Synthesis of limonoid CDE fragments related to limonin and nimbinim

Article abstract of DOI:10.1016/j.tet.2010.07.020

A practical, brief and selective synthesis of limonoid CDE fragments from a readily available starting diketone is described. The key step is a cationic electrocyclization promoted by strong acids. In general the methodology has been demonstrated for comp

Full text of DOI:10.1016/j.tet.2010.07.020

Tetrahedron 66 (2010) 7257e7261
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Synthesis of limonoid CDE fragments related to limonin and nimbinim
,
a
a
a
b
A. Fernández-Mateos a , P. Herrero Teijón , G. Pascual Coca , R. Rubio González , M.S.J. Simmonds
*
a Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Salamanca, Plaza de los Caídos 1-5, 37008 Salamanca, Spain
b Jodrell Laboratory, Royal Botanic Garden, Kew, Richmond, Surrey, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
A practical, brief and selective synthesis of limonoid CDE fragments from a readily available starting
diketone is described. The key step is a cationic electrocyclization promoted by strong acids. In general
the methodology has been demonstrated for compounds with sensitive furane and thiophene sub-
stituents to obtain diverse substituted indenones. Several of the compounds obtained show significant
antifeedant activity against Spodoptera littoralis.
Received 1 March 2010
Received in revised form 28 June 2010
Accepted 9 July 2010
Available online 16 July 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Limonoids
Nazarov cyclization
Antifeedant
Nimbinim
Limonim
1. Introduction
The limonoids are a family of natural products that have been
used in folk and popular medicine for centuries.1
Prominent members of this family are limonin, nomilin, oba-
cunone and gedunin, which share a common CDE ring system and
have shown multiple bioactivities; among others, they have anti-
cancer, cholesterol-lowering, antiviral and antimalarial properties.2
Moreover limonin, nomilin and clausenolide with a C-11 oxygen-
ated function have shown anti-HIV activity3 (Fig. 1).
Related to them structurally are their potential biogenetic pre-
cursors: azadiradione, nimbocinol and nimbinim, with proven in-
sect antifeedant activity.1 Despite the significant bioactivity, little
synthetic effort has been invested in these natural products.4
Studies directed to the synthesis of related model compounds
have been conduced to find simple analogues that display similar
biological activities.5 A successful example is the CDE structural
fragment of the limonoid nimbinim, which has been shown to be
a potent antifeedant and also to have anti-HIV properties6 (Fig. 2).
Over the past few years we have developed a procedure aimed at
the synthesis of model limonoids, based on D ring construction by
cationic electrocyclization of dienones.7 The method can be adapted
by tuning the vicinal function to the synthesis of the CDE structural
fragments of limonoids with an oxygenated function at the position
C-11/C-12. Limonoids with this functionality are among the most
active of this family of naturally occurring compounds.1,2
* Corresponding author. Tel.: þ34 923 294481; fax: þ34 923 294574; e-mail
address: afmateos@usal.es (A. Fernández-Mateos).
Figure 1. Structures of limonoids.
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.07.020

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A. Fernández-Mateos et al. / Tetrahedron 66 (2010) 7257e7261
Scheme 2. Synthesis of 11a from diketone 7. Reaction conditions: (a) LiAlH4, THF,
ꢀ78 ꢁC; (b) m-CPBA, CH2Cl2, ꢀ40 ꢁC; (c) pTsOH, toluene, reflux; (d) PCC, CH2Cl2, rt.
Figure 2. Structures of limonoids and CDE fragment.
2. Results and discussion
2.1. Synthesis of furyl derivatives
Here we describe the synthesis of CDE fragments related to the
above limonoids by a route, that is, both short and stereocontrolled.
The most important step of the synthesis rely on a Nazarov type re-
action used by us with analogues aryl substrates7d,e (Schemes 1e4).
Our synthesis starts with a four-step sequence to assemble all the
carbonsrequiredfortheconstructionof thelimonoidfragmentDring.
The readily available ketoenone 17d underwent sequential chemo-
selective reduction, aldolic condensation with 3-furaldehyde, oxida-
tion and enol-acetylation to give the trienone 5 in good yield. This
compound has the structure and functionalization required to pro-
vide the cationic electrocyclization, which will afford the CDE ring
system.
