Preparation of Aryne-Nickel Complexes from ortho-Borylaryl Triflates

Article abstract of DOI:10.1021/acs.orglett.6b02831

A facile method for preparing diverse aryne-nickel complexes from readily synthesized ortho-borylaryl triflates is described. Exploratory synthetic applications, including the synthesis of 1,2-difunctionalized arenes, based on the nucleophilic character of the aryne-nickel complexes are also demonstrated.

Full text of DOI:10.1021/acs.orglett.6b02831

Letter
pubs.acs.org/OrgLett
Preparation of Aryne−Nickel Complexes from ortho-Borylaryl
Triflates
Yuto Sumida,† Tomoe Sumida,† Daisuke Hashizume,‡ and Takamitsu Hosoya*,†,§
†Chemical Biology Team, Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3
Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan
‡Materials Characterization Support Unit, Supramolecular Chemistry Division, RIKEN Center for Emergent Matter Science, 2-1
Hirosawa, Wako, Saitama 351-0198, Japan
§Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University 2-3-10
Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
S
* Supporting Information
ABSTRACT: A facile method for preparing diverse aryne−nickel
complexes from readily synthesized ortho-borylaryl triflates is described.
Exploratory synthetic applications, including the synthesis of 1,2-
difunctionalized arenes, based on the nucleophilic character of the
aryne−nickel complexes are also demonstrated.
rynes are highly reactive species widely used as synthetic
intermediates for the construction of diverse aromatic
addition of ortho-borylaryl bromide to low-valent nickel, followed
by intramolecular transmetalation, enabling the mild complex-
ation of arynes with d10 transition metals (Figure 2A).4d
A
compounds.1 While arynes are too reactive to be isolated, aryne−
metal complexes, which are generally prepared by the complex-
ation of arynes with a transition metal, are often isolable as
mononuclear or cluster complexes (Figure 1).2−6 The reactivity
Figure 1. Aryne and aryne−metal complex.
ofarynes and aryne−metal complexes contrast starkly; the former
are electrophilic, while the latter are nucleophilic. Nevertheless,
the synthetic application of aryne−metal complexes with
“umpolung7” reactivity of the arynes is largely limited, which
stands in stark contrast to uncomplexed arynes with an enormous
number of synthetic applications.1,8,9 One possible reason for the
paucity of applications is the lack of a general method for
preparing aryne−metal complexes, in particular, for those bearing
functional groups. Here we report a facile method for preparing
aryne−nickel(Ni)complexesfromortho-borylaryltriflates, which
we previously developed as aryne precursors.8
Aryne−metal complexes have been studied for more than half a
century.2 A number of aryne−metal complexes involving early or
late transition metals have been prepared, and their unique
reactivities have been surveyed.2−6 The involvement of aryne−
metal complexes as intermediates in transition-metal-catalyzed
reactions with arynes has also been suggested, albeit the aryne−
metal complexes were not isolated in these cases.10,11 In
particular, Bennett and co-workers reported a series of pioneering
works on the chemistry of aryne−Ni complexes.4 They showed
that aryne−Ni complexes could be prepared via the oxidative
Figure 2. Proposed strategy.
During the course of our studies on aryne chemistry,8,9 we
recently found that ortho-borylaryl triflates 1 serve as efficient
precursors of arynes (Figure 2B).8 A diverse range of 1 were easily
synthesized from the corresponding phenols by a simple two-step
protocol: iridium-catalyzed direct ortho-borylation of phenols,12
followed by triflylation. We presumed that 1 would also serve as
goodprecursors forabroadrangeofaryne−Nicomplexes(Figure
2C);11 however, our initial attempt to achieve the oxidative
additionofortho-borylphenyltriflate1atoNi(0)wasunsuccessful
(Scheme 1). Treatment of 1a with Ni(cod)2 and PCy3 did not
afford the desired aryl−Ni triflate complex, and most of 1a was
recovered after protonation with trifluoroacetic acid (TFA). We
