A novel route towards the synthesis of spirocyclic bislactones

Article abstract of DOI:10.1055/s-2008-1078489

A novel route towards the synthesis of 1,7-dioxaspiro[4.4]nonane-2,6- diones, based on the versatile reactivity of an acyclic trimethylenemethane dianion synthon, is presented. Thieme Stuttgart.

Full text of DOI:10.1055/s-2008-1078489

LETTER
1627
A Novel Route Towards the Synthesis of Spirocyclic Bislactones
Synthesisof
S
r
pirocycl
a
nes cisco Alonso,* Jaisiel Meléndez, Miguel Yus*
Departamento de Química Orgánica, Facultad de Ciencias and Instituto de Química Orgánica (ISO), Universidad de Alicante, Apdo. 99,
03080 Alicante, Spain
Fax +34(96)5903549; E-mail: falonso@ua.es; E-mail: yus@ua.es
Received 4 March 2008
Dedicated to Professor Manfred Reetz on the occasion of his 65th birthday
HO
OH
Abstract: A novel route towards the synthesis of 1,7-dioxa-
spiro[4.4]nonane-2,6-diones, based on the versatile reactivity of an
acyclic trimethylenemethane dianion synthon, is presented.
O
HO2C
O
OH
O
Key words: trimethylenemethane, dianion synthon, lithiation,
OH
spirocyclization, bislactones
O
O
O
O
O
I
II
1,7-Dioxaspiro[4.4]nonanes1 are abundant substructures
present in a variety of natural products with diverse bio-
logical activities, some representative examples of these
type of compounds being prehispanolone,2 leopersin J,3
and sphydrofuran.4 1,7-Dioxaspiro[4.4]nonanes can be
also found in nature in the form of monolactones, such as
longianone,5 hyperolactone A,6 and secosyrins 1 and 2,7 as
well as in the form of bislactones. Among the latter, it is
worth mentioning forbic acid (I, from the leaves of E.
elegans),8 leudrin (II, present in some genera of Proteace-
ae),9 dichotomain B (III, from the fronds of Dicranopteris
dichotoma, which showed anti-HIV-1 activity)10 or
cinatrin A (IV, a potent inhibitor of rat platelet phospholi-
pase A2, from the fermentation broth of the microorgan-
ism Circinotrichum falcatisporum).11 In addition, 1,7-
dioxaspiro[4.4]nonane-2,6-diones, have also been used as
valuable scaffolds in the synthesis of natural products
(e.g. V, in zaragozic acid synthesis,12 Figure 1).
O
OH
O
O
OH
O
HO
O
O
OH
O
O
H
III
OH
OH
HO
CO2H
O
O
O
CO2Me
8
O
O
O
OTMS
OTBDPS
O
IV
V
Figure 1 Examples of 1,7-dioxaspiro[4.4]nonane-2,6-diones
OH
R2
(i)–(iii)
MeO
R1
O
Cl
R4
R3
R5
OH
The unique structural nature of these spirobislactones has
attracted the interest of synthetic organic chemists.13 The
methodologies described in the literature, however, nor-
mally involve intramolecular cyclizations on a preformed
g-lactone ring. The lactonization of 2-carboxy-2-hydroxy-
ethyl-g-lactones14 and the iodolactonization of 2-allyl-2-
carboxy-g-lactones15 are among the most general meth-
ods, whereas the ruthenium-catalyzed carbonylative cy-
cloaddition of a-ketolactones with ethylene,16 as well as
the oxidation of 3-hydroxyethylcyclopentane-1,2-
diones17 are of more particular application. At any rate,
and to the best of our knowledge, the synthesis of 1,7-di-
oxaspiro[4.4]nonane-2,6-diones through the double in-
tramolecular cyclization of a complete acyclic precursor
has never been reported.
R4
R2
R1
R4
R2
R1
O
(iv)
(v)
R3
R5
O
R3
R5
O
O
O
Scheme 1 Reagents and conditions: (i) Li, DTBB (cat.), R1R2CO,
THF, –78 to 0 °C; (ii) R3R4C(O)CHR5, 0–20 °C; (iii) H2O; (iv) I2,
Ag2O, THF or dioxane–H2O, 20 °C; (v) RuO2 (cat.), NaIO4, CCl4–
H2O, 20 °C.
spirocyclic19 polyether skeletons as constituents of impor-
tant biologically active compounds. In particular, we re-
ported the two-step synthesis of 1,7-dioxa-
spiro[4.4]nonanes19c,19d from the versatile trimethyl-
enemethane dianion synthon, 2-chloromethyl-3-(2-
methoxyethoxy)propene (Scheme 1).18b The whole se-
quence involved selective initial lithiation in the presence
of a carbonyl compound, second lithiation and reaction
with an epoxide, and iodocyclization. Additionally, the
compounds obtained could be oxidized to the correspond-
ing 1,7-dioxaspiro[4.4]nonan-6-ones in excellent yields.
