Key words C–O activation - arylation - cross-coupling - secondary phosphine oxide - nickel
Transition-metal-catalyzed cross-coupling reactions have emerged as a uniquely powerful tool for the assembly of substituted biaryl motifs.[1 ] Thus far, these cross-couplings have heavily relied on aryl halides as electrophilic coupling reagents. In contrast, easily accessible phenol-based electrophiles have recently undergone a renaissance as attractive alternatives.[2 ] On the basis of Wenkert’s early studies from 1979,[3 ] the considerable potential of phenol-derived substrates has only recently been fully recognized. Thus, versatile cross-couplings have been realized with challenging carbamates, carbonates, sulfamates, silyloxyarenes, esters and ethers, among others, prominently featuring nickel catalysis.[4 ] Generally, these nickel catalysts largely require electron-rich tertiary phosphines as stabilizing ligands to guarantee efficacy in the key C–O bond scission.[4 ] Unfortunately, these electron-rich tertiary phosphines are usually highly air-sensitive, with a documented half-life for the aerobic oxidation of tri-t -butyl-phosphine of a few minutes.[5 ]
The (heteroatom-substituted) secondary phosphine oxides (HA)SPOs represent uniquely powerful ancillary preligands for metal catalysis because of their unique features, including the air- and moisture-stable nature, among others.[6 ] Notably, air-stable SPOs undergo a self-assembly process in the presence of transition metals to generate a monoanionic bidentate chelate coordination environment (Scheme [1, a ]).[6 ] While Ackermann and others have unraveled 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 sustainable transition-metal-catalyzed transformations[8 ] and selective C–O activation,[9 ] we hence became attracted to probing the unprecedented use of air-stable SPOs preligands 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 efficient C–O activations, (ii) earth-abundant nickel catalysis, and (iii) exceedingly mild reaction conditions at room temperature (Scheme [1, b ]).
Scheme 1 (a) Self-assembly with SPOs, (b) nickel/SPO-catalyzed C–O activation
We initiated our studies by probing reaction conditions for the envisioned cross-coupling of ether 1a with Ni(acac)2 and Ph2 P(O)H (L1 ) in toluene at a room temperature of 23 °C (Table [1 ], entry 1). Among a variety of preligands and solvents, the electron-rich HASPO L7 as well as (n -Bu)2 P(O)H (L8 ) and THF gave optimal results, respectively (entries 2–13). NiCl2 (DME) proved to be most effective (entries 14–17). It is noteworthy that under otherwise identical reaction conditions, the bidentate ligand dppp featured a significantly inferior performance (entry 18). A control experiment verified the essential role of the nickel catalyst (entry 19).
Table 1 Optimization of the Nickel/SPO-Catalyzed C–O Activation of Ether 1a
a
Entry
Ni Catalyst
SPO
Solvent
Yield (%)
1
Ni(acac)2
L1
toluene
10
2
Ni(acac)2
L2
toluene
12
3
Ni(acac)2
L3
toluene
25
4
Ni(acac)2
L4
toluene
35
5
Ni(acac)2
L5
toluene
23
6
Ni(acac)2
L6
toluene
50
7
Ni(acac)2
L6
THF
64
8
Ni(acac)2
L1
THF
15
9
Ni(acac)2
L5
THF
21
10
Ni(acac)2
L3
THF
60
11
Ni(acac)2
L4
THF
48
12
Ni(acac)2
L7
THF
69
13
Ni(acac)2
L8
THF
83
14
Ni(OTf)2
L8
THF
53
15
NiBr2
L8
THF
n.r.
16
NiCl2 (DME)
L8
THF
90
17
NiCl2 (DME)
L8
THF
68b
18
NiCl2 (DME)
dppp
THF
39c
19
–
L8
THF
n.r.
a Reaction conditions: 1a (0.50 mmol), p -TolMgBr (0.75 mmol), [Ni] (5.0 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%).
c dppp (5.0 mol%).
Having the optimized reaction conditions for the nickel/SPO-catalyzed C–O activation in hand, we tested its versatility with a representative set of ethers 1 (Scheme [2 ]). Thus, a variety of naphthyl ethers 1 were identified as viable substrates for the Kumada–Corriu cross-coupling to deliver the desired products 2 with high catalytic efficacy. Notably, 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 ).
Scheme 2 Scope of SPO/nickel-catalyzed C–O activation; a with NiCl2 (DME) (10 mol%) and L8 (20 mol%)
Based on our previous literature reports,[6c ]
[d ]
[10 ]
the working 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 activation by the key hetero-bimetallic intermediate 4 (Scheme [3 ]).
Scheme 3 Plausible working mode of SPOs for C–O activation
In summary, we have reported on the first use of air-stable secondary phosphine oxides (SPOs) for challenging cross-couplings of aryl ethers by C–O activation.[11 ] Thus, in situ generated nickel catalysts enabled efficient Kumada–Corriu arylations of naphthyl ethers at room temperature, even when using sterically hindered aryl nucleophiles.