Received: September 20, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b02831
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Letter
triflates 1b−d with high efficiencies. This method was also
applicable to the preparation of aryne−Ni complexes bearing an
electron-deficientgroup, suchas4-methoxycarbonylbenzyne−Ni
complex 3e-dcpe and 4-trifluoromethylbenzyne−Ni complex 3f-
dcpe, easily widening the scope of available complexes compared
withtheconventional methods. Thestructures ofsomearyne−Ni
complexes were confirmed by X-ray crystal structure analysis,14
showing an η2-coordination of the aryne triple bond to the Ni
atom being in an almost trigonal planar rearrangement similar to
the reported benzyne−Ni(dcpe) complex 3a-dcpe.4a Interest-
ingly, the distance of C1−C2 (1.368(2) Å) of [Ni(η2-2,3-
naphthalyne)dcpe] (3b-dcpe) is slightly shorter than other
aromatic C−C bonds (C2−C3 = 1.374(2) Å, C1−C10 =
1.375(2) Å) (Figure 4). This is probably due to the long π-
Scheme 1. An Initial Attempt
assumed that the oxidative addition process was problematic due
to the instability of the cationic divalent-nickel complex.13
After extensive screening of reaction conditions,14 we found
that the addition of an equimolar amount of lithium bromide
afforded the desired aryl−Ni(II)Br complex [NiBr(2-
BpinC6H4)(PCy3)2] (2a-PCy3) in excellent yield (Figure 3A),
which was identical to the spectroscopic data reported
previously.4d The addition of lithium bromide must have
accelerated the oxidative addition step and served to stabilize
the aryl−Ni(II) complex.15 Conversely, attempts to prepare 2a-
PCy3 from 2-trimethylsilylphenyl triflate,16 a popular benzyne
precursor, under similar procedures were unsuccessful, probably
due to sluggish oxidative addition.14 With an aim toprepare stable
aryne−Ni complexes, we exchanged the ligand of the aryl−
Ni(II)Br complex from PCy3 with a bulky bidentate ligand,
bis(dicyclohexylphosphino)ethane (DCPE).17 Thus, similar to
the reported procedure,4d treatment of 2a-PCy3 with DCPE
smoothly afforded the ligand-exchanged complex [NiBr(2-
BpinC6H4)dcpe] (2a-dcpe), which was treated with potassium
tert-butoxide to give the benzyne−Ni complex [Ni(η2-benzyne)-
dcpe] (3a-dcpe).4a,d
Figure 4. X-ray structure of 3b-dcpe. Displacement ellipsoids show 50%
probability levels; hydrogen atoms are omitted for clarity.
This simple three-step procedure made various aryne−Ni
complexes easily accessible (Figure 3).14 For example, the 2,3-
naphthalyne−Ni complex 3b-dcpe,4b 4-methylbenzyne−Ni
complex 3c-dcpe, and 4-methoxybenzyne−Ni complex 3d-
dcpe were prepared from the corresponding ortho-borylaryl
conjugated system of the naphthalene structure, because larger
differences are usually observed in monocyclic aryne−Ni(dcpe)
complexes such as 3a-dcpe,4a 3d-dcpe, and 3f-dcpe.14
The same procedure was unavailable for the synthesis of dcpe-
coordinated aryne−Ni complexes from 3-substituted ortho-
Figure 3. Preparation of various aryne−nickel complexes coordinated with dcpe (A) and PEt3 (B). a The reaction was performed at 0 °C. b The reaction
was performed for 6.5 h.
B
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Letter
borylaryl triflates 1, such as 1g−i, probably because oxidative
addition of bulky substrates to Ni(0) with PCy3 was very slow.
Fortunately, the oxidative addition of these bulky substrates
proceeded smoothly by using triethylphosphine (PEt3) instead of
PCy3 to give the corresponding adducts 2g−i-PEt3, which
expanded the scope of accessible aryne−Ni complexes, including
3g−i-PEt3 (Figure 3B). Furthermore, the 5,6-indolyne−Ni
complex 3j-PEt3 was prepared in a similar manner from 1j, of
which oxidative addition using PCy3 was sluggish. Because the
PEt3-coordinated aryne−Ni complexes 3-PEt3 could not be
transformed to DCPE-coordinated complexes and also they were
less stable than 3-dcpe, we handled them as a THF-d8 solution.
S5andS6).14 Unexpectedly, benzylbromide, whichusuallyserves
as a good electrophile, did not react with 3b-dcpe. Iodobenzene
was also an inert substrate for this reaction.