Scheme 3. Oxidation of enone 11a. Reaction conditions: (a) UHP, NaOH, MeOH,
ꢀ20 ꢁC; (b) H2O2, NaOH, MeOH, 0 ꢁC.
Scheme 4. Synthesis of CDE fragments 24 and 25 from ketone 2. Reaction conditions:
(a) Thienyl/CHO, NaOH, EtOH, ꢀ20 ꢁC; (b) Jones, CH3COCH3, 0 ꢁC; (c) (i) NaH, DMPU,
THF, rt; (ii) Ac2O, THF, rt; (d) HClO4ꢂ10ꢀ2 M, Ac2O, AcOEt; (e) NaBH4, CeCl3$7H2O,
MeOH, 0 ꢁC; (f) m-CPBA, CH2Cl2, rt; (g) p-TsOH, toluene, reflux.; (h) UHP, NaOH, MeOH,
ꢀ20 ꢁC; (i) H2O2, NaOH, MeOH, 0 ꢁC.
Scheme 1. Synthesis of enones 11a/11b from diketone 1.Reaction conditions: (a)
NaBH4, CeCl3$7H2O, MeOH, ꢀ40 ꢁC; (b) Fur-CHO, NaOH, EtOH, ꢀ20 ꢁC; (c) Jones,
CH3COCH3, 0 ꢁC; (d) (i) NaH, DMPU, THF, rt; (ii) Ac2O, THF, rt; (e) HClO4 10ꢀ2 M, Ac2O,
AcOEt; (f) KOH, MeOH, 0 ꢁC; (g) (CH2OH)2, TsOH, Benzene, reflux.; (h) LiAlH4, ether,
Although the furane ring in enone 5 is extremely sensitive to the
very strong acidic conditions required to carry out the Nazarov
cyclization, we will demonstrate in this paper that this type of
0
ꢁC; (i) m-CPBA, CH2Cl2, ꢀ40 ꢁC; (j) pTsOH, toluene, reflux.

A. Fernández-Mateos et al. / Tetrahedron 66 (2010) 7257e7261
7259
reaction is viable, using as reagent a dilute solution of perchloric
acid in a mixture of acetic anhydride and ethyl acetate, that we have
used successfully in precedent works.7d,e,l In these conditions, the
cyclization is sufficiently fast to prevent the damage to the furane.
The reaction of enol acetate 5 with a 10ꢀ2 M perchloric acid solu-
tion was instantaneous, giving the ketoester 6 in 60% yield. This
result is somewhat lower compared with the analogue phenyl
derivative, which yield the Nazarov product quantitatively.7d After
the quantitative acetate hydrolysis of 6 we obtained the ketoenone
7. We next turned our attention to the efficient functionalization of
the D ring. First, diketone 7 was selectively protected to provide the
monoketal enone 8 in 86% yield. This transformation is done to
direct7d the reduction of the carbonyl group, stereoselectively by
the endo face of the molecule, by coordination of the reagent
(LiAlH4) to the acetal oxygen. Reduction of ketone 8 with LiAlH4 in
ether at 0 ꢁC afforded the unsaturated alcohol 9 quantitatively. The
next step towards the limonoid functionalization of the D ring was
the obtention of an epoxy-alcohol, which by rearrangement would
provide the desired enone system. Thus, treatment of 9 with m-
chloroperoxybenzoic acid gave in an exo stereoselective manner7d
the epoxy-alcohol 10. The subsequent treatment of 10 with TsOH
in degassed toluene under reflux afforded a 2:1 epimeric mixture of
the unsaturated diketones 11a and 11b in 76% overall yield.
An alternative and more stereoselective route to the fragment
11a were devised from diketone 7. The sequence consists of four
steps: stereoselective reduction of 7 with LiAlH4 in THF at ꢀ78 ꢁC to
give the diol 12; subsequent stereoselective epoxidation to epox-
ydiol 13, followed by rearrangement with p-TsOH to the enone 14a
and further oxidation with PCC to afford the diketone 11a 74%
overall yield.
thienyl azadiradione fragment 23a by the same methods as the
furyl derivatives.
