The prenyl group: A versatile hydroxy protecting group, removable chemoselectively under mild conditions

Article abstract of DOI:10.1016/S0040-4020(02)00539-2

Iodine in dichloromethane (in the presence of 3? molecular sieves for acid-sensitive substrates) and 2,3-dichloro-5,6-dicyanoquinone (DDQ) in dichloromethane-water (9:1) are mild and efficient methods to cleave prenyl ethers. These reaction conditions are compatible with the presence of other protecting groups such as acetals, acetates, allyl, benzyl and TBDPS groups. Exposure of aryl prenyl ethers to iodine led to the formation of 3-iodo-2,2-dimethylchroman derivatives in acceptable yields via a tandem Friedel-Crafts/iodocyclization reactions. Facile one-step transformation of two iodinated dimethylchroman derivatives allowed the synthesis of natural flavanoids among them: zanthoxylol, an anti-sickling agent.

Full text of DOI:10.1016/S0040-4020(02)00539-2

TETRAHEDRON
Pergamon
Tetrahedron 58 2002) 5689±5698
The prenyl group: a versatile hydroxy protecting group,
removable chemoselectively under mild conditions
p
Á
Jean-Michel Vatele
Laboratoire de Chimie Organique 1, UMR 5622 CNRS, Domaine Scienti®que de la Doua,
CPE 3 rue Victor Grignard, 69616 Villeurbanne cedex, France
Received 5 March 2002; revised 29 April 2002; accepted 21 May 2002
Ê
AbstractÐIodine in dichloromethane in the presence of 3 A molecular sieves for acid-sensitive substrates) and 2,3-dichloro-5,6-di-
cyanoquinone DDQ) in dichloromethane±water 9:1) are mild and ef®cient methods to cleave prenyl ethers. These reaction conditions
are compatible with the presence of other protecting groups such as acetals, acetates, allyl, benzyl and TBDPS groups. Exposure of aryl
prenyl ethers to iodine led to the formation of 3-iodo-2,2-dimethylchroman derivatives in acceptable yields via a tandem Friedel±Crafts/
iodocyclization reactions. Facile one-step transformation of two iodinated dimethylchroman derivatives allowed the synthesis of natural
¯avanoids among them: zanthoxylol, an anti-sickling agent. q 2002 Published by Elsevier Science Ltd.
1. Introduction
completely unexplored. Indeed, only three methods of
cleavage of prenyl ethers have been described.4 Two of
them used drastic conditions t-BuOK4a or TiCl4,
n-Bu4NI4c) and are not compatible with acid or base sensi-
Organic synthesis has not yet matured to the point where
protective groups are not needed for the synthesis of natural
and unnatural products and so selective protection, and
more importantly, deprotection of functional groups still
play a central role in the success of the synthesis of complex
natural products.
tive functionalities. The third one employed Yb OTf)3,4b
a
mild Lewis acid catalyst, which anyhow is able to cleave
acid-sensitive protecting groups.5
We have recently reported in preliminary accounts two mild
and selective methods to regenerate alcohols from prenyl
ethers Scheme 1).6
One of the most present functional group in natural products
is the hydroxy group for which a number of protecting
groups has been designed. However, because of the
increasing complexity of the molecules synthesized and
the emergence of new ®elds in organic synthesis such as
supported-oligosaccharide synthesis,1 new protecting
groups with modulated reactivity and new techniques of
cleavage of existing protecting groups are needed.
We now reported, in full details, studies of these methods of
prenyl ethers deprotection, particularly of their chemo-
selectivity against other protecting groups and probable
mechanisms involved in these processes.
In connection with a program devoted to the development of
new safety-catch protecting groups,2 a hydroxy protecting
group stable under both acid and base conditions and
cleaved under neutral conditions was needed. Among the
numerous existing protecting groups, the allyl group does
ful®ll acid±base stability requirements but none of the
several deprotecting methods for this group were satis-
factory for our purpose.3
2. Results and discussion
2.1. Deprotection of prenyl ethers with iodine
Inspired by the report of Cossy and co-workers about a
method for the deprotection of prenyl esters,7 the prenyl
ether of diacetone glucose 1a was treated at room tempera-
ture with iodine in cyclohexane. Disappointingly, TLC
Next, we focused our attention to a related allyl group: the
3-methylbut-2-enyl prenyl) group in which surprisingly
the potentialities as an OH protecting group was almost
Keywords: DDQ; iodine; protecting groups; prenyl ethers; chromans.
Tel.: 133-472431151; fax: 133-472431214;
e-mail: vatele@univ-lyons1.fr
p
Scheme 1.
0040±4020/02/$ - see front matter q 2002 Published by Elsevier Science Ltd.
PII: S0040-4020 02)00539-2

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J.-M. Vatele / Tetrahedron 58 32002) 5689±5698
5690
Table 1. Cleavage of prenyl ethers with iodine or 2,3-dichloro-5,6-dicyanoquinone
Substrate
I2
Product equiv., time, yield)
DDQ
1a R1ˆPre, R2, R3ˆCMe2
1b R1ˆBn, R2, R3ˆPre
1.5, 5 h, 61%)
3, 3 h, 50%)
1.2, 2 h, 54%)
2a R1ˆH, R2, R3ˆCMe2
2b R1ˆBn, R2, R3ˆH
1.2, 9 h, 65%)
1.2, 4 h, 68%)
1, 4 h, 33%)
3b R1ˆBn, R2ˆH, R3ˆPre
1.5, 8 h, 72%)
1.5, 1 h, 92%)
3, 3 h, 79%)
1.2, 4 h, 89%)
1.2, 15 min, 86%)
1.2, 0.75 h, 89%)
1.2, 1.5 h, 78%)
1.2, 0.5 h, 0%)
1.5, 1 h, 75%)
3, 1.5 h, 80%)
1.2, 1.5 h, 72%)
1.2, 3 h, 86%)
1.5, 1 h, 77%)
1.5, 4 h, 22%)
2, 3 h, 70%)
1.2, 4 h, 94%)
1,2,3 h, 80%)
1.2, 3 h, 83%)
showed the presence almost exclusive of polar compounds.