We found that methylation of the 4-methoxybenzyne−Ni
complex3d-dcpewithiodomethaneproceeded fasterthanforthe
4-trifluoromethylbenzyne−Ni complex 3f-dcpe (Figure S7).14
We also observed faster decomposition of 3d-dcpe in C6D6 than
14
1
3f-dcpe by H NMR analysis (Figures S10 and S11). These
results indicated that the electron-rich aryne-coordinated Ni
complex is more reactive than the electron-deficient complex, as
contrasted with uncomplexed aryne species.9d
The intermediary aryl−Ni(II) complexes formed from the
reaction of aryne−Ni complexes with an electrophile were
available for functionalizations other than protonation. For
example, treatment of crude allylated Ni complex 5, prepared
from the reaction of 3b-dcpe with neat allyl bromide followed by
removal of the remaining allyl bromide under reduced pressure,
with trimethylsilyl cyanide20 afforded 3-allyl-2-naphthonitrile (6)
in high yield (Scheme 2). This one-pot double functionalization
1
Their structures were determined based on H and 31P NMR
analyses, in which a single product, except PEt3, was observed,
indicating that the formation of aryne−Ni(PEt3)2 complexes
proceeded almost exclusively.14
With various aryne−Ni complexes in hand, we explored their
synthetic applicability. Previous reports indicated that aryne−
metal complexes have a nucleophilic character, unlike uncom-
plexed arynes, which have an electrophilic nature. For example,
the reaction of aryne−Ni complexes with electrophiles, such as
iodomethane, alkynes, and carbon dioxide, was shown to proceed
promptly.4,6 We revisited the reactivity of aryne−Ni complexes
withvarious electrophiles usingthe2,3-naphthalyne−Nicomplex
3b-dcpe (Table 1). Similar to the reported case for 3a-dcpe,4d
Scheme 2. Double Functionalization of Aryne−Ni Complexes
Table 1. Reactions of 3b-dcpe with Various Electrophiles
procedure was applicable toother substrates, such as the electron-
deficient 4-substituted aryne−Ni complexes 3e-dcpe and 3f-
dcpe, which afforded 7/7′ and 8/8′, respectively, without
significant regioselectivity. Similarly, the PEt3-bound 9,10-
phenanthryne−Ni complex 3i-PEt3, prepared in situ from 2i-
PEt3, also participated in this transformation to afford 10-
allylphenanthrene-9-carbonitrile (9). Interestingly, the reaction
of 3-methoxy substrate 3g-PEt3 afforded a regioisomeric mixture
of 10 and 10′ in a ratio of 49:51, which was in stark contrast to the
reactions of 3-methoxybenzyne with nucleophiles, where high
regioselectivity is usually observed.21
Furthermore, exchangingtheligandofanintermediaryaryl−Ni
complex from phosphine to a bipyridyl-type ligand, such as 1,10-
phenanthroline (Phen), dramatically altered the reactivity;22
treatment of the methylated product 11, prepared insitu from 3b-
PEt3 and methyl iodide, with Phen, followed by heating with
another electrophile, such as methyl 4-iodobutanoate, afforded
2,3-dialkylated naphthalene 12 (Scheme 3).
a
b
Isolated yields, unless otherwise noted. Yield determined by 1H
c
NMR analysis. The reaction was performed using 5 equiv of
iodomethane. Yields based on neat conditions are shown in
parentheses. The reaction was performed using 10 equiv of
electrophile in THF (0.2 M). CH2Cl2 was used as a solvent instead
d
e
f
of THF.
treatment of 3b-dcpe with excess amounts of iodomethane and
subsequent protonation with TFA afforded 2-methylnaphthalene
(4a) (entry 1). The reactions with allyl, 3,3-dimethylallyl, and
propargyl bromides also took place to afford the corresponding
alkylatedproducts4b−d(entries2−4).18 SinceNMRmonitoring
of the methylation and allylation reactions showed almost
quantitative formation of the corresponding alkylnaphthyl−Ni
complexes (Figures S2 and S3), the yield of the products must
have decreased during the protonation step (entries 1 and 2).
Reactions with acetyl chloride or bromide afforded 2-acetylnaph-
thalene (4e) in moderate yields (entries 5 and 6). We also found
that an α,β-unsaturated ester participated as an electrophile in the
reactionwith3b-dcpetoaffordtheformal1,4-adduct4f(entry7).
Although we have not succeeded in obtaining an X-ray structure
of the presumed intermediate, the heteronickelacycle,19 its in situ
formation was suggested by 1H and 31P NMR analyses (Figures
Scheme 3. Double Alkylation of 3b-PEt3
C
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Organic Letters
Letter
8348. (e) Bennett, M. A.; Kopp, M. R.; Wenger, E.; Willis, A. C. J.
Organomet. Chem. 2003, 667, 8.
(5) For the pioneering work regarding the preparation of benzyne−Ni
complex from 1,2-dibromobenzene, see: Dobson, J. E.; Miller, R. G.;
Wiggen, J. P. J. Am. Chem. Soc. 1971, 93, 554.
(6) (a) Deaton, K. R.; Gin, M. S. Org. Lett. 2003, 5, 2477. (b) Deaton, K.
R.; Strouse, C. S.; Gin, M. S. Synthesis 2004, 3084.
(7) Seebach, D. Angew. Chem., Int. Ed. Engl. 1979, 18, 239.
In summary, we have shown that ortho-borylaryl triflates serve
as aryne precursors, as well as precursors of aryne−Ni complexes.
Several exploratory studies have revealed the potential ability of
aryne−Ni complexes as synthetic intermediates, which would be
used differently compared with noncoordinated aryne species.
Further synthetic applications are currently underway in our
group.
(8) (a) Sumida, Y.; Kato, T.; Hosoya, T. Org. Lett. 2013, 15, 2806.
