Palladium-Catalyzed Suzuki-Miyaura, Heck and Hydroarylation Reactions on (-)-Levoglucosenone and Application to the Synthesis of Chiral γ-Butyrolactones

Article abstract of DOI:10.1002/ejoc.201501083

The chiral pool material (-)-levoglucosenone (6,8-dioxabicyclo[3.2.1]oct-2-en-4-one, LGO) has been substituted by using a series of Pd-mediated cross-coupling reactions. Iodination of LGO followed by Suzuki-Miyaura cross-coupling reaction with boronic acids by employing the Buchwald ligand SPhos with Pd(OAc)₂ afforded 3-aryl derivatives in excellent yields. Selective Heck arylation reaction at the 2-position was achieved with aryl iodides with K₃PO₄ as base and SPhos ligand with Pd(OAc)₂ (1-5 mol-%). A selective hydroarylation reaction (formal conjugate addition) was developed by using the same aryl iodides, benzyldiethylamine, Pd(OAc)₂, and P(o-tol)₃. The products were converted, either directly or after alkene reduction, through a Baeyer-Villiger oxidation into chiral 3- and 4-substituted 5-(hydroxymethyl)dihydrofuran-2(3H)-ones. Three new cross-coupling approaches to the derivatization of levoglucosenone are described and the products converted into butyrolactones.

Full text of DOI:10.1002/ejoc.201501083

FULL PAPER
DOI: 10.1002/ejoc.201501083
Palladium-Catalyzed Suzuki–Miyaura, Heck and Hydroarylation Reactions on
(–)-Levoglucosenone and Application to the Synthesis of Chiral γ-Butyrolactones
Kieran P. Stockton,[a] Christopher J. Merritt,[a] Christopher J. Sumby,[b] and
Ben W. Greatrex*[a]
Keywords: Homogeneous catalysis / Lactones / Cross-coupling / Levoglucosenone / Chiral pool
The chiral pool material (–)-levoglucosenone (6,8-dioxabi-
cyclo[3.2.1]oct-2-en-4-one, LGO) has been substituted by
using a series of Pd-mediated cross-coupling reactions.
SPhos ligand with Pd(OAc)2 (1–5 mol-%). A selective hydro-
arylation reaction (formal conjugate addition) was developed
by using the same aryl iodides, benzyldiethylamine, Pd-
Iodination of LGO followed by Suzuki–Miyaura cross-cou- (OAc)2, and P(o-tol)3. The products were converted, either
pling reaction with boronic acids by employing the Buchwald
ligand SPhos with Pd(OAc)2 afforded 3-aryl derivatives in ex-
cellent yields. Selective Heck arylation reaction at the 2-posi-
tion was achieved with aryl iodides with K3PO4 as base and
directly or after alkene reduction, through a Baeyer–Villiger
oxidation into chiral 3- and 4-substituted 5-(hydroxymethyl)-
dihydrofuran-2(3H)-ones.
liger-type reactions have been reported on LGO and di-
hydrolevoglucosenone.[8]
Introduction
(–)-Levoglucosenone (6,8-dioxabicyclo[3.2.1]oct-2-en-4-
one, 1, LGO) is obtained from the pyrolysis of acidified
cellulose and has attracted interest as a chiral synthon since
its characterization by Broido in 1973.[1] The main barrier
to LGO use has been the failure to scale up production,
and so LGO has historically had a high price despite the
ready availability of the starting material cellulose. Reactors
have recently been developed to allow large-scale pro-
duction and have provided new opportunities to use this
chiral molecule in synthesis.[2]
The development of new transformations that utilize
LGO is crucial to make use of this biorenewable resource.
Reactions previously reported for LGO include the reaction
of the alkene with electrophiles,[3] cycloaddition reactions,[4]
redox chemistry,[1b] and conjugate addition chemistry.[5]
First investigated by Shafidazeh et al.,[6] the Baeyer–Villiger
reaction of LGO was used extensively by Ebata et al. to
generate butyrolactones that include naturally occurring
eldanolide and whiskey lactone.[7] In these reports, the LGO
scaffold was derivatized with organometallic reagents that
used the anhydro bridge to direct conjugate addition reac-
tions, and only a limited set of substitution patterns were
produced. More recently, enzyme-catalyzed Baeyer–Vil-
Chiral butyrolactones are found in many flavors, fra-
grances,[9] and natural products,[10] and LGO could be a
useful starting material for their construction if additional
methods for derivatization of the bicyclic skeleton were
available. Few examples exist of palladium-catalyzed cross-
coupling reactions on LGO or its 3-halo derivatives.[11]
However, modern metal-catalyzed cross-coupling tech-
niques would provide opportunities to derivatize LGO into
arylglycals such as 3 and 5 to access chiral butyrolactones
shown by general structures 4 and 6 (Scheme 1). In this cur-
rent report we describe attempts to derivatize LGO by using
Suzuki,[12] Heck[13] and palladium-catalyzed hydroarylation
reactions (also referred to as a reductive Heck reaction)[14]
and have converted selected products into chiral 5-
hydroxymethyl-γ-butyrolactones.
[a] School of Science and Technology, University of New England
Armidale, New South Wales, Australia
Scheme 1. Palladium-catalyzed cross-coupling reactions of LGO.
E-mail: ben.greatrex@une.edu.au
http://www.une.edu.au
[b] Department of Chemistry, School of Physical Sciences,
University of Adelaide
Results and Discussion
We have found no reports of Suzuki–Miyaura reactions
that use 2 despite this seeming a straightforward way to
North Terrace, Adelaide, South Australia, Australia
Supporting information and ORCID(s) from the author(s) for
this article are available on the WWW under http://dx.doi.org/
10.1002/ejoc.201501083.
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further functionalize LGO. Iodination of LGO with I2/pyr- ing to 1.0 mol-% and gave clean reactions with excellent
idine afforded 3-iodolevoglucosenone (2) in 96% yields (Table 1, Entries 6, 8, and 10). Electron-poor boronic
yield.[11a,15] The isolation of 2 required only filtration acids, 2-formylphenylboronic acid and 2-fluorophenyl
through a pad of silica gel then evaporation of volatiles and boronic acid, afforded the cross-coupled products, but re-
so could be performed on a multi-gram scale. The reaction quired Pd (5 mol-%) and SPhos (10 mol-%) for complete
of phenylboronic acid with 2 and Cs2CO3 as base with reaction (Table 1, Entries 14 and 15).
Pd(OAc)2 (5 mol-%) and triphenylphosphine as ligand pro-
The coupling of the unreactive sp3 benzyl boronate ester
vided expected coupled product 3a in 67% yield (Scheme 2; was unsuccessful, the literature conditions for this ester fail-
Table 1, Entry 1). Following this success, we applied these ing due to the sensitivity of 2 to water under basic condi-
conditions to the series of boronic acids shown in Table 1, tions (Table 1, Entry 11).[17]
which gave the coupled products in moderate to good yield
Heck reactions with LGO as the alkene seemed another
(Table 1, Entries 5, 7, and 12). As yields were somewhat exciting and unexplored way to derivatize the 2-position of
lower than expected with significant byproducts of protode- LGO. We envisaged that hydrogenation of product 5 would
boronation, we examined alternative ligands and condi- occur from the face opposite the anhydro bridge to give
tions. Superior results were obtained with Buchwald ligand derivatives epimeric to those obtained from conjugate ad-
SPhos,[16] which allowed a reduction of the palladium load- dition reactions with organometallic reagents.[18] A com-
pounding factor in these reactions is that the palladium-
catalyzed hydroarylation reaction[14] (formal conjugate ad-
dition) competes with the Heck reaction of LGO. The cen-
tral role of base selection to promote either the Heck reac-
tion or hydroarylation in addition reactions to enones was
recently identified by de Vries et al. with a Pd0-NHC com-
plex.[14a] Trialkylamine bases gave rise to hydroarylation
products, whereas CsOPiv afforded Heck-type adducts.
Scheme 2. Suzuki–Miyaura coupling reactions of iodide 2.
This work built upon the pioneering reports of Cacchi et
al., who first studied the Pd-mediated hydroarylation reac-
Table 1. Suzuki–Miyaura coupling reactions of iodide 2.
tions with trialkylammonium formate, and recent reports
that have used formate as a reducing agent.[14b,14c,19]
A base and solvent optimization study was conducted
on the Heck reaction of LGO with iodobenzene (Table 2,
Scheme 3). The reaction catalyzed by 5 mol-% Pd(OAc)2,
with P(o-tol)3 with Cs2CO3 as the base gave a moderate
yield of 2-phenyl adduct 5a in toluene (Table 2, Entry 1).
No products of cross coupling were observed when the re-
action was conducted in N,N-dimethylformamide (DMF)
with Cs2CO3, which we attributed to the sensitivity of the
Table 2. Heck selective reactions of LGO (1), see Scheme 3.
[a] Reactions performed with Cs2CO3 (2 equiv.), with a 2:1 Pd/L
ratio at a concentration of 50 mg/mL. [b] Benzyl pinacol boronate
ester was used with PdCl2(dppf) and CsF (2 equiv.) as base.