Switching from cyclohexane to toluene permitted the iso-
lation of diacetone glucose 2a in 32% yield after heating 4 h
at 708C. In more polar solvents CH2Cl2, CH3CN), the
disappearance of the starting material was much faster 1
versus 24 h) but still polar compounds were formed.
Assuming that during the cleavage of prenyl ethers with
iodine an acid species might be generated HI) deprotect-
ing acetal functions of 1a, acid scavengers were added
prior to iodine. Addition of 1 equiv. of Et3N inhibited
completely the cleavage reaction whereas sodium carbo-
nate 2 equiv.) slowed it down suggesting that HI

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J.-M. Vatele / Tetrahedron 58 32002) 5689±5698
5691
Scheme 2.
was produced during the cleavage and catalyzed this
process.
along with the vic-diiodo compound 5 ratio 2h/5ˆ1/3).
Treatment of the mixture of compounds 2h and 5 with
zinc gave 2h in 80% overall yield Scheme 2). Unfortu-
nately, even in the presence of molecular sieves, the
O-prenyl group of 1j could not be removed selectively in
the presence of a t-butyldimethysilyl group. Treatment of
prenyl ether 1f with iodine, at 2108C, did not give the
expected nopol 2f but several unidenti®ed products. The
known facile skeletal rearrangement of a-pinene derivatives
in the presence of electrophiles may explain this result.9
Ê
In the presence of 3 A molecular sieves a known hydrogen
halides scavenger)8 the deprotection of prenyl ether 1a in
CH2Cl2 proceeded at room temperature at a reasonable rate
5 h) to give diacetone glucose in 61% yield. The use of
Ê
iodine in CH2Cl2, in the presence of 3 A molecular sieves
for acid-sensitive substrates, was examined on diversely
funtionalized substrates and the results of this study are
summarized in Table 1.
Interestingly, aryl prenyl ether 1l in the presence of
1.5 equiv. of iodine gave the 3-iodo-2,2-dimethylchroman
derivative 4 in an acceptable yield. Ring opening of the
b-iodo cyclic ether unit of 4 via the Boord reaction zinc
in boiling toluene) led cleanly to natural anti-sickling agent
zanthoxylol in 88% yield Scheme 3).10
Firstly, exposure of the diprenyl ether 1b to 1.2 equiv. of
iodine led to the formation of the 5-O-deprotected
compound 3b in 54% yield; the 6-O-deprotected compound
was not observed by TLC. Conversely, treatment of 1b with
1 equiv. of DDQ gave approximately an equal mixture of
the two monoprotected compounds along with some of the
dideprotected product 2b.
In order to clarify the reaction pathway 1l!4 and to isolate
the intermediates of the cyclization reaction, the reaction
was carried out with only 0.4 equiv. of iodine. Four
compounds were isolated Scheme 4). Formation of 7,
major product of the reaction and corresponding to the
cleavage of the aryl prenyl ether, excluded that ortho-prenyl
phenol 6, the immediate precursor of 4, was formed via a
[1,3]-sigmatropic rearrangement.11 Exclusive formation of
the iodo 4 obtained by treatment of 7 by an excess of iodine
con®rmed this hypothesis.
Protecting groups such as acetonides 1a±1c), acetates 1i),
benzyl 1b) and t-butyldiphenylsilyl 1k) groups or the
conjugated ketone function of 1e were unaffected in the
reaction conditions. In the case of compound 1h bearing
an allyl group, the desired compound 2h was obtained
Taking into account the above mentioned facts, we presume
that the iodo 4 was formed from 1l by a Friedel±Crafts
reaction directed by the proximal phenol function with an
electrophilic prenyl species such as prenyl iodide which
itself can result of the addition of HI to isoprene,12 followed
Scheme 3.
Scheme 4.
Scheme 5.

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J.-M. Vatele / Tetrahedron 58 32002) 5689±5698
5692
Scheme 6.
by iodocyclization 6 cyclized to 4 in the presence of iodine)
clearly the ®ve carbon signals of the prenyl iodide dˆ
4.0, 17.4, 25.8, 122.1, 138.8 ppm)16 which represents 15±
20 mol% in comparison with menthol. Along with some
minor products, 13C and 1H NMR also revealed the presence
of the unstable diiodo 11 5±7 mol%) Scheme 7) which
could be obtained in almost pure form by chromatography
on silica gel.
Scheme 5).13
This reaction of aryl prenyl ethers with iodine was applied
to the synthesis of natural product 10, recently isolated from
the stems of Paramignya grif®thii, used in Thailand for
the treatment of nose infections.14 Bis-O-prenylation
of commercially available 2- 4-hydroxyphenyl)ethanol
followed by exposure to iodine and double bond formation
induced by DBU in hot toluene furnished the 2,2-dimethyl-
chromene 10 in 49% overall yield Scheme 6).
Armed with these information and those concerning the
probable mechanism of formation of 2,2-iodochroman 4
from 1l Scheme 5), a possible mechanism for the iodine
catalyzed-cleavage of prenyl ethers is outlined in Scheme 7.
2.1.1. Mechanistic studies of the cleavage of prenyl
ethers by iodine. As mentioned earlier in this article,
addition of bases to the reaction mixture inhibits or retards
the deprotection of prenyl ethers suggesting that an acid
species HI) is necessary for the cleavage to occur. More-
over, in contrast to 3-O-allyl diacetone glucose which, in the
presence of 1.5 equiv. of iodine, gave isolable vicinal
diiodides,15 no addition product of iodine to the double
bond of prenyl ether 1a was observed by TLC, even at
2788C, precluding that a vic-diiodo could be an inter-
mediate in the cleavage of prenyl ethers. We next wondered
if a stoechiometric amount of iodine was necessary. It
turned out not to be the case because the deprotection of
the prenyl ether of menthol 1d could be done with 0.4 equiv.
of iodine at room temperature in 89% yield, albeit at the
expense of the rate of the reaction 4 h 30 versus 15 min
with 1.5 equiv. of I2).
