Cobalt-catalyzed addition of arylzinc reagents to norbornene derivatives through 1,4-cobalt migration

Article abstract of DOI:10.1021/ol501449j

A cobalt-diphosphine catalyst promotes the addition of an arylzinc reagent to a norbornene derivative to afford o-(2-exo-norbornyl)arylzinc species. This migratory arylzincation reaction is considered to involve insertion of norbornene into an arylcobalt species, alkyl-to-aryl 1,4-cobalt migration, and transmetalation between the resulting o-(2-exo-norbornyl)arylcobalt species and the arylzinc reagent. The o-(2-exo-norbornyl)arylzinc species can be intercepted by common organic electrophiles under copper or palladium catalysis.

Full text of DOI:10.1021/ol501449j

Letter
pubs.acs.org/OrgLett
Cobalt-Catalyzed Addition of Arylzinc Reagents to Norbornene
Derivatives through 1,4-Cobalt Migration
Boon-Hong Tan and Naohiko Yoshikai*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371, Singapore
S
* Supporting Information
ABSTRACT: A cobalt−diphosphine catalyst promotes the
addition of an arylzinc reagent to a norbornene derivative to
afford o-(2-exo-norbornyl)arylzinc species. This “migratory
arylzincation” reaction is considered to involve insertion of
norbornene into an arylcobalt species, alkyl-to-aryl 1,4-cobalt
migration, and transmetalation between the resulting o-(2-exo-
norbornyl)arylcobalt species and the arylzinc reagent. The o-(2-exo-norbornyl)arylzinc species can be intercepted by common
organic electrophiles under copper or palladium catalysis.
emote metal migrations of organorhodium and -palladium
species, 1,4-migration in particular, have been extensively
involving 1,4-rhodium migration (Scheme 1b).5 Thus, this
apparently simple reaction goes through insertion of the alkyne
into an arylrhodium species, vinyl-to-aryl 1,4-rhodium migration,
and protoderhodation of the resulting o-alkenylarylrhodium
species.
R
utilized to achieve novel catalytic transformations involving C−
H activation and cascade bond forming processes.1−3 With
respect to the rhodium catalysis, the origin of this particular area
of research dates back to two seminal reports in the early 2000s.
In 2000, Miura and co-workers reported a rhodium-catalyzed
merry-go-round addition reaction of an arylboronic acid to
norbornene (Scheme 1a).4 The reaction affords multiply
norbonylated arenes through repetition of a sequence consisting
of insertion of norbornene into arylrhodium species and alkyl-to-
aryl 1,4-rhodium migration. One year later, Hayashi and co-
workers reported on rhodium-catalyzed hydroarylation of an
intenal alkyne with an arylboronic acid, revealing its mechanism
Recently, we disclosed the first example of 1,4-cobalt
migration in a cobalt-catalyzed addition of an arylzinc reagent
to an internal alkyne (Scheme 1c).6,7 Compared to the rhodium-
catalyzed hydroarylation, the reaction is unique in that it
produces o-alkenylarylzinc species, which can be intercepted by
an external electrophile. This “migratory arylzincation” also finds
its application in modular synthesis of benzoheterole deriva-
tives.8 Here, we report that a cobalt complex is also capable of
catalyzing migratory arylzincation of norbornene derivatives
(Scheme 1d). Thus, unlike the rhodium-catalyzed merry-go-
round addition, the present reaction affords o-(2-exo-norbornyl)-
arylzinc species through alkyl-to-aryl cobalt migration and
subsequent cobalt-to-zinc transmetalation. The reaction is also
reminiscent of Catellani’s palladium-catalyzed coupling reactions
involving norbornene.9
Scheme 1. Rhodium and Cobalt Catalysis Involving 1,4-Metal
Migration
The present study began with a screening of cobalt catalysts for
the addition of 4-methoxyphenylzinc reagent (1a, 1.7 equiv;
prepared from a 1:2 mixture of ZnCl2·TMEDA and 4-
MeOC6H4MgBr and denoted as type A reagent) to norbornene
2a, which was conducted at 60 °C for 12 h (Table 1). A CoCl2−
Xantphos catalyst, which is the optimum catalyst for the
migratory arylzincation to an internal alkyne,6 exhibited poor
catalytic activity, affording the arylation product 3aa only in a low
yield of 2% (entry 1). Upon subsequent screening of common
diphosphine ligands (entries 2−8), we identified dppf as the
most effective ligand, which promoted the addition reaction to
afford 3aa in 69% yield (entry 3). Among other diphosphine
ligands, dppp, dppb, and BISBI (2,2′-bis(diphenylphosphino-
Received: May 19, 2014
Published: June 6, 2014
© 2014 American Chemical Society
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Letter
a
NMR spectrum, demonstrating that the 3-exo-position of the
norbornyl group was virtually not deuterated.