3. Biological activity
Larvae of the African cotton leafworm Spodoptera littoralis were
used to assess the antifeedant activity of our racemic CDE limonoid
fragments of nimbinim 15 and 24, which show an antifeedant index
of 45 and 24, respectively.8 The furyl 15 exhibited the best anti-
feedant value when compared with the thienyl or phenyl
fragments.7d
4. Experimental section
4.1. General methods
Melting points are uncorrected. 1H NMR spectra were measured
at either 200 or 400 MHz and 13C NMR were measured at 50 or
100 MHz in CDCl3 and referenced to TMS (1H) or solvent (13C),
except where indicated otherwise. IR spectra were recorded for
neat samples on NaCl plates, unless otherwise noted. Standard
mass spectrometry data were acquired by using GCeMS system in
EI mode with a maximum m/z range of 600. When required, all
solvents and reagents were purified by standard techniques: tet-
rahydrofuran (THF) was purified by distillation from sodium and
benzophenone ketyl and degassed before use. Dimethylformamide
(DMF) was dried over CaH2, distilled. Under reduced pressure and
degassed before use. All reactions were conducted under a positive
pressure of argon, utilizing standard bench-top techniques for the
handling of air-sensitive materials. Chromatographic separations
were carried out under pressure on silica gel using flash column
techniques on Merck silica gel 60 (0.040e0.063 mm). Yields
reported are for chromatographically pure isolated products unless
otherwise mentioned.
The target compounds, the CDE fragment of nimbinim and rel-
atives 15, and CDE limonin fragment of 16, were obtained selec-
tively by oxidation of enone 11a with urea-hydrogen peroxide
complex at ꢀ20 ꢁC, and hydrogen peroxide at 0 ꢁC, respectively, in
good yields. In both cases, a trans configuration was assigned to the
oxiranic oxygen with respect to the angular methyl group, after
the usual endocyclic attack, and on the basis of the upfield shift of
the 13C NMR signal for the homoallylic carbon bearing an axial
hydrogen cis to the oxirane.
4.1.1. (E)-3-(Furan-3-yl)-1-(4-hydroxy-2,6,6-trimethylcyclohex-2-
enyl) prop-2-en-1-one (3). To a solution of the hydroxyketone 2
(5.10 g, 28.0 mmol) and 3-furylaldehyde (2.69 g, 28.0 mmol) in
ethanol (34 mL) at ꢀ20 ꢁC was gradually added NaOH (2.24 g,
50.0 mmol) in H2O (6 mL). The reaction was stirred vigorously for
2 h at ꢀ20 ꢁC. The mixture was concentrated in vacuo to afford
a residue, which was dissolved with water and extracted with
diethyl ether. The organic layers were washed with brine, dried and
filtered. The solvent was evaporated, and the residue was purified
by flash chromatography using hexane/diethylether (7:3) to give
a product identified as the hydroxyketone 3 as a colourless oil
2.2. Synthesis of thienyl derivatives
The methodology employed for the synthesis of CDE limonoid
fragments 15 and 16 was applied to the thienyl analogues, in which
the furane is substituted by the thiophene ring.
Thus, a synthetic sequence parallel to the one described above
was developed from hydroxyketone 2 to indenone 20, with an
overall yield of 42%. The electrocyclization step, 19e20, took place
in better yield (85%), than for the furyl derivative (60%). This result
could be explained by the more robust character against strong
acids of the thienyl derivative. The reduction of indenone 20 was
done with sodium borohydride and cerium trichloride at 0 ꢁC to
afford, after hydrolysis, the unsaturated alcohol 21, with the hy-
droxyl group trans respects the angular methyl group.7d The oxi-
dation of 21 afforded only the exo-epoxide 22. It is worth noting
that reduction and epoxidation occurred by the same exo face of
molecules 20 and 21, while the reduction of related 7 and 8 took
place by the endo face. Brief exposure of epoxide 22 to p-TsOH at
100 ꢁC provided three isomeric tricyclic ketones at a 79:7:14 ratio,
with ketone 23c as the major component. The predominating di-
astereomer in the other two products mixture was 23a in which the
furane is cis respect to the angular methyl group. The trans isomer
23b could be isomerized to 23a by treatment of the crude mixture
with acid or base. The thienyl derivatives of CDE nimbinim frag-
ment 24, and CDE limonin fragment 25 was obtained from the
(5.61 g, 77%): IR,
n
(liquid film) 3435, 2961, 1661, 1607 cmꢀ1
;
1H
NMR (200 MHz CDCl3)
(s, 1H), 1.69 (s, 1H), 2.98 (br s, 1H), 4.44 (m, 1H), 5.91 (br s, 1H), 6.63
d
: 0.91 (s, 3H), 1.00 (s, 3H), 1.62 (m, 3H), 1.65
(m,1H), 6.64 (d, J¼16 Hz,1H), 7.45 (m,1H) 7.54 (d, J¼16 Hz,1H), 7.72
(m, 1H) ppm; 13C NMR (50 MHz CDCl3)
d: 23.0 (CH3), 28.4 (CH3),
28.7 (CH3), 35.0 (C), 41.0 (CH2), 62.2 (CH), 65.7 (CH), 107.7 (CH),
123.0 (C), 126.2 (CH), 128.3 (CH), 132.7 (CH), 133.1 (C), 144.5 (CH),
145.6 (CH), 201.2 (C) ppm; HRMS (ESI): MNaþ, found 283.1321.
