Ipso- borylation of aryl ethers via Ni-Catalyzed C-OMe Cleavage

Article abstract of DOI:10.1021/jacs.5b03955

A Ni-catalyzed ipso-borylation of aryl ethers via C(sp²)-OMe and C(sp³)-OMe cleavage is described. The transformation is characterized by its wide substrate scope under mild conditions and an exquisite divergence in site selectivity that can be easily switched by selecting the appropriate boron reagent.

Full text of DOI:10.1021/jacs.5b03955

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Communication
Ipso-Borylation of Aryl Ethers via Ni-catalyzed C–OMe Cleavage
Cayetana Zárate, Ruben Manzano, and Ruben Martin
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 15 May 2015
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Ipso-Borylation of Aryl Ethers via Ni-catalyzed C–OMe Cleavage
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†
†
†§
Cayetana Zarate, Rubén Manzano and Ruben Martin*
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†
Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007, Tarragona, Spain
§
Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluïs Companys, 23, 08010, Barcelona, Spain
Supporting Information Placeholder
9
,10
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2
, path a),
or CꢀH activation (path b). From a synꢀ
ABSTRACT: A Niꢀcatalyzed ipso-borylation of aryl
2
3
ethers via C(sp )– & C(sp )–OMe cleavage is described.
The transformation is characterized by its wide substrate
scope under mild conditions and an exquisite divergence
in siteꢀselectivity that can be easily switched by an apꢀ
propriate selection of the boron reagent.
thetic standpoint, the ability to promote a complemenꢀ
tary ipsoꢀborylation of aryl methyl ethers would be highꢀ
ly rewarding, offering a counterintuitive, yet practical,
new retrosynthetic approach to organoborane reagents
from simple precursors. At the outset of our investigaꢀ
tions, it was unclear whether such scenario would be
feasible given the exceptional inertness of C–OMe
bonds, the natural proclivity of aryl ethers to promote
functionalization at orthoꢀ or para-positions and the
virtual lack of precedents for C–heteroatom bondꢀ
formation via C–OMe cleavage. If successful, such a
11
2
12
In recent years, C–O electrophiles have emerged as
powerful alternatives to aryl halides as coupling partners
1,2
3
in the crossꢀcoupling arena. While the utilization of
activated aryl esters, carbamates or sulfonates has beꢀ
come routine, it comes as a surprise that aryl methyl
ethers, the simplest derivatives in the phenol series, have
strategy would not only open up new vistas in C–B
bondꢀformation but also might represent a significant
stepꢀforward for implementing aryl methyl ethers as2
privileged counterparts in crossꢀcoupling endeavours.
2
received much less attention. This is likely due to the
13
high activation energy required for C–OMe scission and
the low propensity of methoxy residues to act as leaving
groups. Not surprisingly, these reactions remain essenꢀ
tially confined to C–C bondꢀformations using highly
reactive, wellꢀdefined, stoichiometric and, in many casꢀ
es, airꢀsensitive organometallic reagents (Scheme 1, path
As part of our interest in C–O bondꢀfunctionalization,
we describe herein the first catalytic ipsoꢀborylation of
2
3
aryl methyl ethers via C(sp )– and even C(sp )–O cleavꢀ
age, thus exploiting a previously unrecognized opporꢀ
1
4,15
tunity in this field.
This protocol is characterized by
its wide scope under mild conditions and by an exquisite
divergence in siteꢀselectivity that can be modulated by a
judicious choice of the corresponding boron reagent.
2
a). Intriguingly, a C–heteroatom bondꢀformation has
3
been virtually unexplored (path b), thus constituting a
unique opportunity to implement unconventional strateꢀ
gies not apparent at first sight in our chemical portfolio.
Scheme 2. Borylation Events of Aryl Methyl Ethers.
2
Scheme 1. Catalytic C(sp )-OMe Bond-Cleavage
.
The pivotal role of organoboron reagents as synthetic
intermediates has attracted the attention of both industriꢀ
4
al and academic laboratories for decades. Not surprisꢀ
We began our investigations by evaluating the reaction
ingly, the recent years have witnessed the development
of 1a with B (nep) (2a). After extensive experimentaꢀ
5
ꢀ8
2
2
of a myriad of catalytic methods for their synthesis. At
present, the inclusion of aryl methyl ethers has merely
been employed as a control element for promoting C–B
bondꢀforming reactions at either ortho-, meta- or para-
position via orthoꢀmetalation or the intermediacy of aryl
halides via electrophilic aromatic substitution (Scheme
16
tion, we found that a cocktail containing Ni(COD)2,
PCy and HCO Na promoted the targeted reaction at 95
3
2
ºC, affording 3a in 80% isolated yield. Although
HCO Na has commonly been employed as reducing
2
17
agent in crossꢀcoupling reactions, marginal formation
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of naphthalene was detected in the crude mixtures
<9%). Interestingly, the utilization of other bases proꢀ
vided inferior results (entries 11 and 12). As anticipatꢀ
ed, the nature of the ligand employed had a profound
influence on the reaction outcome (entries 5ꢀ7). Strikingꢀ
(3g) and amines (3i) could all be equally accommodated.