[a] Reactions performed at an LGO concentration of 50 mg/mL
with Pd/L ratio of 1:2 with base (2 equiv.). [b] NaOAc
(1.05 equiv.) was used.
a
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Coupling Reactions on (–)-Levoglucosenone
substrate to amines generated by the base (not shown). The Table 3. Hydroarylation selective reactions of LGO (1), see
Scheme 3.
substrate LGO is also sensitive to water in the presence of
strong bases, and we found that yields were variable with
Cs2CO3 (0–34%), so alternatives were examined. At-
tempted Heck–Matsuda coupling reactions with phenyl-
diazonium tetrafluoroborate in methanol as reported by
Sotiropoulos et al.[20] for reactions of methyl acrylate gave
only products from methanol conjugate addition (not
shown), and other polar aprotic solvents were not exam-
ined. We also found that de Vries’ ligand-free Pd nanoparti-
cle conditions[21] gave low yields, which we attributed to
slow decomposition of LGO (TLC) in N-methyl-2-pyrrol-
idone (NMP) at 130 °C (Table 2, Entry 5).
Scheme 3. Heck and hydroarylation reactions of LGO.
We achieved complete selectivity for the Heck reaction
of LGO at the expense of the hydroarylation with iodo-
benzene, SPhos, and K3PO4 in toluene (Table 2, Entry 4).
The Heck reactions of electron-rich aromatics proceeded
more quickly than the electron-poor aromatics and in better
yield (Table 2, Entries 6–8 and 9). In all reactions, 0–3% of
3-substituted product 3a–3h was also observed. The Heck
reaction product was confirmed for 5h by single-crystal X-
ray diffraction (see Supporting Information, Figure S4).
The reactions performed to optimize the hydroarylation
[a] Reactions performed at a concentration of 20 mL/g LGO with a
Pd/L ratio of 1:2 with base (4.5 equiv.) and aryl iodide (1.2 equiv.).
on LGO are shown in Table 3, and the proposed mecha-
nism for the reaction that gives the hydroarylation reaction
Reactions performed with 1.0 mmol of
1 unless indicated.
is shown in Scheme 4.[14a,14e] The reaction initially proceeds [b] 0.50 mmol scale. [c] [{Pd(iPr)(NQ)}2] was used in place of
Pd(OAc)2. [d] [{Pd(Mes)(NQ)}2] was used in place of Pd(OAc)2.
[e] 4.0 mmol scale.
as per the Heck reaction and transfer of the aryl group to
the enone gives 9. The facial selectivity in the transfer of
the aryl group results from the selective coordination of the
palladium atom to the face of LGO opposite the anhydro
bridge. The syn-dehydropalladation that usually occurs in
the Heck reaction is not possible due to restricted rotation,
and instead coordinated amine complex 10 transfers a
hydride from the carbon atom attached to the nitrogen
atom to the palladium center. Reductive elimination from
palladium hydride intermediate 11 gives observed hydro-
arylation product 7, and the process also affords iminium
byproduct 12. Evidence for this mechanism has previously
been found in the observation of products from the cross
coupling of the imine byproduct and aryl iodide.[14b]
We began our investigation into the hydroarylation reac-
tion with PhI, triethylamine with the ligand P(o-tol)3, and
we obtained only moderate selectivity for diastereomerically
pure hydroarylation product 7a (Table 3, Entry 1). It oc-
curred to us that by reducing the C–H bond strength by the
use of a benzylic amine could improve selectivity towards
Scheme 4. Mechanism for the hydroarylation of LGO.
the hydroarylation reaction as long as coordination to the
palladium center was not affected. This hypothesis was (Table 3, Entry 7). The crude reaction mixture showed the
tested by using tribenzylamine, which gave excellent selec- presence of dibenzylamine as well as the Schiff base N-
tivity for the hydroarylation product; however, this resulted benzylidenebenzylamine by GC–MS (data not shown). The
in a moderately complex mixture and poor yield of product Schiff base was formed from the transfer of a second
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hydride from the byproduct dibenzylamine, and the pres- shows a C4–C3–C10–C11 torsion angle of 54° consistent
ence of both adducts are consistent with the proposed with these results. The X-ray crystal structure of benzodiox-
mechanism. We thought it likely that the imine formed from ole substituted 3b exhibits a 31° torsion angle between the
the base was reacting with one of the palladated intermedi- aryl ring and the C3–C4 bond. The X-ray structure of 3a is
ates to give the complex reaction outcome. By reducing the more complex and has three distinct conformations present
number of benzyl groups by using benzyldiethylamine im- in the unit cell, two of which have the aryl ring twisted
proved the selectivity over the trialkylamines and gave good relative to the enone, whereas one is planar, likely a result
selectivity for the hydroarylation products (Table 3, En- of solid-state packing effects (see Supporting information,
tries 1, 6 and 8). When the cross-coupling reaction of 1 with Figures S1 and S2).
PhI with BnNEt2 was performed in a sealed tube to trap
volatile components and followed by GC–MS, an 8:1 ratio,
corrected by using authentic standards, of the byproduct N-
benzyl-N-ethylamine/diethylamine was observed. This indi-
cated that greater hydride transfer occurred from the N-
alkyl groups rather than the benzylic position, and the role
of the benzyl group in improving selectivity is therefore not
clear.
The hindered base N,N-diisopropylethylamine (DIPEA)
showed poor selectivity, probably as a result of decreased
coordination to the palladium center (Table 3, Entry 4), al-
Figure 1. Perspective view of the single-crystal X-ray structure of
though this base has been used with excellent results in the
enone 3d with the 54° C4–C3–C10–C11 torsion angle atoms
labeled.
reductive Heck reactions reported recently by Zhou et al.[22]
The bicyclic base 1,4-diazabicyclo[2.2.2]octane (DABCO)
also showed poor selectivity, which we attributed to slow
hydride transfer to the palladium atom (Table 3, Entry 3).
The optimized conditions were then applied to a range
of aryl iodides to give hydroarylation products 7b, 7c, 7h,
and 7i in improved yield and selectivity relative to the reac-
tions with trialkylamines (Table 3, Entries 13–18). In the
case of 7i (Table 3, Entry 17) the stereochemistry of the C2
position of the hydroarylation product was confirmed as
(R) by single-crystal X-ray crystallography (see Supporting
Information, Figure S5), consistent with the coupling con-
stants around the bicyclic ring, which were conserved in the
series.
The isolation of hydroarylation products 7a–7h free of
Heck adducts was challenging. In cases for which it was
not possible to remove all traces of the Heck adduct by
chromatography, the reaction mixture was treated with
potassium permanganate (1.0 m) in water/dioxane or water/
ethyl acetate, which oxidized the remaining alkene in the
Heck adducts without affecting the hydroarylation prod-
ucts. Flash chromatography then provided analytically pure
material.
The reduction of enone 3a with a mixture of Red-Al/
CuBr, which generates a CuH species in situ,[23] afforded
reduced product 13a in good yield. The stereochemistry of
13a is opposite to that expected from hydrogenation and
presumably results from protonation on the face syn to the
anhydro bridge that gives the sterically less crowded equato-
rial phenyl group. The structural assignments are based on
a trans-diaxial H2-H3 coupling and are supported by a sin-
gle-crystal X-ray structure of 13a that shows the equatorial
reaction product (Figure 2). These same conditions were
then applied to 3b and 3c, which afforded reduced di-
oxabicyclo[3.2.1]octanes 13b and 13c, respectively. Baeyer–
Villiger reactions of 3-aryl ketones 13a and 13c with perace-
tic acid afforded expected γ-butyrolactones 14a and 14c,
respectively, in good yields. The benzodioxole group in 13b
led to slower oxidation, and there was only 40% consump-
tion of the ketone after 1 week. Oxidations of the Heck and
hydroarylation-type products were straightforward and also
afforded substituted butyrolactones 15, 16a, 16b, 16h, and
16i in good yields (Scheme 5). In all Baeyer–Villiger oxid-
ation reactions, a mixture of alcohol and formate ester was
With a series of substituted glycals in hand we turned
our attention to their conversion to the corresponding γ-
butyrolactones. Attempts to convert cross-coupled product
3a into the butenolide by using meta-chloroperoxybenzoic
acid catalyzed by p-toluenesulfonic acid (p-TSA) gave only
unreacted starting material. We also attempted hydrogen-
ation of 3a (ethyl acetate, Pd/C or PdCl2, 45 psi, 48 h); how-
ever, the starting material was recovered unchanged. These
results may be explained by the preferred conformation of
the phenyl ring, which twists to avoid unfavorable steric in-
teractions. Together with the anhydro bridge in 3, this re-
duces the accessibility of the alkene to the catalyst or the
carbonyl group to the oxidant. The single-crystal X-ray
Figure 2. Perspective view of the single-crystal X-ray structure of
crystal structure of trifluorophenyl adduct 3d (Figure 1) 13a that shows the equatorial phenyl substituent.
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Coupling Reactions on (–)-Levoglucosenone
formed, and a second hydrolysis step with HCl (1 n) in spire new uses for the interesting chiral synthon LGO,
water/tetrahydrofuran (THF) was required to convert all which is currently available in kilogram quantities and may
products into the alcohols.[7a,8]
soon be available in bulk.
Experimental Section
General Experimental: Solvents were dried in accordance with lit-
erature procedures. Cs2CO3 and K3PO4 were dried at 100 °C under
vacuum and were used immediately. All other reagents are commer-
cially available and were used as received. 1H NMR spectra re-
corded in CDCl3 are referenced to tetramethylsilane (δ = 0 ppm)
and 13C NMR spectra are referenced to the residual solvent.