2.2. Oxidative cleavage of prenyl ethers by DDQ
If the method of deprotection of prenyl ethers by iodine
gave satisfactory results on most subtrates, it is not com-
patible with very acid-sensitive functions such as TBS and
with substrates which are reactive with electrophiles such as
phenols, terpenes. So, we decided to look for another more
general and milder method.
From the literature, we learned that allylic ethers are easily
oxidized by 2,3-dichloro-5,6-dicyanoquinone DDQ) to
corresponding carbonyl compounds and alcohols.17 Con-
®dent that DDQ can oxidize prenyl ethers as well, the
O-prenyl ether of menthol 1d was treated at room tempera-
ture, by 1.2 equiv. of DDQ in a mixture CH2Cl2±H2O 9:1).
After stirring for 30 min, TLC indicated the disappearance
of the starting material and formation of two compounds
with very close Rf. Separation of the two compounds on
silca gel gave menthol in 86% along with volatile 3-methyl-
2-butenal.
Another experiment to go insight the mechanism consisted
to carry out the reaction with O-prenyl menthol 1d, in an
NMR tube using CDCl3 as solvent. 13C NMR showed
Scheme 7.
Scheme 8.

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J.-M. Vatele / Tetrahedron 58 32002) 5689±5698
5693
ambiant probe temperature on a Bruker AC 200 200
MHz) spectrometer. Data are presented as follows: chemical
shift in ppm on the d scale relative to dTMSˆ0), multiplicity
sˆsingulet, dˆdoublet, tˆtriplet, mˆmultiplet, brˆbroad);
integration, coupling constant and interpretation). 13C NMR
spectra were recorded at ambiant probe temperature on a
Bruker AC 200 50.3 MHz) in CDCl3 used as reference
dCˆ77.0). IR spectra were recorded on a Perkin±Elmer
298 spectrophotometer. Optical rotations were measured on
a Perkin±Elmer 141 polarimeter at the sodium D line
598 nm). Melting points were determined on a BuÈchi 530
apparatus and are uncorrected. Combustion analyses were
performed by the Service de Microanalyse, CNRS, Solaize.
Reagents and solvents were puri®ed by standard means.
Tetrahydrofuran was distilled from sodium wire/benzo-
phenone and stored under a nitrogen atmosphere. Dichloro-
methane, dimethylformamide, pyridine and toluene were
Scheme 9.
Then we tested the applicability of this method to func-
tionalized substrates and the results of this study is sum-
marized in Table 1. As shown in the Table, the reaction
time is very dependent on the substrate varying from
45 min to 9 h. This method is compatible with substrates
containing protecting groups such as acetonides 1a±1c),
acetates 1i), benzyl 1b), t-butyldimethylsilyl 1j), t-butyl-
diphenylsilyl 1k) and allyl 1h) groups. In the latter case,
the good selectivity was unexpected because it has been
reported that under the same conditions, albeit in longer
time, primary allyl ethers were cleaved.17b Exposure of 1l,
bearing an aryl ether, to DDQ gave the monoprotected
compound 2l in only 36% yield; no compound bearing a
phenol function was detected. DDQ is known as a powerful
oxidizing agent of phenols18 and that may explained the low
yield of the reaction.
Ê
distilled from calcium hydride. Powdered 3 A molecular
sieves Aldrich) was dried at 1008C for 10 h. All other
chemicals were used as received.
4.2. General procedure for the preparation of prenyl
ethers 1a±1g and 1l
To 1 mmol of the substrate dissolved in 3 mL of DMF,
cooled to 08C, were successively added prenyl bromide
0.18 mL, 1.5 equiv.; for 1b and 1l 3 equiv.) and NaH
60% dispersion in mineral oil, 0.048 g, 1.2 equiv., for 1b
and 1l 2.4 equiv.). The reaction mixture was allowed to
warm up to room temperature and the stirring was continued
for 2 h. Excess of NaH was destroyed by MeOH and ether
and water were added. The aqueous phase was extracted
with ether and the combined organic layers were washed
once with water, dried Na2SO4) and evaporated under
reduced pressure. The residue was puri®ed by ¯ash chroma-
tography on silica gel.
Because DDQ is an expensive reagent and the removal of its
corresponding hydroquinone is sometimes cumbersome,
Sharma and co-workers developed a method which allowed
the use of DDQ in catalytic amount 0.1 equiv.) in the
presence of Mn31 salts as a reoxidant.19 Under these con-
ditions, the O-prenyl ether menthol 1d afforded menthol in
84% yield Scheme 8). The yield of this protocol is similar
of that using a stoechiometric amount of DDQ but the
reaction time is longer 18 h versus 90 min).
Mechanistically, the oxidation/deprotection of prenyl ethers
with DDQ must proceed by hydride abstraction from
the activated methylene by DDQ followed by trapping the
carbonium by water giving a hemiacetal which decomposes
to give an alcohol, DDQH2 and 3-methylbut-2-enal
Scheme 9).20
4.2.1. 1,2:5,6-Di-O-isopropylidene-3-O-33-methyl-2-bu-
tenyl)-a-d-glucofuranose 1a. Ether±petroleum ether
20
1:4), 97% yield, oil, [a]D ˆ220.6 c 2, CHCl3) lit.21
[a]Dˆ221.6 c 1, CHCl3)). NMR data were identical with
those described in the literature.21
4.2.2. 3-O-Benzyl-1,2-O-isopropylidene-5,6-di-O-33-methyl-
2-butenyl)-a-d-glucofuranose 1b. Obtained from 3-O-
Ether±
3. Conclusion
benzyl-1,2-isopropylidene-a-d-glucofuranose.22
20
petroleum ether 1:3), 93%, oil, [a]D ˆ233 c 3.4,
In summary, we have shown that prenyl ethers could be
cleaved by I2 or oxidatively by DDQ in the presence of a
number of other commonly used protecting groups but are
not applicable to aryl prenyl ethers. These mild conditions
broaden the synthetic applications of prenyl ethers and the
good chemoselectivity of these methods extends its utility as
an orthogonal protecting group. Other applications of the
prenyl group in organic synthesis are currently under
studies.