C16H20O3Na requires 283.1310.
4.1.2. (3aR
*
,7aS
*
)-3-(Furan-3-yl)-3a,7,7-trimethyl-1-oxo-3a,6,7,7a-
(2.57 g,
tetrahydro-1H-inden-5-yl acetate (6). Compound
5
8.6 mmol) was dissolved in 230 mL of the 10ꢀ2 M HClO4 reagent,
and the solution was allowed to stand under argon for 18 h at room
temperature. The solution was washed with saturated sodium bi-
carbonate solution and extracted with ethyl acetate. The combined
organic layers were washed with sodium carbonate solution and
brine, dried and evaporated. The remaining residue was flash
chromatographed (hexane/diethylether, 7:3) to yield the acetate 6
as a colourless oil (1.54 g, 60%): IR,
n (liquid film) 3174, 2961, 1750,

7260
A. Fernández-Mateos et al. / Tetrahedron 66 (2010) 7257e7261
1684 cmꢀ1
;
1H NMR (200 MHz CDCl3)
d
: 0.92 (s, 3H), 1.27 (s, 3H),
142.9 (CH), 207.1 (C), 207.4 (C) ppm; MS EI, m/z (relative intensity):
1.49 (s, 3H), 1.91 (d, J¼16 Hz, 1H), 2.11 (s, 3H), 2.12 (s, 1H), 2.30 (dd,
274 (Mþ, 10), 190 (37), 176 (83), 108 (100), 91 (36), 69 (53), 55 (56);
HRMS (ESI): MNaþ, found 297.1112. C16H18O4Na requires 297.1103.
J1¼16 Hz, J2¼2 Hz, 1H), 5.70 (d, J¼2 Hz, 1H), 6.08 (s, 1H), 6.58 (m,
1H), 7.49 (m, 1H), 7.80 (m, 1H) ppm; 13C NMR (50 MHz CDCl3)
d:
20.9 (CH3), 23.9 (CH3), 28.9 (CH3), 31.1 (CH3), 35.4 (C), 41.7 (CH2),
48.0 (C), 63.4 (CH),110.0 (CH),115.2 (CH),119.6 (C),126.8 (CH),142.3
(CH), 143.9 (CH), 148.3 (C), 168.8 (C), 169.8 (C), 207.4 (C) ppm; m/z
(relative intensity): 300 (Mþ, 5), 258 (33), 243 (100), 91 (31), 77
(10), 55 (59); HRMS (ESI): MNaþ, found 323.1268. C18H20O4Na re-
quires 323.1259.