HRMS data were recorded in positive ESI V mode (source tem-
perature 80 °C, desolvation temperature 150 °C, capillary 2.5 kV).
MS (EI) data were recorded with an Agilent GC–MS 5975C mass
spectrum detector. [{Pd(Mes)(NQ)}2] {[1,3-bis(2,6-diisoprop-
ylphenyl)imidazol-2-ylidene](1,4-naphthoquinone)palladium(0) di-
mer (649736-75-4)} and [{Pd(Mes)(NQ)}2] [(1,3-bis(2,4,6-trimeth-
ylphenyl)imidazol-2-ylidene)(1,4-naphthoquinone)palladium(0) di-
mer (467220-49-1)] were obtained from Sigma–Aldrich, St. Louis,
USA.
(1S,5R)-3-Iodo-6,8-dioxabicyclo[3.2.1]oct-2-en-4-one (2):[11a,15] To a
solution of 1 (1.5 g, 11.9 mmol) in 1,2-dichloroethane (20 mL) was
added I2 (4.2 g, 16.5 mmol), then pyridine (1.08 mL, 13.4 mmol),
and the reaction mixture was stirred for 15 min. Toluene (20 mL)
was added and the resulting suspension poured onto a 5 cm plug
of silica and the product eluted with toluene. Concentration of the
filtrate gave a yellow crystalline solid (2.86 g, 96%). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.97 (d, J = 4.9 Hz, 1 H), 5.57 (s, 1
H), 4.94 (dd, J = 4.9, 4.5 Hz, 1 H), 3.88 (dd, J = 7.0, 4.5 Hz, 1 H),
3.82 (d, J = 7.0 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C):
δ = 183.1, 155.7, 100.7, 99.7, 74.2, 66.5 ppm. FTIR: ν = 3067, 2975,
˜
Scheme 5. Preparation of butyrolactones.
2902, 1697 cm–1. MS (EI): m/z (%) = 251.9 (trace) [M]+, 224.0
(100), 179.0 (16), 126.9 (15), 97.1 (31), 53.1 (14), 41.1 (13), 39.1
(19).
To demonstrate the versatility of this chemistry, the
hydrogenation of Heck adduct 5a was also examined
(Scheme 5). The unoptimized reduction afforded equatorial General Procedure for Suzuki Reactions with 2: To a stirred solution
of 2 (250 mg, 0.99 mmol) in toluene (5 mL) under N2 were added
arylboronic acid (1.5 equiv.), phosphine (2–10 mol-%), anhydrous
Cs2CO3 (2.0 equiv.), and Pd(OAc)2 (1–5 mol-%), and the reaction
mixture was heated to 90–110 °C until complete by TLC (3:7, ethyl
acetate/hexanes). The resulting mixture was washed with H2O
(10 mL) and the aqueous phase extracted with CH2Cl2 (20 mL),
then the combined organic extracts were dried (MgSO4) and con-
centrated under reduced pressure. Products 3a–3d, 3f, and 3g were
purified by flash chromatography and then further purified as
specified.
product 17, overreduced alcohol 18, and small amounts of
axial product 7a. The greater than 10:1 selectivity for the
equatorial reduction product, which is epimeric to products
of hydroarylation, further demonstrates the flexibility of
these cross-coupling approaches for the derivatization of
LGO.
Conclusions
(1S,5R)-3-Phenyl-6,8-dioxabicyclo[3.2.1]oct-2-en-4-one (3a): The ge-
neral procedure performed with 2 (2.10 g, 8.33 mmol) afforded a
product that was crystallized from CH2Cl2/hexanes to give 3a as
off-white crystals (1.12 g, 67%). M.p. 82–85 °C. [α]2D3 = –301 (c =
We have reported a series of reactions that can be used
to derivatize LGO to afford chiral 2-aryl- and 3-aryl-substi-
tuted 6,8-dioxabicylo[3.2.1]octan-4-ones, which can be con-
verted into γ-butyrolactones by means of a Baeyer–Villiger
oxidation reaction. These substituted butyrolactones, which
can be used as synthons for the construction of more com-
plex molecules, can now be accessed from the chiral pool
material LGO without the use of air-sensitive organometal-
lic reagents and low temperatures. Further applications of
these chiral butyrolactones will be reported in due course.
We have also described new conditions for a diastereoselec-
tive hydroarylation of LGO optimized with BnNEt2, which
may have applications in the addition of aryl iodides to
1
1.53, CH2Cl2). H NMR (300 MHz, CDCl3, 25 °C): δ = 7.48–7.30
(m, 5 H), 7.24 (d, J = 4.9 Hz, 1 H), 5.49 (s, 1 H), 5.12 (dd, J = 4.9,
4.5 Hz, 1 H), 3.91 (dd, J = 7.0, 4.5 Hz, 1 H), 3.81 (d, J = 7.0 Hz,
1 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 187.9, 143.1,
137.8, 133.1, 128.6, 128.2, 128.1, 101.6, 72.4, 66.5 ppm. FTIR
(neat): ν = 3047, 2968, 2897, 1686 cm–1. MS (ESI): m/z = 203.0 [M
˜
+ H]+, 225.0 [M + Na]+. C12H10O3 (202.21): calcd. C 71.28, H
4.98; found C 71.53, H 4.95.
(1S,5R)-3-(Benzo[d][1,3]dioxol-5-yl)-6,8-dioxabicyclo[3.2.1]oct-2-en-
4-one (3b): The general procedure performed with 2 (250 mg,
other cycloalkenones. We envisage that this work will in- 0.99 mmol) afforded a product that crystallized upon standing to
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K. P. Stockton, C. J. Merritt, C. J. Sumby, B. W. Greatrex
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give 3b as yellow crystals (208 mg, 85%). M.p. 129–131 °C. [α]2D6
–260 (c = 1.43, CH2Cl2). H NMR (300 MHz, CDCl3, 25 °C): δ = 25 °C): δ = 7.38–7.27 (m, 3 H), 7.19–7.07 (m, 2 H), 5.53 (s, 1 H),
7.17 (d, J = 5.1 Hz, 1 H), 6.93–6.86 (m, 2 H), 6.85–6.74 (m, 1 H), 5.17 (dd, J = 4.7, 4.7 Hz, 1 H), 3.98 (dd, J = 6.7, 4.7 Hz, 1 H), 3.91
=
[α]1D6 = –300 (c = 0.20, CH2Cl2). 1H NMR (500 MHz, CDCl3,
1
5.95 (s, 2 H), 5.46 (s, 1 H), 5.12 (dd, J = 5.1, 4.5 Hz, 1 H), 3.92
(dd, J = 6.8, 4.5 Hz, 1 H), 3.81 (d, J = 6.8 Hz, 1 H) ppm. 13C = 186.8, 160.0 (d, JCF = 248.9 Hz), 146.0 (d, JCF = 3.6 Hz), 132.6,
NMR (75 MHz, CDCl3, 25 °C): δ = 188.1, 148.1, 147.6, 142.0, 131.0 (d, JCF = 3.6 Hz), 130.4 (d, JCF = 8.2 Hz), 123.9 (d, JCF
136.5, 127.1, 122.1, 108.7, 108.3, 101.7,101.3, 72.6, 66.7 ppm. FTIR 3.6 Hz), 120.9 (d, JCF = 14.5 Hz), 115.8 (d, JCF = 22.7 Hz), 101.7,
(neat): ν = 3012, 2974, 2924, 1695 cm–1. MS (EI): m/z (%) = 246.1
72.3, 66.7 ppm. FTIR (neat): ν = 1698, 1485, 1214, 1108, 980, 884,
(d, J = 6.7 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ
=
˜
˜
(44) [M]+, 215 (35), 173 (100), 131 (48), 116 (32), 115 (62), 103 (32). 819, 765 cm–1. MS (ESI): m/z = 221.0 [M + H]+. C12H9FO3
C13H10O5 (246.22): calcd. C 63.42, H 4.09; found C 63.30, H 4.05. (220.20): calcd. C 65.45, H 4.12; found C 65.21, H 4.04.
(1S,5R)-3-(4-Methoxyphenyl)-6,8-dioxabicyclo[3.2.1]oct-2-en-4-one General Procedure for Heck Reactions of 1: Aryl iodide (2.4 mmol),
(3c): The general procedure performed with 2 (250 mg, 0.99 mmol) SPhos (16 mg, 0.04 mmol), anhydrous K3PO4 (4.0 mmol), and
afforded a product that was crystallized from hot iPr2O to give 3c Pd(OAc)2 (4.4 mg, 0.02 mmol) were added to a stirred solution of
as colorless crystals (205 mg, 89%). M.p. 101–102 °C. [α]2D2 = –264
(–)-LGO (1; 252 mg, 2.0 mmol) under N2 in toluene (5 mL), and
1
(c = 0.96, CH2Cl2). H NMR (300 MHz, CDCl3, 25 °C): δ = 7.43– the reaction mixture was heated at reflux to 110 °C until the reac-
7.31 (m, 2 H), 7.18 (d, J = 4.9 Hz, 1 H), 6.96–6.82 (m, 2 H), 5.47 tion was complete according to TLC (3:7, ethyl acetate/hexanes).
