to previously
unattainable scaffolds and isomers of medicinally relevant
heterocycles. Expanding on these fronts represents steps
toward solidifying carboiodination as a valuable synthetic tool.
phosphite,11 (or in the cases with phosphines, Mn is the
reducing agent) followed by oxidative addition into the aryl
iodide bond. Subsequent alkene co-ordination is followed by
migratory insertion of the tethered alkene into the Ar−Ni
bond, and finally, the cycle is completed by a stereoretentive
reductive elimination of the C−I bond to regenerate the Ni(0)
catalyst. Oxidation states are not specified, as Ni is known to
have access to the (I), (II), and (III) oxidation states.1c,12
We postulate that the necessity of the carbonyl in all of the
nickel-catalyzed carboiodination reactions may be related to
the ortho effect, a known phenomenon where Lewis basic ortho
substituents chelate to the oxidative addition complex and
stabilize it in the (II) oxidation state.12
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02797.
Experimental procedures, optimization, characterization
and X-ray data (PDF)
NMR spectra (PDF)
We have also explored the divergent reactivity of the C−I
bond (Scheme 6). 2a in the presence of nucleophiles such as
NaN3 or NaCN in DMF at 100 °C with 15-crown-5 yields the
SN2-displaced products in good yields. The cyano (2v) and
azido (2w) products were obtained in 65% and 74% isolated
yield, respectively, as single diastereomers. The success of the
Accession Codes
CCDC 1946885−1946886 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
e-mailing data_request@ccdc.cam.ac.uk, or by contacting The
D
DOI: 10.1021/acs.orglett.9b02797
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
́
1780. (o) Phapale, V. B.; Cardenas, D. J. Nickel-catalysed Negishi
cross-coupling reactions: scope and mechanisms. Chem. Soc. Rev.
2009, 38, 1598.
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, U.K.; fax: +44 1223 336033.
(2) For examples of Ni-catalyzed carboiodination, see: (a) Marchese,
A. D.; Lind, F.; Mahon, A.; Yoon, H.; Lautens, M. Forming Benzylic
AUTHOR INFORMATION
■
́
Corresponding Author
*E-mail: mark.lautens@utoronto.ca.
ORCID
Iodides via a Nickel Catalyzed Diastereoselective Dearomative
Carboiodination Reaction of Indoles. Angew. Chem., Int. Ed. 2019,
58, 5095. (b) Takahashi, T.; Kuroda, D.; Kuwano, T.; Yoshida, Y.;
Kurahashi, T.; Matsubara, S. Nickel-catalyzed intermolecular
carboiodination of alkynes with aryl iodides. Chem. Commun. 2018,
54, 12750. (c) Yoon, H.; Marchese, A. D.; Lautens, M.
Carboiodination Catalyzed by Nickel. J. Am. Chem. Soc. 2018, 140,
10950.
Austin D. Marchese: 0000-0002-3090-2748
Mark Lautens: 0000-0002-0179-2914
Notes
The authors declare no competing financial interest.
(3) For examples of Pd-catalyzed carboiodination, see: (a) Zhang,
Z.-M.; Xu, B.; Wu, L.; Zhou, L.; Ji, D.; Liu, Y.; Li, Z.; Zhang, J.
Palladium/XuPhos-Catalyzed Enantioselective Carboiodination of
Olefin-Tethered Aryl Iodides. J. Am. Chem. Soc. 2019, 141, 8110.
(b) Lee, Y. H.; Morandi, B. Palladium-Catalyzed Intermolecular
Aryliodination of Internal Alkynes. Angew. Chem., Int. Ed. 2019, 58,
6444. (c) Sun, Y.-L.; Wang, X.-B.; Sun, F.-N.; Chen, Q.-Q.; Cao, J.;
Xu, Z.; Xu, L.-W. Enantioselective Cross-Exchange between C−I and
C−C σ-Bonds. Angew. Chem., Int. Ed. 2019, 58, 6747. (d) Hou, L.;
Zhou, Z. Z.; Wang, D.; Zhang, Y.; Chen, X.; Zhou, L.; Hong, Y.; Liu,
W.; Hou, Y.; Tong, X. DPPF-Catalyzed Atom-Transfer Radical
Cyclization via Allylic Radical. Org. Lett. 2017, 19, 6328. (e) Petrone,
D. A.; Yoon, H.; Weinstabl, H.; Lautens, M. Additive effects in the
palladium-catalyzed carboiodination of chiral N-allyl carboxamides.
Angew. Chem., Int. Ed. 2014, 53, 7908. (f) Petrone, D. A.; Lischka, M.;
Lautens, M. Harnessing Reversible Oxidative Addition: Application of
Diiodinated Aromatic Compounds in the Carboiodination Process.
Angew. Chem., Int. Ed. 2013, 52, 10635. (g) Jia, X.; Petrone, D. A.;
Lautens, M. A conjunctive carboiodination: indenes by a double
carbopalladation-reductive elimination domino process. Angew.
Chem., Int. Ed. 2012, 51, 9870. (h) Petrone, D. A.; Malik, H. A.;
Clemenceau, A.; Lautens, M. Functionalized Chromans and Isochro-
mans via a Diastereoselective Pd (0)-Catalyzed Carboiodination. Org.
