DOI: 10.1002/chem.201406290
Communication
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CÀO Coupling |Hot Paper|
Selenium-Catalyzed C(sp3)ÀH Acyloxylation: Application in the
Expedient Synthesis of Isobenzofuranones
Felix Krꢀtzschmar, Martin Kaßel, Daniel Delony, and Alexander Breder*[a]
Dedicated to Professor Barry M. Trost
linear allylic acetates using molecular O2 as an oxidant. In addi-
Abstract: Oxidative Se-catalyzed C(sp3)ÀH bond acyloxyla-
tion to palladium complexes, other promoters, such as copper
salts[4c,8] or iodine compounds,[9] proved very efficient in the al-
tion has been used to construct a diverse array of isoben-
lylic acyloxylation of alkenes. Early reports on asymmetric var-
iants of such transformations date back to the work of Denney
and co-workers in 1965.[10] A conceptually cognate yet mecha-
nistically dissimilar, selenium-mediated protocol for the direct
insertion of oxygen substituents into allylic carbon-hydrogen
bonds is the Riley-Guillemonat oxidation.[11] Due to the mild re-
action conditions and the high functional group tolerance, this
selenium dioxide-based allylic hydroxylation has experienced
widespread application in the total synthesis of biologically
active natural products.[12] Although catalytic versions of this
reaction have been described,[11d] the corresponding direct acy-
loxylation has, to the best of our knowledge, remained elusive
until this day.
zofuranones from simple ortho-allyl benzoic acid deriva-
tives. The synthetic procedure employs mild reaction con-
ditions and gives high chemoselectivity enabled by an in-
expensive organodiselane catalyst. The presented ap-
proach offers a new synthetic pathway toward the core
structures of phthalide natural products.
The direct and controlled installation of oxygen and nitrogen
functionalities into hydrocarbon architectures constitutes
a powerful yet extraordinarily challenging strategy in contem-
porary synthetic chemistry.[1] Due to the omnipresence of
carbon–hydrogen bonds in organic molecules with low oxida-
tion states, the chemo- and regioselective functionalization of
a single CÀH entity is extremely difficult.[2] However, the dis-
criminative and forthright manipulation of a particular bond
class can significantly streamline the overall synthetic scheme
of a given target molecule.[2] Consequently, the continuous de-
velopment of new reaction concepts and the advancement of
efficient and economical protocols to overcome these intrica-
cies are of paramount importance to numerous scientific disci-
plines, such as medicinal chemistry, material sciences,[3] and
natural product synthesis.[1,2] With regard to allylic C(sp3)ÀH
oxygenation reactions, numerous elegant transition metal-cata-
lyzed methods have been devised throughout the last three
decades.[3,4] In 2004, White and co-workers reported an early
example of a Pd-catalyzed allylic acetoxylation reaction of ter-
minal alkenes with switchable regioselectivity.[6] The formation
of linear products was predominant when Pd(OAc)2 and ben-
zoquinone as the terminal oxidant were used. In contrast, use
of a bis-sulfoxide-ligated PdII catalyst furnished the correspond-
ing branched products with moderate to excellent selectivi-
ty.[6,7] Stahl and co-workers recently described the use of
Pd(OAc)2 as a precatalyst and 4,5-diazafluorenone as an ancil-
lary ligand to enable the conversion of terminal olefins into
We previously reported the first examples of allylic and
C(sp2)ÀH aminations of unactivated linear olefins and cycloal-
kenes, respectively, facilitated by simple, redox-active diaryldi-
selane catalysts.[13] On the basis of these initial studies, we
became interested in further exploring the potential and utility
of selenium-catalyzed oxidations in the context of the cognate
allylic acyloxylation using N-fluorobenzenesulfonimide (NFSI) as
the terminal oxidant (Scheme 1).[14] This method design is par-
ticularly challenging because of two critical factors—namely
chemoselectivity (acyloxylation vs. amination) and regioselec-
tivity (allylic vs. vinylic position of the carboxylate group) in
the course of the carbon–oxygen bond-forming event. To ad-
dress these issues, we decided to investigate the intramolecu-
lar benzoyloxylation of tethered alkene moieties to form iso-
benzofuranone scaffolds.[15] Such a strategy does not only pro-
vide new insights into selenium catalysis but it also offers
a novel, step-economic avenue towards core-structures of
phthalide natural products (Scheme 1).[16] Consequently, we
present herein the first Se-catalyzed synthesis of isobenzofura-
nones from ortho-allyl benzoic acid derivatives through C(sp3)À
H oxidation.
At the outset of our investigations, we had the intention to
assemble isobenzofuranones of type 2 by C(sp2)ÀH acyloxyla-
tion [Equation (1)]. Thus, we used (E)-2-(prop-1-en-1-yl)benzoic
acid (1a) as a representative substrate to explore the feasibility
of this approach. When compound 1a was treated with NFSI
(1 equiv) and (PhSe)2 (5 mol%) in dichloromethane at room
temperature, we observed the formation of a 1.3:1 mixture of
isobenzofuranone 2a and isocoumarine 3a, with a total yield
of 61%.[17]
[a] F. Krꢀtzschmar, M. Kaßel, D. Delony, Dr. A. Breder
Institut fꢁr Organische und Biomolekulare Chemie
Georg-August-Universitaet Gçttingen
Tammannstrasse 2, 37077 Gçttingen (Germany)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201406290.
Chem. Eur. J. 2015, 21, 1 – 6
1
ꢁ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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