(s, 1 H), 5.11 (dd, J = 4.9, 4.6 Hz, 1 H), 3.91 (dd, J = 6.8, 4.6 Hz, The resulting mixture was washed with H2O (10 mL) and the aque-
1 H), 3.81 (d, J = 6.8 Hz, 1 H), 3.79 (s, 3 H) ppm. 13C NMR ous phase extracted with CH2Cl2 (20 mL), then the combined or-
(75 MHz, CDCl3, 25 °C): δ = 188.3, 160.0, 141.5, 136.2, 129.4, ganic extracts were dried (MgSO4) and concentrated under reduced
125.6, 113.8, 101.7, 72.6, 66.6, 55.2 ppm. FTIR (neat): ν = 3027,
pressure. The products 5a–5c, 5h, and 5i were purified by flash
˜
3007, 2967, 2889, 2840, 1688, 1602 cm–1. MS (ESI): m/z = 233 [M chromatography (1:3, ethyl acetate/hexanes) and then further puri-
+ H]+, 255 [M + Na]+. C13H12O4 (232.24): calcd. C 67.23, H 5.21;
found C 67.26, H 5.26.
fied as specified.
(1S,5R)-2-Phenyl-6,8-dioxabicyclo[3.2.1]oct-2-en-4-one (5a): The ge-
(1S,5R)-3-(2,3,4-Trifluorophenyl)-6,8-dioxabicyclo[3.2.1]oct-2-en-4- neral procedure for the Heck reaction of 1 (500 mg, 3.97 mmol)
one (3d): The general procedure performed with iodide 2 (250 mg,
0.99 mmol) afforded a product that was crystallized from hot iPr2O
gave a product that was crystallized from CH2Cl2/hexanes to give
5a as off-white crystals (483 mg, 60%). M.p. 98–100 °C. [α]1D9
=
1
to give 3d as colorless crystals (187 mg, 74 %). M.p. 91–92 °C. –384 (c = 0.25, CH2Cl2). H NMR (300 MHz, CDCl3, 25 °C): δ =
[α]2D5 = –247 (c = 1.10, CH2Cl2). 1H NMR (300 MHz, CDCl3,
7.54–7.41 (m, 5 H), 6.31 (d, J = 1.5 Hz, 1 H), 5.51 (d, J = 5.0 Hz,
25 °C): δ = 7.35 (d, J = 4.9 Hz, 1 H), 7.07–6.92 (m, 2 H), 5.49 (br. 1 H), 5.41 (d, J = 1.5 Hz, 1 H), 4.04 (dd, J = 6.8, 5.0 Hz, 1 H),
s, 1 H), 5.17 (dd, J = 4.9, 4.7 Hz, 1 H), 3.97 (dd, J = 6.9, 4.5 Hz, 3.80 (d, J = 6.8 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C):
1 H), 3.89 (br. d, J = 6.9 Hz, 1 H) ppm. 13C NMR (75 MHz, δ = 189.4, 159.1, 133.8, 131.1, 129.4, 126.4, 120.5, 101.2, 74.0,
CDCl3, 25 °C): δ = 186.3, 151.2 (ddd, JCF = 251.6, 9.9, 2.4 Hz), 67.6 ppm. FTIR (neat): ν = 3030, 2961, 2922, 2886, 2852, 1683,
˜
149.1 (ddd, JCF = 252.4, 10.7, 3.2 Hz), 146.8, 140.0 (ddd, JCF
=
1258, 1110 cm–1. MS (EI): m/z (%) = 173 (20) [M – HCO], 157
252.2, 15.2, 15.2 Hz), 131.2, 124.6 (ddd, JCF = 7.6, 4.5, 4.5 Hz), (25), 129 (100), 128 (28), 115 (32), 101.8 (15). C12H10O3 (202.21):
118.5 (dd, JCF = 12.0, 4.2 Hz), 111.9 (dd, JCF = 17.6, 3.6 Hz),
101.4, 72.2, 66.6 ppm. FTIR (neat): ν = 3101, 2996, 2961, 1704,
calcd. C 71.28, H 4.98; found C 71.49, H 4.78.
˜
(1S,5R)-2-(Benzo[d][1,3]dioxol-5-yl)-6,8-dioxabicyclo[3.2.1]oct-2-en-
4-one (5b): The general procedure for the Heck reaction of 1
(504 mg, 4.0 mmol) gave a product that was further crystallized
from hot iPr2O to give 5b as a yellow crystalline solid (612 mg,
62%). M.p. 147–149 °C. [α]2D0 = –412 (c = 0.50, CH2Cl2). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 7.03 (dd, J = 8.2, 1.5 Hz, 1 H), 6.98
(d, J = 1.5 Hz, 1 H), 6.89 (d, J = 8.2 Hz, 1 H), 6.22 (br. d, J =
1.0 Hz, 1 H), 6.05 (s, 2 H), 5.47 (d, J = 5.0 Hz, 1 H), 5.40 (s, 1 H),
4.03 (dd, J = 6.6, 5.0 Hz, 1 H), 3.77 (d, J = 6.6 Hz, 1 H) ppm. 13C
1507, 1469 cm–1
.
13C NMR (125 MHz, CDCl3, 125 MHz): δ =
186.3, 151.2 (ddd, JCF = 251.6, 9.9, 2.4 Hz), 149.1 (ddd, JCF
=
252.4, 10.7, 3.2 Hz), 146.8, 140.0 (ddd, JCF = 252.2, 15.2, 15.2 Hz),
131.2, 124.6 (ddd, JCF = 7.6, 4.5, 4.5 Hz), 118.5 (dd, JCF = 12.0,
4.2 Hz), 111.9 (dd, JCF = 17.6, 3.6 Hz), 101.4, 72.2, 66.6 ppm. MS
(EI): m/z (%) = 228.1 (50) [M – CO], 207.1 (40), 183.1 (100), 182.1
(65), 169 (43), 156 (47), 151 (45). C12H7F3O3 (256.18): calcd. C
56.26, H 2.75; found C 56.35, H 2.66.
(1S,5R)-3-(2-Formylphenyl)-6,8-dioxabicyclo[3.2.1]oct-2-en-4-one NMR (75 MHz,CDCl3, 25 °C): δ = 189.5, 158.5, 150.4, 148.8,
(3f): The general procedure performed with 2 (250 mg, 0.99 mmol)
afforded a product that was crystallized from hot iPr2O to give 3f
127.7, 121.3, 118.8, 108.9, 106.2, 101.9, 101.1, 73.8, 67.6 ppm.
FTIR (neat): ν = 2985, 2901, 1668, 1504, 1490, 1254, 866 cm–1. MS
˜
as bright orange crystals (120 mg, 53%). M.p. 150–151 °C. [α]2D0
=
(ESI): m/z = 247.0 [M + H]+, 269.0 [M + Na]+. C13H10O5 (246.22):
1
–306 (c = 2.67, CH2Cl2). H NMR (300 MHz, CDCl3, 25 °C): δ = calcd. C 63.42, H 4.09; found C 63.69, H 3.94.
9.86 (s, 1 H), 7.90 (dd, J = 7.5, 1.5 Hz, 1 H), 7.60 (ddd, J = 7.5,
(1S,5R)-2-(4-Methoxyphenyl)-6,8-dioxabicyclo[3.2.1]oct-2-en-4-one
7.5, 1.5 Hz, 1 H), 7.53 (ddd, J = 7.5, 7.5, 1.1 Hz, 1 H), 7.24–7.14
(m, 2 H), 5.52 (s, 1 H), 5.18 (dd, J = 4.7, 4.7 Hz, 1 H), 4.00 (dd, J
= 6.8, 4.7 Hz, 1 H), 3.94 (d, J = 6.8 Hz, 1 H) ppm. 13C NMR
(75 MHz, CDCl3, 25 °C): δ = 190.9, 187.1, 144.8, 137.2, 135.1,
134.7, 133.8, 130.7, 130.2, 129.2, 101.4, 72.3, 66.8 ppm. FTIR
(5c): The general procedure for the Heck reaction of 1 (250 mg,
1.98 mmol) gave a product that was recrystallized from hot iPr2O
to give 5c as colorless crystals (269 mg, 59%). M.p. 108–110 °C.
[α]1D7 = –432 (c = 0.44, CH2Cl2). 1H NMR (300 MHz, CDCl3,
25 °C): δ = 7.57–7.35 (m, 2 H), 7.07–6.89 (m, 2 H), 6.24 (br. dd, J
= 1.3, 0.6 Hz, 1 H), 5.51 (br. d, J = 5.0 Hz, 1 H), 5.39 (d, J =
1.3 Hz, 1 H), 4.01 (dd, J = 6.6, 5.0 Hz, 1 H), 3.84 (s, 3 H), 3.75 (d,
J = 6.6 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ =
(neat): ν = 3010, 2974, 2844, 2761, 1692 (br.), 1601, 1591 cm–1. MS
˜
(ESI): m/z = 231 [M + H]+, 253 [M + Na]+. C13H10O4 (230.22):
calcd. C 67.82, H 4.38; found C 67.65, H 4.38.
(1S,5R)-3-(2-Fluorophenyl)-6,8-dioxabicyclo[3.2.1]oct-2-en-4-one 189.6, 162.1, 158.6, 128.0, 125.8, 118.2, 114.8, 101.2, 73.6, 67.5,
(3g): The general procedure performed with 2 (250 mg, 0.99 mmol)
afforded a product that was crystallized from hot iPr2O to give 3g
as a colorless crystalline solid (191 mg, 88 %). M.p. 96–97 °C.