On the other hand, in recent years we have shown an in-
creasing interest in the synthesis of bicyclic18 and
SYNLETT 2008, No. 11, pp 1627–1630
x
x
.x
x
.2
0
0
8
Advanced online publication: 11.06.2008
DOI: 10.1055/s-2008-1078489; Art ID: D06808ST
© Georg Thieme Verlag Stuttgart · New York

1628
F. Alonso et al.
LETTER
R2
R2
R2
(i)
R1
MeO
R1
O
(i)
R1
O
O
Cl
Li
HO
OLi
OH
1
5
4
2
(ii,iii)
O
O
R2
R2
O
R1
R1
(iv)
O
HO
THPO
5a
5b
OH
OH
4
3
Scheme 3 Reagents and conditions: (i) I2, Ag2O, THF, 20 °C, 24 h
(5a, 83%; 5b, 89%).
HO
HO
formed with a catalytic amount of PTSA in methanol, to
furnish the corresponding methylidene diols 4 in quantita-
tive yields.24
OH
OH
4a
4b
The isolated diols 4a and 4b were subjected to double in-
tramolecular cyclization by treatment with iodine and sil-
ver(I) oxide in THF at room temperature.25 The
corresponding 1,7-dioxaspiro[4.4]nonanes 5 were ob-
tained in high yields and with such a high purity that they
did not need any further purification (Scheme 3).
HO
HO
4c
Scheme 2 Reagents and conditions: (i) Li, DTBB (2.5 mol%),
R1R2CO, THF, –78 to 0 °C, 3.5 h; (ii) ICH2CH2OTHP, 0–20 °C, 3.5
h (3a, 43%; 3b, 45%; 3c, 42%); (iii) H2O; (iv) PTSA, MeOH, 1 h
(4a–c, quantitative yield).
We believed that the spirocyclic compounds synthesized
5 could be used as adequate precursors of the 1,7-dioxa-
spiro[4.4]nonane-2,6-diones 6. As an example, 1,7-dioxa-
spiro[4.4]nonane 5b was successfully transformed into
the corresponding spirocyclic bislactone 6b by oxidation
with a system composed of catalytic ruthenium(IV) oxide
and sodium periodate.26 The yield obtained for 6b was
high without the need of any further purification
(Scheme 4). The structure of 6b was unambiguously con-
firmed by X-ray crystallography (Figure 2).
This methodology, however, did not allow access to the
corresponding 1,7-dioxaspiro[4.4]nonane-2,6-diones, due
to the presence of one or two substituents at the 2-posi-
tion. We wish to present herein our preliminary results on
the synthesis of spirocyclic bislactones of the 1,7-dioxa-
spiro[4.4]nonane-2,6-dione type, using as the key step the
selective arene-catalyzed lithiation20 of 2-chloromethyl-3-
(2-methoxyethoxy)propene in the presence of a carbonyl
compound (Barbier conditions)21 and subsequent reaction
with protected 2-iodoethanol.
O
O
(i)
O
O
The reaction of 2-chloromethyl-3-(2-methoxyethoxy)pro-
pene (1) with an excess of lithium powder and a catalytic
amount of DTBB (4,4¢-di-tert-butylbiphenyl, 2.5 mol%),
in the presence of a ketone in THF, at temperatures rang-
ing from –78 °C to 0 °C, led to the organolithium interme-
diate 2. Subsequent reaction of 2 with 2-iodoethanol,
protected as the tetrahydro-2H-pyranyl derivative at 0–20
°C gave, after hydrolysis with water, the corresponding
products 3 (Scheme 2).22 This sequential incorporation of
two different electrophilic fragments arises from the dif-
ferent reactivity of the carbon–chlorine and carbon–oxy-
gen bonds in arene-catalyzed lithiations.18,19 In spite of the
fact that the yields of compounds 3 are modest, we must
take into account that this process allows the introduction
of two different electrophiles in one pot, the second elec-
trophile being an alkyl iodide, which is prone to undergo
side reactions under the reaction conditions. It is notewor-
thy that, in the case of using (–)-fenchone as the first elec-
O
O
6b
5b
Scheme 4 Reagents and conditions: (i) RuO2 (15 mol%), NaIO4,
CCl4–H2O, 20 °C, 24 h (6b, 87%).