Lett. 2012, 14, 4806. (i) Newman, S. G.; Lautens, M. Palladium-
catalyzed carboiodination of alkenes: carbon-carbon bond formation
with retention of reactive functionality. J. Am. Chem. Soc. 2011, 133,
1778. (j) Liu, H.; Li, C.; Qiu, D.; Tong, X. Palladium-Catalyzed
Cycloisomerizations of (Z)-1-Iodo-1,6-dienes: Iodine Atom Transfer
and Mechanistic Insight to Alkyl Iodide Reductive Elimination. J. Am.
Chem. Soc. 2011, 133, 6187. (k) Newman, S. G.; Howell, J. K.;
Nicolaus, N.; Lautens, M. Palladium-catalyzed carbohalogenation:
bromide to iodide exchange and domino processes. J. Am. Chem. Soc.
2011, 133, 14916. (l) Liu, H.; Chen, C.; Wang, L.; Tong, X. Pd(0)-
Catalyzed Iodoalkynation of Norbornene Scaffolds: The Remarkable
Solvent Effect on Reaction Pathway. Org. Lett. 2011, 13, 5072.
(4) Chen, L.; Feng, L.; He, Y.; Huang, M.; Liu, M.; Zhou, M. Novel
Tetrahydroquinoline Derivatives. WO 2012/001020 A1, Jan 5, 2012.
(5) Aguilar, N.; Fernandez, J. C.; Terricabras, E.; Carceller Gonzalez,
E.; Salas Solana, J. Substituted Tricyclic Compounds with Activity
towards EP1 Receptors. WO 2013/149997 A1, Oct 10, 2013.
(6) Other phosphites examined included P(OPh)3, P(OtBu)3, and
tris(2-ethylhexyl)phosphite, but little to no conversion was observed.
Additionally, combinations of P(OiPr)3 and these aforementioned
ligands were tried but were again unsuccessful. Di-tert-butyl-N,N-
diethyl phosphoramidite was also employed but failed in the reaction.
(7) Triphenylphosphine and ethoxydiphenylphosphine in the
presence of Mn (0.6 equiv) were employed but failed to show any
reactivity.
ACKNOWLEDGMENTS
■
We thank the University of Toronto, the Natural Science and
Engineering Research Council (NSERC), Alphora Research
Inc., and Kennarshore Inc. for financial support. A.D.M. thanks
OGS and NSERC for an NSERC Vanier Fellowship. We thank
Alan Lough (University of Toronto) for X-ray analysis of 2b
and 2l, Dr. Darcy Burns and Dr. Jack Sheng (University of
Toronto) for their assistance with NMR experiments, and Dr.
Hyung Yoon and Dr. Dave Petrone for the synthesis of
substrates 1b and 1d−i.
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were saplike liquids and it was necessary to have enough solvent to
dissolve them. Adding an amine such as triethylamine did not
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E
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Pd[P(tBu)3]2 (5 mol %) and Et3N (100 mol %) in PhMe (0.2 M) at
110 °C for 24 h.
(10) A substate where the N-acetyl group was replaced by an N-
benzyl moiety showed no reaction.
(11) For literature pertaining to the reduction of NiX2 species to
́
́
Ni(0), see: (a) Villemin, D.; Elbilali, A.; Simeon, F.; Jaffres, P.-A.;
Maheut, G.; Mosaddak, M.; Hakiki, A. Nickel and palladium catalysed
reaction of triethyl phosphite with aryl halides under microwave
irradiation. J. Chem. Res. 2003, 2003, 436. Vinal, R. S.; Reynolds, L. T.
The Reduction of Nickel(II) Halides by Trialkyl Phosphites. Inorg.
Chem. 1964, 3 (7), 1062.
(12) (a) Bajo, S.; Laidlaw, G.; Kennedy, A.; Sproules, S.; Nelson, D.
J. Oxidative Addition of Aryl Electrophiles to a Prototypical Nickel(0)
Complex: Mechanism and Structure/Reactivity Relationships. Orga-
nometallics 2017, 36, 1662. (b) Mohadjer Beromi, M.; Nova, A.;
Balcells, D.; Brasacchio, A. M.; Brudvig, G. W.; Guard, L. M.; Hazari,
N.; Vinyard, D. J. Mechanistic Study of an Improved Ni Precatalyst
for Suzuki−Miyaura Reactions of Aryl Sulfamates: Understanding the
Role of Ni(I) Species. J. Am. Chem. Soc. 2017, 139, 922. (c) Wada,
M.; Kusabe, K.; Oguro, K. Ary 1(pentachlorophenyl) nickel(II)
Complexes. Lack of Free Rotation about Toly 1-Nickel Bonds and
Lack of “Ortho Effect” in Carbonylation. Inorg. Chem. 1977, 16 (2),
446.
(13) Petrone, D. A.; Franzoni, I.; Ye, J.; Rodriguez, J. F.; Poblador-
Bahamonde, A. L.; Lautens, M. Palladium-Catalyzed Hydrohalogena-
tion of 1,6-Enynes: Hydrogen Halide Salts and Alkyl Halides as
Convenient HX Surrogates. J. Am. Chem. Soc. 2017, 139 (9), 3546−
3557.
F
DOI: 10.1021/acs.orglett.9b02797
Org. Lett. XXXX, XXX, XXX−XXX