55.4 ppm. FTIR (neat): ν = 3054, 2992, 2981, 2844, 1669, 1587,
˜
1109 cm–1. MS (ESI): m/z = 233.1 [M + H]+, 255.1 [M + Na]+.
C13H12O4 (232.24): calcd. C 67.23, H 5.21; found C 67.63, H 5.33.
7004
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 6999–7008

Coupling Reactions on (–)-Levoglucosenone
(1S,5R)-2-(p-Tolyl)-6,8-dioxabicyclo[3.2.1]oct-2-en-4-one (5h): The
general procedure for the Heck reaction of 1 (250 mg, 1.98 mmol)
128 °C (iPr2O). [α]2D0 = –309 (c = 0.51, CH2Cl2). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 6.80–6.71 (m, 2 H), 6.67 (dd, J =
7.9, 0.9 Hz, 1 H), 5.94 (s, 2 H), 5.19 (s, 1 H), 4.64 (d, J = 5.3 Hz,
gave 5h as colorless crystals (243 mg, 57%). M.p. 99–100 °C. [α]2D0
1
= –410 (c = 1.24, CH2Cl2). H NMR (300 MHz, CDCl3, 25 °C): δ 1 H), 4.15 (d, J = 7.4 Hz, 1 H), 4.05 (dd, J = 7.4, 5.3 Hz, 1 H),
= 7.43–7.33 (m, 2 H), 7.29–7.20 (m, 2 H), 6.27 (br. d, J = 1.5 Hz, 3.37 (br. d, J = 8.5 Hz, 1 H), 3.06 (dd, J = 16.8, 8.5 Hz, 1 H), 2.52
1 H), 5.50 (d, J = 5.0 Hz, 1 H), 5.38 (d, J = 1.5 Hz, 1 H), 4.01 (dd, (br. d, J = 16.8 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3,
J = 6.6, 5.0 Hz, 1 H), 3.76 (d, J = 6.6 Hz, 1 H), 2.37 (s, 3 H) ppm. 25 °C): δ = 200.2, 148.0, 146.8, 135.9, 120.6, 108.4, 108.0, 101.5,
13C NMR (75 MHz, CDCl3, 25 °C): δ = 189.5, 158.9, 141.8, 130.7,
101.1, 78.2, 68.3, 46.4, 37.4 ppm. FTIR (neat): ν = 2992, 2909,
˜
129.9, 126.2, 119.2, 101.1, 73.7. 67.4, 21.3 ppm. FTIR (neat): ν = 2796, 1731, 1499, 1250, 906, 1109, 643 cm–1. MS (ESI): m/z = 271.1
˜
3043, 2996, 2904, 1683, 1596, 1107 cm–1. MS (ESI): m/z = 217.1
[M + H]+, 239.1 [M + Na]+. C13H12O3 (216.24): calcd. C 72.21, H
5.59; found C 72.47, H 5.46.
[M + Na]+. C13H12O5 (248.23): calcd. C 62.90, H 4.87; found C
62.97, H 4.90.
(1S,2R,5R)-2-(4-Methoxyphenyl)-6,8-dioxabicyclo[3.2.1]octan-4-one
(7c): The general procedure for hydroarylation of 1 (1.0 g,
7.92 mmol) gave a mixture of 5c/7c, 1:4 (1.29 g, 70%). The reaction
mixture was dissolved in dioxane (10 mL) and stirred with KMnO4
(1.0 m, 10 mL) for 30 min. The reaction mixture was filtered
through silica, eluted with ethyl acetate, the filtrate concentrated
and the product purified by flash chromatography to give 7c as a
crystalline solid (1.03 g, 56%). M.p. 119–120 °C. [α]2D1 = –320 (c =
Methyl 2-[(1S,5R)-4-Oxo-6,8-dioxabicyclo[3.2.1]oct-2-en-2yl]benzo-
ate (5i): The general procedure for the Heck reaction of 1 (250 mg,
1.98 mmol) gave a product that was further crystallized from hot
iPr2O to give 5i as colorless crystals (181 mg, 35 %). M.p. 149–
150 °C. [α]2D1 = –447 (c = 1.09, CH2Cl2). 1H NMR (300 MHz,
CDCl3, 25 °C): δ = 8.06 (ddd, J = 7.5, 1.5, 1.5 Hz, 1 H), 7.57 (ddd,
J = 7.5, 7.5, 1.5 Hz, 1 H), 7.51 (ddd, J = 7.5, 1.5, 1.5 Hz, 1 H),
7.18 (dd, J = 7.5, 1.5 Hz, 1 H), 5.90 (dd, J = 1.3, 0.6 Hz, 1 H), 5.36
(d, J = 1.3 Hz, 1 H), 5.04 (dd, J = 4.0, 0.6 Hz, 1 H), 3.89 (s, 3 H),
3.84–3.73 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ =
188.9, 166.5, 163.9, 136.9, 133.0, 131.3, 130.1, 129.9, 128.7, 122.4,
1
0.51, CH2Cl2). H NMR (300 MHz, CDCl3, 25 °C): δ = 7.21–7.08
(m, 2 H), 6.92–6.81 (m, 2 H), 5.19 (s, 1 H), 4.63 (br. d, J = 5.2 Hz,
1 H), 4.16 (d, J = 7.6 Hz, 1 H), 4.04 (dd, J = 7.6, 5.2 Hz, 1 H),
3.78 (s, 3 H), 3.40 (d, J = 8.6 Hz, 1 H), 3.07 (dd, J = 16.8, 8.6 Hz,
1 H), 2.54 (dd, J = 16.8, 0.9 Hz, 1 H) ppm. 13C NMR (75 MHz,
CDCl3, 25 °C): δ = 200.5, 158.7, 134.1, 128.5, 114.1, 101.5, 78.2,
101.1, 76.6, 66.6, 52.7 ppm. FTIR (neat): ν = 3010, 2957, 2922,
˜
2851, 1707, 1693, 1265 cm–1. MS (ESI): m/z = 261.1 [M + H]+,
283.1 [M + Na]+. C14H12O5 (260.25): calcd. C 64.61, H 4.65; found
C 64.26, H 4.62.
68.2, 55.3, 45.9, 37.3 ppm. FTIR (neat): ν = 3061, 2983, 2836, 1753,
˜
1730, 1697, 1510, 1244, 1109 cm–1. MS (ESI): m/z = 257.1 [M +
Na]+. C13H14O4 (234.25): calcd. C 66.66, H 6.02; found C 66.40,
H 6.19.
General Procedure for Hydroarylation Reactions of 1: Aryl iodide
(1.2 equiv.), tri-o-tolylphosphine (2.0 mol-%), benzyldiethylamine
(4.5 equiv.) and Pd(OAc)2 (1.0 mol-%) were added to a stirred solu-
tion of (–)-LGO (1; 250 mg, 1.98 mmol) under N2 in DMF (5 mL),
and the reaction mixture was heated at reflux (80–110 °C) until the
reaction was complete according to TLC (1:3, ethyl acetate/hex-
anes). The resulting mixture was washed with H2O (10 mL) and the
aqueous phase extracted with CH2Cl2 (20 mL), then the combined
organic extracts were dried (MgSO4) and concentrated under re-
duced pressure. The products 7a–7c, 7h, and 7i were purified by
flash chromatography (1:19, ethyl acetate/toluene) and then further
purified as specified.
(1S,2R,5R)-2-(p-Tolyl)-6,8-dioxabicyclo[3.2.1]octan-4-one (7h): The
general procedure for hydroarylation of 1 (1.0 g, 7.92 mmol) gave
a mixture of 5h/7h, 1:3 (1.21 g, 70%). The reaction mixture was
dissolved in dioxane (10 mL) and stirred with KMnO4 (1.0 m,
10 mL) for 30 min. The biphasic mixture was filtered through silica,
eluted with ethyl acetate, and the product was purified by flash
chromatography (1:3, ethyl acetate/hexanes) to give colorless crys-
tals of 7h (940 mg, 54%). M.p. 91–93 °C. [α]2D3 = –340 (c = 0.15,
1
CH2Cl2). H NMR (300 MHz, CDCl3, 25 °C): δ = 7.19–7.05 (m, 4
H), 5.19 (s, 1 H), 4.65 (br. d, J = 5.2 Hz, 1 H), 4.16 (dd, J = 7.7,
1.0 Hz, 1 H), 4.04 (dd, J = 7.7, 5.2 Hz, 1 H), 3.40 (d, J = 8.7 Hz,
1 H), 3.06 (dd, J = 16.8, 8.7 Hz, 1 H), 2.56 (ddd, J = 16.8, 1.0,
1.0 Hz, 1 H), 2.33 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3,
25 °C): δ = 200.5, 139.0, 136.9, 129.4, 127.3, 101.5, 78.2, 68.2, 46.2,
(1S,2R,5R)-2-Phenyl-6,8-dioxabicyclo[3.2.1]octan-4-one (7a): The
general procedure for hydroarylation of 1 (1.0 g, 7.92 mmol) gave
a mixture of 5a/7a, 1:5.5 (1.11 g, 69%). A portion of the mixture
(5a/7a, 2:5, 0.50 g) was dissolved in ethyl acetate (5 mL) and stirred
with KMnO4 (1.0 m, 5 mL) for 3 h. The biphasic mixture was fil-
tered through silica, the filtrate concentrated under reduced pres-
sure and crystallized from iPr2O to give colorless crystals of 7a
(330 mg, 92% recovery). M.p. 104 °C (ref.[24] 68 °C). [α]1D9 = –342
37.1, 20.9 ppm. FTIR (neat): ν = 3047, 3000, 2954, 2924, 1737,
˜
1721, 1111 cm–1. MS (EI): m/z (%) = 218.1 (8) [M]+, 144.1 (53),
131.1 (85), 130.1 (22), 129.1 (100), 117.1 (24), 116.1 (20), 115.1 (38),
91.1 (37). C13H14O3 (218.25): calcd. C 71.54, H 6.47; found C
71.33, H 6.26.