1
CHCl3). IR ®lm): 3080, 3060, 3020, 1670, 1585 cm21. H
NMR: 1.31 s, 3H, CH3), 1.47 s, 3H, CH3), 1.61 s, 3H,
CH3), 1.67 s, 3H, CH3), 1.69 s, 3H, CH3), 1.74 s, 3H,
CH3), 3.56 dd, 1H, Jˆ6 and 10.8 Hz, H-6), 3.78±4.14
m, 6H, H-3, H-5, H-6, 3 CH2±CHvC), 4.21 dd, 1H,
Jˆ3 and 9.4 Hz, H-4), 4.32 dd, 1H, Jˆ7.8 and 10.8 Hz,
CH2±CHvC), 4.58 d, 1H, Jˆ3.7 Hz, H-2), 4.60 d, 1H,
Jˆ11.6 Hz, ChaPh), 4.69 d, 1H, CHbPh), 5.3 brt, 1H,
Jˆ6.95 Hz, CHvCMe2), 5.34 brt, 1H, Jˆ6.83 Hz,
CHvCMe2), 5.90 d, 1H, Jˆ3.7 Hz, H-1), 7.34 brs, 5H,
Ph). 13C NMR: 18.0, 18.1, 25.8 2C), 26.4, 26.8, 67.1, 67.9,
71.0, 72.1, 74.9, 79.2, 81.9, 82.0, 105.2, 111.7, 121.6, 121.7,
127.5 2C), 127.8, 128.5 2C), 136.3, 136.4, 137.8. Anal.
calcd for C28H38O6: C, 69.93, H, 8.58, O, 21.5. Found: C,
69.84, H, 8.64, O, 21.25.
4. Experimental
4.1. General procedures
1H NMR spectra were recorded in CDCl3 dHˆ7.25) at

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J.-M. Vatele / Tetrahedron 58 32002) 5689±5698
5694
4.2.3. 1,2:3,4-Di-O-isopropylidene-6-O-33-methyl-2-
butenyl)-a-d-galactopyranose 1c. Ether±petroleum ether
CHvCMe2). 13C NMR: 18.0, 22.4 2C), 24.6, 25.8, 25.9,
36.6 2C), 57.3, 73.4, 122.6, 135.1. Anal. calcd for C12H22O:
C, 79.06, H, 12.16, O, 8.78. Found: C, 79.38, H, 12.11, O,
8.51.
20
1:4), 87%, oil, [a]D ˆ273.5 c 1, CHCl3). IR ®lm):
1660 cm21 1H NMR: 1.31 s, 3H, CH3), 1.33 s, 3H,
.
CH3), 1.44 s, 3H, CH3), 1.52 s, 3H, CH3), 1.66 s, 3H,
CH3), 1.72 s, 3H, CH3), 3.54 dd, 1H, Jˆ6.5 and 9.9 Hz,
H-6), 3.63 dd, 1H, Jˆ6.1 and 10 Hz, H-6), 3.96 dt, 1H,
Jˆ1.8 and 6.3 Hz, H-5), 4.02 d, 2H, Jˆ7 Hz, CH2±
CHvC), 4.27 dd, 1H, Jˆ1.8 and 7.9 Hz, H-4), 4.3 dd,
1H, Jˆ2.3 and 5 Hz, H-2), 4.58 dd, 1H, Jˆ2.3 and
7.9 Hz, H-3), 5.33 brt, 1H, Jˆ6.9 Hz, CHvCMe2), 5.52
d, 1H, Jˆ5 Hz, H-1). 13C NMR: 18.0, 24.5, 25.0, 25.8,
26.0, 26.1, 66.8, 67.8, 68.4, 70.67, 70.69, 71.2, 96.4,
108.5, 109.2, 121.3, 136.9. Anal. calcd for C17H28O6: C,
62.17, H, 8.59, O, 29.23. Found: C, 62.08, H, 8.63, O, 29.34.
4.2.8. 3-Methyl-2-butenyl 3-[4-33-methyl-2-butenyloxy)-
phenyl]propyl ether 1l. Ether±petroleum ether 1:9), 93%
1
yield, oil. IR ®lm): 1670, 1610, 1580 cm21. H NMR: 1.7
s, 3H, CH3), 1.75 s, 3H, CH3), 1.76 s, 3H, CH3), 1.8 s,
3H, CH3), 1.88 q, 2H, Jˆ6.4 Hz, CH2±CH2O), 2.65 t, 2H,
Jˆ6.5 Hz, CH2Ar), 3.42 t, 2H, Jˆ6.5 Hz, Ar CH2)2CH2O),
3.95 d, 2H, Jˆ6.9 Hz, CH2±CHvC), 4.49 d, 2H, Jˆ
6.75 Hz, CH2OAr), 5.39 brt, 1H, Jˆ6.9 Hz, CHvCMe2),
5.51 brt, 1H, Jˆ6.8 Hz, CHvCMe2), 6.83 d, 2H, Jˆ
8.6 Hz, Ar), 7.10 d, 2H, Jˆ8.6 Hz, Ar). 13C NMR: 18.1,
18.2, 25.8 2C), 31.5, 31.6, 64.8, 67.3, 69.4, 114.5 2C),
120.0, 121.4, 129.3 2C), 134.1, 136.7, 137.9, 157.1. Anal.
calcd for C19H28O2: C, 79.12, H, 9.78, O, 11.09. Found: C,
78.96, H, 9.75, O, 11.04.
