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Can. J. Chem. Vol. 85, 2007
Scheme 3.
the absence of a catalyst even after a long reaction time
(12 h). As solvent, dichloromethane appeared to give the
best result. In all cases, the reactions proceeded rapidly at
room temperature under mild conditions. The reactions were
clean and the products were obtained in excellent yields
with high diastereoselectivity. Only a single isomer was ob-
tained in each reaction, the structure of which was con-
with aqueous sodium thiosulfate and brine and dried over
anhydr. Na2SO4. The removal of solvent, followed by purifi-
cation on silica gel (Merck, 100–200 mesh, ethyl acetate –
hexane, 0.5:9.5), gave pure 4-iodotetrahydropyran. The
products thus obtained were characterized by IR and NMR
spectroscopy. The characterization data was found to be
consistent with the authentic samples (6).
1
firmed by H NMR and also by comparison with authentic
samples (6). The formation of the products may be further
explained by hemi-acetal formation and subsequent Prins-
type cyclization (Scheme 3).
4-Iodo-1-oxaspiro[5.5]undecane (a)
Liquid. IR (KBr, cm–1) ν: 2924, 2853, 1630, 1457, 1075.
1H NMR (200 MHz, CDCl3) δ: 1.19–1.66 (m, 10H), 1.99 (d,
J = 12.8 Hz, 2H), 2.19–2.24 (m, 2H), 3.51–3.60 (m, 2H),
4.37–4.38 (m, 1H). 13C NMR (75 MHz, CDCl3) δ: 21.0,
21.2, 26.0, 29.2, 39.8, 39.8, 40.3, 49.6, 61.9, 74.6. LCMS:
279 (M – 1). Anal. calcd for C10H17OI: C 42.87, H 6.12;
found: C 42.92, H 6.08.
Other iodide sources such as LiI, t-Bu4NI, and NaI failed
to produce the desired product. Cyclic ketones gave slightly
higher yields when compared with acyclic ketones. As de-
picted in Table 1, a variety of ketones participated in Prins-
cyclization under these reaction conditions. The scope and
generality of this process is illustrated with respect to vari-
ous ketones and homoallylic and homopropargylic alcohols,
and the results are presented in Table 1.
In summary, we describe a rapid and efficient Prins-
cyclization of ketones to produce spirocyclic-4-iodo-tetra-
hydropyrans in high yields with high selectivity. The use of
inexpensive and readily available molecular iodine has made
this procedure simple, convenient, and practical. In addition
to its simplicity, efficiency, and milder reaction conditions,
this method provides a rapid access for spirocyclic-4-iodo
tetrahydropyran derivatives with diverse chemical structures.
4-Iodo-2-phenyl-1-oxaspiro[5.5]undecane (i)
Liquid. IR (KBr, cm–1) ν: 3063, 3028, 2926, 2853, 1637,
1
1492, 1448, 1059, 757, 698. H NMR (200 MHz, CDCl3) δ:
d 1.25–1.75 (m, 10H), 2.08–2.16 (m, 2H), 2.33 (dd, J = 4.5,
12.8 Hz, 1H), 2.56 (d, J = 12.8 Hz, 1H), 4.52–4.62 (m, 2H),
7.23–7.33 (m, 5H). 13C NMR (75 MHz, CDCl3) δ: 21.5,
26.2, 26.2, 30.1, 30.1, 40.0, 47.4, 49.2, 72.3, 75.5, 125.6,
125.6 125.6, 125.6, 128.5, 128.5. LCMS: 355 (M – 1). Anal.
calcd for C16H21OI: C 53.94, H 5.94; found: C 53.99, H
5.89.
Experimental
4-Iodo-1-oxaspiro[5.5]undec-4-ene (l)
Melting points were recorded on Buchi R-535 apparatus
and are uncorrected. IR spectra were recorded on a
PerkinElmer FT-IR 240-c spectrophotometer using KBr op-
Liquid. IR (KBr, cm–1) ν: 2927, 2854, 1633, 1452, 1333,
1268, 1208, 1084, 759. 1H NMR (200 MHz, CDCl3) δ:
1.25–1.72 (m, 10H), 2.51 (td, J = 2.2, 5.2 Hz, 2H), 3.76 (t,
J = 5.2 Hz, 1H), 6.26 (s, 1H). 13C NMR (75 MHz, CDCl3)
δ: 21.4, 21.4, 25.5, 35.2, 39.4, 39.4, 60.2, 60.2, 91.1, 144.2.
LCMS: 277 (M – 1). Anal. calcd for C10H15OI: C 43.18, H
5.44; found: C 43.24, H 5.39.
1
tics. H, 13C NMR spectra were recorded on Gemini-200
spectrometer in CDCl3 using TMS as internal standard.
Mass spectra were recorded on a Finnigan MAT 1020 mass
spectrometer operating at 70 eV. TLC was monitored on
0.25 mm precoated silica gel plates (60F-254).
General procedure
A mixture of homoallylic alcohol (2 mmol), ketone
(1 mmol), and iodine (1 mmol) in dichloromethane (5 mL)
was stirred at 23 °C for a specified time (Table 1). After
completion of the reaction as indicated by TLC, the reaction
mixture was quenched with water and extracted with ether
(2 × 10 mL). The combined organic layers were washed
Acknowledgements
VHK, TS, and GGKSNK thank the Council of Scientific
and Industrial Research (CSIR, New Delhi) for the award of
fellowships.
© 2007 NRC Canada