1
(c = 0.33, CH2Cl2). H NMR (300 MHz, CDCl3, 25 °C): δ = 7.48–
Methyl 2-[(1S,2R,5R)-4-Oxo-6,8-dioxabicyclo[3.2.1]octan-2-yl]-
benzoate (7i): The general procedure for hydroarylation of 1 (1.0 g,
7.92 mmol) and purification by flash chromatography gave color-
less crystals of 7i (1.11 g, 53%). M.p. 113–116 °C. [α]2D5 = –277 (c
= 0.57, CH2Cl2). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 7.94 (dd,
J = 8.3, 1.5 Hz, 1 H), 7.50 (ddd, J = 8.3, 7.0, 1.5 Hz, 1 H), 7.38–
7.28 (m, 2 H), 5.18 (s, 1 H), 4.80 (br. d, J = 5.2 Hz, 1 H), 4.42 (d,
J = 8.8 Hz, 1 H), 4.22 (dd, J = 7.7, 0.9 Hz, 1 H), 4.07 (dd, J = 7.7,
5.2 Hz, 1 H), 3.87 (s, 3 H), 3.07 (dd, J = 17.2, 8.8 Hz, 1 H), 2.49
(ddd, J = 17.2, 0.9, 0.9 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3,
7.13 (m, 5 H), 5.21 (s, 1 H), 4.68 (br. d, J = 5.3 Hz, 1 H), 4.18 (dd,
J = 7.5, 1.0 Hz, 1 H), 4.06 (dd, J = 7.5, 5.3 Hz, 1 H), 3.44 (d, J =
8.7 Hz, 1 H), 3.09 (dd, J = 16.8, 8.7 Hz, 1 H), 2.60 (ddd, J = 16.8.
1.0, 1.0 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ =
200.3, 142.0, 128.8, 127.5, 127.3, 101.5, 78.1, 68.3, 46.6, 37.0 ppm.
FTIR (neat): ν = 3028, 2951, 1741, 1716, 1110 cm–1. MS (EI): m/z
˜
(%) = 204.1 (trace) [M]+, 130.1 (100), 129.1 (74), 117.1 (86), 115.1
(81), 104.1 (29), 91.1 (37), 77.1 (28). C12H12O3 (204.23): calcd. C
70.57, H 5.92; found C 70.35, H 5.80.
(1S,2R,5R)-2-(Benzo[d][1,3]dioxol-5-yl)-6,8-dioxabicyclo[3.2.1]- 25 °C): δ = 201.1, 167.7, 143.8, 132.6, 130.9, 128.8, 128.3, 127.0,
octan-4-one (7b): The general procedure for hydroarylation of 1
(0.50 g, 7.92 mmol) gave a mixture of 5b/7b, 1:4 (0.80 g, 93%). An
analytical sample of 7b was purified by careful flash chromatog-
raphy (1:19, ethyl acetate/toluene) to give colorless crystals. M.p.
101.5, 77.7, 68.6, 52.1, 42.6, 37.0 ppm. FTIR (neat): ν = 3000, 2953,
˜
2913, 1739, 1714, 1266, 1253, 1072 cm–1. MS (ESI): m/z = 263.1
[M + H]+, 285.1 [M + Na]+. C14H14O5 (262.26): calcd. C 64.12, H
5.38; found C 64.38, H 5.30.
Eur. J. Org. Chem. 2015, 6999–7008
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7005

K. P. Stockton, C. J. Merritt, C. J. Sumby, B. W. Greatrex
FULL PAPER
General Procedure for the Conjugate Reduction of 3a, 3b, and 3c:
To a suspension of CuBr (4 equiv.) in dry THF (20 mL) under N2
cooled to –5 °C was added a solution of sodium bis(2-methoxy-
ethoxy)aluminum hydride (Red-Al; 4 equiv., 60%, w/w), and the
reaction mixture was stirred for 10 min. The reaction mixture was
cooled to –65 °C, and enone 3a, 3c, or 3d (1 equiv.) was added and
the mixture stirred at this temperature for 10 min, then carefully
quenched with methanol. The resulting mixture was filtered
through a plug of silica and eluted with ethyl acetate. The filtrate
was then concentrated under reduced pressure, and the resulting
mixture was taken up in CH2Cl2 (20 mL) and filtered through Ce-
lite. The volatiles were removed under reduced pressure, and the
residue was purified by column chromatography (1:3, ethyl acetate/
hexanes) to give 13a, 13b, or 13c.
O2 had ceased and a negative test for peroxides was obtained
(starch/iodide). The mixture was then filtered through Celite, con-
centrated under reduced pressure and taken up in 1:1, THF/HCl
(1 m; 12 mL) and stirred for 3 h. The volatiles were removed under
reduced pressure, and the residue was purified by flash chromatog-
raphy (1:1–7:3, ethyl acetate/hexanes).
(3S,5S)-5-(Hydroxymethyl)-3-phenyldihydrofuran-2(3H)-one (14a):
Treatment of 13a (75 mg, 0.37 mmol) in accordance with the gene-
ral procedure gave a colorless oil that crystallized upon standing
(55 mg, 78%). M.p. 97–99 °C. [α]2D0 = +57.1 (c = 0.98, CH2Cl2). 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 7.47–7.16 (m, 5 H), 4.77–4.67
(m, 1 H), 4.04 (dd, J = 10.0, 8.2 Hz, 1 H), 3.94 (br. d, J = 11.9 Hz,
1 H), 3.69 (dd, J = 11.9, 2.8 Hz, 1 H), 3.17 (br. s, 1 H), 2.66 (ddd,
J = 13.2, 10.0, 4.5 Hz, 1 H), 2.43 (ddd, J = 13.2, 8.2, 8.2 Hz, 1 H)
(1S,3S,4R)-3-Phenyl-6,8-dioxabicyclo[3.2.1]octan-4-one (13a): ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 178.3, 137.5, 128.9,
Treatment of 3a (106 mg, 0.52 mmol) as per the general method 127.7, 127.5, 78.9, 64.1, 46.0, 32.6 ppm. FTIR (neat): ν = 3458,
gave 13a as a white crystalline solid (74 mg, 69%). M.p. 138–145 °C 3033, 2968, 1749, 1184, 1056, 1027 cm–1. MS (ESI): m/z = 193.1
(CH2Cl2/hexanes). [α]3D3 = –174 (c = 1.08, CH2Cl2). 1H NMR [M + H]+, 215.1 [M + Na]+. C11H12O3 (192.21): calcd. C 68.74, H
˜
(300 MHz, CDCl3, 25 °C): δ = 7.42–7.23 (m, 3 H), 7.20–7.10 (m, 2 6.29; found C 68.53, H 6.46.
H), 5.29 (s, 1 H), 4.85–4.73 (m, 1 H), 4.20 (br. d, J = 7.2 Hz, 1 H),
(3S,5S)-3-(Benzo[d][1,3]dioxol-5-yl)-5-(hydroxymethyl)dihydrofuran-
4.02 (ddd, J = 7.2, 5.4, 1.5 Hz, 1 H), 3.96 (dd, J = 11.9, 7.9 Hz, 1
H), 2.48 (dddd, J = 13.9, 11.9, 3.6, 1.5 Hz, 1 H), 2.35 (dddd, J =
13.9, 7.9, 1.5, 0.6 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3,
25 °C): δ = 199.8, 136.8, 128.9, 128.7, 127.5, 102.0, 73.5, 67.7, 47.8,
2(3H)-one (14b): To a solution of 13b (91 mg, 0.37 mmol) in
CH2Cl2 (1 mL) was added m-chloroperbenzoic acid (70%, 99 mg,
0.40 mmol), then p-TSA (30 mg, 0.17 mmol), and the reaction mix-
1
ture was stirred for 10 d. The H NMR spectrum of an aliquot of
39.7 ppm. FTIR (neat): ν = 3028, 2952, 2920, 1731 cm–1. MS (ESI):
˜
the reaction mixture showed 40% conversion of starting material
to desired lactone 14b and its formate ester derivative. The reaction
was quenched by pouring the mixture onto iron filings, and the
m/z = 205.0 [M + H]+, 227.0 [M + Na]+. HRMS: calcd. for
C12H12O3Na [M + Na]+ 227.0679; found: 227.0680.