4.2.4. 31R,2S,5R)-Menthyl 3-methylbuten-2-yl ether 1d.
20
Ether±petroleum ether 2:98), 92%, oil, [a]D ˆ291.4 c 2,
CHCl3). IR ®lm): 1670 cm21 1H NMR: 0.77 d, 3H,
.
Jˆ6.9 Hz, CH3), 0.88 d, 3H, Jˆ6.6 Hz, CH3), 0.92 d,
3H, Jˆ6.6 Hz, CH3), 0.95±1.5 m, 5H), 1.55±1.67 m,
2H), 1.68 s, 3H, CH3), 1.74 s, 3H, CH3), 2.02±2.37 m,
2H), 3.04 td, 1H, Jˆ4.2 and 10.4 Hz, CHOR), 3.82 dd, 1H,
Jˆ7.1 and 11 Hz, CHa±CvC), 4.1 dd, 1H, Jˆ7 and 11 Hz,
4.2.9. 1-[33-Methyl-2-butenyl)oxy]-5-32-propenyloxy)-
pentane 1h. To a solution of 1,5-butanediol monoprenyl
ether23 0.5 g, 2.9 mmol) in 6 mL of DMF, cooled to
2108C, were successively added allyl bromide 0.38 mL,
1.5 equiv.) and NaH 60% dispersion in mineral oil,
0.14 g, 1.2 equiv.). The reaction mixture was allowed to
warm up to room temperature and stirred for 2 h. Excess
of NaH was destroyed with MeOH and ether and water were
added. The aqueous phase was extracted once with water,
dried Na2SO4) and evaporated under reduced pressure. The
residue was puri®ed by chromatography on silica gel
ether±petroleum ether, 1:9) to give 1h as a liquid 0.58 g,
CHb±CHvC), 5.36 brt, 1H, Jˆ6.95 Hz, CHvCMe2). 13
C
NMR: 16.2, 18.0, 21.0, 22.4, 23.4, 25.5, 25.8, 31.7, 34.7,
40.6, 48.3, 64.8, 78.3, 121.9, 136.3. Anal. calcd for
C15H28O: C, 80.29, H, 12.58, O, 7.13. Found: 80.01, H,
12.56, O, 7.18.
4.2.5. 17-b-33-Methyl-2-butenyloxy)androst-4-en-3-one
1e. Ether±petroleum ether 1:1), 46% yield, crystalline
94%). IR ®lm): 3070, 1670, 1640 cm21. H NMR: 1.28±
20
solid: mp 64±658C, [a]D ˆ189.3 c 1.6, CHCl3). IR
1
KBr): 1670, 1613 cm21
.
1H NMR: 0.8 s, 3H, CH3),
1.72 m, 6H), 1.67 s, 3H, CH3), 1.74 s, 3H, CH3), 3.41 m,
4H, CH2OAll, CH2OPre), 3.94 m, 4H, 2 CH2±CHvC),
5.15 brd, 1H, Jˆ10 Hz, CHvCH2), 5.26 brd, 1H, Jˆ
17 Hz, CHvCH2), 5.35 brd, 1H, Jˆ6.9 Hz, CHvCMe2),
5.89 ddd, 1H, Jˆ5.6, 10 and 17 Hz, CHvCH2). 13C NMR:
18.0, 22.9, 25.8, 29.6, 29.7, 67.3, 70.2, 70.4, 71.8, 116.6,
121.4, 135.1, 136.5. Anal. calcd for C13H24O2: C, 73.54, H,
11.39, O, 15.07. Found: C, 73.50, H, 11.46, O, 14.97.
0.81±1.1 m, 3H), 1.16 s, 3H, CH3), 1.2±1.62 m, 7H),
1.63 s, 3H, CH3), 1.74 s, 3H, CH3), 1.9±2.12 m, 4H),
2.15±2.5 m, 4H), 3.31 t, 1H, Jˆ8.2 Hz, CHOR), 3.90 q,
1H, Jˆ7 and 11.45 Hz, CHa±CHvC), 3.98 q, 1H, Jˆ7
and 11.5 Hz, CHb±CHvC), 5.3 brt, 1H, Jˆ6.9 Hz,
CHvCMe2), 5.7 brs, 1H, CO±CHvC). 13C NMR: 11.7,
17.5, 18.1, 20.8, 23.4, 25.9, 28.2, 31.6, 32.9, 34.0, 35.5,
35.8, 37.8, 38.7, 42.9, 50.8, 54.0, 66.7, 88.3, 122.0, 123.9,
136.1, 171.3, 199.6. Anal. calcd for C24H36O2: C, 80.85, H,
10.18, O, 8.97. Found: C, 80.7, H, 10.24, O, 8.91.
4.2.10. 5-33-Methyl-2-butenyloxy)-1-pentanol acetate 1i.
To a solution of 1,5-butanediol monoprenyl ether23 0.38 g,
2.2 mmol) in 4 mL of pyridine was added acetic anhydride
2 mL). The solution was stirred for 2 h at room tempera-
ture. After evaporation of the solution to dryness, the
residue was puri®ed by chromatography on silica gel
ether±petroleum ether, 1:4), to afford 1i as a liquid
4.2.6. 31R,2S)-6,6-Dimethyl-2-[2-32-methylbuten-2-yloxy)-
ethylbicyclo[3.1.1]hept-2-ene 1f. Ether±petroleum ether
20
5:95), 94% yield, oil, [a]D ˆ229.7 c 1, CHCl3). IR
®lm): 3010, 1675, 1650 cm21 1H NMR: 0.84 s, 3H,
.
