Remarkable template effect of a Lewis acid receptor in the intramolecular radical cyclization: Control of reaction pathway as well as stereochemistry

Article abstract of DOI:10.1016/S0040-4020(00)01007-3

A remarkable template effect in the intramolecular radical cyclization process has been observed by the successful utilization of Lewis acid receptor, aluminum tris(2,6-diphenylphenoxide) (ATPH). The origin of this efficient template effect by ATPH would

Full text of DOI:10.1016/S0040-4020(00)01007-3

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 135±144
Remarkable template effect of a Lewis acid receptor in the
intramolecular radical cyclization: control of reaction pathway as
well as stereochemistry
Takashi Ooi,a,b Yasutoshi Hokke,a,b Eiji Tayamaa,b and Keiji Maruokaa,b,
*
aDepartment of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
bDepartment of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan
Received 2 October 2000; accepted 26 October 2000
AbstractÐA remarkable template effect in the intramolecular radical cyclization process has been observed by the successful utilization of
Lewis acid receptor, aluminum tris(2,6-diphenylphenoxide) (ATPH). The origin of this ef®cient template effect by ATPH would be
ascribable to the well-de®ned reaction environment created in front of the aluminum coordination center; this enables appropriate proximity
of initially generated carbon radical to unsaturated carbon±carbon bond in the transition state for smooth cyclization and hence completely
suppresses the undesired intermolecular reduction pathway. Moreover, such conformational restriction provided by the unique cavity of
ATPH alters the stereoselectivity of the cyclization. q 2000 Elsevier Science Ltd. All rights reserved.
During the last 15 years, radical chemistry has been exten-
sively investigated and a great deal of success in the devel-
opment of new methods has appeared in the literature,
dramatically changing the common sense about free radical
reactions.1 Along with this stream, intramolecular radical
additions to multiple bonds, i.e. radical cyclization, has
been visualized as a powerful new methodology for ring
construction via C±C bond forming process and it actually
serves as one of the most reliable tools in organic synthesis.2
Although the chemo-, regio-, and stereoselectivities of
many classes of radical cyclizations are well understood
and the preparative importance has been growing at an
incredible rate, the full potential of this reaction including
stereochemical control at the newly created carbon centers
is yet to be realized; hence only limited structural types of
cyclization products have been accessible by this reaction.3
In this context, we have been interested in the development
of a conceptually new method for obtaining hitherto
unattainable reactivity and selectivity in the intramolecular
radical additions to multiple bonds by the successful utiliza-
tion of rationally designed Lewis acids.4 Aluminum tris(2,6-
diphenylphenoxide) (ATPH),5 a structurally well-de®ned
Lewis acid receptor possessing a unique bowl-shaped reac-
tion cavity created by three phenyl substituents in front of
the highly oxygenophilic aluminum center, certainly
appeared to be ideal for our purpose, and we envisaged
that oxygen-containing substrates such as halo ethers of
type 1 could adopt the chair-like conformation by precom-
plexation with ATPH. This conformational restriction
within the cavity, upon subsequent exposure to the radical
reaction conditions, would play a crucial role in allowing an
appropriate proximity of initially generated carbon radical
to triple bond in the transition state, thereby smoothly facili-
tating the desired cyclization process and yet altering the
stereoselectivity as illustrated in Scheme 1.6
First, we examined intramolecular radical cyclization of
2-iodoethyl 3-phenylpropynyl ether (1, nˆ1) under several
representative radical reaction conditions and the results are
summarized in Table 1. The reaction of 1 (nˆ1) with
Bu3SnH and catalytic amount of AIBN in re¯uxing benzene
for 1 h gave rise to an E/Z mixture of cyclic ether, 3-benzyl-
idenetetrahydrofuran (2) in 96% yield (E/Zˆ50:50) (entry
1). Use of catalytic Et3B as radical initiator allowed the
cyclization to be conducted at 2788C, which brought
slightly higher stereoselectivity (E/Zˆ61:39) (entry 2).7 In
contrast, however, initial complexation of 1 (nˆ1) with
ATPH (2 equiv.) in toluene and subsequent addition of
Bu3SnH (1.5 equiv.) and catalytic Et3B (0.2 equiv.) afforded
2 quantitatively with totally opposite preference of ole®n
geometry (E/Zˆ14:86) (entry 3). Since the geometry of
the newly formed double bond is likely to be determined
in the hydrogen abstraction process,8 the observed
(Z)-selectivity can be accounted for by the preferable
approach of Bu3SnH from the less hindered site to trap the
ATPH-coordinated vinyl radical (B), avoiding the steric
repulsion with 2,6-diphenylphenoxy ligand of ATPH (A).
This argument is strongly supported by the fact that the
Keywords: intramolecular radical cyclization; Lewis acid; ATPH.
* Corresponding author. Department of Chemistry, Graduate School of
Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan. Tel.: 181-
75-753-4041; fax: 181-75-753-4000;
e-mail: maruoka@kuchem.kyoto-u.ac.jp
0040±4020/01/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01007-3

136
T. Ooi et al. / Tetrahedron 57 (2001) 135±144
Scheme 1.
stereoselectivity was further improved by the use of
(Me3Si)3SiH9 instead of Bu3SnH (entry 4).
commonly expected 6-exo cyclizations are usually slower
than related 5-exo cyclizations, and therefore simple reduc-
tion of alkyl iodide rather than relatively unfamiliar 7-endo
cyclization can often compete, which obviously diminishes
the synthetic utility of this type of reaction. Indeed, treat-
ment of 1 (nˆ2) with Bu3SnH and catalytic Et3B in toluene
at 2788C for 1 h resulted in predominant formation of the
reduction product 4 and the desirable cyclic ether 3 was
obtained in only 16% yield. In marked contrast, radical
cyclization of 1 (nˆ2) under the in¯uence of ATPH under
otherwise similar reaction conditions afforded 3 as the sole
isolable product quantitatively, demonstrating a remarkable
template effect of ATPH for acceleration of the otherwise
disfavored 6-exo cyclization (Scheme 2). It should be
emphasized that the E/Z selectivity in the cyclization
Based on the results, intramolecular cyclization of one-
carbon elongated halo ether, 3-iodopropyl 3-phenyl-
propynyl ether (1, nˆ2), which can be categorized as
heptynyl radical cyclization, was also examined. Here,
Table 1. Intramolecular radical cyclization of 2-iodoethyl 3-phenylpropynyl ether (1, nˆ1) under various conditions (unless otherwise speci®ed, the radical
cyclization was carried out in toluene with 1.2 equiv. of reagent and catalytic amount of radical initiator under the given reaction conditions)
Entry
Reagent (R3MH)
Initiator
Condition
% Yielda (E/Z ratio)b
1
2
3
4
Bu3SnH
Bu3SnH
AIBN
Et3B
Et3B
Et3B
808C, 1 h
96 (50:50)c
94 (61:39)
99 (14:86)
99 (,1:.99)
2788C, 1 h
2788C, 1 h
2788C, 1 h
ATPHd/Bu3SnH
ATPHd/(Me3Si)3SiH
a Isolated yield.