Table 1. Screening of Reaction Conditions
The putative 1,4-cobalt migration process was further
supported by another deuterium-labeling experiment (Scheme
2). Thus, the addition of pentadeuteriophenylzinc reagent 1b-d5
a
Scheme 2. Reaction of Pentadeuteriophenylzinc Reagent
b
entry
ArZnX type
ligand
yield (%)
1
2
3
4
5
6
7
8
A
A
A
A
A
A
A
A
A
A
A
B
C
Xantphos
DPEphos
dppf
2
6
69
c
dppe
18
a
dppp
38
35
The proton content on each carbon atom was estimated by1H NMR
dppb
analysis.
c
dppbz
BISBI
PPh3
3
42
7
(type A) to 2a under the cobalt−dppf catalysis took place with
concomitant migration of one of the o-deuterium atoms to the
exo-2-norbornyl position, as revealed by 1H NMR analysis of the
product 3ba-d5.
d
9
10
none
1
e
11
dppf
76
<1
82
e
12
dppf
Having established the cobalt−diphosphine catalytic system,
we next explored the scope of the present migratory arylzincation
reaction using different arylzinc reagents and norbornene
derivatives (Scheme 3). Note that each reaction was quenched
with D2O in order to confirm the 1,4-cobalt migration process.
First, we performed reactions of a series of arylzinc reagents with
norbornene 2a. 4-(Trimethylsilyl)phenylzinc and 4-tert-butyl-
phenylzinc reagents afforded the desired adducts 3ca-d and 3da-
d in excellent yields. On the other hand, the reaction of 4-
fluorophenylzinc reagent resulted in the formation of a mixture
of mono- and diaddition products 3ea-d and 4ea-d in an
approximate ratio of 1:1 (Scheme 4a). The latter product would
have been formed through a merry-go-round process as
proposed for Miura’s rhodium-catalyzed reaction.4 No desired
reaction was observed with electron-poor 4-(trifluoromethyl)-
phenylzinc reagent. As was the case with the migratory
arylzincation of alkynes,6 the meta-oxygen atom of 3-methoxy-
and 3,4-methylenedioxyphenylzinc reagents caused secondary
directing effect to induce regioselective 1,4-metal migration to its
proximity (see 3ga-d and 3ha-d). 3,5-Dimethoxyphenylzinc
reagent also afforded the desired adduct 3ia-d in an excellent
yield. The reaction of 2-naphthylzinc reagent took place cleanly
through exclusive 1,4-migration to the less hindered 3-position,
thus affording the adduct 3ja-d. Like the case of 4-
fluorophenylzinc reagent (Scheme 4a), a merry-go-round
process was observed in the reaction of 2-methoxyphenylzinc
reagent, which afforded a mixture of mono-, di-, and triaddition
products 3ka-d, 4ka-d, and 5ka-d, respectively (Scheme 4b).
Note that mesitylzinc reagent failed to participate in the reaction.
A norbornene derivative bearing an endo-diester moiety 2b
failed to participate in the reaction with 4-methoxyphenylzinc
reagent under the Co−dppf catalysis. However, the use of dppe
instead of dppf promoted the reaction to afford the desired
product 3ab-d in 70% yield. 4-Fluoro-, 3-methoxy-, 3,4-
methylenedioxy-, and 3,5-dimethoxyphenylzinc reagents also
underwent addition to 2b to afford the corresponding adducts
3eb-d, 3gb-d, 3hb-d, and 3ib-d, respectively, albeit in modest
yields. Curiously, the reaction of 3-methoxyphenylzinc reagent
and 2b exhibited the opposite regioselectivity to that observed in
the reaction of the same reagent with 2a (see 3ga-d), thus
resulting in deuteration of the position distal to the methoxy
f
13
dppf
a
Unless otherwise noted, the reaction was performed on a 0.3 mmol
b
scale and was quenched with H2O. Determined by GC using n-
tridecane as an internal standard. 1,2-Di-2-norbonylated product was
obtained (44% and 34% for entries 4 and 7, respectively). 10 mol %
of PPh3 was used. The reaction was performed with 1.2 equiv of
c
d
e
f
arylzinc reagent at 40 °C for 18 h. The reaction was performed with
1.5 equiv of arylzinc reagent at 40 °C for 12 h and quenched with
D2O. The yield was determined by 1H NMR using 1,1,2,2-
tetrachloroethane as an internal standard.
