Rhodium-Catalyzed Arylzincation of Alkynes: Ligand Control of 1,4-Migration Selectivity

Article abstract of DOI:10.1021/acs.orglett.8b02668

The addition of arylzinc reagents ArZnCl 1 to alkynes 2 was found to be catalyzed by rhodium complexes in the presence of a catalytic amount of zinc chloride. The selectivity in giving 2-arylalkenylzinc species 3 or ortho-alkenylarylzinc species 4, the la

Full text of DOI:10.1021/acs.orglett.8b02668

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Rhodium-Catalyzed Arylzincation of Alkynes: Ligand Control of
1,4‑Migration Selectivity
Jialin Ming and Tamio Hayashi*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
21 Nanyang Link, Singapore 637371, Singapore
S
* Supporting Information
ABSTRACT: The addition of arylzinc reagents ArZnCl 1 to
alkynes 2 was found to be catalyzed by rhodium complexes in
the presence of a catalytic amount of zinc chloride. The
selectivity in giving 2-arylalkenylzinc species 3 or ortho-
alkenylarylzinc species 4, the latter of which is generated
through 1,4-Rh migration from alkenyl to aryl in the catalytic cycle, is controlled by the ligands on rhodium. Ligands cod and
binap gave 3 and 4, respectively, with high selectivity.
reports have appeared on the carbozincation of unfunctional-
arbometalation of alkynes is one of the most efficient
Cmethods of generating substituted alkenylmetals which ized alkynes using Rh catalysis. In 2012, Yoshikai reported5 a
new type of Co-catalyzed arylzincation of alkynes where ortho-
alkenylarylzinc species are formed through 1,4-migration of
cobalt from an alkenyl carbon to aryl carbon (Scheme 1c).
Here, we report our findings that arylzincation of unfunction-
alized alkynes is catalyzed by Rh complexes in the presence of a
catalytic amount of ZnCl2 and the arylzincation with or
without 1,4-migration is controlled with high selectivity by the
ligands on rhodium (Scheme 1d). The 1,4-shift of rhodium
from alkenyl to aryl carbons has been reported to be involved
in the catalytic cycle of Rh-catalyzed multiple carbon−carbon
bond forming reactions including asymmetric reactions.6−8 As
a related arylmetalation reaction, we recently reported that the
addition of arylstannanes to alkynes giving ortho-alkenylaryl-
stannanes is catalyzed cooperatively by a rhodium complex and
zinc chloride.9
are useful synthetic intermediates for the multisubstituted
alkenes, and addition of arylmetals to simple unfunctionalized
alkynes has been a challenging reaction because of their low
reactivity.1 The first-row transition metals including Ni, Co, Fe,
Mn, and Cr have been reported to catalyze the addition of
arylmagnesium2 and -zinc3 reagents to the unfunctionalized
alkynes (Scheme 1a). A Rh complex has been reported to
catalyze the carbozincation of ynamides4 (Scheme 1b), but no
Scheme 1. Addition of ArZnX to Alkynes and 1,4-Migration
In our present studies, arylzinc reagents ArZnCl were
prepared by lithiation of ArBr with BuLi in THF at −80 °C
followed by addition of an excess amount (1.3 equiv) of ZnCl2
to the THF solution of ArLi.10,11 The results obtained for the
reaction of 3,5-(MeO)2C6H3ZnCl (1a) with 4-octyne (2a) in
the presence of several rhodium catalysts are summarized in
Table 1. The reaction mixture containing 2-arylalkenylzinc 3aa
and/or ortho-alkenylarylzinc 4aa was hydrolyzed with D2O,
1
2
and the location of D (5aa/6aa) was analyzed by H and H
NMR spectra. The yield of the arylzincation and the selectivity
with or without 1,4-migration are heavily dependent on the
ligand on rhodium. Thus, the THF solution of ArZnCl (1a,
0.60 mmol, 3.0 equiv to 2a) containing ZnCl2 (0.18 mmol, 0.9