1
b Determined by H NMR analysis.
c Use of benzene as solvent.
d 2 equiv. of ATPH was used.

T. Ooi et al. / Tetrahedron 57 (2001) 135±144
137
Scheme 2.
products 3 is again opposite in the presence or absence of
ATPH and nearly perfect Z selectivity was also obtained
with (Me3Si)3SiH,9 despite the signi®cant rate retardation
under similar reaction conditions [30% yield of 3;
E/Zˆ,1:.99 and 70% recovery of 1 (nˆ2)].
structure 9, and either 7 or 9 underwent smooth cyclization
to furnish the corresponding hydropyrane derivative 6
(Scheme 3).
Our approach has been successfully applied to the radical
cyclization of (bromomethyl)dimethylsilyl propargyl
ethers, which is usually carried out in re¯uxing benzene
with catalytic amount of AIBN by slow addition of
R3SnH (RˆPh or Bu) with a syringe pump to avoid
undesired reduction of the relatively stable a-silyl radical.11
Actually, the reaction initiated by the addition of catalytic
Et3B to the premixed toluene solution of (bromomethyl)di-
methylsilyl ether of 3-phenyl-1-propynol (10) and Bu3SnH
at 2788C resulted in formation of allylic alcohol 11 in only
5% yield (E/Zˆ28:72) after the treatment with MeLi
(3 equiv.) at 2788C. Surprisingly, the reaction with ATPH
under otherwise identical reaction conditions gave rise to 11
in 70% yield with the opposite preference of ole®n
geometry (E/Zˆ54:46). Here, template effect of ATPH did
not seem enough to achieve high stereochemical control
probably due to the steric and electronic demand of silyl
substituents upon complexation, resulting a rather weak
aluminum±oxygen coordination bond (Scheme 4).
In the examples described above the reaction was termi-
nated by the hydrogen abstraction of vinyl radicals which
are considered to have linear structure as reported by Giese.8
However, it seemed dif®cult to rule out the possibility that
the vinyl radicals exist in a nonlinear con®guration capable
of extremely facile isomeric interconversion.10 This thought
stimulated our interest in the effect of the stereochemistry of
vinyl radicals on cyclization processes and eventually led
us to compare the reactivity of stereochemically de®ned (Z)-
and (E)-3-iodo-2-butenyl 3-phenylpropynyl ethers (5a, b) in
the ATPH-assisted intramolecular radical cyclization. The
reaction of 5a with Bu3SnH (1.2 equiv.) and Et3B
(0.6 equiv.) under the in¯uence of ATPH in toluene at
2208C for 6 h gave rise to the cyclization product 6 in
55% yield with the E/Z ratio of 23:77. Interestingly, the
cyclization of 5b under similar reaction conditions reached
the almost identical result with the slight difference of the
stereoselectivity, suggesting that the initially generated two
con®gurationally isomeric vinyl radicals 7 and 8 with bent
structure experienced rapid isomerization through linear
Typically, 4-substituted hexenyl radicals cyclize with a high
level of selectivity and closure of the 4-methylhexenyl
radical is known to provide predominantly the trans isomer,
as expected from the Beckwith±Houk model.12 For
instance, radical cyclization of 2-iodoethyl trans-1-methyl-
2-hexenyl ether (12) proceeded in toluene at 2208C with
catalytic Et3B/Bu3SnH to furnish tetrahydrofuran 13 in 95%
yield with a cis/trans ratio of 3:97. Examination of the two
chairlike transition state conformations as illustrated in
Scheme 3.

138
T. Ooi et al. / Tetrahedron 57 (2001) 135±144
Scheme 4.
Scheme 5.
Scheme 5 can reveal why such excellent diastereoselectivity
was observed. Conformation 14b, with the methyl group
equatorial, can minimize the allylic strain leading to trans
isomer, whereas less likely conformation 14a, with the
methyl group axial, leads to cis isomer. As easily expected,
the participation of the conformation would be dramatically
decreased in the cyclization of the substrates possessing
either bulky 4-substituent or cis double bond, which conse-
quently manifest the dif®culty in attaining the cis selectivity.
Here, the template effect of ATPH was found to be greatly
Scheme 6.

T. Ooi et al. / Tetrahedron 57 (2001) 135±144
139
appreciated, altering the transition state structure of the
present cyclization; i.e. initial treatment of 12 with ATPH
followed by the addition of catalytic Et3B/Bu3SnH at 2208C
resulted in formation of 13 almost quantitatively with totally
opposite diastereoselectivity (cis/transˆ92:8). Apparently,
steric requirement for ®tting inside the cavity of ATPH
through Lewis acid±base complexation made the less likely
conformation 15a more favorable than 15b, leading to the
preferential formation of cis tetrahydrofuran (Scheme 5).
furan (THF) were purchased from Kanto Chemical Co., Inc.
as `Dehydrated'. Hexane and toluene were dried over
sodium metal. Dichloromethane, DMF and hexamethyl-
Ê
phosphoric triamide (HMPA) were stored over 4 A
molecular sieves. Pyridine was stored over KOH pellets.
Trimethylaluminum (Me3Al) and triethylborane (Et3B)
were kindly supplied from Toso-Akzo Chem. Co. Ltd.,
Japan. Other simple chemicals were purchased and used
as such.