(b) Sumida, Y.; Harada, R.; Kato-Sumida, T.; Johmoto, K.; Uekusa, H.;
Hosoya, T. Org. Lett. 2014, 16, 6240.
ASSOCIATED CONTENT
* Supporting Information
■
S
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S.; Uchida, K.; Hosoya, T. Chem. Lett. 2014, 43, 116. (c) Yoshida, S.;
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(d) Yoshida, S.; Uchida, K.; Igawa, K.; Tomooka, K.; Hosoya, T. Chem.
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Chem. Commun. 2015, 51, 8745. (g) Yoshida, S.; Hazama, Y.; Sumida, Y.;
Yano, T.; Hosoya, T. Molecules 2015, 20, 10131. (h) Yoshida, S.;
Shimomori, K.; Nonaka, T.; Hosoya, T. Chem. Lett. 2015, 44, 1324.
(i) Yoshida, S.;Yano, T.;Misawa, Y.;Sugimura, Y.; Igawa, K.;Shimizu, S.;
Tomooka, K.;Hosoya, T.J.Am. Chem.Soc. 2015,137,14071. (j)Yoshida,
S.; Morita, T.; Hosoya, T. Chem. Lett. 2016, 45, 726. (k) Uchida, K.;
Yoshida, S.; Hosoya, T. Synthesis 2016, in press; doi: 10.1055/s-0035-
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M.; Matsushita, T.; Igawa, K.; Tomooka, K.; Hosoya, T. Chem. Commun.
2016, 52, 11199.
TheSupportingInformationisavailablefreeofchargeontheACS
Publications website at DOI: 10.1021/acs.orglett.6b02831.
Experimental procedures and characterization for new
compounds including copies of NMR spectra (PDF)
X-ray data for 2d-PCy3 (CCDC 1438693) (CIF)
X-ray data for 2e-PCy3 (CCDC 1438698) (CIF)
X-ray data for 2f-dcpe (CCDC 1438694) (CIF)
X-ray data for 3b-dcpe (CCDC 1438692) (CIF)
X-ray data for 3d-dcpe (CCDC 1438696) (CIF)
X-ray data for 3f-dcpe (CCDC 1438695) (CIF)
X-ray data for 2g-PEt3 (CCDC 1438690) (CIF)
AUTHOR INFORMATION
Corresponding Author
■
(10) For selected examples, see: (a) Hsieh, J.-C.; Rayabarapu, D. K.;
Cheng, C.-H. Chem. Commun. 2004, 532. (b) Yoshida, H.; Tanino, K.;
Ohshita, J.; Kunai, A. Angew. Chem., Int. Ed. 2004, 43, 5052. (c) Liu, Z.;
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*E-mail: takamitsu.hosoya@riken.jp.
Notes
The authors declare no competing financial interest.
(11) For catalytic generation of aryne−Pd complexes from ortho-
́
borylaryltriflates,see:García-Lopez, J.-A.;Greaney, M.F. Org.Lett. 2014,
ACKNOWLEDGMENTS
■
16, 2338.
The authors thank Central Glass Co., Ltd. for providing Tf2O,
Materials Characterization team, CEMS, RIKEN for Elemental
Analyses, and Dr. Takemichi Nakamura (Molecular Structure
Characterization Unit, CSRS, RIKEN) for HRMS analyses. This
research was supported by Japan Prize Foundation (Y.S.); the
Incentive Research Grant from RIKEN (Y.S.); and the Terumo
Life Science Foundation (Y.S.).
(12) Boebel, T. A.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 7534.
(13) For a related example of a cationic Pd(II) complex, see: Roy, A. H.;
Hartwig, J. F. Organometallics 2004, 23, 194.
(14) See Supporting Information for details.
(15) Rahman, O.; Kihlberg, T.; Langstrom, B. Eur. J. Org. Chem. 2004,
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474.
(16) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett. 1983, 12,
1211.
(17) An attempt to directly obtain 2a-dcpe via oxidative addition of 1a
by the treatment with Ni(cod)2, DCPE, and LiBr was unsuccessful.
(18) Generation of the 2-allyl-3-naphthyl−Ni complex was confirmed
by the deuteration experiment using TFA-d1 (99.5%D) which afforded
4b-d (98%D). See Supporting Information.
(19) For other conceivable structures, see Supporting Information.
(20) (a) Garcia, J. J.; Brunkan, N. M.; Jones, W. D. J. Am. Chem. Soc.
2002, 124, 9547. (b) Sundermeier, M.; Mutyala, S.; Zapf, A.;
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(22) It was reported that single electron transfer from an aryl−Ni
complex coordinated with a bipyridyl-type ligand to an alkyl halide
smoothly occurs to generate alkyl radical species. For examples, see:
(a) Biswas, S.; Weix, D. J. J. Am. Chem. Soc. 2013, 135, 16192.
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