methyl)-1,1′-biphenyl) exhibited moderate performances, af-
fording 3aa in ca. 40% yield (entries 5, 6, and 8), while DPEphos
was almost ineffective (entry 2). Interestingly, the reaction using
dppe or dppbz as the ligand produced, like Miura’s merry-go-
round reaction (Scheme 1a), a 1,2-di-2-norbonylated product in
ca. 30−40% yield, as judged from GC and GCMS analysis of the
reaction mixture (entries 4 and 7). Monodentate phosphines
such as PPh3 as well as a ligand-free system were not effective
(entries 9 and 10).
Upon further examination of reaction conditions, we found
that the Co−dppf-catalyzed addition reaction could be achieved
with a reduced amount of the type A arylzinc reagent (1.2−1.5
equiv) at a lower temperature of 40 °C (entry 11). Unlike the
migratory arylzincation reaction to internal alkynes,6
a
monoarylzinc reagent prepared from a 1:1 mixture of ZnCl2·
TMEDA and 4-MeOC6H4MgBr (type B reagent) as well as one
prepared from 4-MeOC6H4I and Zn·LiCl10 were almost
unreactive (entry 12), indicating that only one of two aryl
groups on the type A reagent is transferable in the present
reaction. The reactivity of this unreactive reagent could be
restored by the addition of a “dummy” Grignard reagent, i.e.,
Me3SiCH2MgCl. Thus, the mixed diorganozinc reagent (type C
reagent) underwent addition to 2a, and upon quenching with
D2O, afforded a deuterated adduct 3aa-d in 82% yield (entry
13).11 The 1H NMR spectrum of 3aa-d showed an integration of
1.12 for the position ortho to the 2-norbornyl group, indicating
substantial deuterium incorporation into this position and hence
formation of an o-(2-exo-norbornyl)arylzinc species via 1,4-
cobalt migration. Consistent with this, all of the norbornyl
carbon atoms of 3aa-d appeared as clear singlet signals in the 13C
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a
Scheme 3. Scope of Migratory Arylzincation
Scheme 4. Merry-Go-Round Addition to Norbornene and
Ring-Opening Arylation of Oxabicyclic Alkene
a
a
cat. Co = CoCl2 (5 mol %), dppf (5 mol %). The identities and
quantities of norbornylated products were estimated by 1H NMR, GC,
and GCMS analysis of the product mixture. The yields in parentheses
are based on 2a.
reagent) or by lowering the reaction temperature did not change
the course of the reaction.13
The o-(2-exo-norbornyl)arylzinc species formed by the
present reaction is amenable to transition-metal-catalyzed
cross-coupling with organic electrophiles (Scheme 5).14 The
reaction of 4-(trimethylsilyl)phenylzinc reagent 1c and 2a was
followed by copper-catalyzed allylation with allyl bromide and
acylation with benzoyl chloride to afford the desired products 7
and 8, respectively, in excellent yields.15 The same o-(2-exo-
norbornyl)arylzinc intermediate also participated in the Negishi
a
The reaction was performed on a 0.5 mmol scale. Unless otherwise
noted, type A arylzinc reagent was used, and the isolated yield is
Scheme 5. Electrophilic Trapping of o-Norbornylarylzinc
Species
b
c
a
shown. Type C arylzinc reagent was used. The yield was determined
1
by H NMR analysis using 1,1,2,2-tetrachloroethane as an internal
d
standard. Merry-go-round addition was observed (see Scheme 4).
e
f
Dppe was used instead of dppf. Obtained as a diastereomeric
mixture.
group (see 3gb-d), while the regioselectivity did not change for
3,4-methylenedioxyphenylzinc reagent (see 3ha-d and 3hb-d).