Further, we applied the unique property of ATPH as a Lewis
acid receptor to the tandem intramolecular radical cycliza-
tions of halo ethers 16 based on our recent ®nding of the
encapsulation of 1,4-carbonyl guests by ATPH through
Lewis acid±base interaction.5g The bis-ether 16 can be
prepared from cis-2-buten-1,4-diol and reaction of 16 with
Bu3SnH (1.2 equiv.) and Et3B (0.5 equiv.) in toluene at
2208C for 4 h gave rise to the simple reduction product
18 in 93% yield. In marked contrast, however, initial
complexation of 16 with ATPH (2.4 equiv.) and the subse-
quent treatment with Et3B/Bu3SnH at 2208C for 4 h
resulted in the formation of the corresponding tandem
cyclization product 17 in 90% yield as a mixture of dia-
stereomers and none of reduction product 18 was obtained
as shown in Scheme 6. Noteworthy is the fact that use of
1.2 equiv. of ATPH signi®cantly diminished the chemical
yield of 17 (38%), suggesting the importance of simul-
taneous coordination of ATPH on both the oxygen atoms
of 16 to smoothly facilitate the present tandem cyclization
process. A similar tendency was observed in the intra-
molecular radical cyclization of 19, exhibiting completely
opposite product distribution with or without ATPH as
included in Scheme 6.
1.2. General procedure for the preparation of iodoalkyl
ethers
1.2.1. Preparation of 2-iodoethyl 3-phenylpropynyl ether
(1, nˆ1) To a solution of 3-phenyl-2-propyn-1-ol (1.15 g,
8.7 mmol) in ether (15 mL) was added some drops of
pyridine and phosphorous tribromide (0.33 mL,
3.48 mmol) at 08C under argon and the reaction mixture
was stirred for 4 h. The resulting mixture was then poured
into saturated NaHCO3 and extracted with ether. The
organic extracts were dried over Na2SO4 and concentrated.
Puri®cation of the residue by column chromatography on
silica gel (ether/pentaneˆ1:50 as eluent) gave 3-bromo-1-
phenyl-1-propyne as a colorless oil (1.57 g, 8.7 mmol)
quantitatively: 1H NMR (CDCl3) d 7.27±7.48 (5H, m,
Ph), 4.17 (2H, s, CH2Br).
To a suspension of sodium hydride (65% assay, 359 mg,
9.7 mmol) in THF (20 mL) was added 1,2-ethanediol
(4.5 mL) at 08C under argon and the bromide obtained
above (8.7 mmol) was introduced at 08C. After the addition
of hexamethylphosphoric triamide (HMPA, 4 mL), the
reaction mixture was allowed to warm to room temperature
and stirred for additional 6 h. The mixture was then poured
into brine and extracted with ether. The organic extracts
were dried over Na2SO4. Evaporation of solvent and puri®-
cation of the residual oil by column chromatography on
silica gel (ether/hexaneˆ1:1 as eluent) furnished 3-oxa-6-
phenyl-6-hexyn-1-ol as a colorless oil (1.34 g, 7.6 mmol,
1. Experimental
1.1. General
1
Infrared (IR) spectra were recorded on Shimadzu FT-IR
8200A spectrometer. H NMR spectra were measured on
94%): H NMR (CDCl3) d 7.42±7.48 (2H, m, Ph), 7.27±
1
7.35 (3H, m, Ph), 4.42 (2H, s, CuCCH2O), 3.81 (2H, m,
CH2OH), 3.74 (2H, m, O±CH2), 2.02 (1H, t, Jˆ6.2 Hz,
OH).
Varian Gemini-300 (300 MHz) spectrometer. Analytical
gas±liquid phase chromatography (GLC) was performed
on Shimadzu GC-14B instrument equipped with a ¯ame
ionization detector and a capillary column of PEG-HT
(0.25£25,000 mm) using nitrogen as carrier gas. Analytical
gas±liquid phase chromatography-mass spectrometer (GC-
MS) was performed on Shimadzu GC-17A instrument
equipped with a EI-detector and a capillary column of
DB-1 (J&W SCIENTIFIC, 0.25£30,000 mm) using helium
as carrier gas, and GCMS-QP5000. All experiments were
carried out under an atmosphere of dry argon. For thin-layer
chromatography (TLC) analysis throughout this work,
This alcohol (7.6 mmol) was dissolved into dichloro-
methane (20 mL) and pyridine (2.5 mL, 31 mmol) and
triphenylphosphine (2.2 g, 8.4 mmol) were added at 08C
under argon. After being stirred for 30 min, iodine (2.2 g,
8.4 mmol) was added portionwise and stirring was contin-
ued for 1 h at 08C. The mixture was treated with saturated
Na2SO3 until the color turned into yellow. Then the whole
mixture was poured into saturated NaHCO3 and extracted
with ether. The organic extracts were dried over Na2SO4 and
concentrated. The residue was puri®ed by column chroma-
tography on silica gel (ether/hexaneˆ1:30 as eluent) to give
1 (nˆ1) as a colorless oil (1.97 g, 6.9 mmol, 91%): 1H NMR
(CDCl3) d 7.27±7.50 (5H, m, Ph), 4.45 (2H, s, CuCCH2O),
3.88 (2H, t, Jˆ6.9 Hz, O±CH2), 3.32 (2H, t, Jˆ6.9 Hz,
CH2I); IR (liquid ®lm) 3058, 2848, 2239, 1489, 1443,
1354, 1256, 1190, 1168, 1109, 1085, 1029, 964, 918, 758,
690 cm21. MS: 286 (M1), 173, 155, 145, 131, 115 (100%),
103. Anal. Calcd for C11H11IO: C, 46.18; H, 3.88; I, 44.35.
Found: C, 46.42; H, 3.89; I, 44.17.
Merck precoated TLC plates (silica gel 60 GF254
,
0.25 mm) were used. The products were puri®ed by prepara-
tive column chromatography on silica gel (E. Merck 9385).
Microanalyses were accomplished at the Center for Instru-
mental Analysis, Hokkaido University. The high-resolution
mass spectra (HRMS) were conducted at the School of
Agriculture, Hokkaido University and the School of
Engineering, Kyoto University.
In experiments requiring dry solvents, ether and tetrahydro-

140
T. Ooi et al. / Tetrahedron 57 (2001) 135±144
1
described above from the (E)-b-iodocrotonate: H NMR
1.2.2. 3-Iodopropyl 3-phenylpropynyl ether (1, nˆ2). 1H
NMR (CDCl3) d 7.28±7.51 (5H, m, Ph), 4.38 (2H, s,
CuCCH2O), 3.66 (2H, t, Jˆ6.0 Hz, O±CH2), 3.31 (2H, t,
Jˆ6.9 Hz, CH2I), 2.12 (2H, tt, Jˆ6.0, 6.9 Hz, CH2CI); IR
(liquid ®lm) 3053, 2943, 2860, 1489, 1443, 1360, 1258,
1182, 1101, 1069, 1028, 758, 691 cm21. MS: 300 (M1),
243, 155, 145, 129, 115 (100%), 103. Anal. Calcd for
C12H13IO: C, 48.02; H, 4.37; I, 42.28. Found: C, 48.14; H,
4.39; I, 42.39.
