Air-Stable Secondary Phosphine Oxides for Nickel-Catalyzed Cross-Couplings of Aryl Ethers by C-O Activation

Article abstract of DOI:10.1055/s-0037-1611663

Air- and moisture-stable secondary phosphine oxides (SPOs) enabled nickel-catalyzed Kumada-Corriu cross-couplings of various arylmethyl ethers at room temperature by challenging C-O activation.

Full text of DOI:10.1055/s-0037-1611663

SYNLETT
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Georg Thieme Verlag Stuttgart · New York
2019, 30, A–D
letter
A
en
Synlett
D. Ghorai et al.
Letter
Air-Stable Secondary Phosphine Oxides for Nickel-Catalyzed
Cross-Couplings of Aryl Ethers by C–O Activation
Debasish Ghoraia,b
Joachim Loupa
Giuseppe Zanonib
Lutz Ackermann*a
n-Bu
O
P
MgBr
Ar'
n-Bu
H
Ar'
OMe
Ar
Ni
Ar
0
0
0
0-0
0
0
1-7
0
3
4-
8
7
7
2
a
Earth-abundant nickel catalysis
efficient C–O activation
air- and moisture-stable SPO
room temperature
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität,
Tammannstraße 2, 37077 Göttingen, Germany
Lutz.Ackermann@chemie.uni-goettingen.de
Department of Chemistry, University of Pavia, Viale Taramelli 10, 27100 Pavia,
Italy
b
Published as part of the 30 Years SYNLETT – Pearl Anniversary Issue
6
Received: 02.12.2018
ers. Notably, air-stable SPOs undergo a self-assembly pro-
cess in the presence of transition metals to generate a
Accepted after revision: 06.01.2019
Published online: 15.01.2019
DOI: 10.1055/s-0037-1611663; Art ID: st-2018-b0782-l
monoanionic bidentate chelate coordination environment
6
(Scheme 1, a). While Ackermann and others have unrav-
License terms:
eled the considerable potential of SPO complexes towards a
wealth of efficient cross-coupling reactions with various
aryl halides,7 the possibility of employing air-stable SPO
preligands for more challenging C–O activations with aryl
ethers has thus far proven elusive. Within our program on
Abstract Air- and moisture-stable secondary phosphine oxides (SPOs)
enabled nickel-catalyzed Kumada–Corriu cross-couplings of various
arylmethyl ethers at room temperature by challenging C–O activation.
Key words C–O activation, arylation, cross-coupling, secondary phos-
phine oxide, nickel
8
sustainable transition-metal-catalyzed transformations
9
and selective C–O activation, we hence became attracted
to probing the unprecedented use of air-stable SPOs preli-
gands for cross-couplings with easily available aryl ethers,
the result of which we report herein. Notable features of
our findings include (i) air- and moisture-stable SPOs for ef-
ficient C–O activations, (ii) earth-abundant nickel catalysis,
and (iii) exceedingly mild reaction conditions at room tem-
perature (Scheme 1, b).
Transition-metal-catalyzed cross-coupling reactions
have emerged as a uniquely powerful tool for the assembly
of substituted biaryl motifs. Thus far, these cross-couplings
1
have heavily relied on aryl halides as electrophilic coupling
reagents. In contrast, easily accessible phenol-based elec-
trophiles have recently undergone a renaissance as attrac-
2
tive alternatives. On the basis of Wenkert’s early studies
3
(a)
from 1979, the considerable potential of phenol-derived
H
O
H
R
R
R
OH
O
O
TM
substrates has only recently been fully recognized. Thus,
versatile cross-couplings have been realized with challeng-
ing carbamates, carbonates, sulfamates, silyloxyarenes, es-
ters and ethers, among others, prominently featuring nickel
P
P
R2P
PR2
R
TM
(b)
n-Bu
n-Bu
O
H
cat.
P
4
catalysis. Generally, these nickel catalysts largely require
MgBr
cat. [NiCl2(DME)]
electron-rich tertiary phosphines as stabilizing ligands to
Ar'
OMe
4
guarantee efficacy in the key C–O bond scission. Unfortu-
Ar
Ar'
Ni
Ar
nately, these electron-rich tertiary phosphines are usually
highly air-sensitive, with a documented half-life for the aer-
obic oxidation of tri-t-butyl-phosphine of a few minutes.5
The (heteroatom-substituted) secondary phosphine ox-
ides (HA)SPOs represent uniquely powerful ancillary preli-
gands for metal catalysis because of their unique features,
including the air- and moisture-stable nature, among oth-
23 °C
C–O activation
Earth-abundant nickel catalysis
air- and moisture-stable SPO
room temperature
Scheme 1 (a) Self-assembly with SPOs, (b) nickel/SPO-catalyzed C–O
activation
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–D

