.
Angewandte
Communications
Hypervalent Iodine
Dual Hypervalent Iodine(III) Reagents and Photoredox Catalysis
Enable Decarboxylative Ynonylation under Mild Conditions**
Hanchu Huang, Guojin Zhang, and Yiyun Chen*
Abstract: A combination of hypervalent iodine(III) reagents
(HIR) and photoredox catalysis with visible light has enabled
chemoselective decarboxylative ynonylation to construct
ynones, ynamides, and ynoates. This ynonylation occurs
effectively under mild reaction conditions at room temperature
and on substrates with various sensitive and reactive functional
groups. The reaction represents the first HIR/photoredox dual
catalysis to form acyl radicals from a-ketoacids, followed by an
unprecedented acyl radical addition to HIR-bound alkynes. Its
efficient construction of an mGlu5 receptor inhibitor under
neutral aqueous conditions suggests future visible-light-
induced biological applications.
O
rganic carboxylates are readily available and stable, and
a removable carboxylate acts as a latent activating group for
organic synthesis.[1] Transition metals are widely used to
activate carboxylates through formation of a transition-metal/
carboxylate complex which facilitates extrusion of carbon
dioxide.[2] Hypervalent iodine(III) reagents (HIR) demon-
strate reactivity similar to transition metals, however, the
analogous reactivity of HIR–carboxylate complexes has been
less explored [Eq. (1)].[3] Our group recently discovered that
HIR activated vinyl carboxylates similar to transition metals,
which enabled radical addition followed by decarboxylation
[Eq. (2)].[4] a-Ketoacids are important acyl synthons in
organic synthesis; however, transition-metal-mediated decar-
boxylation requires activation by a transition metal followed
by heating or strong oxidants.[2,5] We speculate that by
forming the hypothetical HIR–ketoacid intermediate and
subsequent photoredox catalysis, the decarboxylative acyl
radical formation might be possible under mild reaction
conditions [Eq. (3)].[6]
molecules.[7] Although the transition-metal-catalyzed ynony-
lation by cross-coupling the acyl equivalent and the alkyne
equivalent has been reported, such an ynonylation approach
is limited and has poor functional-group tolerance because of
the instability of the acyl halides used [Eq. (4)].[8,9] By using
the readily available and stable a-ketoacids, we herein report
the first decarboxylative ynonylation to construct ynones,
ynamides, and ynoates by a HIR/photoredox dual catalysis
[Eq. (4)].
We started our investigation with benzoylformic acid (1)
by using the hypervalent iodine photoredox system[4,10] under
irradiation with blue light-emitting diodes (LEDs, lmax
=
Ynones, ynamides, and ynoates are important structural
motifs for the syntheses of natural products and heterocyclic
468 Æ 25 nm). Although terminal alkynes gave no ynonylation
adducts, alkynyl bromides and alkynyl sulfones with acetoxy-
benziodoxole (BI-OAc) as additives gave the desired ynone
3 in low yields (Table 1, entries 1–3). To our delight, an
alkynyl benziodoxole (BI-alkyne) gave ynone 3 in 81% yield.
BI-alkyne was known as an electrophilic alkyne acceptor, but
its tendency for acyl radical addition was unprecedented
(entries 4).[10–12] Cyclic HIR reagents[13] including BI-OAc,
hydroxybenziodoxole (BI-OH), and methoxybenziodoxole
(BI-OMe) were all effective, among which BI-OAc was the
most efficient with a yield of 85% (77% yield of isolated
product; entries 5–7). Photosensitizer, light, and BI-OAc
were all critical for this reaction (see Table S3 in the
Supporting Information).[14]
[*] H. Huang,[+] G. Zhang,[+] Prof. Dr. Y. Chen
State Key Laboratory of Bioorganic and Natural Products Chemistry
Collaborative Innovation Center of Chemistry for Life Sciences
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
345 Lingling Road, Shanghai 200032 (China)
E-mail: yiyunchen@sioc.ac.cn
[+] These authors contributed equally to this work.
[**] Financial support was provided by the National Basic Research
Program of China 2014CB910304, National Natural Science
Foundation of China 21272260, 21472230, “Thousand Talents
Program” Young Investigator Award, and start up fund from State
Key Laboratory of Bioorganic and Natural Products Chemistry, and
Chinese Academy of Sciences.
We evaluated the substrate scope of the reaction under
the optimized reaction conditions (Table 1, entry 5). Ben-
zoylformic acids bearing an electron-rich 4-methyl or 4-
methoxyl group yielded ynones 4 and 5 smoothly, and
Supporting information for this article is available on the WWW
7872
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 7872 –7876