(CDCl3) d 7.40±7.48 (2H, m, Ph), 7.28±7.36 (3H, m, Ph),
6.39 (1H, t, Jˆ6.9 Hz, ICvCH), 4.37 (2H, s, CuCCH2O),
4.09 (2H, d, Jˆ6.9 Hz, OCH2CvCI), 2.50 (3H, s,
CH3CvC); IR (liquid ®lm) 3057, 2954, 2847, 2359, 1638,
1489, 1443, 1354, 1256, 1084, 1055, 962, 927, 758, 690 cm21
.
1.2.5. Preparation of (bromomethyl)dimethylsilyl
3-phenylpropynyl ether (10). To a solution of 3-phenyl-
2-propyn-1-ol (661 mg, 5.0 mmol) in DMF (10 mL) was
added imidazole (681 mg, 10.0 mmol) and bromomethyl-
dimethylchlorosilane (1.13 g, 6.0 mmol) sequentially at
08C under argon. The mixture was stirred for 3 h and poured
into saturated NaHCO3. Extractive workup was performed
with ether and the organic extracts were dried over Na2SO4.
Evaporation of solvents and puri®cation of the residual oil
by column chromatography on silica gel (ether/
hexaneˆ1:50 as eluent) gave 10 as a colorless oil (1.04 g,
1.2.3. Preparation of 3-iodo-(2Z)-butenyl 3-phenylpro-
pynyl ether (5a). To a solution of sodium iodide (2.69 g,
18 mmol) in tri¯uoroacetic acid (5 mL) was added ethyl
tetrolate (1.68 g, 15 mmol) dropwise at 08C under argon.
The mixture was then heated to 808C and stirred for 5 h.
After the resulting mixture was cooled to room temperature,
it was poured into water and extracted with ether. The
ethereal extracts were neutralized by saturated NaHCO3,
washed with brine and dried over Na2SO4. Evaporation of
solvents and puri®cation of the residual oil by column
chromatography on silica gel (ether/hexaneˆ1:30 then
1:10 as eluent) gave ethyl b-iodocrotonate as a colorless
oil (E-isomer: 576 mg, 2.4 mmol; Z-isomer: 2.52 g,
10.5 mmol, 86% combined yield): 1H NMR (CDCl3)
E-isomer: d 6.63 (1H, s, ICvCH), 4.15 (2H, q, Jˆ6.9 Hz,
OCH2CH3), 2.98 (3H, s, CH3CvC), 1.28 (3H, t, Jˆ6.9 Hz,
OCH2CH3); Z-isomer: d 6.29 (1H, s, ICvCH), 4.22 (2H, q,
Jˆ6.9 Hz, OCH2CH3), 2.73 (3H, s, CH3CvC), 1.30 (3H, t,
Jˆ6.9 Hz, OCH2CH3).
1
3.7 mmol, 74%): H NMR (CDCl3) d 7.40±7.47 (2H, m,
Ph), 7.29±7.37 (3H, m, Ph), 4.59 (2H, s, CuCCH2O), 2.91
(1H, s, CHBr), 2.59 (1H, s, CHBr), 0.37 (3H, s, SiCH3), 0.35
(3H, s, SiCH3); IR (liquid ®lm) 3058, 2963, 2864, 2362,
1491, 1369, 1258, 1084, 999, 964, 847, 758, 691 cm21
.
MS: 284 ([M12]1), 282 (M1), 239, 237, 203, 189, 159
(100%), 115. HRMS Calcd for C12H15BrOSi: 282.0075
(M1). Found: 282.0080 (M1).
1.2.6. Preparation of 2-iodoethyl trans-1-methyl-2-hexenyl
ether (12). The two-neck ¯ask equipped with re¯ux conden-
ser and Dean Stark trap was charged with a solution of
3-hepten-2-one (2.24 g, 20 mmol) in hexane (10 mL),
p-toluenesulfonic acid monohydrate (95 mg, 0.5 mmol)
and 1,2-ethanediol (1.2 mL). The solution was heated to
re¯ux and stirred for 2 h with continuous removal of
water. After cooled to room temperature, the mixture was
concentrated and the residual oil was puri®ed by column
chromatography on silica gel (ether/pentaneˆ1:30 as
eluent) to give the corresponding acetal as a colorless oil
(1.26 g, 8.0 mmol, 40%): 1H NMR (CDCl3) d 5.80 (1H, dt,
Jˆ6.9, 15.2 Hz, CH3(CH2)2CHvC), 5.42 (1H, d, Jˆ
15.2 Hz, CvCHC(CH3)O), 3.84±3.99 (4H, m, 2(CH2O)),
2.02 (2H, q, Jˆ6.9 Hz, CH2CvC), 1.46 (3H, s, CH3C±
O), 1.41 (2H, sex, Jˆ7.5 Hz, CH3CH2CH2), 0.90 (3H, t,
Jˆ7.5 Hz, CH3(CH2)2).
Aluminum chloride (1.40 g, 10.5 mmol) was treated with
lithium aluminum hydride (1.20 g, 31.5 mmol) in ether
(100 mL) at 08C for 30 min and the (Z)-b-iodocrotonate
(10.5 mmol) was added dropwise. The mixture was stirred
for 1 h and the excess aluminum hydride was quenched by
the addition of 1N HCl at 08C. The whole mixture was
poured into saturated NaHCO3 and extracted with ether.
The organic extracts were dried over Na2SO4 and concen-
trated. The crude (Z)-b-iodocrotyl alcohol was converted
without any puri®cation to the corresponding bromide by
PBr3 and cat. pyridine in ether.
To a suspension of sodium hydride (385 mg, 10.4 mmol) in
THF (10 mL) was added 3-phenyl-2-propyn-1-ol (1.15 g,
8.7 mmol) at 08C under argon. After stirring for 15 min,
the bromide obtained above was added. The mixture was
allowed to warm to room temperature and stirred for 3 h. It
was then poured into brine and extracted with ether. The
organic extracts were dried over Na2SO4 and concentrated.