equiv to 2a) was added to the alkyne (2a, 0.20 mmol) in the
presence of a rhodium catalyst generated from [RhCl(coe)2]2
(3 mol % of Rh) and binap12 (3.3 mol %) in THF, and the
mixture was heated at 50 °C for 5 h. The arylzincation
Received: August 21, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02668
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
selectivity control in giving arylzincation products with or
without 1,4-migration was observed in the arylzincation of 4-
octyne (2a), whose results are summarized in Table 2. The
Table 1. Rhodium-Catalyzed Arylzincation of 4-Octyne (2a)
with 3,5-(MeO)2C6H3ZnCl (1a)
a
d
e
ligand on
additive
yield (%)
ratio of
b
c
entry
Rh
(mmol)
5aa + 6aa
5aa/6aa
Table 2. Rhodium-Catalyzed Arylzincation of 4-Octyne (2a)
with Arylzinc Reagents 1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
binap
cod
ZnCl2 (0.18)
ZnCl2 (0.18)
ZnCl2 (0.09)
−
91
82
90
22
<3
81
87
23
52
27
83
78
<3
83
<1:99
92:8
<1:99
4:96
−
a
f
b
c
d
binap
binap
binap
binap
binap
dppe
dppp
dppf
biphep
PPh3
xantphos
nbd
L on Rh (A) or yield (%) of ratio of
a
entry
1
1: Ar in ArZnCl
1a:
(B)
5 + 6
5:6
g
−
binap (B)
cod (A)
binap (A)
cod (A)
binap (B)
cod (A)
binap (A)
cod (A)
binap (B)
cod (A)
binap (B)
cod (A)
binap (B)
cod (A)
binap (B)
cod (A)
binap (B)
cod (A)
binap (A)
cod (A)
binap (B)
cod (A)
binap (B)
cod (A)
binap (B)
cod (A)
binap (A)
cod (A)
90
82
87
80
91
68
94
84
87
71
85
86
83
52
93
87
87
72
93
82
95
72
87
79
97
79
88
64
<1:99
92:8
2:98
80:20
1:99
77:23
1:99
74:26
1:99
94:6
h
3,5-(MeO)2C6H3
ZnBr2 (0.18)
ZnI2 (0.18)
ZnCl2 (0.18)
ZnCl2 (0.18)
ZnCl2 (0.18)
ZnCl2 (0.18)
ZnCl2 (0.18)
ZnCl2 (0.18)
ZnCl2 (0.18)
5:95
3:97
37:63
48:52
19:81
12:88
6:94

h
2
1b: Ph
3
1c: 4-MeC6H4
1d: 4-MeOC6H4
1e: 4-Me2NC6H4
1f: 4-Me3SiC6H4
1g: 4-FC6H4
4
5
5:95
a
6
6:94
Reaction conditions: 4-Octyne (2a) (0.20 mmol), ArZnCl (1a)
(0.60 mmol), ZnCl2 (0.18 mmol), and Rh catalyst (3 mol % of Rh) in
THF (2.0 mL) at 50 °C for 5 h. The reaction was quenched with D2O
(0.2 mL). [RhCl(coe)2]2 (6.0 μmol of Rh) + bisphosphine (6.6
μmol), RhCl(PPh3)3 (6.0 μmol), or ([RhCl(diene)]2 (diene = cod or
nbd, 6 μmol of Rh). The excess amount of ZnX2 used at the
generation of ArZnX. Isolated yield. Determined by H and H
NMR spectra. ArZnCl (1a) (0.30 mmol), ZnCl2 (0.09 mmol), THF
81:19
<1:99
49:51
<1:99
<1:99
1:99
7
b
8
1h: 4-CF3C6H4
1i: 3-MeC6H4
c
d
e
1
2
e
e
f
9
f
86:14
1:99
g
(1.0 mL) for 1 h. Reaction of Ar2Zn generated from ArLi (0.60
mmol) and ZnCl2 (0.30 mmol). ArZnX was generated from ArLi
(0.60 mmol) and ZnX2 (0.78 mmol, X = Br or I).
h
10
11
12
13
14
1j: 3-MeOC6H4
1k: 3-Me2NC6H4
1l: 3-Me3SiC6H4
f
80:20
1:99
e
e
95:5
e
e
e
accompanied by the 1,4-migration proceeded selectively to
give, after the D2O quenching, a 91% yield of 6aa, where the
deuterium is incorporated at the ortho-position of the phenyl
ring (entry 1). On the other hand, the reaction in the presence
of a rhodium catalyst coordinated with cod12 under otherwise
the same conditions gave an 82% yield of the arylation product
where the deuterium is found mainly at the alkenyl carbon
(5aa/6aa = 92:8) (entry 2). In the Rh/binap-catalyzed
reaction, the amounts of ArZnCl 1a and ZnCl2 were reduced
to 1.5 and 0.45 equiv, respectively, without loss of the
arylzincation yield or 1,4-migration selectivity (entry 3). The
presence of ZnCl2 as a catalyst, which was added in an excess
amount (1.3 equiv to ArLi) at the generation of ArZnCl from
ArLi, is essential for the present arylzincation. The yield of
arylzincation was much lower (22%) in the reaction with
ArZnCl generated with 1.0 equiv of ZnCl2 (entry 4).