(1S,3S,5R)-3-(Benzo[d][1,3]dioxol-5-yl)-6,8-dioxabicyclo[3.2.1]- mixture was stirred for 5 min until the evolution of O2 had ceased
octan-4-one (13b): Treatment of 3b (500 mg, 2.15 mmol) as per the
general method gave 13b as a colorless crystalline solid (306 mg,
61%). M.p. 122–126 °C (iPr2O). [α]2D1 = –140 (c = 0.35, CH2Cl2).
1H NMR (500 MHz, CDCl3, 25 °C): δ = 6.78 (d, J = 7.9 Hz, 1 H),
and a negative test for peroxides was obtained (starch/iodide). The
mixture was then filtered through Celite, concentrated under re-
duced pressure and taken up in 1:1, THF/HCl (1 m; 2 mL) and
stirred for 3 h. The volatiles were removed under reduced pressure,
6.63 (d, J = 1.8 Hz, 1 H), 6.60 (dd, J = 7.9, 1.8 Hz, 1 H), 5.95 (s, and the residue was purified by flash chromatography (7:3, ethyl
2 H), 5.27 (br. s, 1 H), 4.80 (dddd, J = 4.4, 3.4, 1.8, 0.8 Hz, 1 H), acetate/hexanes) to give 14b as a colorless syrup (17 mg, 50% based
4.19 (dd, J = 7.5, 0.9 Hz, 1 H), 4.03 (ddd, J = 7.5, 4.4, 1.4 Hz, 1 on conversion of starting material). [α]1D5 = +45 (c = 0.80, CH2Cl2).
H), 3.89 (dd, J = 11.8, 7.9 Hz, 1 H), 2.43 (dddd, J = 13.7, 11.8, 1H NMR (500 MHz, CDCl3, 25 °C): δ = 6.95–6.60 (m, 3 H), 5.96
3,4, 1.4 Hz, 1 H), 2.34 (dddd, J = 13.7, 7.9, 1.8, 0.9 Hz, 1 H) ppm.
13C NMR (75 MHz, CDCl3, 25 °C): δ = 200.0, 148.0, 147.0, 130.4,
122.2, 109.1, 108.5, 101.9, 101.1, 73.5, 67.7, 47.6, 40.0 ppm. FTIR
(s, 2 H), 4.74 (dddd, J = 8.2, 4.6, 4.1, 3.1 Hz, 1 H), 4.06–3.89 (m,
2 H), 3.74 (dd, J = 12.4, 4.1 Hz, 1 H), 2.66 (ddd, J = 13.1, 9.8,
4.6 Hz, 1 H), 2.43 (ddd, J = 13.1, 8.2, 8.2 Hz, 1 H), 2.12 (br. s, 1
(neat): ν = 2974, 2931, 2891, 1731, 1614, 1231, 1100 cm–1. MS H) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 177.6, 148.2,
˜
(ESI): m/z 249.1 [M + H]+. C13H12O5 (248.23): calcd. C 62.90, H
147.1, 131.0, 121.0, 108.6, 108.1, 101.2, 78.4, 64.5, 45.0, 32.7 ppm.
4.87; found C 63.06, H 4.65.
FTIR (neat): ν = 3450, 2950, 2922, 2852, 1765, 1736, 1233,
˜
1034 cm–1. MS (ESI): m/z = 259.1 [M + Na]+. HRMS: calcd. for
(1S,3S,5R)-3-(4-Methoxyphenyl)-6,8-dioxabicyclo[3.2.1]octan-4-one
(13c): Treatment of 3c (260 mg, 1.06 mmol) as per the general
method gave 13c as a colorless crystalline solid (134 mg, 54 %).
M.p. 99–102 °C (iPr2O). [α]2D2 = –152 (c = 0.29, CH2Cl2). 1H NMR
C12H12O5Na [M + Na]+ 259.0577; found 259.0573.
(3S,5S)-5-(Hydroxymethyl)-3-(4-methoxyphenyl)dihydrofuran-
2(3H)-one (14c): Treatment of 13c (115 mg, 0.49 mmol) in accord-
(300 MHz, CDCl3, 25 °C): δ = 7.10–7.00 (m, 2 H), 6.93–6.81 (m, 2 ance with the general procedure gave 14c as a white crystalline solid
H), 5.26 (s, 1 H), 4.86–4.68 (m, 1 H), 4.18 (br. d, J = 7.2 Hz, 1 H), (69 mg, 63%). M.p. 90–93 °C (toluene). [α]1D8 = +42.4 (c = 0.33,
1
4.00 (ddd, J = 7.2, 5.8, 1.3 Hz, 1 H), 3.91 (dd, J = 11.7, 7.9 Hz, 1 CH2Cl2); H NMR (500 MHz, CDCl3, 25 °C): δ = 7.23–7.14 (m, 2
H), 3.78 (s, 3 H), 2.43 (dddd, J = 13.5, 11.7, 3.4, 1.3 Hz, 1 H), 2.32 H), 6.95–6.82 (m, 2 H), 4.73 (dddd, J = 8.0, 5.0, 4.7, 2.7 Hz, 1 H),
(dddd, J = 13.5, 7.9, 0.9, 0.9 Hz, 1 H) ppm. 13C NMR (75 MHz,
4.06–3.93 (m, 2 H), 3.80 (s, 3 H), 3.74 (ddd, J = 12.2, 6.3, 5.0 Hz,
CDCl3, 25 °C): δ = 200.3, 158.8, 129.8, 128.7, 114.1, 101.8, 73.5, 1 H), 2.65 (ddd, J = 13.2, 9.8, 4.7 Hz, 1 H), 2.43 (ddd, J = 13.2,
67.6, 55.1, 46.9, 39.8 ppm. FTIR (neat): ν = 3036, 2985, 2952, 2931,
8.0, 8.0 Hz, 1 H), 2.07 (dd, J = 6.3, 6.3 Hz, 1 H) ppm. 13C NMR
˜
2840, 1731 1511, 1260, 1240, 1099 cm–1. MS (ESI): m/z = 235.1 [M (125 MHz, CDCl3, 25 °C): δ = 177.8, 159.0, 129.4, 128.7, 114.4,
+ H]+. C13H14O4 (234.25): calcd. C 66.66, H 6.02; found C 66.70,
H 6.10.
78.4, 64.5, 55.3, 45.1, 32.7 ppm. FTIR (neat): ν = 3499, 3421, 3032,
˜
3008, 2954, 2831, 1762, 1746, 1249, 1030 cm–1. MS (ESI): m/z =
223.1 [M + H]+, 245.0 [M + Na]+. C12H14O4 (222.24): calcd. C
64.85, H 6.35; found C 64.81, H 6.40.
General Procedure for the Baeyer–Villiger Oxidation of 5a, 7a, 7c,
7h, 13a, 13b, and 13c: Peracetic acid (32%, 600 μL, 2.78 mmol) was
added to a stirred solution of bicyclo[3.2.1]octane derivative
(1 mmol) dissolved in CH2Cl2 (3 mL), and the reaction mixture
was stirred overnight. The reaction was quenched with Pd/C (10%,
15 mg) and the mixture stirred for 20 min or until the evolution of
(S)-5-(Hydroxymethyl)-4-phenylfuran-2(5H)-one (15a): Treatment
of 5a (100 mg, 0.50 mmol) in accordance with the general pro-
cedure gave 15a as a white crystalline solid (78 mg, 92%). M.p.
1
135 °C (MeOH/Et2O). [α]1D7 = –172 (c = 0.25, CH2Cl2). H NMR
7006
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 6999–7008

Coupling Reactions on (–)-Levoglucosenone
(500 MHz, CD3OD, 25 °C): δ = 6.25–6.01 (m, 2 H), 5.99–5.86 (m, (1S,2S,5R)-2-Phenyl-6,8-dioxabicyclo[3.2.1]octan-4-one (17): To a
3 H), 4.94 (s, 1 H), 4.19 (br. dd, J = 3.8, 2.6 Hz, 1 H), 2.51 (dd, J
solution of 5a (202 mg, 1.0 mmol) in ethyl acetate (3 mL) was
= 12.7, 2.6 Hz, 1 H), 2.21 (dd, J = 12.7, 3.8 Hz, 1 H) ppm. 13C added Pd/C (10%; 20 mg), and the reaction mixture was stirred
NMR (125 MHz, CD3OD, 25 °C): δ = 175.7, 167.4, 132.6, 131.6, under H2 overnight. The reaction mixture was filtered through Ce-
130.4, 128.8, 116.3, 85.3, 62.8 ppm. FTIR (neat): ν = 3393, 3110,
lite and concentrated under reduced pressure to give a residue that
was then purified by column chromatography (1:3–1:1, ethyl acet-
ate/hexanes) to give a 10:1 mixture of isomers 17/7a (166 mg, 81%)
and alcohol 18 (30 mg, 15%). An analytical sample of 17 was ob-
tained by careful chromatography. 17: Crystalline solid. M.p. 83–
86 °C. [α]1D4 = –77.9 (c = 1.72, CH2Cl2). 1H NMR (500 MHz,
CDCl3): δ = 7.45–7.36 (m, 2 H), 7.35–7.29 (m, 1 H), 7.28–7.21 (m,
2 H), 5.18 (br. s, 1 H), 4.79–4.72 (m, 1 H), 4.14 (dd, J = 8.1, 1.1 Hz,
1 H), 3.82 (br. ddd, J = 12.5, 5.9, 3.7 Hz, 1 H), 3.78 (dddd, J =
8.1, 5.5, 0.9, 0.9 Hz, 1 H), 3.03 (dd, J = 15.6, 12.5 Hz, 1 H), 2.63
(dddd, J = 15.6, 5.9, 0.9, 0.9 Hz, 1 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 200.1, 136.9, 129.1, 127.8, 127.4, 100.9, 78.0, 64.2,
˜
2932, 1723, 1707, 1614, 1513 cm–1. MS (ESI): m/z = 191.1 [M +
H]+, 213.1 [M + Na]+. C11H10O3 (190.20): calcd. C 69.46, H 5.30;
found C 69.35, H 5.24.