CH3), 1.16 d, 1H, Jˆ8.4 Hz), 1.27 s, 3H, CH3), 1.67 s,
3H, CH3), 1.74 s, 3H, CH3), 1.96±2.12 m, 2H), 2.12±2.41
m, 5H), 3.42 t, 2H, Jˆ7.2 Hz, CHOR), 3.94 d, 2H, Jˆ
6.9 Hz; CH2±CHvC), 5.26 m, 1H, CvCH), 5.35 brt, 1H,
Jˆ6.8 Hz, CHvCMe2). 13C NMR: 18.0, 21.2, 25.8, 26.4,
31.4, 31.7, 37.3, 38.0, 40.8, 45.9, 67.1, 68.6, 117.7, 121.4,
136.6, 145.3. Anal. calcd for C16H26O2: C, 81.99, H, 11.18,
O, 6.83. Found: C, 82.04, H, 11.20, O, 6.76.
0.43 g, 91%). IR ®lm): 1740, 1670 cm21 1H NMR:
.
1.35±1.48 m, 2H), 1.53±1.65 m, 4H), 1.65 s, 3H, CH3),
1.73 s, 3H, CH3), 2.02 s, 3H, CH3), 3.39 t, 2H, Jˆ6.4 Hz,
CH2OPre), 3.93 d, 2H, Jˆ6.9 Hz, CH2±CHvC), 4.04
t, 2H, Jˆ6.5 Hz, CH2OAc), 5.33 brt, 1H, Jˆ6.9 Hz,
CHvCMe2). 13C NMR: 18.0, 21.0, 22.8, 25.8, 28.5, 29.5,
64.5, 67.3, 70.0, 121.3, 136.7, 171.1. Anal. calcd for
C12H22O3: C, 67.26, H, 10.35, O, 22.40. Found: C, 67.04,
H, 10.40, O, 22.81.
4.2.7. 3-Methyl-2-butenyl 1-methylcyclohexyl ether 1g.
Ether±petroleum ether 2:98), 82% yield, liquid. IR ®lm):
4.2.11. 31,1-Dimethylethyl)dimethyl[5-33-methyl-2-
butenyloxy)pentyl]oxy silane 1j. To a solution of
1,5-butanediol monoprenyl ether23 0.4 g, 2.3 mmol) in
8 mL of DMF were successively added imidazole 0.35 g,
1
3020, 1670 cm21. H NMR: 1.14 s, 3H, CH3), 1.19±1.63
m, 10H, 5CH2), 1.66 s, 3H, CH3), 1.73 s, 3H, CH3), 3.84
d, 2H, Jˆ6.75 Hz, OCH2), 5.32 brt, 1H, Jˆ6.78 Hz,

Á
J.-M. Vatele / Tetrahedron 58 32002) 5689±5698
5695
2.2 equiv.) and t-butyldimethylchlorosilane 0.42 g, 1.2
equiv.). After stirring for 2 h at room temperature, the
solution was diluted with ether, washed twice with water,
dried Na2SO4) and evaporated to dryness. The residue was
chromatographed on silica gel ether±petroleum ether, 5:95)
4.3.1. 1,2:5,6-Di-O-isopropylidene-a-d-glucofuranose 2a.
Method A. Ether±petroleum ether, 2:1), 61% yield, crystal-
line solid, mp 107±1108C, [a]D ˆ218 c 4.2, H2O) lit.24
20
mp 1108C, [a]Dˆ218.5 c 5, H2O)). Spectroscopic data are
in accordance with those of an authentic sample.
to give 1j as a liquid 0.625 g, 94%). IR ®lm): 1670 cm21
.
1H NMR: 0.04 s, 6H, SiMe2), 0.89 s, 9H, Sit-Bu), 1.32±
1.47 m, 2H), 1.48±1.65 m, 4H), 1.67 s, 3H, CH3), 1.74 s,
3H, CH3), 3.40 t, 2H, Jˆ6.5 Hz, CH2OPre), 3.61 t, 2H,
Jˆ6.4 Hz, CH2OSi), 3.94 d, 2H, Jˆ6.9 Hz, CH2±CHvC),
5.35 brt, 1H, Jˆ6.9 Hz, CHvCMe2). 13C NMR: 18.0, 18.4,
22.5, 24.6, 25.8, 26.0 3C), 29.6, 32.7, 63.2, 67.3, 70.3,
121.4, 136.6. Anal. calcd for C16H34O2Si: C, 67.07, H,
11.96. Found: C, 66.84, H, 11.90.
20
Method B. 65% Yield, solid, mp 110±1118C, [a]D ˆ217.5
c 3, H2O).
4.3.2. 3-O-Benzyl-1,2-isopropylidene-a-d-glucofuranose
2b. Method A. I2, 3 equiv., ether), 50% yield, oil,
20
20
[a]D ˆ250.4 c 1.6, CHCl3) lit.22 [a]D ˆ249.9 c
1
1.08, CHCl3). H NMR data were in perfect agreement
with those described.22
20
Method B. DDQ, 3 equiv., 68% yield, [a]D ˆ249.5 c 1,
4.2.12.
31,1-Dimethylethyl)diphenyl[5-33-methyl-2-
butenyloxy)pentyl]oxy silane 1k. To a solution of
1,5-butanediol monoprenyl ether23 0.5 g, 2.9 mmol) in
10 mL of DMF were successively added imidazole
0.434 g, 2 equiv.) and t-butyldiphenylchlorosilane
0.9 mL, 1.2 equiv.). After stirring for 3 h at room tempera-
ture, the solution was diluted with ether, washed twice with
water, dried Na2SO4) and evaporated to dryness. The
residue was puri®ed by chromatography on silica gel
ether±petroleum ether, 5:95) to give 1k as a liquid
1.15 g, 97%). IR ®lm): 3120, 3060, 3040, 3010, 1670,
CHCl3).