The residue was puri®ed by column chromatography on
silica gel (ether/hexaneˆ1:1 as eluent) to furnish 3-iodo-
(2Z)-butenyl 3-phenylpropynyl ether (5a) as a colorless oil
(1.64 g, 5.3 mmol, 50% in three steps): 1H NMR (CDCl3) d
7.41±7.50 (2H, m, Ph), 7.28±7.36 (3H, m, Ph), 5.76 (1H, t,
Jˆ5.7 Hz, ICvCH), 4.38 (2H, s, CuCCH2O), 4.18 (2H, d,
Jˆ5.7 Hz, OCH2CvCI), 2.56 (3H, s, CH3CvC); IR (liquid
®lm) 3057, 2849, 1654, 1599, 1489, 1443, 1352, 1256,
1078, 1028, 964, 918, 758, 691 cm21. MS: 312 (M1), 184,
155, 141, 131, 115 (100%), 91. HRMS Calcd for C13H13IO:
311.9970 (M1). Found: 312.0013 (M1).
DIBAH (3.0 mL, 16.8 mmol) was added dropwise to a solu-
tion of the acetal obtained above (8.0 mmol) in dichloro-
methane (20 mL) at 2788C under argon and the mixture
was stirred for 1 h. The reaction was quenched by the care-
ful addition of 1N HCl at 08C. The whole mixture was then
poured into water and extracted with ether. The ethereal
extracts were dried over Na2SO4 and concentrated. Puri®ca-
tion of the residual oil by column chromatography on silica
gel (ether/hexaneˆ1:1 as eluent) furnished 3-oxa-4-methyl-
5-nonan-1-ol as a colorless oil (1.16 g, 7.3 mmol, 91%): 1H
NMR (CDCl3)
CH3(CH2)2CHvC), 5.34 (1H, dd, Jˆ6.9, 15.2 Hz,
CvCHC(CH3)O), 3.82 (1H, quint,
d
5.60 (1H, dt, Jˆ6.9, 15.2 Hz,
Jˆ6.9 Hz,
CH(CH3)O), 3.70 (2H, m, CH2OH), 3.58 (1H, m, CH±O),
3.40 (1H, m, CH±O), 2.02 (1H, s, OH), 2.01 (2H, q,
Jˆ6.9 Hz, CH2CvC), 1.40 (2H, sex, Jˆ7.5 Hz,
CH3CH2CH2), 1.25 (3H, d, Jˆ6.9 Hz, CH3C±O), 0.90
(3H, t, Jˆ7.5 Hz, CH3(CH2)2).
1.2.4. 3-Iodo-(2E)-butenyl 3-phenylpropynyl ether (5b).
The title compound was prepared in exactly the same way

T. Ooi et al. / Tetrahedron 57 (2001) 135±144
141
1
80%): H NMR (CDCl3) d 5.92 (1H, ddt, Jˆ5.7, 10.4,
17.2 Hz, CHvC), 5.67±5.87 (2H, m, O±CCHvCHC±O),
5.29 (1H, d, Jˆ17.2 Hz, O±CCvCH), 5.20 (1H, d,
Jˆ10.4 Hz, O±CCvCH), 4.21 (2H, t, Jˆ5.6 Hz,
CvCCH2OH), 4.07 (2H, d, Jˆ6.0 Hz, CvCCH2O), 4.00
(2H, d, Jˆ5.7 Hz, OCH2CvC), 1.84 (1H, t, Jˆ5.6 Hz, OH)
(Scheme 7).
Sodium hydride (65% assay, 532 mg, 14.4 mmol) was
suspended in THF (20 mL) and 22 obtained above
(12.0 mmol) was added at 08C under argon. The mixture
was stirred for 15 min and the mesylate 23 (4.03 g,
15 mmol), prepared from 1,3-propanediol by the silyla-
tion±mesylation sequence (70% in two steps), was
introduced. After the addition of hexamethylphosphoric
triamide (HMPA, 4 mL), the mixture was warmed to
room temperature and stirred for 5 h. The reaction was
quenched with brine and extracted with ether. The organic
extracts were dried over Na2SO4 and concentrated. Puri®ca-
tion of the residue by column chromatography on silica gel
(ether/hexaneˆ1:1 as eluent) furnished 24 as a colorless oil
(2.49 g, 8.4 mmol, 70%): 1H NMR (CDCl3) d 5.92 (1H, ddt,
Jˆ5.7, 10.5, 17.1 Hz, CHvC), 5.72 (2H, m, O±
CCHvCHC±O), 5.29 (1H, d, Jˆ17.1 Hz, O±CCvCH),
5.20 (1H, d, Jˆ10.5 Hz, O±CCvCH), 4.06 (2H, d,
Jˆ4.5 Hz, OCH2CvCC), 4.03 (2H, d, Jˆ4.5 Hz,
OCH2CvCC), 3.97 (2H, d, Jˆ5.7 Hz, OCH2CvC), 3.69
(2H, t, Jˆ6.3 Hz, CH2OSi), 3.50 (2H, t, Jˆ6.3 Hz, O±
CH2), 1.78 (2H, quint, Jˆ6.3 Hz, CH2), 0.88 (9H, s, t-Bu),
0.04 (6H, s, 2CH3).
Scheme 7.
The alcohol (7.3 mmol) was dissolved into dichloromethane
(20 mL) and pyridine (2.4 mL, 30 mmol) and triphenyl-
phosphine (2.31 g, 8.8 mmol) were added at 08C under
argon. After being stirred for 30 min, iodine (2.23 g,
8.8 mmol) was added portionwise and stirring was con-
tinued at 08C for additional 1 h. The resulting mixture was
treated with saturated Na2SO3 to reduce excess iodine and
then poured into saturated NaHCO3. Extractive workup was
conducted with ether and the organic extracts were dried
over Na2SO4. Evaporation of solvents and puri®cation of
the residual oil by column chromatography on silica gel
(ether/hexaneˆ1:30 as eluent) yielded 12 as a colorless oil
(1.45 g, 5.42 mmol, 74%): 1H NMR (CDCl3) d 5.60 (1H, dt,
Jˆ6.6, 15.3 Hz, CH3(CH2)2CHvC), 5.34 (1H, dd, Jˆ7.8,
15.3 Hz, CvCHC(CH3)O), 3.85 (1H, quint, Jˆ6.3 Hz,
CH(CH3)O), 3.69 (1H, dt, Jˆ6.9, 10.8 Hz, CH±O), 3.56
(1H, dt, Jˆ6.9, 10.8 Hz, CH±O), 3.22 (2H, t, Jˆ6.9 Hz,
CH2I), 2.01 (2H, q, Jˆ6.6 Hz, CH2CvC), 1.40 (2H, sex,
Jˆ7.5 Hz, CH3CH2CH2), 1.24 (3H, d, Jˆ6.3 Hz, CH3C±O),
0.91 (3H, t, Jˆ7.5 Hz, CH3(CH2)2); IR (liquid ®lm) 2961,
2930, 2872, 2370, 1458, 1369, 1317, 1261, 1109, 1076,
972 cm21. MS: 268 (M1), 253, 225, 212, 199, 155
(100%), 141, 113, 97. Anal. Calcd for C9H17IO: C, 40.31;
H, 6.39; I, 47.33. Found: C, 40.31; H, 6.33; I, 47.30.