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(
Importantly, the presence of nitrogenꢀcontaining heteroꢀ
cycles did not interfere with productive C−B bondꢀ
formation (3d and 3h). As shown for 3j, the reaction was
not hampered by the presence of orthoꢀsubstituents. It is
worth noting that no racemization of the chiral center in
3k was observed when exposing enantioenriched 1k
(96% ee) under our optimized reaction conditions. Intriꢀ
guingly, the inclusion of CsF and B pin (2b) cleanly
18
ly, the inclusion of otherwise related PCy Ph had a deleꢀ
2
terious effect on reactivity, thus showing the subtleties of
our protocol (entry 5). Similarly, N-heterocyclic carꢀ
19
benes provided 3a in lower yields (entries 6 and 7).
2
2
3
21ꢀ23
Notably, a difference in reactivity was found when operꢀ
ating under a NiCl (PCy ) , Ni(PCy ) (C H ) or
afforded 3l and 3m via C(sp )–OMe cleavage.
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3 2
3 2
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Likewise, benzyl methyl ethers posessing βꢀhydrogens
24,25
[
Ni(PCy ) ] N regime (entries 8ꢀ10). Although tentaꢀ
posed no problems, obtaining 3n in 81% yield.
3
2 2
2
tive, we believe that COD might be acting as a nonꢀ
innocent ancillary ligand to stabilize the putative
Table 2. Ipso-Borylation of Naphthyl Methyl Ethers
Ni(PCy ) species and prevent decomposition pathꢀ
3 2
2
0
ways. The lack of reactivity of B (pin) (2b; entry 13)
2
2
is noteworthy, suggesting an intimate interplay between
steric effects and productive C–B bondꢀformation. In
line with this notion, ethoxy, isopropoxy or benzyloxy
16
groups gave lower conversions to 3a. As anticipated,
control experiments revealed that all reaction parameters
16
were critical for success (entries 2ꢀ4).
a
Table 1. Optimization of the Reaction Conditions.
a
b
As for Table 1 (entry 1) using 2a. Isolated yields, averꢀ
c
d
age of at least two independent runs. 120 ºC. As for
Table 1 (entry 1), but employing 2b (1.00 mmol) and CsF
d
(
1.50 mmol) at 120 ºC. Determined by GC (decane as
internal standard). Bnep: 5,5ꢀdimethylꢀ1,3,2ꢀdioxaborolane;
Bpin: 4,4,5,5ꢀtetramethylꢀ1,3,2ꢀdioxaborolane.
a
Conditions: 1a (0.50 mmol), 2a (1.00 mmol), Ni(COD)2
(
10 mol%), PCy (20 mol %), HCO Na (1.50 mmol) in
A close inspection into the literature data indicates that
regular arenes are several orders of magnitude less reacꢀ
3
2
b
PhMe (2.0 mL) at 95 ºC, 15 h. GC yields using decane as
internal standard. Isolated yield. +NaOtBu (25 mol%).
c
d
tive than non πꢀextended systems in C–O bondꢀcleavage
26,27
protocols.
At present, such lack of reactivity has
With a reliable procedure in hand, we next turned our
attention to explore the preparative scope of our catalytic
been overcome primarily by employing stoichiometric
1,2
2
and highly reactive organometallic species, thus repreꢀ
ipsoꢀborylation technique via C(sp )–OMe bondꢀ
senting a drawback from a practical and synthetic point
of view. In light of these precedents, we wondered
whether our Niꢀcatalyzed ipsoꢀborylation event could be
applied to more challenging aryl methyl ethers. Altꢀ
hough such scenario proved to be difficult, we speculatꢀ
ed that the presence of suitable orthoꢀsubstituents might
facilitate the elusive C–OMe bondꢀcleavage in anisole
cleavage (Table 2). As shown, a wide variety of naphthyl
ethers possessing a diverse set of substitution patterns
could perfectly be tolerated, obtaining in all cases good
yields of 3a-3k. The chemoselectivity profile of our
method was nicely illustrated by the fact that silyl
groups (3b), silyl ethers (3e), esters (3f and 3k), ketones
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a,b
derivatives. As shown in Table 3, this was indeed the
case for a variety of aryl methyl ethers possessing ortho-
esters (5a-5c), trifluoromethyl groups (5d) or amides
Figure 1. Orthogonal Borylation via C–OMe Cleavage.
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(5e).
Importantly, the presence of such groups in
para or meta position gave negligible conversion to
products, thus providing compelling evidence that elecꢀ
30
tronic effects are not the only factor coming into play.