Diarylzinc Ar2Zn generated from ArLi and 0.50 equiv of
ZnCl2 did not give the arylzincation products (entry 5). Other
zinc salts, ZnX2 (X = Br and I), which were used in an excess
amount at the generation of ArZnX13 from ArLi, also catalyzed
the reaction, but the yields and the migration selectivity were
somewhat lower (entries 6 and 7). The lower yield and
selectivity were observed with other phosphine ligands, dppe,
dppp, dppf, biphep, and PPh3 (entries 8−12). The
arylzincation did not proceed with the xantphos ligand
(entry 13), which has been reported to be the best ligand in
the cobalt-catalyzed migratory arylzincation.5 Interestingly, the
high selectivity in giving 3aa without the 1,4-migration was
observed only with 1,5-cyclooctadiene (cod). Other diene
ligands including norbornadiene (nbd) promoted the
migratory arylzincation, giving 4aa preferentially (entry 14).
The rhodium-catalyzed arylzincation was also successful
with several other arylzinc reagents ArZnCl, and similar
1:99
83:17
1:99
>99:1
13:87
94:6
1m:
3-Me-5-MeOC6H3
1n: 2-MeOC6H4
a
Reaction condition (A): ArZnCl 1 (0.60 mmol), ZnCl2 (0.18
mmol), 4-octyne (2a) (0.20 mmol), and Rh catalyst (3 mol % of Rh),
THF (total 2.0 mL) at 50 °C for 5 h. The reaction was quenched with
D2O (0.2 mL). (B): ArZnCl 1 (0.30 mmol), ZnCl2 (0.09 mmol), 4-
octyne (2a) (0.20 mmol), and Rh catalyst (3 mol % of Rh), THF
b
(total 1.0 mL) at 50 °C for 1 h. [RhCl(coe)2]2 (6 μmol of Rh) +
c
binap (6.6 μmol) or [RhCl(cod)]2 (6 μmol of Rh). Isolated yield.
d
e
Determined by 1H and 2H NMR. Regioselective 1,4-shift giving the
f
products 6 shown below. A mixture of 6ja and 6ja′ in a ratio of 2:1
and 4:1 with binap and cod, respectively.
selectivity of the addition/1,4-migration sequence giving ortho-
alkenylphenylzinc 4 with binap as a ligand is very high for all
the arylzinc reagents shown in Table 2, including unsubstituted
phenylzinc (entry 2) and para-substituted ones with both
electron-donating and -withdrawing groups (entries 3−8). The
ratio of 5:6 ranges between <1:99 and 6:94. The 1,4-shift was
regioselective in the reaction of meta-substituted phenylzinc
reagents with Me, NMe2, and SiMe3, deuterium being
incorporated at the less hindered position exclusively (entries
9, 11, 12). The regioselectivity was low with 3-MeOC6H4ZnCl
(entry 10). Interestingly, the 1,4-migration took place
selectively to the position next to the MeO group in the
B
DOI: 10.1021/acs.orglett.8b02668
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Letter
reaction of 3-Me-5-MeOC6H3ZnCl (entry 13). The selective
formation of 2-arylethenylzincs 3 without 1,4-migration was
also realized using cod as a ligand of the rhodium catalyst for
most of the arylzinc reagents examined, although the selectivity
is generally not as high as that for the reaction with migration.