The tert-butyldimethylsilyl ether (24) was cleaved quanti-
tatively by the treatment with TBAF in THF. To a solution
of the alcohol 25 (8.4 mmol) in dichloromethane (10 mL)
was added pyridine (2.7 mL, 33.6 mmol) and triphenyl-
phosphine (2.62 g, 10.0 mmol) at 08C under argon. After
stirring for 30 min, iodine (2.53 g, 10.0 mmol) was added
portionwise and the resulting mixture was stirred for addi-
tional 1 h at 08C. The excess iodine was reduced by the
addition of saturated Na2SO3 and the whole mixture was
poured into saturated NaHCO3. Extractive workup was
performed with ether and the ethereal extracts were dried
over Na2SO4. Evaporation of solvents and puri®cation of the
residual oil by column chromatography on silica gel (ether/
hexaneˆ1:30 as eluent) gave 16 as a colorless oil (1.74 g,
1
5.88 mmol, 70% in two steps): H NMR (CDCl3) d 5.92
(1H, ddt, Jˆ5.7, 10.5, 17.1 Hz, CHvC), 5.67±5.79 (2H,
m, O±CCHvCHC±O), 5.29 (1H, d, Jˆ17.1 Hz, O±
CCvCH), 5.20 (1H, d, Jˆ10.5 Hz, O±CCvCH), 4.06
(4H, m, OCH2CvCCH2O), 3.98 (1H, d, Jˆ5.7 Hz,
OCH2CvC), 3.48 (1H, t, Jˆ5.4 Hz, O±CH2), 3.28 (2H, t,
Jˆ6.9 Hz, CH2I), 2.05 (2H, tt, Jˆ5.4, 6.9 Hz, CH2CI); IR
(liquid ®lm) 3022, 2860, 1474, 1420, 1329, 1236, 1182,
1105, 1012, 929 cm21. MS: 296 (M1), 238, 186, 169
(100%), 141, 128, 110. Anal. Calcd for C10H17IO2: C,
40.56; H, 5.79; I, 42.85. Found: C, 40.59; H, 5.67; I, 43.19.
1.2.7. Preparation of cis-4,9-dioxa-12-iodo-1,6-dodeca-
diene (16). To a suspension of sodium hydride (65%
assay, 554 mg, 15 mmol) in THF (20 mL) was added cis-
2-butene-1,4-diol (3 mL) at 08C under argon. After being
stirred for 15 min, allyl bromide (1.81 g, 15 mmol) was
introduced dropwise at 08C. The mixture was warmed to
room temperature and stirred there for 3 h. It was then
poured into brine and extracted with ether. The ethereal
extracts were dried over Na2SO4 and concentrated. The
residue was puri®ed by column chromatography on silica
gel (ether/hexaneˆ1:1 as eluent) to afford 5-oxa-2,7-
octadiene-1-ol (22) as a colorless oil (1.54 g, 12.0 mmol,
1.2.8. cis-4,9-Dioxa-12-iodo-6-dodecen-1-yne (19). 1H
NMR (CDCl3) d 5.67±5.81 (2H, m, O±CCHvCHC±O),
4.17 (2H, d, Jˆ5.1 Hz, OCH2CvCC), 4.16 (2H, s,
OCH2CuC), 4.09 (2H, d, Jˆ5.1 Hz, OCH2CvCC), 3.50
(2H, t, Jˆ5.7 Hz, OCH2CCI), 3.28 (2H, t, Jˆ6.7 Hz,
CH2I), 2.45 (1H, m, CuCH), 2.06 (2H, tt, Jˆ5.7, 6.7 Hz,

142
T. Ooi et al. / Tetrahedron 57 (2001) 135±144
CH2CI); IR (liquid ®lm) 3294, 3026, 2860, 2116, 1474,
1439, 1354, 1331, 1269, 1236, 1182, 1099, 1028,
677 cm21. MS: 293 ([M2H]1), 238, 225, 184, 169
(100%), 155, 141, 128, 107. Anal. Calcd for C10H15IO2:
C, 40.84; H, 5.14; I, 43.15. Found: C, 41.05; H, 5.19; I,
43.11.
4.33 (2H, s, CvCCH2O, Z-isomer), 4.17 (2H, s,
CvCCH2O, E-isomer), 3.81 (2H, t, Jˆ5.1 Hz, CH2±O,
E-isomer), 3.77 (2H, t, Jˆ5.4 Hz, CH2±O, Z-isomer), 2.59
(2H, dt, Jˆ1.5, 6.3 Hz, CH2CvC, E-isomer), 2.46 (2H, dt,
Jˆ1.5, 6.0 Hz, CH2CvC, Z-isomer), 1.81 (2H, m, CH2C±
O, Z-isomer), 1.70 (2H, m, CH2C±O, E-isomer); IR (liquid
®lm) 3022, 2954, 2835, 1491, 1439, 1259, 1209, 1090,
1030, 951, 920, 880, 745, 700, 667 cm21. MS: 174 (M1)
(100%), 155, 145, 131, 115, 104.
1.2.9. Preparation of ATPH. A solution of 2,6-diphenyl-
phenol (739 mg, 3 mmol) in toluene (5 mL) was carefully
degassed and a 2 M hexane solution of Me3Al (0.5 mL,
1 mmol) was added at room temperature under argon. The
methane gas evolved immediately. The resulting slightly
yellow solution was stirred at room temperature for
30 min and used as a solution of ATPH in toluene without
any puri®cation.
Stereochemistries were ascertained by conducting the
difference NOE spectra measurement of (Z)-3 in a similar
manner as described above.