B
Synlett
D. Ghorai et al.
Letter
We initiated our studies by probing reaction conditions
Entry
Ni Catalyst
SPO
Solvent
Yield (%)
for the envisioned cross-coupling of ether 1a with Ni(acac)2
1
1
1
6
7
8
NiCl
2
(DME)
(DME)
(DME)
L8
L8
THF
THF
THF
THF
90
and Ph P(O)H (L1) in toluene at a room temperature of
2
NiCl
NiCl
–
2
2
68b
39c
n.r.
23 °C (Table 1, entry 1). Among a variety of preligands and
dppp
L8
solvents, the electron-rich HASPO L7 as well as (n-
Bu) P(O)H (L8) and THF gave optimal results, respectively
19
2
(
entries 2–13). NiCl (DME) proved to be most effective (en-
a
2
Reaction conditions: 1a (0.50 mmol), p-TolMgBr (0.75 mmol), [Ni] (5.0
tries 14–17). It is noteworthy that under otherwise identi-
cal reaction conditions, the bidentate ligand dppp featured
a significantly inferior performance (entry 18). A control
experiment verified the essential role of the nickel catalyst
mol%), (HA)SPO (10 mol%), solvent (1.5 mL), 23 °C, 16 h; yield of isolated
product given; n.r. = no reaction.
b
SPO L8 (5.0 mol%).
dppp (5.0 mol%).
c
(entry 19).
Having the optimized reaction conditions for the nick-
el/SPO-catalyzed C–O activation in hand, we tested its ver-
satility with a representative set of ethers 1 (Scheme 2).
Thus, a variety of naphthyl ethers 1 were identified as via-
ble substrates for the Kumada–Corriu cross-coupling to de-
liver the desired products 2 with high catalytic efficacy. No-
tably, the nickel catalyst derived from the air-stable SPO L8
even proved amenable to the chemoselective synthesis of
biaryl 2b and the sterically congested mesityl nucleophiles
with comparable levels of activity (2d and 2i).
Table 1 Optimization of the Nickel/SPO-Catalyzed C–O Activation of
Ether 1a
a
Me
OMe p-tolyl-MgBr (1.5 equiv)
[Ni] (5.0 mol%)
(
HA)SPO (10.0 mol%)
solvent (1.5 mL)
23 °C, 16 h
2a
1a
O
H
O
H
O
H
P
P
P
t-Bu t-Bu
Ar'MgBr
NiCl2(DME)] (5.0 mol%)
Ar'
[
OMe
L1
L2
L3
L8 (10.0 mol%)
Ar
1
Ar
THF, 23 °C, 16 h
O
H
O
N
H
P
2
O
H
P
t-Bu
i-Pr
t-Bu
P
N
Me
OMe
n-Hex n-Hex
L4
L5
L6
i-Pr
O
H
P
2a: 90%
2b: 71%
2c: 59%
N
N
O
H
P
Me
n-Bu n-Bu
i-Pr
i-Pr
L7
L8
Me
Me
Entry
Ni Catalyst
SPO
Solvent
Yield (%)
1
2
3
4
5
6
7
8
9
Ni(acac)
Ni(acac)
Ni(acac)
Ni(acac)
Ni(acac)
Ni(acac)
Ni(acac)
Ni(acac)
Ni(acac)
Ni(acac)
Ni(acac)
Ni(acac)
Ni(acac)
2
2
2
2
2
2
2
2
2
2
2
2
2
L1
L2
L3
L4
L5
L6
L6
L1
L5
L3
L4
L7
L8
L8
L8
toluene
toluene
toluene
toluene
toluene
toluene
THF
10
12
25
35
23
50
64
15
21
60
48
69
83
53
n.r.
Me
2
d: 86%
2
e: 77%
2f: 53%
Me
Me
Me
2h: 61%a
2g: 58%
THF
Me
Me
THF
Me
10
11
12
13
14
15
THF
Me
THF
Me
N
R
THF
Me
Me
THF
R = H, Me
2j: traces
2
i: 54%a
Ni(OTf)
NiBr
2
THF
Scheme 2 Scope of SPO/nickel-catalyzed C–O activation; a with
NiCl (DME) (10 mol%) and L8 (20 mol%)
2
THF
2
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–D