The ratio of 5:6 after D2O quenching is higher than 7:3, except
for the arylzinc reagents substituted with electron-withdrawing
groups. Zinc reagents 4-FC6H4ZnCl and 4-CF3C6H4ZnCl gave
the corresponding arylation products with 5:6 = 49:51 and
<1:99, respectively14 (entries 7 and 8).
regiochemistry at carbometalation of alkyl(aryl)alkynes.1 The
high regioselectivity was also observed in the arylzincation of
methyl(alkyl)alkyne 2g, where the alkyl group is much bigger
than methyl (entry 7). The iodination of arylzinc reagents, 2-
arylalkenylzinc 3 and ortho-alkenylarylzinc 4, with I2 proceeded
smoothly to give the corresponding alkenyl and aryl iodides in
high yields (entries 8−11). As another example of trans-
formation of the resulting zinc reagents, Rh-catalyzed
conjugate addition of the arylzinc species16 generated from
4-octyne (2a) and PhZnCl (1b) is shown in entry 12.17
The catalytic cycle of the present arylzincation of alkynes
with/without 1,4-migratory is proposed as shown in Scheme 3.
The reaction conditions used for the arylzincation of 4-
octyne are applicable to other unfunctionalized alkynes. The
results are summarized in Scheme 2, which also contains
Scheme 3. A Catalytic Cycle Proposed for Arylzincation of
Alkynes Catalyzed by Rh Complexes and ZnCl2
Scheme 2. Rhodium-Catalyzed Arylzincation of Alkynes 2
with Arylzinc Reagents 1
a
Thus, the syn-addition of aryl−Rh intermediate A to the
alkyne generates 2-arylalkenyl−Rh species B. Transmetalation
of the alkenyl group from Rh to ZnCl2 takes place to produce
alkenylzinc product 3 and Cl−Rh C. Arylation of C with
ArZnCl regenerates aryl−Rh A.18,19 Direct transmetalation
between alkenyl−Rh B and ArZnCl 2 giving aryl−Rh A and
alkenylzinc 3 is less likely because a catalytic amount of ZnCl2
is necessary for the present arylzincation to take place (see
entries 4 and 5 in Table 1). When the transmetalation of
alkenyl−Rh intermediate B with ZnCl2 is relatively slow, it
undergoes 1,4-migration of Rh giving ortho-alkenylpheny-Rh
intermediate D, which is thermodynamically more stable than
B.7e Transmetalation with ZnCl2 finally leads to the ortho-
alkenylarylzinc 4.20 The selectivity in producing 3 or 4 is
dependent on the reactivity of alkenyl−Rh intermediate B
toward transmetalation with ZnCl2. It is our understanding
that the transmetalation, which is an intermolecular reaction, is
faster with a smaller cod ligand and the Rh 1,4-migration which
is an intramolecular event is not strongly affected by the
ligands on rhodium.
The reactions starting with alkenylzinc 3ba and ortho-
alkenylarylzinc 4ba (eq 1) gave us further insight into the
reaction mechanism. The isomerization of 3ba into 4ba was
observed in the presence of ZnCl2 with both Rh/binap and
Rh/cod catalysts, while the isomerization is very slow without
ZnCl2. The isomerization from 4ba to 3ba was not observed
under the same conditions with the binap or cod ligand. These
results demonstrate that ZnCl2 plays a key role at the
transmetalation steps in the catalytic cycle and that ortho-
alkenylarylzinc 4ba is thermodynamically more stable than
alkenylzinc 3ba. It is remarkable that the ratio of 2-
arylalkenylzinc 3 to ortho-alkenylarylzinc 4 in the reaction of
alkyne 2 with arylzinc 1 is not dependent on the reaction time
a
For reaction conditions (A) and (B), see footnote a in Table 2. For
iodination, I2 (0.60 mmol) was added after the Rh-catalyzed
arylzincation. THF solutions of [RhCl(cod)]2 and alkyne 2d were
added dropwise to PhZnCl (1b) and ZnCl2 in THF over 40 min. 1.5
mol % of Rh catalyst. Containing 5% of its regioisomer. 5 mmol
scale. 20 mmol scale, 1 mol % of Rh catalyst. Cyclohex-2-enone
(0.36 mmol) and [RhCl(cod)]2 (15 mol % Rh) were added, and the
mixture was heated at THF reflux for 12 h.