1.3. General method for the intramolecular radical
cyclizations with ATPH
To a solution of ATPH (1 mmol) in toluene (5 mL) was
added iodoalkyl ether (0.5 mmol) at 2788C, and the result-
ing mixture was stirred for 10 min to generate ATPH±ether
complex. Then tributyltin hydride (Bu3SnH, 161 mL,
0.6 mmol) and Et3B (100 mL, 0.1 mmol) were introduced
sequentially at the same temperature. The reaction was
monitored by TLC analysis. After the completion of the
reaction, the resulting mixture was poured into saturated
NaHCO3 and extracted with ether. The organic extracts
were dried over Na2SO4 and concentrated. Puri®cation by
column chromatography on silica gel (dichloromethane/
hexaneˆ1:4, then ether/hexaneˆ1:10 as eluent) gave the
corresponding cyclic ether as a colorless oil except 6
(light yellow oil).
1.3.3. 3-Phenylpropynyl propyl ether (4).14 1H NMR
(CDCl3) d 7.42±7.48 (2H, m, Ph), 7.28±7.35 (3H, m, Ph),
4.37 (2H, s, CuCCH2O), 3.54 (2H, t, Jˆ6.6 Hz, CH2±O),
1.66 (2H, sex, Jˆ7.5 Hz, CH2C±O), 0.96 (2H, t, Jˆ7.5 Hz,
CH3); IR (liquid ®lm) 2963, 2937, 2877, 2189, 1663, 1599,
1491, 1443, 1358, 1256, 1097, 1045, 961, 916, 758,
692 cm21. MS: 174 (M1), 159, 145, 131, 115 (100%), 103.
1.3.4. 3-Benzylidene-4-methyl-2H,6H-dihydropyran (6).
1H NMR (CDCl3) d 7.13±7.36 (5H, m, Ph), 6.51 (1H, s,
PhCHvC, Z-isomer), 6.41 (1H, s, PhCHvC, E-isomer),
5.78 (1H, m, CvCHC±O, Z-isomer), 5.57 (1H, m,
CvCHC±O, E-isomer), 4.58 (2H, s, PhCvCCH2O,
Z-isomer), 4.31 (2H, m, OCH2CvCCH3, E-isomer), 4.25
(2H, m, OCH2CvCCH3, Z-isomer), 4.23 (2H, s,
PhCvCCH2O, E-isomer), 1.97 (3H, s, CH3, Z-isomer),
1.49 (3H, s, CH3, E-isomer); IR (liquid ®lm) 3022, 2932,
2812, 2361, 1705, 1597, 1491, 1445, 1394, 1292, 1217,
1130, 1074, 1032, 968, 894, 864, 729, 698 cm21. MS: 186
(M1), 171, 157, 142 (100%), 129, 115. HRMS Calcd for
C13H14O: 186.1045 (M1). Found: 186.1043 (M1).
1.3.1. 3-Benzylidenetetrahydrofuran (2). 1H NMR
(CDCl3) d 7.10±7.40 (5H, m, Ph), 6.45 (1H, m, CHvC,
Z-isomer), 6.37 (1H, m, CHvC, E-isomer), 4.58 (2H, m,
CvCCH2O, Z-isomer), 4.46 (2H, m, CvCCH2O,
E-isomer), 4.01 (2H, t, Jˆ6.9 Hz, CH2±O, E-isomer), 3.90
(2H, t, Jˆ6.9 Hz, CH2±O, Z-isomer), 2.82 (2H, m, CH2C±
O, E-isomer), 2.77 (2H, m, CH2C±O, Z-isomer); IR (liquid
®lm) 3024, 2953, 2852, 1603, 1491, 1448, 1317, 1142,
1072, 1053, 964, 922, 862, 752, 696 cm21. MS: 160 (M1),
142, 131 (100%), 115, 104, 91. Anal. Calcd for C11H12O: C,
82.46; H, 7.55. Found: C, 82.30; H, 7.71.
Stereochemistries were con®rmed by the difference NOE
spectra measurement of (Z)-6 as shown below.
Stereochemical assignment of (E)- and (Z)-2 was performed
by the difference NOE spectra measurement. Irradiation of
the a-proton of the furan ring resulted in a 7% NOE to the
ole®nic proton in the case of Z-isomer, while no NOE was
observed between the a-proton and the ole®nic proton with
E-isomer as shown below.
1.3.5. 3-Phenyl-2-trimethylsilylmethyl-2-propen-1-ol (11).15
1H NMR (CDCl3) d 7.17±7.47 (5H, m, Ph), 6.43 (1H, s,
PhCHvC, Z-isomer), 6.30 (1H, s, PhCHvC, E-isomer),
4.26 (2H, d, Jˆ5.7 Hz, CH2O, E-isomer), 4.15 (2H, d,
Jˆ6.3 Hz, CH2O, Z-isomer), 1.92 (2H, s, CvCCH2Si,
Z-isomer), 1.83 (2H, s, CvCCH2Si, E-isomer), 1.46 (1H, t,
Jˆ6.3 Hz, OH, Z-isomer), 1.31 (1H, t, Jˆ5.7 Hz, OH,
1.3.2. 3-Benzylidenetetrahydropyran (3).13 1H NMR
(CDCl3) d 7.11±7.35 (5H, m, Ph), 6.37 (1H, s, CHvC),

T. Ooi et al. / Tetrahedron 57 (2001) 135±144
143
E-isomer), 0.10 (9H, s, 3CH3, E-isomer), 0.00 (9H, s, 3CH3, Z-
isomer); IR (liquid ®lm) 3341, 2955, 2358, 1647, 1599, 1491,
1447, 1418, 1250, 1157, 1034, 853, 756, 698 cm21. MS: 220
(M1), 205, 145, 131, 129 (100%), 115, 91.
850, 681 cm21. MS: 169 ([M2H]1), 155, 143, 129, 117,
104, 83 (100%). Anal. Calcd for C10H18O2: C, 70.55; H,
10.66. Found: C, 70.72; H, 10.47.
1.3.9. cis-4,9-Dioxa-1,6-dodecadiene (18). 1H NMR
(CDCl3) d 5.92 (1H, ddt, Jˆ5.7, 10.5, 17.1 Hz, CHvC),
5.71±5.74 (2H, m, O±CCHvCHC±O), 5.28 (1H, d,
Jˆ17.1 Hz, O±CCvCH), 5.20 (1H, d, Jˆ10.5 Hz, O±
CCvCH), 4.07 (2H, d, Jˆ4.8 Hz, OCH2CvCC), 4.04
(2H, d, Jˆ4.8 Hz, OCH2CvCC), 3.98 (2H, d, Jˆ5.7 Hz,
OCH2CvC), 3.38 (2H, t, Jˆ6.6 Hz, OCH2CH2CH3), 1.60
(2H, sex, Jˆ7.5 Hz, CH2CH2CH3), 0.92 (3H, t, Jˆ7.5 Hz,
(CH2)2CH3); IR (liquid ®lm) 2964, 2932, 2855, 1650, 1456,
1329, 1269, 1099, 993, 926, 714, cm21. MS: 169
([M2H]1), 153, 145, 129, 112, 95, 83 (100%). HRMS
Calcd for C10H17O2 ([M2H]1): 169.1228. Found: 169.1234.
