Tetrahedron Letters
A singlet oxygen approach to oxaspirocycles
⇑
Kevin M. Jones, Tim Hillringhaus, Martin Klussmann
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A method for the preparation of oxygen containing spirocycles using singlet oxygen is reported. A series
of phenols were converted into the corresponding peroxy-cyclohexadienone derivatives by irradiation
with visible light in the presence of a sensitizer and oxygen. The resulting peroxides could be converted
into ether and lactone spirocycles in one or two steps. The synthesis of the oxaspirocycles from the phe-
nols can also be performed in a one-pot fashion, avoiding the isolation of the peroxide intermediates.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 25 March 2013
Revised 15 April 2013
Accepted 16 April 2013
Available online 24 April 2013
Keywords:
De-aromatization
Singlet oxygen
Spirocycles
Peroxides
The oxidative dearomatization of phenols provides an expedi-
ent route to oxaspirocycles, which serve as useful building blocks
in organic chemistry and represent important intermediates in
natural product synthesis.1 As a result, several reagent combina-
tions have been developed to promote this reaction. Most promi-
nent among those methods is the use of hypervalent iodine
reagents,2 which have been shown to efficiently promote the direct
conversion of phenol derivatives to the oxaspirocycles.3 These
reactions are usually performed with stoichiometric amounts of
hypervalent iodine(III) reagents, but the catalytic use of iodine
compounds together with a simpler terminal oxidant is also possi-
ble (Scheme 1a).4 Alternative methods using other oxidants have
also been reported.5
In recent years, we have become interested in developing
synthetic methodologies which harness the reactivity of molecular
oxygen or proceed via intermediate peroxides.6 In line with this
research theme, we were intrigued by the reaction of singlet
oxygen with substituted phenols7 and wondered if we could incor-
porate this into a new approach to oxaspirocycles. We reasoned
that a substituted phenol bearing an appropriate electrophile 1
could be reacted with singlet oxygen to give the corresponding
peroxy quinol 2. Reduction of the hydro peroxide to the alcohol
and subsequent cyclization would then provide the desired spiro-
cyclic product 3 (Scheme 1b). A related reaction was studied by
Matsuura, Saito et al., who observed the formation of two spirolac-
tones in low yield as byproducts of the photooxidation of phenols,
without optimizing their synthesis.8
We began our study by examining the photochemical conver-
sion of methyl 3-(4-hydroxyphenol)propionate (1a) to the corre-
sponding peroxy-quinol. A brief survey of reaction conditions
revealed that irradiation of a methanol solution of 1a containing
5 mol % tetraphenylporphin (TPP) with white visible light using
LEDs provided 2a in 90% yield after 16 h. Pleasingly, this method
was found to be reasonably general and could be extended to a
variety of phenol derivatives (Table 1). The starting materials were
synthesized from commercially available phenol derivatives by
known procedures: esterification in methanol in case of 1a–c and
1f,9 chlorination of the alcohol in case of 1d,10 reaction with
dimethylcarbonate in case of 1e11 and bromination with NBS in
case of 1f12 (see the Supplementary data for details). The reaction
was tolerant of sterically demanding substrates such as tert-butyl
substituted phenol 1b and provided peroxy quinol 2b in near
OH
O
(a)
Previous strategy
using hypervalent
iodine compounds:
Ar-IX2
or: [Ar-I], mCPBA/R-OOH
X
X
OH
O
O
i) reduction
ii) cyclization
1O2
(b)
This work:
OOH
O
X
X
1
2
3
⇑
Corresponding author. Tel.: +49 208 306 2453; fax: +49 208 306 2980.
Scheme 1. Singlet oxygen approach to oxaspirocycles vs use of hypervalent iodine
compounds.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.