trophile, only one diastereoisomeric product was Figure 2 Plot showing the X-ray crystal structure and atomic numbe-
obtained.23 Deprotection of compounds 3 was readily per-
ring for compound 6b
Synlett 2008, No. 11, 1627–1630 © Thieme Stuttgart · New York

LETTER
Synthesis of Spirocyclic Bislactones
1629
(18) (a) Alonso, F.; Lorenzo, E.; Yus, M. Tetrahedron Lett. 1997,
38, 2187. (b) Alonso, F.; Lorenzo, E.; Yus, M. Tetrahedron
Lett. 1998, 39, 3303. (c) Lorenzo, E.; Alonso, F.; Yus, M.
Tetrahedron Lett. 2000, 41, 1661. (d) Lorenzo, E.; Alonso,
F.; Yus, M. Tetrahedron 2000, 56, 1745. (e) Alonso, F.;
Lorenzo, E.; Meléndez, J.; Yus, M. Tetrahedron 2003, 59,
5199. (f) Alonso, F.; Meléndez, J.; Yus, M. Russ. Chem.
Bull. 2003, 52, 2628. (g) Alonso, F.; Meléndez, J.; Yus, M.
Tetrahedron Lett. 2005, 46, 6519.
(19) (a) Alonso, F.; Falvello, L. R.; Fanwick, P. E.; Lorenzo, E.;
Yus, M. Synthesis 2000, 949. (b) Alonso, F.; Meléndez, J.;
Yus, M. Helv. Chim. Acta 2002, 85, 3262. (c) Alonso, F.;
Meléndez, J.; Yus, M. Tetrahedron Lett. 2004, 45, 1717.
(d) Alonso, F.; Dacunha, B.; Meléndez, J.; Yus, M.
Tetrahedron 2005, 61, 3437. (e) Dacunha, B.; Alonso, F.;
Meléndez, J.; Yus, M. Acta Crystallogr., Sect. A: Found.
Crystallogr. 2005, 61, C157. (f) Meléndez, J.; Alonso, F.;
Yus, M. Tetrahedron Lett. 2006, 47, 1187. (g) Alonso, F.;
Meléndez, J.; Soler, T.; Yus, M. Tetrahedron 2006, 62,
2264. (h) Alonso, F.; Meléndez, J.; Yus, M. Tetrahedron
2006, 62, 4814.
In conclusion, we have developed a novel synthesis of spi-
rocyclic bislactones of the 1,7-dioxaspiro[4.4]nonane-
2,6-dione type, starting for the first time from an acyclic
precursor (a trimethylenemethane dianion synthon),
through a selective arene-catalyzed lithiation (using a ke-
tone and protected 2-iodoethanol as electrophiles), fol-
lowed by double intramolecular iodocyclization, and final
ruthenium-catalyzed oxidation. Further research to ex-
pand the scope of this methodology to the synthesis of spi-
rocyclic bislactones with different substitution and ring
sizes is under way.
Acknowledgment
This work was generously supported by the Spanish Ministerio de
Educación y Ciencia (MEC; grants no. CTQ2004-01261 and
CTQ2007-65218; Consolider Ingenio 2010-CSD2007-00006) and
the Generalitat Valenciana (GV; grants no. GRUPOS03/135 and
GV05/005). J.M. also thanks the GV for a predoctoral grant.
(20) For reviews, see: (a) Yus, M. Synlett 2001, 1197. (b) Yus,
M. In The Chemistry of Organolithium Compounds;
Rappoport, Z.; Marek, I., Eds.; Wiley: Chichester, 2004,
Chap. 11.
References and Notes
(1) For a microreview, see: Wong, H. N. C. Eur. J. Org. Chem.
1999, 1757.
(21) For a review, see: Alonso, F.; Yus, M. Recent Res. Dev. Org.
Chem. 1997, 1, 397.
(2) Hon, P. M.; Lee, C. M.; Shang, H. S.; Cui, Y. X.; Wong, H.