4.1.6. (1S
*
,4S
*
,4aS
*
,8aR
*
)-4,4a-Epoxy-1-(furan-3-yl)-5,5,8a-tri-
(16). To
methyl-5,6-dihydro-1H-isochromene-3,7(8H,8aH)-dione
a stirred solution of diketone 11a (26 mg, 0.1 mmol) in methanol
(0.5 mL) maintained under argon at 0 ꢁC was added H2O2 (0.1 mL,
30%). Then a solution of NaOH (0.2 mL, 6 M, 1.2 mmol) was added
dropwise. The resulting solution was stirred for 40 min at this
temperature and then poured into a solution of NaHSO3 (10%). The
aqueous solution was extracted with diethyl ether, dried and fil-
tered. Removal of the solvent afforded the epoxide compound 16
4.1.3. (3a0R
*
, 7a0S )-30-(Furan-3-yl)-3a0,70,70-trimethyl-
*
3a0,40,70,7a0-tetrahydrospiro[[1,3]dioxolane-2,50-inden]-10(60H)-one
(8). The diketone 7 (483 mg, 1.8 mmol), ethyleneglycol (223 mg,
3.6 mmol) and a catalytic amount of TsOH were heated to 80 ꢁC in
anhydrous benzene (25 mL) under argon for 12 h with a Dean and
Stark apparatus. Saturated sodium bicarbonate was added, and the
mixture was extracted with diethyl ether. The combined ethereal
layers were washed with aqueous NaHCO3 (10%) and brine, dried,
filtered and evaporated in vacuo to give a clear oil. Purification by
flash chromatography (hexane/diethylether, 8:2) gave the com-
(22 mg, 76%): IR,
CDCl3)
n
(liquid film) 1694, 1593 cmꢀ1; 1H NMR (400 MHz
d
: 0.98 (s, 3H), 1.13 (s, 3H), 1.27 (s, 3H), 2.08 (dd, J1¼2 Hz,
J2¼13 Hz, 1H), 2.33 (dd, J1¼2 Hz, J2¼14 Hz, 1H), 2.53 (d, J¼13 Hz,
1H), 2.64 (d, J¼14 Hz,1H), 3.81 (s,1H), 5.77 (s,1H), 6.30 (m,1H), 7.40
(m, 1H), 7.42 (m, 1H) ppm; 13C NMR (100 MHz CDCl3)
d: 17.2 (CH3),
25.7 (CH3), 27.6 (CH3), 38.4 (C), 42.6 (C), 47.5 (CH2), 52.8 (CH2), 53.3
(CH), 68.5 (C), 77.6 (CH), 109.6 (CH), 119.1 (C), 141.2 (CH), 143.4 (CH),
166.7 (C), 206.5 (C) ppm; MS EI, m/z (relative intensity): 290 (Mþ,
4), 233 (50), 167 (78), 137 (82), 109 (100), 67 (62), 55 (62); HRMS
(ESI): MNaþ, found 313.1063. C16H18O5Na requires 313.1052.
pound 8 (481 mg, 86%): IR,
NMR (200 MHz CDCl3) : 0.85 (s, 3H), 1.22 (s, 3H), 1.38 (s, 3H),
1.7e2.1 (m, 5H), 3.7e4.0 (m, 4H), 6.09 (s, 1H), 6.52 (m, 1H), 7.40 (m,
1H), 7.75 (m, 1H) ppm; 13C NMR (50 MHz CDCl3)
: 23.4 (CH3), 28.8
n
(liquid film) 3148, 1684, 1607 cmꢀ1; 1H
d
d
Acknowledgements
(CH3), 32.4 (CH3), 33.5 (C), 41.8 (CH2), 45.9 (C), 48.6 (CH2), 63.5 (CH),
63.6 (CH2), 63.8 (CH2), 109.0 (CH), 110.0 (C), 119.7 (C), 127.1 (CH),
142.7 (CH), 143.7 (CH), 173.1 (C), 207.9 (C) ppm; MS EI, m/z (relative
intensity): 302 (Mþ, 24), 287 (25), 245 (7), 174 (24), 127 (100), 113
(73), 67 (8), 55 (31); HRMS (ESI): 325.1421 (MþþNa, C18H22O4Na),
calcd 325.1416.
Financial support for this work from the Ministerio de Ciencia y
Tecnología of Spain (CTQ2005-05026/BQU) and the Junta de Cas-
tilla y León (SA079A06) is gratefully acknowledged. We also thank
the Universidad de Salamanca for the fellowship to P.H.T.
Supplementary data
4.1.4. (1R
*
,6S
*
,7aS )-1-(Furan-3-yl)-6-hydroxy-4,4,7a-trimethyl-
*
5,6,7,7a-tetrahydro-1H-inden-2(4H)-one (14). To a solution of ep-
oxide alcohol 13 (52 mg, 0.19 mmol) in degassed toluene (3 mL)
was added a catalytic amount of TsOH, and the mixture was heated
at reflux under argon for 30 min. Then, a saturated solution of
NaHCO3 was added, and the mixture was extracted with diethyl
ether. The extracts were washed with H2O and brine and dried. The
solvent was evaporated under reduced pressure to afford a crude
oil. Purification by flash chromatography (hexane/diethylether, 6:4)
Experimental procedures and copies of 1H and 13C NMR spectra
for all new compounds can be found. Supplementary data associ-
ated with this article can be found in online version at. doi:10.1016/
j.tet.2010.07.020. These data include MOL files and InChIKeys of the
most important compounds described in this article.