Stereochemical assignment was carried out by measuring
the difference NOE spectra of (E)- and (Z)-11.
1.3.10. 3-Methylene-4-(3-tetrahydropyranyl)tetrahydro-
furan (20). 1H NMR (CDCl3) d 5.03 (1H, s, CvCH), 4.97
(1H, m, CvCH), 4.26 (2H, br s, OCH2CvC), 3.77±4.01
(4H, m, 4(O±CH)), 3.30±3.40 (1H, m, O±CH), 3.21 (0.6H,
t, Jˆ11.1 Hz, O±CH), 3.16 (0.4H, t, Jˆ11.1 Hz, O±CH),
2.42±2.58 (1H, m, O±CCHCvC), 1.70±1.95 (2H, m, O±
CCHCCH), 1.55±1.69 (2H, m, O±CCHCH), 1.19±1.37
(1H, m, O±CCH); IR (liquid ®lm) 2936, 2847, 2364,
1665, 1466, 1450, 1281, 1205, 1178, 1093, 1064, 921,
893, 669 cm21. MS: 167 ([M2H]1), 149, 121, 107, 93, 83
(100%). HRMS Calcd for C10H15O2 ([M2H]1): 167.1072.
Found: 167.1039.
1.3.6. cis-1-Butyl-2-methyltetrahydrofuran (cis-13).16 1
H
NMR (CDCl3) d 4.06 (1H, quint, Jˆ6.3 Hz, CH(CH3)O),
3.91 (1H, dt, Jˆ3.9, 8.4 Hz, CH±O), 3.68 (1H, dt, Jˆ7.2,
8.4 Hz, CH±O), 2.03±2.14 (1H, m, CHC(CH3)O), 1.93±
2.04 (1H, m, CHC±O), 1.52±1.65 (1H, m, CHC±O),
1.19±1.47 (6H, m, CH3(CH2)3), 1.06 (3H, d, Jˆ6.3 Hz,
CH3C±O), 0.90 (3H, t, Jˆ6.9 Hz, CH3(CH2)3); IR (liquid
®lm) 2961, 2930, 2860, 1460, 1379, 1101, 1076, 1043, 856,
734 cm21. MS: 141 ([M2H]1), 127, 111, 97, 83 (100%).
1.3.11. cis-4,9-Dioxa-6-dodecen-1-yne (21). 1H NMR
(CDCl3) d 5.65±5.83 (2H, m, O±CCHvCHC±O), 4.17
(2H, d, Jˆ6.0 Hz, OCH2CvCC), 4.15 (2H, s, OCH2CuC),
4.06 (2H, d, Jˆ6.0 Hz, OCH2CvCC), 3.39 (2H, t,
Jˆ6.6 Hz, OCH2CH2CH3), 2.44 (1H, m, CuCH), 1.62
(2H, sex, Jˆ7.2 Hz, CH2CH2CH3), 0.93 (3H, t, Jˆ7.2 Hz,
(CH2)2CH3); IR (liquid ®lm) 3296, 2963, 2936, 2862, 2359,
1464, 1360, 1331, 1267, 1096, 1045, 945, 669 cm21. MS:
168 (M1), 153, 138, 125, 112 (100%), 107. Anal. Calcd for
C10H16O2: C, 71.39; H, 9.59. Found: C, 71.11; H, 9.59.
1.3.7. trans-1-Butyl-2-methyltetrahydrofuran (trans-
13).16 1H NMR (CDCl3) d 3.84 (1H, dt, Jˆ5.7, 8.1 Hz,
CH±O), 3.78 (1H, dt, Jˆ3.3, 8.1 Hz, CH±O), 3.47 (1H,
quint, Jˆ6.3 Hz, CH(CH3)O), 2.05±2.18 (1H, m, CHC±
O), 1.49±1.63 (1H, m, CHC±O), 1.40±1.49 (1H, m,
CHC(CH3)O), 1.16±1.38 (6H, m, CH3(CH2)3), 1.23 (3H,
d, Jˆ6.3 Hz, CH3C±O), 0.91 (3H, t, Jˆ6.9 Hz,
CH3(CH2)3); IR (liquid ®lm) 2963, 2926, 2860, 1456,
1381, 1111, 1086, 1032, 866, 733 cm21
.
References
Stereochemistries of cis- and trans-13 were determined by
comparing their CH3 signals of 1H NMR spectra with those
of (2a,3a)- and (2a,3b)-(^)-tetrahydro-2,3-dimethylfur-
ans. The characteristic peaks were as follows; cis-13: d
1.06 (3H, d, Jˆ6.3 Hz, CH3C±O); (2a,3a)-(^)-tetra-
hydro-2,3-dimethylfuran: d 1.05 (3H, d, Jˆ6 Hz, CH3C±
O); trans-13: d 1.23 (3H, d, Jˆ6.3 Hz, CH3C±O);
(2a,3b)-(^)-tetrahydro-2,3-dimethylfuran: d 1.15 (3H, d,
Jˆ6 Hz, CH3C±O).
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1.3.8. 4-Methyl-3-(3-tetrahydropyranyl)tetrahydrofuran
(17). H NMR (CDCl3) d 3.80±4.00 (3H, m, 3(O±CH)),
1
3.29±3.80 (4H, m, 4(O±CH)), 3.08±3.19 (1H, m, O±CH),
2.01±2.34 (1H, m, O±CCH), 1.88±2.00 (1H, m, O±CCH),
1.45±1.71 (4H, m, O±CCHCH, 2(O±CCH)), 1.15±1.34
(1H, m, O±CCCH), 1.05 (0.6H, d, Jˆ6.6 Hz, CH3), 1.02
(0.3H, d, Jˆ6.9 Hz, CH3), 0.95 (0.7H, d, Jˆ6.9 Hz, CH3),
0.94 (1.4H, d, Jˆ7.2 Hz, CH3); IR (liquid ®lm) 2932, 2851,
1458, 1387, 1281, 1221, 1180, 1096, 1030, 982, 910, 874,
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