N. C.; Chang, H. M. Phytochemistry 1991, 30, 354.
(3) Tasdemir, D.; Sitcher, O. J. Nat. Prod. 1997, 60, 874.
(4) Bindseil, K. U.; Henkel, T.; Zeeck, A.; Bur, D.; Niederer, D.;
Séquin, U. Helv. Chim. Acta 1991, 74, 1281.
(5) (a) Edwards, R. L.; Maitland, D. J.; Oliver, C. L.; Pacey, M.
S.; Shields, L.; Whalley, A. J. S. J. Chem. Soc., Perkin
Trans. 1 1999, 715. (b) Goss, R. J. M.; Fuchser, J.;
O’Hagan, D. Chem. Commun. 1999, 2255.
(22) General Procedure for the Preparation of Compounds 3
A solution of 2-chloromethyl-3-(2-methoxyethoxy)propene
(164 mg, 1 mmol) and the corresponding ketone (0.95
mmol) in THF (2 mL), was added over 1.5 h to a green
suspension of lithium powder (50 mg, 7 mmol) and DTBB
(27 mg, 0.1 mmol) in THF (3 mL) at –78 °C. The mixture
was allowed to reach 0 °C and then neat 2-(2-iodoeth-
oxy)tetrahydro-2H-pyran27 (1.5 mmol) was added over 1.5 h
continuing the stirring for 2 h at r.t. The reaction mixture was
hydrolyzed with H2O (5 mL), extracted with EtOAc (3 × 10
mL), and the organic phase was dried over anhyd MgSO4.
After removal of the solvent under reduced pressure (2·10–2
bar), the resulting residue was purified by column chroma-
tography (SiO2, hexane–EtOAc) to yield compounds 3.
1-[2-Methylidene-5-(tetrahydro-2H-pyran-2-
(6) Aramaki, Y.; Chiba, K.; Tada, M. Phytochemistry 1995, 38,
1419.
(7) Midland, S. L.; Keen, N. T.; Sims, J. J. J. Org. Chem. 1995,
60, 1118.
(8) Randi, K. Phytochemistry 1975, 14, 2710.
(9) Perold, G. W.; Carlton, L.; Howard, A. S.; Michael, J. P.
J. Chem. Soc., Perkin Trans. 1 1988, 881.
(10) Li, X.-L.; Cheng, X.; Yang, L.-M.; Wang, R. R.; Zheng,
Y.-T.; Xiao, W.-L.; Zhao, Y.; Xu, G.; Lu, Y.; Chang, Y.;
Zheng, Q.-T.; Zhao, Q.-S.; Sun, H.-D. Org. Lett. 2006, 8,
1937.
(11) (a) Itazaki, H.; Nagashima, K.; Kawamura, Y.; Matsumoto,
K.; Nakai, H.; Terui, Y. J. Antibiot. 1992, 45, 38.
(b) Tanaka, K.; Itazaki, H.; Yoshida, T. J. Antibiot. 1992, 45,
50.
(12) Naito, S.; Escobar, M.; Kym, P. R.; Liras, S.; Martin, S. F.
J. Org. Chem. 2002, 67, 4200.
(13) For some total syntheses, see: (a) Poss, A. J. Tetrahedron
Lett. 1987, 28, 5469. (b) Cuzzupe, A. N.; Di Florio, R.;
Rizzacasa, M. A. J. Org. Chem. 2002, 67, 4392.
(c) Cuzzupe, A. N.; Di Florio, R.; White, J. M.; Rizzacasa,
M. A. Org. Biomol. Chem. 2003, 1, 3572.
(14) (a) Paju, A.; Kanger, T.; Pehk, T.; Lindmaa, R.; Müürisepp,
A.-M.; Lopp, M. Tetrahedron: Asymmetry 2003, 14, 1565.
(b) Paju, A.; Kanger, T.; Niitsoo, O.; Pehk, T.; Müürisepp,
A.-M.; Lopp, M. Tetrahedron: Asymmetry 2003, 14, 2393.