In contrast to the results of Table 1 (entry 13), we found
that B (pin) (2b) could be utilized for effecting the
2
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2
31
C(sp )–OMe bondꢀcleavage (5b, 5e). As for Table 2,
we found that a C(sp )–OMe bondꢀcleavage was within
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reach (5f and 5g).
a,b
Table 3. Ipso-Borylation of Aryl Methyl Ethers
.
a
3
C(sp )–OMe cleavage: 6a or 6b (0.50 mmol), 2b (1.00
mmol), Ni(COD) (10 mol%), PCy (20 mol%), CsF (1.50
2
3
b
2
mmol) in PhMe (2.0 mL) at 120 ºC. C(sp )–OMe cleavꢀ
age: as for Table 1 (entry 1), followed by NaI (1.50 mmol)
and chloramine T·3H O (1.50 mmol) in 4mL THF/H O
2
2
c
d
(
1:1) at rt. Borylation conducted at 120 ºC. Borylation
conducted with HCO Na (0.15 mmol)
2
In summary, we have developed the first ipso-borylation
of aryl methyl ethers via Niꢀcatalyzed C–OMe bondꢀ
cleavage, complementing classical ortho-, meta- and
para-borylation techniques. This protocol is distinꢀ
guished by its broad substrate scope and by an intriguing
selectivity switch depending on the boron reagent emꢀ
ployed. Further investigations into related projects will
be reported in due course.
a
b
As for Table 1 (entry 1). Isolated yields, average of at
c
d
least two independent runs. Using 2b (1.0 mmol).
HCO Na (0.50 mmol) GC yield using decane as internal
standard. CsF (1.00 mmol) at 120 ºC.
e
2
f
ASSOCIATED CONTENT
Supporting Information. Experimental procedures and
spectral data. This material is available free of charge via
the Internet at http://pubs.acs.org
On the basis of the results of Tables 1ꢀ3, we concluded
that the nature of the boron reagent might not be entirely
innocent in the reaction outcome. Challenged by such
perception, we speculated that an orthogonal site-
selective C–B bond-formation via C–OMe bondꢀ
cleavage could be achieved. To such end, we examined
the reactivity of 6a and 6b under a 2a or 2b regime
.
AUTHOR INFORMATION
Corresponding Author
* rmartinromo@iciq.es
(
Figure 1). Interestingly, while the utilization of 2b lead
Funding Sources
3
exclusively to 7a and 7b via C(sp )–OMe cleavage, a
C(sp )–B bondꢀformation was invariably observed with
2
2
No competing financial interests have been declared.
32
a. At present, we have no explanation for such intriꢀ
ACKNOWLEDGMENT
guing dichotomy. Encouraged by these results, we wonꢀ
dered whether our Niꢀcatalyzed ipso-borylation could be
employed as a manifold to promote an unprecedented
We thank ICIQ, the European Research Council (ERCꢀ
277883), MINECO (CTQ2012ꢀ34054 & Severo Ochoa
Excellence Accreditation 2014ꢀ2018; SEVꢀ2013ꢀ0319) and
Cellex Foundation for support. Johnson Matthey, Umicore
and Nippon Chemical Industrial are acknowledged for a
gift of metal & ligand sources. C.Z. and R.M. thank
MINECO for a FPU and COFUND scholarship.
33
ipso-halogenation of aryl methyl ethers, thus compleꢀ
menting classical ortho- or para-electrophilic aromatic
34
halogenation techniques. As shown in Figure 1 (bot-
tom), this turned out to be the case and a oneꢀpot borylaꢀ
tion/iodination sequence allowed for rapidly obtaining
35
8
a and 8b in good overall yield. Taken together, the
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(
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2 2
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Chem. Soc., 2012, 134, 10693. (d) JoshiꢀPangu, A.; Ma, X.;
Diane, M.; Iqbal, S.; Kribs, R. J.; Huang, R.; Wang, C. –Y.;
Biscoe, M. R. J. Org. Chem. 2012, 77, 6629.
(25) Racemization occurred with enantioenriched 1n, an observaꢀ
tion that is tentatively attributed to bimolecularꢀtype mechaꢀ
nisms. For a related scenario, see: Yonova, I. M.; Johnson, A.
G.; Osborne, C. A.; Moore, C. E.; Morrissette, N. S.; Jarvo,
E. R. Angew. Chem. Int. Ed. 2014, 53, 2422.
(26) For selected C–O bondꢀcleavage procedures in which the
presence of πꢀextended systems was required: (a) Wisniewꢀ
ska, H. M.; Swift, E. C.; Jarvo, E. R. J. Am. Chem. Soc. 2013,
135, 9083. (b) Zhou, Q.; Srinivas, H. D.; Dasgupta, S.; Watꢀ
son, M. P. J. Am. Chem. Soc. 2013, 135, 3307. (c) Taylor, B.