(4R,5S)-5-(Hydroxymethyl)-4-phenyldihydrofuran-2(3H)-one
(16a):[25] Treatment of 7a (330 mg, 1.62 mmol) in accordance with
the general procedure afforded 16a as a straw-colored oil that crys-
tallized upon standing (279 mg, 90 %). M.p. 89–91 °C (iPr2O).
[α]1D9 = +41.6 (c = 0.89, CHCl3). 1H NMR (300 MHz, CDCl3,
25 °C): δ = 7.44–7.12 (m, 5 H), 4.61–4.43 (m, 1 H), 3.95 (d, J =
12.8 Hz, 1 H), 3.80–3.55 (m, 2 H), 3.03 (dd, J = 17.7. 9.0 Hz, 1 H),
2.78 (dd, J = 17.7, 9.6 Hz, 1 H), 2.35 (s, 1 H) ppm. 13C NMR
(125 MHz, CDCl3, 25 °C): δ = 176.1, 139.1, 129.1, 127.7, 127.2,
46.0, 35.9 ppm. FTIR (neat):
ν = 2989, 2917, 2852, 1735,
˜
1599 cm–1. MS (ESI): m/z = 227 [M + Na]+. HRMS: calcd. for
87.0, 61.9, 42.0, 37.2 ppm. FTIR (neat): ν = 3479, 3065, 3036, 2949,
˜
C12H12O3Na [M + Na]+ 227.0679; found 227.0677.
2926, 1762, 1743 cm–1. MS (ESI): m/z = 193.1 [M + H]+, 215.1 [M
+ Na]+.
(1S,2S,4S,5R)-2-Phenyl-6,8-dioxabicyclo[3.2.1]octan-4-ol (18): Col-
orless syrup. [α]1D8 = –50.4 (c = 1.17, CH2Cl2). 1H NMR (500 MHz,
CDCl3): δ = 7.45–7.32 (m, 2 H), 7.32–7.21 (m, 3 H), 5.43 (br. s, 1
H), 4.78–4.47 (m, 1 H), 3.95 (dd, J = 7.6, 0.6 Hz, 1 H), 3.85 (dddd,
J = 10.0, 10.0, 5.8, 1.7 Hz, 1 H), 3.68 (dd, J = 7.6, 5.2 Hz, 1 H),
3.38 (ddd, J = 12.8, 4.0. 4.0 Hz, 1 H), 2.32 (ddddd, J = 12.8, 5.8,
4.0, 1.4, 1.4 Hz, 1 H), 1.90 (ddd, J = 12.8, 10.0 Hz, 10.0 1 H), 1.78
(d, J = 10 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 138.6,
128.8, 127.5, 127.2, 102.5, 77.6, 69.5, 65.2, 42.7, 30.7 ppm. FTIR
(4R,5S)-5-(Hydroxymethyl)-4-(4-methoxyphenyl)dihydrofuran-
2(3H)-one (16c): Treatment of 7c (184 mg, 0.79 mmol) in accord-
ance with the general procedure afforded 16c as a colorless oil that
crystallized upon standing (116 mg, 66%). M.p. 92–93 °C (iPrOH/
Et2O). [α]2D0 = +22.7 (c = 0.75, CH2Cl2). 1H NMR (500 MHz,
CDCl3, 25 °C): δ = 7.22–7.14 (m, 2 H), 6.98–6.83 (m, 2 H), 4.50
(ddd, J = 8.2, 3.7, 2.4 Hz, 1 H), 3.95 (dd, J = 12.8, 2.4 Hz, 1 H),
3.81 (s, 3 H), 3.71–3.59 (m, 2 H), 3.00 (dd, J = 17.7, 9.2 Hz, 1 H),
2.76 (dd, J = 17.7 Hz, 10.1 1 H), 2.09 (br. s, 1 H) ppm. 13C NMR
(125 MHz, CDCl3, 25 °C): δ = 175.8, 159.2, 130.7, 128.3, 114.6,
(neat): ν = 3481, 3090, 2981, 2932, 2949, 2866, 1602 cm–1. MS
˜
(ESI): m/z = 229 [M + Na]+. HRMS: calcd. for C12H14O3Na [M
+ Na]+ 229.0835; found 229.0835.
87.0, 61.9, 55.3, 41.4, 37.3 ppm. FTIR (neat): ν = 3441, 2963, 2910,
˜
2840, 1757, 1733, 1610, 1029 cm–1. MS (ESI): m/z = 245.1 [M +
Na]+. C12H14O4 (222.24): calcd. C 64.85, H 6.35; found C 64.58,
H 6.22.
Single-Crystal X-ray Crystallography: Single crystals were mounted
in paratone-N oil on a plastic loop. X-ray diffraction data were
collected at 150(2) K with an Oxford X-calibur single-crystal dif-
fractometer by using Mo-Kα radiation.[26] Data sets were corrected
for absorption by using a multi-scan method, and structures were
solved by direct methods by using SHELXS-2014 and refined by
full-matrix least squares on F2 by SHELXL-2014,[27] interfaced
through the program X-Seed.[28] In general, all non-hydrogen
atoms were refined anisotropically and hydrogen atoms were in-
cluded as invariants at geometrically estimated positions, unless
specified otherwise in additional details below. Table S1 lists the X-
ray experimental data and refinement parameters for the crystal
structures. CCDC-1412235, -1412236, -1412237, -1412238,
-1412239, and -1412240 (for 3a, 3b, 3d, 5h, 7i, and 13a, respectively)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
(4R,5S)-5-(Hydroxymethyl)-4-(p-tolyl)dihydrofuran-2(3H)-one
(16h): Treatment of 7h (152 mg, 0.70 mmol) in accordance with the
general procedure afforded 16h as a colorless syrup (110 mg, 77%).
[α]2D1 = +29.2 (c = 0.24, CH2Cl2). 1H NMR (500 MHz, CDCl3,
25 °C): δ = 7.24–6.93 (m, 4 H), 4.44 (ddd, J = 7.9, 4.0, 2.4 Hz, 1
H), 3.86 (dd, J = 12.8, 2.4 Hz, 1 H), 3.66–3.50 (m, 2 H), 2.92 (dd,
J = 17.7, 9.0 Hz, 1 H), 2.68 (dd, J = 17.7, 9.8 Hz, 1 H), 2.56 (br.
s, 1 H), 2.26 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ
= 176.1, 137.5, 136.0, 129.8, 127.0, 87.1, 61.9, 41.6, 37.2, 20.9 ppm.
FTIR (neat): ν = 3417, 3025, 2923, 2869. 1769, 1755, 1516 cm–1.
˜
MS (ESI): m/z = 207.1 [M + H]+, 229.1 [M + Na]+. HRMS: calcd.
for C12H14O3Na [M + Na]+ 229.0835; found 229.0840.
Methyl 2-[(2S,3R)-2-(Hydroxymethyl)-5-oxotetrahydrofuran-3-yl]-
benzoate (16i): Treatment of 7i (152 mg, 0.58 mmol) in accordance
with the general procedure afforded 16i as a colorless syrup
(106 mg, 73%). [α]1D7 = +21.2 (c = 0.33, CH2Cl2). 1H NMR
(500 MHz, CDCl3, 25 °C): δ = 7.90 (dd, J = 7.9, 1.2 Hz, 1 H), 7.57
(ddd, J = 7.9, 7.7, 1.2 Hz, 1 H), 7.44 (dd, J = 7.9, 0.9 Hz, 1 H),
7.37 (ddd, J = 7.9, 7.7, 0.9 Hz, 1 H), 4.59 (ddd, J = 6.9, 3.7, 2.7 Hz,
1 H), 4.51 (ddd, J = 9.5, 7.3, 6.9 Hz, 1 H), 4.00–3.87 (m, 1 H), 3.93
(s, 3 H), 3.82 (ddd, J = 12.1, 6.1, 4.8 Hz, 1 H), 3.12 (dd, J = 18.0,
9.5 Hz, 1 H), 2.94 (dd, J = 6.1, 6.1 Hz, 1 H), 2.72 (dd, J = 18.0,
7.3 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 176.2,
168.2, 141.5, 132.9, 130.9, 129.9, 127.4, 127.3, 87.0, 62.8, 52.5, 38.1,
Acknowledgments
We acknowledge the kind donation of levoglucosenone from Mr.
Tony Duncan and Dr. Warwick Raverty from Circa, Melbourne
Australia. K. S. thanks the Australian government for an APA
scholarship.
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˜
1577 cm–1. MS (ESI): m/z = 251.1 [M + H]+, 273.1 [M + Na]+.
HRMS: calcd. for C13H14O5Na [M + Na]+ 273.0733; found
273.0734.
Eur. J. Org. Chem. 2015, 6999–7008
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7007

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Published Online: October 12, 2015
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