b
c
d
e
f
g
examples where the generated zinc reagents were used for a
few transformations other than the deuteration.15 The
arylzincation with 1a took place for symmetrically substituted
dialkylalkynes 2b−2c and diphenylacetylene (2d) to give the
corresponding ortho-alkenylarylzinc or 2-arylalkenylzinc prod-
ucts with high selectivity using binap or cod (entries 1−4). In
the reactions of alkyl(aryl)alkynes 2e−2f, high regioselectivity
was observed for the bond formation between the aryl group of
the arylzinc and the alkyl-substituted alkyne carbon (entries 5
and 6). This selectivity is as expected from the reported
C
DOI: 10.1021/acs.orglett.8b02668
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Organic Letters
Letter
or conversion. Thus, D2O quench of the reaction of 1a with 2a
at 15 min reaction time gave a 47% yield of 5aa/6aa (1/99)
and a 29% yield of 5aa/6aa (93/7) with binap and cod ligands,
respectively. The 5aa/6aa ratios are essentially the same as
those observed in entries 1 and 2 in Table 1. The organozincs
3 and 4 generated by the reaction of alkyne 2 with an excess
amount of ArZnCl 1 do not go back to the catalytic cycle
shown in Scheme 2 in the presence of excess 1, although both
Rh/binap and Rh/cod catalyze the isomerization of 3 to 4 in
the absence of ArZnCl 1 (eq 1).
REFERENCES
■
(1) For reviews on catalytic carbometalation of alkynes: (a) Mur-
akami, K.; Yorimitsu, H. Beilstein J. Org. Chem. 2013, 9, 278.
(b) Lorthiois, E.; Meyer, C. Carbozincation of Alkenes and Alkynes.
Patai’s Chemistry of Functional Groups; Wiley: New York, 2009.
(c) Itami, K.; Yoshida, J.-I. Carbomagnesiation Reactions. In The
Chemistry of Organomagnesium Compounds; Rappoport, Z., Marek, I.,
Eds.; Wiley: Chichester, 2008; pp 631−679. (d) Negishi, E.-I.;
Huang, Z.-H.; Wang, G.-W.; Mohan, S.; Wang, C.; Hattori, H. Acc.
Chem. Res. 2008, 41, 1474. (e) Flynn, A. B.; Ogilvie, W. W. Chem. Rev.
2007, 107, 4698.
(2) Ni catalyst: (a) Duboudin, J. G.; Jousseaume, B.; Saux, A. J.
Organomet. Chem. 1978, 162, 209. (b) Xue, F.; Zhao, J.; Hor, T. S. A.
Chem. Commun. 2013, 49, 10121. (c) Xue, F.; Zhao, J.; Hor, T. S. A.;
Hayashi, T. J. Am. Chem. Soc. 2015, 137, 3189. Mn catalyst:
(d) Yorimitsu, H.; Tang, J.; Okada, K.; Shinokubo, H.; Oshima, K.
Chem. Lett. 1998, 27, 11. Fe or Fe/Cu catalyst: (e) Shirakawa, E.;
Yamagami, T.; Kimura, T.; Yamaguchi, S.; Hayashi, T. J. Am. Chem.
Soc. 2005, 127, 17164. (f) Yamagami, T.; Shintani, R.; Shirakawa, E.;
Hayashi, T. Org. Lett. 2007, 9, 1045. Cr catalyst: (g) Murakami, K.;
Ohmiya, H.; Yorimitsu, H.; Oshima, K. Org. Lett. 2007, 9, 1569. Ag
catalyst: (h) Kambe, N.; Moriwaki, Y.; Fujii, Y.; Iwasaki, T.; Terao, J.
Org. Lett. 2011, 13, 4656.
In summary, we have disclosed that the addition of arylzinc
reagents ArZnCl to unfunctionalized alkynes is efficiently
catalyzed by rhodium complexes in the presence of a catalytic
amount of zinc chloride. One of the divergent pathways in
giving 2-arylalkenylzincs or ortho-alkenylarylzincs, the latter of
which are generated through 1,4-Rh migration from alkenyl to
aryl in the catalytic cycle, is chosen by use of the appropriate
ligands on rhodium.
(3) Ni catalyst: (a) Stu
Ed. Engl. 1997, 36, 93. (b) Stu
̈
demann, T.; Knochel, P. Angew. Chem., Int.
demann, T.; Ibrahim-Ouali, M.;
̈
Knochel, P. Tetrahedron 1998, 54, 1299. Co catalyst: (c) Murakami,
K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2009, 11, 2373. (d) Corpet,
M.; Gosmini, C. Chem. Commun. 2012, 48, 11561. (e) Murakami, K.;
Yorimitsu, H.; Oshima, K. Chem. - Eur. J. 2010, 16, 7688.
(f) Nishikawa, T.; Yorimitsu, H.; Oshima, K. Synlett 2004, 1573.
(g) Yasui, H.; Nishikawa, T.; Yorimitsu, H.; Oshima, K. Bull. Chem.