L.; Harris, M. R.; Jarvo, E. R. Angew. Chem., Int. Ed. 2012,
51, 7790. (d) Yu, D.ꢀG.; Shi, Z.ꢀJ. Angew. Chem., Int. Ed.
2011, 50, 7097. (e) Yu, D. G.; Li, B. J.; Zheng, S. F.; Guan,
B. T.; Wang, B. Q.; Shi, Z. J. Angew. Chem. Int. Ed. 2010,
49, 4566. (f) Tobisu, M.; Shimasaki, T.; Chatani, N. Angew.
Chem., Int. Ed. 2008, 47, 4866, and citations therein.
(
(
2
41. (d) Muetterties, E. L. J. Am. Chem. Soc. 1960, 82, 4163.
(11) For selected catalytic borylation of particularly activated aryl
C–O electrophiles, see: (a) Kinuta, H.; Hasegawa, J.; Tobisu,
M.; Chatani, N. Chem. Lett. 2015, 44, 366 (pivalates). (b)
Huang, K.; Yu, D. –G.; Zheng, S. –F.; Wu, Z. –H.; Shi, Z. –J.
Chem. –Eur. J. 2011, 17, 786 (carbamates). (c) Chow, W. K.;
So, C. M.; Lau, C. P.; Kwong, F. Y. Chem. –Eur. J. 2011, 17,
6
913 (mesylates & tosylates). (d) Wilson, D. A.; Wilson, C.
J.; Moldoveanu, C.; Resmerita, A.ꢀM.; Corcoran, P.; Hoang,
L. M.; Rosen, B. M.; Percec, V. J. Am. Chem. Soc. 2010,
132, 1800 (mesylates & tosylates).
(12) Klumpp, G. W. Reactivity in Organic Chemistry; Wiley:
New York, 1982; pp 227ꢀ378.
(27) πꢀExtended systems are known to bind stronger than regular
(
13) (a) Zarate, C.; Martin, R. J. Am. Chem. Soc. 2014, 136, 2236.
b) Liu, Y.; Cornella, J.; Martin, R. J. Am. Chem. Soc. 2014,
36, 11212. (c) Moragas, T.; Cornella, J.; Martin, R. J. Am.
2
arenes low valent metal complexes in a η ꢀfashion, probably
(
1
due to the retention of a certain degree of aromaticity: Bauer,
D. J.; Krueher, C. Inorg. Chem. 1977, 16, 884. Alternatively,
πꢀextended systems might generate easier Meisenheimerꢀtype
complexes (ref. 23f) or scenarios dealing with the intermediꢀ
acy of dearomatized products (ref. 13f)
Chem. Soc. 2014, 136, 17702. (d) Correa, A.; Martin, R. J.
Am. Chem. Soc. 2014, 136, 7253. (e) Cornella, J.; Martin, R.
Org. Lett. 2013, 15, 6298. (f) Cornella, J.; GómezꢀBengoa,
E.; Martin, R. J. Am. Chem. Soc. 2013, 135, 1997. (g) Barꢀ
bero, N.; Martin, R. Org. Lett. 2012, 14, 796. (h) Álvarezꢀ
Bercedo, R.; Martin, R. J. Am. Chem. Soc. 2010, 132, 17352.
(
28) No C–B bondꢀformation was found when utilizing electronꢀ
donating dimethylamino groups in orthoꢀposition. For the
utilization of other anisole derivatives, see ref. 16.
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(29) In sharp contrast with the utilization of ortho tert-butyl esꢀ
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ters, we found that ortho methyl esters provided lower yields
(~25% GC yields), thus revealing an intimate interplay beꢀ
tween steric effects and C–B bondꢀformation.
(
30) No biaryl formation via SuzukiꢀMiyaura coupling of in situ
generated aryl boronates with aryl ethers was observed.
31) Intriguingly, while 5e was cleanly obtained with B pin , an
(
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otherwise related reaction with B (nep) did not result in proꢀ
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ductive C–B bondꢀformation.
(32) Unreacted starting material and marginal reduction of C–
OMe bond account for the mass balance.
(33) For halogenation of in situ generated aryl boronates, see for
example: (a) Shi, H.; Babinski, D. J.; Ritter, T. J. Am. Chem.
Soc. 2015, 137, 3775. (b) Murphy, J. M.; Liao, X.; Hartwig,
J. F. J. Am. Chem. Soc. 2007, 129, 15434.
34) Bew, S. P. In Comprehensive Organic Functional Group
Transformations II; Eds., Katritzky, A. R.; Taylor, R. J. K.
Elsevier, Oxford, 2005.
(35) The isolation of the corresponding aryl neopentyl boronates
was particularly cumbersome due to the instability of the boꢀ
ronic esters during purification by column chromatography.
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