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D. Ghorai et al.
Letter
Based on our previous literature reports,6c–d,10 the work-
ing mode of the air-stable SPO-enabled C–O activation is
suggested to initially involve the formation of complex 3
through self-assembly, along with the subsequent C–O acti-
vation by the key hetero-bimetallic intermediate 4 (Scheme 3).
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O
H
n-Bu
n-Bu
OH
P
P
n-Bu
n-Bu
+
+
[Ni]
H+
(n-Bu)2P(O)H
Br
H
Mg
O
n-Bu
P
n-Bu
O
O
O
n-Bu
n-Bu
ArMgBr
– RH
n-Bu
n-Bu
n-Bu
n-Bu
P
P
P
(
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Scheme 3 Plausible working mode of SPOs for C–O activation
(
(
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In summary, we have reported on the first use of air-
stable secondary phosphine oxides (SPOs) for challenging
11
cross-couplings of aryl ethers by C–O activation. Thus, in
situ generated nickel catalysts enabled efficient Kumada–
Corriu arylations of naphthyl ethers at room temperature,
even when using sterically hindered aryl nucleophiles.
2004, 43, 5883.
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Generous support by the European Research Council under the Euro-
pean Community’s Seventh Framework Program (FP7 2007-
2
–
013)/ERC Grant agreement no. 307535, and the Regione Lombardia
Cariplo Foundation is gratefully acknowledged.()
(f) Ackermann, L.; Kapdi, A. R.; Fenner, S.; Kornhaass, C.;
Schulzke, C. Chem. Eur. J. 2011, 17, 2965. (g) Ackermann, L.;
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Supporting Information
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Supporting information for this article is available online at
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https://doi.org/10.1055/s-0037-1611663.
S
u
p
p
orti
n
g Inform ati
o
n
S
u
p
p
orit
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g Inform ati
o
n
(j) Christiansen, A.; Selent, D.; Spannenberg, A.; Baumann, W.;
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Chem. 2010, 2733. (l) Ackermann, L.; Barfüßer, S. Synlett 2009,
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Metals for Organic Synthesis; Wiley-VCH: Weinheim, 2004.
(o) Ackermann, L.; Born, R.; Spatz, J. H.; Meyer, D. Angew. Chem.
Int. Ed. 2005, 44, 7216.
(e) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
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8) (a) Gandeepan, P.; Müller, T.; Zell, D.; Cera, G.; Warratz, S.;
Ackermann, L. Chem. Rev. 2019, in press; doi: 10
(2) Kozhushkov, S. I.; Potukuchi, H. K.; Ackermann, L. Catal. Sci.
Technol. 2013, 3, 562.
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Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–D

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11) Representative Experimental Procedure and Characteriza-
tion Data
The combined organic layers were dried with anhydrous Na SO4
2
(
and concentrated in vacuo. The remaining residue was purified
by column chromatography on silica gel (n-hexane) to yield 2a
(98 mg, 90%) as a colorless solid. Mp 93–95 °C. IR (ATR): 3054,
(
(
−1 1
3024, 1501, 1351, 893, 856, 811, 748 cm . H NMR (300 MHz,
CDCl ):  = 8.14 (d, J = 1.4 Hz, 1 H), 8.03–7.93 (m, 3 H), 7.85 (dd,
3
A mixture of 2-methoxynaphthalene (1a) (79 mg, 0.5 mmol),
J = 8.5, 1.9 Hz, 1 H), 7.74 (d, J = 8.1 Hz, 2 H), 7.64–7.54 (m, 2 H),
13
[
NiCl (DME)] (6.0 mg, 0.025 mmol, 5.0 mol%), and L8 (8.0 mg,
7.40 (dd, J = 8.5, 0.6 Hz, 2 H), 2.53 (s, 3 H). C NMR (75 MHz,
CDCl ):  = 138.5 (C ), 138.3 (C ), 137.2 (C ), 133.8 (C ), 132.5
2
0.05 mmol, 10.0 mol%) was stirred in THF (1.5 mL) for 2 min at
3
q
q
q
q
ambient temperature under N . Then, p-TolMgBr (1.0 M in THF,
(C ), 129.6 (CH), 128.4 (CH), 128.2 (CH), 127.7 (CH), 127.3 (CH),
2
q
0
.75 mL, 0.75 mmol) was added, and the resulting solution was
126.3 (CH), 125.8 (CH), 125.6 (CH), 125.5 (CH), 21.2 (CH ). MS
3
+
stirred for 16 h at ambient temperature. To the reaction was
added aqueous HCl (1 M, 5 mL) and then EtOAc (5 mL), and the
separated aqueous phase was extracted with EtOAc (2 × 5 mL).
(EI): m/z (relative intensity) = 218 [M] (100), 217 (41), 202 (35).
+
+
HRMS (EI): m/z [M] calcd for [C17H14] : 218.1096; found:
218.1094.
Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–D