Soc. Jpn. 2006, 79, 1271.
ASSOCIATED CONTENT
(4) (a) Gourdet, B.; Lam, H. W. J. Am. Chem. Soc. 2009, 131, 3802.
(b) Gourdet, B.; Rudkin, M. E.; Watts, C. A.; Lam, H. W. J. Org.
Chem. 2009, 74, 7849.
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b02668.
(5) (a) Tan, B.-H.; Dong, J.; Yoshikai, N. Angew. Chem., Int. Ed.
2012, 51, 9610. See also: (b) Tan, B.-H.; Yoshikai, N. Org. Lett.
2014, 16, 3392. (c) Wu, J.; Yoshikai, N. Angew. Chem., Int. Ed. 2016,
55, 336. (d) Yan, J.; Yoshikai, N. Org. Chem. Front. 2017, 4, 1972.
(6) For reviews dealing with 1,4-metal shift, see: (a) Croisant, M. F.;
van Hoveln, R.; Schomaker, J. M. Eur. J. Org. Chem. 2015, 2015, 5897.
(b) Shi, F.; Larock, R. C. Top. Curr. Chem. 2009, 292, 123. (c) Miura,
T.; Murakami, M. Chem. Commun. 2007, 217. (d) Ma, S.; Gu, Z.
Angew. Chem., Int. Ed. 2005, 44, 7512.
(7) For 1,4-Rh shift from alkenyl to aryl, see: (a) Hayashi, T.; Inoue,
K.; Taniguchi, N.; Ogasawara, M. J. Am. Chem. Soc. 2001, 123, 9918.
(b) Miura, T.; Sasaki, T.; Nakazawa, H.; Murakami, M. J. Am. Chem.
Soc. 2005, 127, 1390. (c) Shintani, R.; Takatsu, K.; Hayashi, T. Angew.
Chem., Int. Ed. 2007, 46, 3735. (d) Shintani, R.; Isobe, S.; Takeda, M.;
Hayashi, T. Angew. Chem., Int. Ed. 2010, 49, 3795. (e) Sasaki, K.;
Nishimura, T.; Shintani, R.; Kantchev, E. A. B.; Hayashi, T. Chem. Sci.
2012, 3, 1278. (f) Sasaki, K.; Hayashi, T. Tetrahedron: Asymmetry
2012, 23, 373.
(8) For examples of other types of 1,4-Rh shift, see: (a) Oguma, K.;
Miura, M.; Satoh, T.; Nomura, M. J. Am. Chem. Soc. 2000, 122,
10464. (b) Matsuda, T.; Shigeno, M.; Murakami, M. J. Am. Chem. Soc.
2007, 129, 12086. (c) Panteleev, J.; Menard, F.; Lautens, M. Adv.
Synth. Catal. 2008, 350, 2893. (d) Seiser, T.; Roth, O. A.; Cramer, N.
Angew. Chem., Int. Ed. 2009, 48, 6320. (e) Shigeno, M.; Yamamoto,
T.; Murakami, M. Chem. - Eur. J. 2009, 15, 12929. (f) Seiser, T.;
Cramer, N. Chem. - Eur. J. 2010, 16, 3383. (g) Seiser, T.; Cramer, N.
Angew. Chem., Int. Ed. 2010, 49, 10163. (h) Matsuda, T.; Suda, Y.;
Takahashi, A. Chem. Commun. 2012, 48, 2988. (i) Yu, H.; Wang, C.;
Yang, Y.; Dang, Z.-M. Chem. - Eur. J. 2014, 20, 3839. (j) Shintani, R.;
Iino, R.; Nozaki, K. J. Am. Chem. Soc. 2014, 136, 7849. (k) Hepburn,
H. B.; Lam, H. W. Angew. Chem., Int. Ed. 2014, 53, 11605. (l) Sawano,
T.; Hashizume, M.; Nishimoto, S.; Ou, K.; Nishimura, T. Org. Lett.
2015, 17, 2630. (m) Ming, J.; Hayashi, T. Org. Lett. 2016, 18, 6452.
Experimental procedures, compound characterization
data, and crystallographic data (PDF)
Accession Codes
CCDC 1813165 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: hayashi@ntu.edu.sg.
ORCID
Tamio Hayashi: 0000-0001-9187-3664
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by funding from Nanyang
Technological University and the Singapore Ministry of
Education (AcRF MOE 2016-T1-001-247 and 2017-T2-1-
064).