(15) Singh, P.; Mittal, A.; Kaur, P.; Kumar, S. Tetrahedron 2006,
62, 1063.
yloxy)pentyl]cyclohexanol (3b) Colorless oil; Rf = 0.53
(hexane–EtOAc, 4:1). IR (neat): 3472 (OH), 3071, 1638
(C=CH), 1137, 1076, 1033 cm–1 (CO). 1H NMR (300 MHz,
CDCl3): d = 1.40–1.90 [m, 19 H, OH, (CH2)5,
CH2CH2CH2CH, CH2CH2C=CH2], 2.15–2.25 (m, 4 H,
2 × CH2C=CH2), 3.35–3.45, 3.45–3.55, 3.71–3.80, 3.83–
3.90 (3 m, 4 H, 2 × CH2O), 4.56 (t, J = 4.3 Hz, 1 H,
2 × CHO), 4.82, 4.95 (2 s, 2 H, CH2=C). 13C NMR (75 MHz,
CDCl3): d = 19.6, 22.2, 25.4, 25.7, 28.0, 30.7
(CH2CH2CH2CH, CH2CH2C=CH2, CH2CH2CH2CH2COH),
34.4 (CH2CH2C=CH2), 37.8 (2 × CH2COH) 48.1 (CCH2C),
62.3, 67.0 (2 × CH2O), 71.0 (COH), 98.9 (CHO), 113.6
(CH2=C), 146.0 (C=CH2). MS (EI): m/z (%) = 282 (<1)
[M+], 99 (31), 85 (100), 81 (23), 67 (18), 55 (15). HRMS
(EI): m/z calcd for C17H30O3: 270.2195; found: 270.2201.
(23) The stereochemistry in 3c and 4c was established on the
basis of the X-ray crystal structure of the methylidene diol
resulting from the reaction of the analogue 3-methyl-
idenepentane-1,5-dianion synthon with (–)-fenchone.19g
(24) General Procedure for the Deprotection of Compounds 3
A flake of PTSA was added to a solution of the protected
alcohol 3 (1 mmol) in MeOH (5 mL). After stirring for 1 h,
the volatiles were removed under vacuum (2·10–2 bar), and
H2O (10 mL) was added to the residue followed by
extraction with EtOAc (3 × 10 mL). The organic phase was
(16) Chatani, N.; Amako, K.; Tobisu, M.; Asaumi, T.; Fukumoto,
Y.; Murai, S. J. Org. Chem. 2003, 68, 1591.
(17) Paju, A.; Kanger, T.; Phek, T.; Eek, M.; Lopp, M.
Tetrahedron 2004, 60, 9081.
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1630
F. Alonso et al.
LETTER
(26) 1,13-Dioxaspiro[4.1.5.2]tetradecane-2,14-dione (6b)
dried over anhyd MgSO4 and the solvent evaporated under
reduced pressure to give the pure product 4 which did not
require further purification.
A suspension of RuO2 (21 mg, 0.16 mmol) and NaIO4 (1.04
g, 4.88 mmol) in H2O (5 mL) was added to a solution of the
1,7-dioxaspiro[4.4]nonane 5b (1.0 mmol) in CCl4 (5 mL) at
r.t.28 After stirring the reaction for 24 h, i-PrOH (3 mL) was
added, and the resulting mixture was extracted with CCl4
(2 × 5 mL). The organic layer was dried over anhyd MgSO4,
filtered, and evaporated under reduced pressure. The
resulting residue was passed through a pad containing Celite
in order to eliminate the remaining ruthenium compounds,
yielding the corresponding pure spirocyclic bislactone 6b,
which did not require any further purification.
Colorless solid; mp 138–140 °C; Rf = 0.50 (hexane–EtOAc,
4:1). IR (KBr): 1768 (C=O), 1139 cm–1 (CO). 1H NMR (300
MHz, CDCl3): d = 1.30–2.65 (m, 16 H, 8 × CH2). 13C NMR
(75 MHz, CDCl3): d = 22.3, 22.5, 24.6, 28.1, 31.3, 37.1, 38.0
(7 × CH2), 45.4 (CCH2C), 83.9, 85.0 (2 × CO), 173.7, 175.1
(2 × C=O). MS (EI): m/z (%) = 180 (29) [M+ – CO2], 139
(23), 138 (26), 137 (100), 124 (29), 120 (24), 111 (21), 109
(30), 99 (93), 98 (63), 96 (22), 95 (51), 82 (53), 81 (65), 80
(57), 79 (27), 70 (22), 69 (23), 67 (50), 56 (55), 55 (79), 54
(25), 53 (21). Anal. Calcd for C12H16O4: C, 64.27; H, 7.19;
O, 28.54. Found: C, 64.20; H, 7.23.