4.3.3. 3-O-Benzyl-1,2-O-isopropylidene-6-O-33-methyl-
2-butenyl)-a-d-glucofuranose 3b. Method A. Ether±
petroleum ether, 1:1), 54% yield, oil. It was characterized
as its acetate: oil, [a]Dˆ252.9 c 3.6, CHCl3). IR ®lm):
3050, 3040, 3020, 1740, 1670 cm21. 1H NMR: 1.33 s, 6H,
CH3), 1.5 s, 6H, CH3), 1.65 s, 3H, CH3), 1.72 s, 3H, CH3),
1.95 s, 3H, OAc), 3.63 dd, 1H, Jˆ4.6 and 11.4 Hz, H-6a),
3.81 dd, 1H, Jˆ2.3 and 11.4 Hz, H-6b), 3.91±4.1 m, 3H,
H-3, CH2±CHvC), 4.43 dd, 1H, Jˆ3 and 9.5 Hz, H-4),
4.45 d, 1H, Jˆ11.5 Hz, CH2Ph), 4.6 d, 1H, Jˆ3.75 Hz,
H-2), 4.62 d, 1H, Jˆ11.6 Hz, CH2Ph), 5.22±5.38 m, 2H,
H-5 and CHvCMe2), 5.91 d, 1H, Jˆ3.7 Hz, H-1). 13C
NMR: 18.1, 21.1, 25.8, 26.4, 26.8, 67.8, 68.6, 69.9, 72.1,
77.8, 81.1, 81.8, 105.3, 112.0, 121.1, 128.0, 128.2 2C),
128.5 2C), 137.0, 137.1, 159.8. Anal. calcd for C23H32O7:
C, 65.7, H, 7.67, O, 26.63. Found: C, 65.69, H, 7.75, O,
26.55.
1590 cm21. H NMR: 1.08 s, 9H, t-Bu), 1.43±1.63 m,
1
6H), 1.68 s, 3H, CH3), 1.76 s, 3H, CH3), 3.41 t, 2H,
Jˆ6.5 Hz, CH2OPre), 3.69 t, 2H, Jˆ6.4 Hz, CH2OSi),
3.95 d, 2H, Jˆ6.9 Hz, CH2±CHvC), 5.38 brt, 1H, Jˆ
6.9 Hz, CHvCMe2), 7.43 m, 6H, Ar), 7.72 m, 4H, Ar).
13C NMR: 18.1, 19.3, 22.6, 25.9, 27.0 3C), 32.5, 64.0, 67.3,
70.3, 121.6, 127.7 4C), 129.6 2C), 134.2 2C), 135.6 4C),
136.6. Anal. calcd for C26H38O2Si: C, 76.04, H, 9.33. Found:
C, 76.09, H, 9.43.
Method B. With 1 equiv. of DDQ, two products were
formed. Elution with ether±petroleum ether, 1:1) gave
®rst 3b 33% yield) followed by 3-O-benzyl-1,2-O-iso-
propylidene-5-O- 3-methyl-2-butenyl)-a-d-glucofuranose
27% yield). 1H NMR: 1.32 s, 3H, CH3), 1.49 s, 3H, CH3),
1.61 s, 3H, CH3), 1.70 s, 3H, CH3), 3.7±4.02 m, 3H, H-5,
2H-6), 4.05±4.19 m, 3H, H-3, CH2±CHvC), 4.24 dd, 1H,
Jˆ3 and 9.5 Hz, H-4), 4.56 d, 1H, Jˆ11.5 Hz, CH2Ph),
4.62 d, 1H, Jˆ3.8 Hz, H-2), 4.73 d, 1H, Jˆ11.5 Hz,
CH2Ph), 5.28 brt, 1H, Jˆ6.8 Hz, CHvCMe2), 5.91 d,
1H, Jˆ3.8 Hz, H-1). 13C NMR: 18.0, 25.8, 26.4, 26.8,
62.1, 66.6, 72.0, 75.3, 80.0, 81.8, 105.1, 112.0, 121.0,
127.6 2C), 127.9, 128.5 2C), 137.2, 137.5.
4.3. General procedure for the cleavage of prenyl ethers
Method A: iodine in dichloromethane. To a solution of
1 mmol of the prenyl ether in 10 mL of dry dichloro-
methane, cooled to 08C, was added iodine in most cases
0.381 g, 1.5 equiv.) except for 1e and 1h 3 equiv.) and for
Ê
1k 2 equiv.)). In the case of acid sensitive subsrates 3 A
Ê
molecular sieves was added prior to iodine 0.1 g of 3 A
molecular sieves/0.1 g of iodine). The reaction was warmed
up to room temperature and monitored by TLC. After
completion of the reaction, the reaction mixture was diluted
with CH2Cl2, washed with saturated sodium thiosulfate
solution followed by water. After drying the organic phase
Na2SO4), solvent was removed under reduced pressure.
The residue was puri®ed by column chromatography on
silica gel.
4.3.4. 1,2:3,4-Di-O-isopropylidene-a-d-galactopyranose
2c. Method A. Ether±petroleum ether, 2:1), 72% yield,
oil, [a]Dˆ257 c 1.2, CHCl3) lit.24 [a]D ˆ255 c 3.5,
20
CHCl3)). Its spectroscopic data were in accordance with
those of an authentic sample.
Method B: DDQ in CH2Cl2±H2O 39:1). To a stirred solution
of prenyl ether 1 mmol) in 9 mL of CH2Cl2 was added
water 1 mL) and DDQ 0.272 g, 1.2 equiv.). Reaction
progress was monitored by TLC. Upon consumption of
the prenyl ether, 2,3-dichloro-5,6-dicyanohydroquinone
was ®ltered. To the ®ltrate, saturated NaHCO3 solution
was added, and the aqueous phase was extracted twice
with CH2Cl2. Drying over Na2SO4, and evaporation to
dryness gave a material that was puri®ed by ¯ash chroma-
tography.
Method B. 89% Yield, [a]Dˆ254.3 c 2.5, CHCl3).
4.3.5. 31R,2S,5R)-Menthol 2d. Method A. Ether±petro-
leum ether, 1:3), 92% yield, solid, mp 41±438C, [a]Dˆ
248.2 c 2, EtOH) lit.25 mp 41±438C, [a]Dˆ250 10%
alcoholic solution)). NMR data were in accordance with
those of an authentic sample.