D
DOI: 10.1021/acs.orglett.8b02668
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Letter
(9) Ming, J.; Shi, Q.; Hayashi, T. Chem. Sci. 2018, DOI: 10.1039/
C8SC02459F.
(10) Reviews on organozinc reagents: (a) Knochel, P.; Singer, R. D.
Chem. Rev. 1993, 93, 2117. (b) Knochel, P.; Almena Perea, J. J.; Jones,
P. Tetrahedron 1998, 54, 8275. (c) Knochel, P.; Leuser, H.; Gong, L.-
Z.; Perrone, S.; Kneisel, F. F. In Handbook of Functionalized
Organometallics; Knochel, P., Ed.; Wiley- VCH: Weinheim, 2005;
Vol. 1, p 251. (d) Knochel, P.; Calaza, M. I.; Hupe, E. In Metal-
Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere, A., Diederich,
F., Eds.; Wiley-VCH: Weinheim, 2004; p 619. (e) Organozinc
Reagents; Knochel, P., Jones, P., Eds.; Oxford University Press: New
York, 1999. (f) Negishi, E.-I.; Gagneur, S. In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E.-I., Ed.;
́
Wiley: New York, 2002; Vol. 1, p 597. (g) Phapale, V. B.; Cardenas,
D. J. Chem. Soc. Rev. 2009, 38, 1598.
(11) The structure and reactivity of arylzinc reagents are dependent
on what they are generated from, ArMgX or ArLi. For example: Jin,
L.; Liu, C.; Liu, J.; Hu, F.; Lan, Y.; Batsanov, A. S.; Howard, J. A. K.;
Marder, T. B.; Lei, A. J. Am. Chem. Soc. 2009, 131, 16656.
(12) binap = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl. cod =
1,5-cyclooctadiene.
(13) Effects of X in PhZnX (X = Cl, Br, I) on the reactivity have
been reported: Zhang, G.; Li, J.; Deng, Y.; Miller, J. T.; Kropf, A. J.;
Bunel, E. E.; Lei, A. Chem. Commun. 2014, 50, 8709.
(14) The 1,4-shift to aryl groups with electron-withdrawing groups
has been reported in Pd-catalyzed Heck-type reactions: (a) Karig, G.;
Moon, M.-T.; Thasana, N.; Gallagher, T. Org. Lett. 2002, 4, 3115.
(b) Campo, M. A.; Zhang, H.; Yao, T.; Ibdah, A.; McCulla, R. D.;
Huang, Q.; Zhao, J.; Jenks, W. S.; Larock, R. C. J. Am. Chem. Soc.
2007, 129, 6298 and references cited therein .
(15) The synthetic utility of organozinc reagents has been well
established: References 1, 3, and 4. See also: Jin, M.-Y.; Yoshikai, N. J.
Org. Chem. 2011, 76, 1972.
(16) (a) Shintani, R.; Tokunaga, N.; Doi, H.; Hayashi, T. J. Am.
Chem. Soc. 2004, 126, 6240. (b) Shintani, R.; Hayashi, T. Org. Lett.
2005, 7, 2071. (c) Kina, A.; Ueyama, K.; Hayashi, T. Org. Lett. 2005,
7, 5889. (d) Tokunaga, N.; Hayashi, T. Tetrahedron: Asymmetry 2006,
17, 607.
(17) The Rh/cod catalyst was added because the Rh/binap catalyst
used for the migratory arylzincation generating ortho-alkenylarylzinc
4ba was not active for the conjugate addition.
(18) Transmetalation of Ar groups from ArZnX to Rh(I) has been
reported in Rh-catalyzed conjugate arylation with ArZnX (ref 15).
(19) A catalytic cycle involving direct transmetalation between a π-
allyl−Rh intermediate and ArZnX has been proposed in the reaction
of arylzincation of allenes. Yoshida, Y.; Murakami, K.; Yorimitsu, H.;
Oshima, K. J. Am. Chem. Soc. 2010, 132, 8878.
(20) The transmetalation between Ar−Rh and ZnCl2 giving ArZnCl
has been proposed in the migratory arylstannylation catalyzed by a Rh
catalyst and ZnCl2. See ref 9.
E
DOI: 10.1021/acs.orglett.8b02668
Org. Lett. XXXX, XXX, XXX−XXX