[a]Reaction conditions: Arylhydrazine
hydrochloride (1.0 mmol),
PdCl2(PPh3)2 (2 mol %),
Na2CO3 (2 equiv.), CuI (5.0 mol %),
Acetonitrile (10 mL), 4 bar CO/O2 with ratio (3:1),[b] isolated yield.
Simple phenylhydrazine hydrochloride subjected to the oxidative
carbonylation reaction affords a 75% yield of the benzophenone
compound. A wide range of functional groups on phenyl hydrazine, such as
electron-donating and electron-withdrawing groups are compatible.
Generally, phenyl hydrazine with methyl substituents at o -,m -, and p -position to the phenyl ring underwent smooth
carbonylation to form corresponding symmetric biaryl ketone product
2b,2c,2d in moderate to good yield.
The phenyl rings bearing with di
and tri substituted methyl groups could also work well to produce the
corresponding desired products 2e and 2f .
Moreover, the electron-rich
arylhydrazine containing m -OMe, and p -OMe are effectively
worked, and the targeted biaryl ketone in yields of 61%, and 60%
(2g-2h ). The naphthalene-2-ylhydrazine hydrochloride, a poly
aromatic could undergo carbonylative self-coupling to form symmetric
polyaromatic ketone (2i ) in 55% yield. Further,
phenylhydrazine hydrochloride with electron-withdrawing substituents
such as ortho, meta, and para (F, Cl, Br) could be afforded to
corresponding biaryl ketones are 2j, 2k, 2l, 2m, 2n, and 2owith a yield of d 64%, 67%, 61%, 63%, 65%, 60%, respectively.
Notable, the carbonyl group-containing arylhydrazine moiety is also
compatible with this optimal reaction condition to give 2p in
52%, this methodology demonstrating that phenylhydrazine steric
hindrance has little effect on the efficacy of the reaction. However,
biologically active thiophen-3-ylhydrazine (2q ) also performed
well in the standard reaction condition, unfortunately, heteroaryl
hydrazine are not worked well under the optimized condition. After
evaluating the substrate scope for aryl hydrazine hydrochloride, we
conduct a series of control experiments to acquire some insight into the
reaction process. First, we accomplish the reaction in the absence of
oxygen giving only 5% iodobenzene instated of homo-coupled biaryl
ketone, and without CuI, no carbonylative homo-coupled product was
noted. Furthermore, the reaction was performed in the absence of CO, we
obtained selectively 92% yield of symmetric azobenzene. Notably, no
biaryl ketone product was observed when the reaction was performed in
the absence of base and Pd-catalyst. These results are shows that
PdCl2(PPh3)2, base, and
CuI in the presence of molecular oxygen are essential for the reaction,
as the lack of either fails to produce a homo-coupling biaryl ketone
product.
.
Scheme 3. Control Experiments
A plausible reaction mechanism for denitrogenative self-carbonylation of
aryl hydrazine hydrochloride is proposed according to the previous
related literature work and the above experiments (Scheme
5).[20] Initially, arylhydrazine hydrochloride1 is converted into the simple arylhydrazine by sodium
carbonate, and aryl palladium complex A is formed in situ
through oxidative C-N bond activation of arylhydrazine with Pd(II)
catalyst using Cu/O2.[21] Next,
the insertion of CO to species A to form acylpalladim complexB . Subsequently, acyl palladium complex B reacts again with
arylhydrazine 1 via C-N bond activation to generate complexC . Finally, reductive elimination of complex C to form
symmetric coupling biaryl ketone 2a , and regenerated Pd(0)
species reoxidize to Pd(II) for the next
cycle.[21a]
Scheme 4. Plausible Reaction Mechanism
Conclusions
In summary, we have developed the
first Palladium-catalyzed denitrogenative self-carbonylation of
arylhydrazine hydrochloride with Cu/O2 to afford
symmetric biaryl ketones via C-N bond activation. The reaction performed
well with PdCl2(PPh3)2as a catalyst with CO/O2 and
Na2CO3 as a base under mild reaction
conditions. In this protocol the arylhydrazines are employed as a green
arylating agent that released N2 and H2O
as a byproduct. Additionally, this protocol provides a series of
symmetric carbonylative ketones with a wide variety of functional group
tolerance under CO/O2 pressure.
Experimental
Materials and Methods:
All chemicals were procured from commercial providers and used without
any purification technique. The reaction was studied by thin-layer
chromatography (TLC) and GC-MS. The products were purified by column
chromatography using a PET ether/EtOAc system. The 1H
and 13C NMR spectroscopic data of purified products
were recorded on Agilent- 400 MHz (at 400, and 101 MHz respectively)
spectrometer, The residual solvent signals such as
(CHCl3) and (CDCl3) for1H and 13C NMR spectra. Coupling
constant (J) values were expressed in Hz.