References and notes
gave (1R
7,7a-tetrahydro-1H-inden-2(4H)-one 14 (35 mg, 71%): IR,
film) 3430, 1699 cmꢀ1 1H NMR (400 MHz CDCl3)
: 1.02 (s, 3H),
*
,6S
*
,7aS
*
)-1-(furan-3-yl)-6-hydroxy-4,4,7a-trimethyl-5,6,
1. (a) Dreyer, D. L. Prog. Chem. Org. Nat. Prod. 1968, 26, 190e244; (b) Connolly, J. D.;
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n
(liquid
;
d
1.29 (s, 3H), 1.31 (s, 3H), 1.4e2.3 (m, 4H), 3.49 (s, 1H), 4.21 (m, 1H),
6.01 (m, 1H), 6.23 (m, 1H), 7.42 (m, 2H) ppm; 13C NMR (100 MHz
CDCl3) d: 26.0 (CH3), 28.4 (CH3), 31.1 (CH3), 36.4 (C), 47.7 (CH2), 48.6
(C), 49.3 (CH2), 60.0 (CH), 64.1 (CH), 111.1 (CH), 118.3 (C), 125.5 (CH),
141.5 (CH), 142.8 (CH), 188.9 (C), 205.7 (C) ppm; HRMS (ESI): MNaþ,
found 283.1318. C16H20O3Na requires 283.1310.
4.1.5. (1R
*
,3S
*
,3aS
*
,7aS )-3,3a-Epoxy-1-(furan-3-yl)-4,4,7a-tri-
*
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Napaswat, C.; Kasisit, J.; Yoosook, C. Phytother. Res. 2003, 17, 1101e1103.
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Pardeshi, V. H.; Thriveni, P. Tetrahedron: Asymmetry 2008, 19, 1392e1396.
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Tokoroyama, T.; Fukuyama, Y.; Kotsuji, Y. J. Chem. Soc., Perkin Trans. 1 1988,
445e450; (c) Bentley, M. D.; Rajab, M. S.; Mendel, M. J.; Alford, A. R. J. Agric. Food
Chem. 1990, 38, 1400e1403; (d) Fernández-Mateos, A.; de la Fuente, J. A. J. Org.
methyl-4,5-dihydro-1H-indene-2,6(7H,7aH)-dione (15). To a stirred
solution of diketone 11a (70 mg, 0.3 mmol) in methanol (1 mL)
maintained under argon at ꢀ20 ꢁC was added UHP (51 mg,
0.5 mmol). Then a solution of NaOH (0.2 mL, 6 M, 1.2 mmol) was
added. The resulting solution was stirred for 50 min at this tem-
perature and then poured into a solution of NaHSO3 (10%). The
aqueous solution was extracted with diethyl ether, dried and fil-
tered. Removal of the solvent afforded the epoxide compound 15
(60 mg, 81%): IR,
CDCl3) : 0.89 (s, 3H), 1.02 (s, 3H), 1.30 (s, 3H), 2.45 (m, 2H), 2,72 (d,
J¼14 Hz, 1H), 2.75 (d, J¼14 Hz, 1H), 3.67 (s, 1H), 4.03 (s, 1H), 6.17 (m,
1H), 7.42 (m, 1H), 7.46 (m, 1H) ppm; 13C NMR (100 MHz CDCl3)
n
(liquid film) 1755, 1713 cmꢀ1; 1H NMR (400 MHz
d
d:
21.2 (CH3), 27.0 (CH3), 27.2 (CH3), 37.3 (C), 45.5 (C), 49.7 (CH2), 50.3
(CH), 54.4 (CH2), 58.0 (CH), 73.3 (C), 110.8 (CH), 115.4 (C), 141.7 (CH),

A. Fernández-Mateos et al. / Tetrahedron 66 (2010) 7257e7261
7261
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