Selected X-ray Data: C12H16O4, M = 224.25; monoclinic,
a = 8.510(2) Å, b = 6.8849(16) Å, c = 9.445(2) Å,
b = 95.993(4)°; V = 550.3(2) Å3; space group P21; Z = 2;
Dc = 1.353 Mg m–3; l = 0.71073 Å; m = 0.101 mm–1;
F(000) = 240; T = 24 1 °C; CCDC number 679641
contains the supplementary crystallographic data for
compound 6b. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.ac.uk/data_request/cif.
1-(5-Hydroxy-2-methylidenepentyl)cyclohexanol (4b)
Colorless oil; Rf = 0.40 (hexane–EtOAc, 4:1). IR (neat):
3373 (OH), 3072, 1638 (C=CH), 1146, 1059 cm–1 (CO). 1H
NMR (300 MHz, CDCl3): d = 1.40–1.70 [m, 10 H, (CH2)5],
1.72–1.80 (m, 2 H, CH2CH2OH), 2.10–2.20 (m, 6 H,
2 × OH, 2 × CH2C=CH2), 3.65 (t, J = 6.2 Hz, 2 H, CH2OH),
4.82, 4.94 (2 s, 2 H, CH2=C). 13C NMR (75 MHz, CDCl3):
d = 22.2, 25.7, 30.8, 33.8 (2 × CH2CH2CO, CH2CH2CH2CO,
CH2CH2O, CH2CH2CH2O), 37.8 (2 × CH2CO), 48.1
(CCH2C), 62.1 (CH2O), 71.3 (CO), 113.6 (CH2=C), 146.0
(C=CH2). MS (EI): m/z (%) = 180 (<1) [M+ – 18], 99 (100),
81 (54), 55 (18). HRMS (EI): m/z calcd for C12H22O2:
198.1620; [M+ – H2O]: 180.1514; found: 180.1515.
(25) General Procedure for the Cyclization of Compounds 4
Iodine (0.382 g, 1.5 mmol) was added to a solution of the
corresponding diol 4 (1 mmol) in THF (5 mL). The mixture
was stirred for 5 min at r.t. and then Ag2O (0.346 g, 1.5
mmol) was added with additional stirring for 24 h. The
resulting suspension was filtered and H2O (10 mL) was
added to the filtrate, followed by extraction with EtOAc
(3 × 10 mL). The organic phase was successively washed
with a sat. solution of Na2SO3 (2 × 10 mL) and H2O (2 × 10
mL), and dried over anhyd MgSO4. The solvent was
removed under reduced pressure to furnish pure compounds
5.
1,13-Dioxaspiro[4.1.5.2]tetradecane (5b)
Colorless oil; Rf = 0.69 (hexane–EtOAc, 4:1). IR (neat):
1058 cm–1 (CO). 1H NMR (300 MHz, CDCl3): d = 1.30–1.95
[m, 14 H, (CH2)5, CH2CH2CH2O], 1.73, 2.02 (AB system,
J = 13.1 Hz, 2 H, CCH2C), 3.35–3.50, 3.75–3.85 (2 m, 2 H,
CH2CH2O), 3.63, 3.82 (AB system, J = 9.3 Hz, 2 H,
CCH2O). 13C NMR (75 MHz, CDCl3): d = 23.6, 25.7, 29.4,
34.5, 37.7 (7 × CH2), 49.0 (CCH2C), 67.3 (CH2CH2O), 75.1
(CO), 82.9 (CCH2O), 89.2 (OCH2CO). MS (EI): m/z
(%) = 196 (32) [M+], 167 (13), 166 (17), 155 (100), 154 (18),
140 (21), 135 (10), 123 (36), 113 (10), 107 (11), 97 (15), 84
(19), 81 (14), 67 (13), 55 (29). HRMS (EI): m/z calcd for
C12H20O2: 196.1463; found: 196.1467.
(27) 2-Iodoethanol was protected as the tetrahydro-2H-pyranyl
derivative with catalytic PTSA in CH2Cl2 at 0–25 °C for 1.25
h, following a standard literature procedure: Bernady, K. F.;
Floyd, M. B.; Poletto, J. F.; Weiss, M. J. J. Org. Chem. 1979,
44, 1438.
(28) For some applications of this oxidation system, see for
instance: Berkowitz, W. F.; Perumattam, J.; Amarasekara,
A. J. Org. Chem. 1987, 52, 1119.
Synlett 2008, No. 11, 1627–1630 © Thieme Stuttgart · New York