Note that some of these reactions produced a mixture of
diastereomers, presumably due to epimerization of the α-
positions of the diester moiety. The reactions of 3-
methoxyphenyl- and 2-methoxyphenylzinc reagents with an
endo-diether 2c took place under the Co−dppf catalysis and
afforded the corresponding adducts 3gc-d and 3kc-d, respec-
tively, albeit in low yields. In the former case, deuteration took
place at the position proximal to the methoxy group. Note also
that, in these low-yielding cases, the norbornene derivative was
largely recovered without affording any byproducts.
The reaction of 4-methoxyphenylzinc reagent 1a with
oxabicyclic alkene 2d did not afford a migratory arylzincation
product, but resulted in a ring-opening arylation product 6
(Scheme 4c).12 Attempts to suppress the β-oxygen elimination
process by using less reactive arylzinc reagent (i.e., type B
a
CuCN·2LiCl (20 mol %), allyl bromide (3 equiv), 60 °C, 8 h.
CuCN·2LiCl (20 mol %), benzoyl chloride (3 equiv), 60 °C, 8 h.
b
c
Pd(OAc)2 (4 mol %), SPhos (4 mol %), ethyl 4-iodobenzoate (3
equiv), 60 °C, 8 h.
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Letter
(2) For representative examples of rhodium migrations, see: (a) Ishida,
N.; Shimamoto, Y.; Yano, T.; Murakami, M. J. Am. Chem. Soc. 2013, 135,
19103. (b) Zhang, J.; Liu, J.-F.; Ugrinov, A.; Pillai, A. F. X.; Sun, Z.-M.;
Zhao, P. J. Am. Chem. Soc. 2013, 135, 17270. (c) Tobisu, M.; Hasegawa,
J.; Kita, Y.; Kinuta, H.; Chatani, N. Chem. Commun. 2012, 48, 11437.
(d) Sasaki, K.; Nishimura, T.; Shintani, R.; Kantchev, E. A. B.; Hayashi,
T. Chem. Sci. 2012, 3, 1278. (e) Matsuda, T.; Suda, Y.; Takahashi, A.
Chem. Commun. 2012, 48, 2988. (f) Shintani, R.; Isobe, S.; Takeda, M.;
Hayashi, T. Angew. Chem., Int. Ed. 2010, 49, 3795. (g) Seiser, T.; Roth,
O. A.; Cramer, N. Angew. Chem., Int. Ed. 2009, 48, 6320. (h) Shigeno,
M.; Yamamoto, T.; Murakami, M. Chem.Eur. J. 2009, 15, 12929.
(i) Panteleev, J.; Menard, F.; Lautens, M. Adv. Synth. Catal. 2008, 350,
2893. (j) Shintani, R.; Takatsu, K.; Katoh, T.; Nishimura, T.; Hayashi, T.
Angew. Chem., Int. Ed. 2008, 47, 1447. (k) Shintani, R.; Takatsu, K.;
Hayashi, T. Angew. Chem., Int. Ed. 2007, 46, 3735. (l) Matsuda, T.;
Shigeno, M.; Murakami, M. J. Am. Chem. Soc. 2007, 129, 12086.
(m) Yamabe, H.; Mizuno, A.; Kusama, H.; Iwasawa, N. J. Am. Chem. Soc.
2005, 127, 3248. (n) Shintani, R.; Okamoto, K.; Hayashi, T. J. Am.
Chem. Soc. 2005, 127, 2872. (o) Miura, T.; Sasaki, T.; Nakazawa, H.;
Murakami, M. J. Am. Chem. Soc. 2005, 127, 1390.
coupling with ethyl 4-iodobenzoate under Pd/SPhos catalysis,
affording the biaryl product 9 in a moderate yield.
A proposed catalytic cycle for the present migratory
arylzincation is shown in Scheme 6. An arylcobalt species A
Scheme 6. Proposed Catalytic Cycle
(3) For selected examples of palladium migrations, see: (a) Zhou, J.;
He, J.; Wang, B.; Yang, W.; Ren, H. J. Am. Chem. Soc. 2011, 133, 6868.
