M. Bouquin, F. Jaroschik and M. Taillefer
Tetrahedron Letters 75 (2021) 153208
Table 3
Copper catalyzed
a-arylation of several aryl silyl enol ethers 1a–j and diphenyliodo-
nium triflate 2a.ab
Scheme 2. Mechanism proposal.
precursor 1j, we obtained, after work-up, the corresponding depro-
tected -arylated product 3ja in low yield without arylation of the
a
nucleophilic functional group. Note that the reaction also proved to
be suitable for scale-up experimentation (2.5 mmol), delivering the
product 3aa in excellent yield (Table 3).
Concerning the mechanism of the reaction, at this stage, we
believe that a radical-type reaction is unlikely due to the good tol-
erance towards halogen substrates, including iodide. In accordance
with previous reports in the literature [14], a plausible intermedi-
ate for this system involves a Cu(III) species A resulting from the
oxidative addition of Cu(I) into the Ar-I bond of the diaryliodonium
salt (Scheme 2). This key intermediate A could then react with silyl
enol ether to give the mixed copper(III)arylalkyl complex B. The
latter would undergo a reductive elimination to regenerate the
aReaction conditions: aryl silyl enol ether (0.625 mmol), diphenyliodonium triflate
2a (0.25 mmol), Cu(OAc)2 (0.00125 mmol), DCE (0.5 mL) at 70 °C during 0.5 h.
bIsolated yield. cReaction performed with 2.5 mmol scale. dReaction performed with
0.375 mmol of aryl silyl enol ether.
Cu(I) catalytic species and to yield the expected a-arylated ketone
after the removal of the silyl group with the triflate anion.
3ae in good yield. We continued the aryl scope with mesity-
laryliodonium salts 2f–k. It is noteworthy that m- or o-methyl sub-
stituted mesitylaryliodonium salts 2f–2g were compatible,
affording 3af–3ag in good and low yields, respectively, probably
due to steric hindrance. Mesitylaryliodonium salts bearing an elec-
tron withdrawing (EWG) group, such as trifluoromethyl 2h, ethyl
ester 2i or ketone 2j were applied forming 3ah–3aj in moderate
to good yields. A biphenyl group on mesitylaryliodonium 2k was
suitable and gave 3ak in good yield. However, bulky aryls (mesityl
and 1-napthyl) or pyridyl groups on the mesitylaryliodonium salts
were not tolerated in our conditions (see Supporting Information).
Conclusion
In summary, we have reported an efficient copper-catalyzed a-
arylation of aromatic ketones under their silyl enol ether form
using symmetrical diaryliodonium or mesitylaryliodonium salts
as aryl source. This ligand and base-free process showed good tol-
erance toward sensitive functional groups such as triflate or iodine.
Work is in progress to broaden further the scope of this catalytic
system and to study the mechanism.
The scope of this
a-arylation procedure was further explored
with several functionalized aryl silyl enol ethers 1a–j and
diphenyliodonium triflate 2a as aryl source (see Table 3). Halogens
on silyl ether enol 1b–1e, notably iodine, were well tolerated and
gave the corresponding products 3ba–3ea in good yields. In the
same way, the silyl enol ether with a triflate group 1f was success-
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
fully engaged in this
ing product 3fa without any degradation. To the best of our
knowledge, this is the first reported -arylation process tolerating
a-arylation process, affording the correspond-
a
Acknowledgments
the triflate group as a functional group on the ketone. Electron
withdrawing groups on silyl enol ether such as the nitro-substi-
tuted 1g induced a slight drop of the yield and gave 3ga in 66%
yield. However, electron donating groups, such as the p-methoxy
substituted substrate 1h, showed limited reactivity and afforded
product 3ha in moderate yield. Heteroaromatic silyl enol ether
1i, bearing a thienyl group was employed and allowed the forma-
tion of 3ia in good yield. Pyridyl groups were again not suitable
(see Supporting Information). We then tried a temporary protect-
ing strategy in order to assess the tolerance with nucleophilic func-
tional groups such as a hydroxyl one. From the OTMS protected
Financial support was provided by the Institut de France,
Académie des Sciences (PhD fellowship for MB) and the Ecole
Nationale Supérieure de Chimie de Montpellier (ENSCM). They
are greatly acknowledged.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
3