(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. (c) Zhao, J.; Yue, D.; Campo, M. A.; Larock, R. C. J. Am. Chem.
Soc. 2007, 129, 5288. (d) Masselot, D.; Charmant, J. P. H.; Gallagher, T.
J. Am. Chem. Soc. 2006, 128, 694.
(4) Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J. Am. Chem. Soc.
2000, 122, 10464.
(5) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. J. Am. Chem.
Soc. 2001, 123, 9918.
(6) Tan, B.-H.; Dong, J.; Yoshikai, N. Angew. Chem., Int. Ed. 2012, 51,
9610.
(7) Gao, K.; Yoshikai, N. Acc. Chem. Res. 2014, 47, 1208.
(8) (a) Wu, B.; Yoshikai, N. Angew. Chem., Int. Ed. 2013, 52, 10496.
(b) Wu, B.; Santra, M.; Yoshikai, N. Angew. Chem., Int. Ed. 2014,
DOI: 10.1002/anie.201404019.
(9) (a) Catellani, M. Synlett 2003, 298. (b) Catellani, M.; Motti, E.;
Della Ca’, N. Acc. Chem. Res. 2008, 41, 1512.
generated from the cobalt precatalyst and the arylzinc reagent
undergoes insertion of norbornene to give a norbornylcobalt
species B. This species undergoes alkyl-to-aryl 1,4-cobalt
migration presumably through a C−H oxidative addition
intermediate C,2d,4 thus affording an o-(2-exo-norbornyl)-
arylcobalt species D. Subsequent transmetalation between D
and the arylzinc reagent furnishes the o-(2-exo-norbornyl)-
arylzinc species and regenerates the arylcobalt species A.
In summary, we have reported on a cobalt−diphosphine-
catalyzed addition reaction of an arylzinc reagent to a
norbornene derivative, which involves alkyl-to-aryl 1,4-cobalt
migration and cobalt-to-zinc transmetalation as key steps, thus
affording o-(2-exo-norbornyl)arylzinc species. The arylzinc
product is amenable to common electrophilic trapping reactions
under copper or palladium catalysis. Further mechanistic and
synthetic investigations into catalytic transformations involving
1,4-cobalt migration are currently underway.
(10) (a) Jin, M.-Y.; Yoshikai, N. J. Org. Chem. 2011, 76, 1972.
(b) Krasovskiy, A.; Malakhov, V.; Gavryushin, A.; Knochel, P. Angew.
Chem., Int. Ed. 2006, 45, 6040.
(11) In this and some other cases, it was difficult to isolate the addition
product in a pure form because of small polarity differences among the
product and hydrolyzed/homocoupling products of the arylzinc
reagent. In such cases, the crude product mixture was subjected to
ASSOCIATED CONTENT
* Supporting Information
■
1
short silica gel chromatography, and the yield was determined by H
S
NMR analysis of the thus-obtained sample using 1,1,2,2-tetrachloro-
ethane as an internal standard. See the Supporting Information for the
details of each case.
(12) For reviews on transition-metal-catalyzed ring-opening alkylation
of oxa- and azabicyclic alkenes, see: (a) Lautens, M. Synlett 1993, 177.
(b) Chiu, P.; Lautens, M. Top. Curr. Chem. 1997, 190, 1. (c) Lautens, M.;
Fagnou, K.; Hiebert, S. Acc. Chem. Res. 2003, 36, 48. (d) Rayabarapu, D.
K.; Cheng, C.-H. Acc. Chem. Res. 2007, 40, 971.
(13) For arylzincation of oxa- and azabicyclic alkenes promoted by an
iron−diphosphine catalyst, see: Ito, S.; Itoh, T.; Nakamura, M. Angew.
Chem., Int. Ed. 2011, 50, 454.
(14) Quenching of the reaction with iodine afforded o-(2-norbornyl)
aryl iodide, which was, however, difficult to isolate in a pure form due to
formation of other unidentified byproducts.
Experimental details and characterization of new compounds.
This material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: nyoshikai@ntu.edu.sg.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(15) Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J. J. Org. Chem.
1988, 53, 2390.
This work was supported by Singapore National Research
Foundation (NRF-RF2009-05), Nanyang Technological Uni-
versity, and JST, CREST.
REFERENCES
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