Á
J.-M. Vatele / Tetrahedron 58 32002) 5689±5698
5696
Method B. 86% Yield, solid, mp 42±438C, [a]Dˆ250.2
c 5, EtOH).
Method B. 83% Yield.
4.3.13. 3-[4-33-Methyl-2-butenyl)phenyl]-1-propanol 2l.
This compound was obtained, by method B, in pure form
in 36% yield, after puri®cation on silica gel ether±petro-
leum ether, 1:2). Its physical data were in agreement with
those described in the literature.29
4.3.6. Testosterone 2e. Method A. Ether±petroleum ether,
4:1), 79% yield, solid: mp 150±1538C, [a]Dˆ1107 c 2.1,
EtOH). Lit.25 mp 1558C, [a]D ˆ1109 c 4, EtOH)). NMR
24
data were in agreement with a sample from a commercial
source.
4.3.14. 6-33-Hydroxypropyl)-3,4-dihydro-2,2-dimethyl-
3-iodo-2H-1-benzopyran 4. To a solution of the diprenyl
ether 1l 0.15 g, 0.52 mmol) in 6 mL of CH2Cl2, cooled to
08C, was added iodine 0.198 g, 1.5 equiv.). The reaction
mixture was stirred for 90 min at 08C and 30 min at room
temperature. The brownish solution was diluted with
CH2Cl2, washed with a saturated Na2S2O3 solution then
water. The organic phase was dried Na2SO4) and evapo-
rated to dryness. Flash chromatography of the residue
ether±petroleum ether, 1:1) gave 4 as an oil which crystal-
Method B. 89% Yield, solid, mp 152±1558C, [a]Dˆ1110
c 1.5, EtOH).
4.3.7. 32)-Nopol 2f. Method B. Ether±petroleum ether,
1:2), 78% yield, oil. Physical and spectroscopic data were
in agreement with those of an authentic sample.
4.3.8. 1-Methylcyclohexanol 2g. Method A. Puri®cation by
¯ash chromatography ether±petroleum ether, 1:2) followed
by distillation in a Kugelrohr apparatus gave pure 2 g 75%
yield) as an oil which crystallized on standing: mp 25±268C.
Its NMR data were identical with those of a commercial
sample.
1
lized on standing 0.102 g, 56% yield), mp 65±688C. H
NMR: 1.48 s, 3H, CH3), 1.57 s, 3H, CH3), 1.9 m, 2H,
CH2±CH2OH), 2.62 t, 2H, Jˆ7.3 Hz, CH2±CH2±CH2OH),
3.43 d, 1H, Jˆ8.5 Hz, CHa±CHI), 3.44 d, 1H, Jˆ6.3 Hz,
CHb±CHI), 3.68 t, 2H, Jˆ6.4 Hz, CH2OH), 4.42 dd, 1H,
Jˆ6.5 and 8.3 Hz, CHI), 6.72 d, 1H, Jˆ8.3 Hz, Ar), 6.83
d, 1H, Jˆ1.7 Hz, Ar), 6.97 dd, 1H, Jˆ2.1 and 8.3 Hz). 13C
NMR: 23.5, 27.8, 31.2, 32.8, 34.4, 36.9, 62.3, 76.5, 117.4,
120.3, 128.2, 133.8, 151.1. Anal. calcd for C14H19O2: C,
48.57, H, 5.53, O, 9.24. Found: C. 48.64, H, 5.61, O, 9.15.
Method B. 72% Yield, mp 24±268C.
4.3.9. 5-32-Propenyloxy)-1-pentanol 2h. Method A. Two
products were obtained: 2h and its corresponding vic-diiodo
5 puri®ed by ®ltration on a pad of silica gel ether±petro-
leum ether, 2:1). Treatment of the mixture 0.19 g obtained
from 0.15 g of starting material 1h) with powdered zinc
0.13 g) in 4 mL of hot ethanol 608C) and puri®cation by
¯ash chromatography gave pure 2h as a liquid 0.081 g,
4.4. Procedure for cleavage of the prenyl ether 1d using
catalytic amount of I2 or DDQ
1
80% yield). H NMR: 1.28±1.72 6H, m), 2.55 s, 1H,
4.4.1. With iodine. To a solution of prenyl ether 1d 0.15 g,
0.67 mmol) in 5 mL of dry CH2Cl2, cooled to 08C, was
added iodine 0.068 g, 4 mol%. The reaction mixture was
allowed to warm up to room temperature and stirred for
4 h 30. After an usual work-up, puri®cation of the residue
on silica gel ether±petroleum ether, 1:3) afforded menthol
2d as a crystalline solid 0.093 g, 89% yield).
OH), 3.39 t, 2H, Jˆ6.3 Hz, CH2OAll), 3.58 t, 2H, Jˆ
6.4 Hz, CH2OH), 3.93 dt, 2H, Jˆ5.6 and 1.4 Hz, CH2±
CHvCH2), 5.12 brd, 1H, Jˆ10 Hz, CHvCH2), 5.22 dq,
1H, Jˆ1.5 and 17 Hz, CHvCH2), 5.88 ddd, 1H, Jˆ5.6, 10
and 17 Hz, CHvCH2). 13C NMR: 22.4, 29.4, 32.4, 62.5,
70.3, 71.8, 116.8, 134.9. Anal. calcd for C8H16O2: C,
66.63, H, 11.18. Found: C, 66.55, H, 11.22.
4.4.2. With DDQ. To a solution of prenyl ether 1d 0.15 g,
0.67 mmol) in 5 mL of CH2Cl2, were successively added
DDQ 0.015 g, 0.1 equiv.) and Mn OAc)3´2H2O 0.54 g,
3 equiv.). After stirring the brown suspension for 19 h, the
salt was ®ltered and washed once with CH2Cl2. The
combined organic phases were washed with a saturated
NaHCO3 solution and water. Drying Na2SO4) the organic
phase and evaporation under reduced pressure gave a resi-
due puri®ed on silica gel ether±petroleum ether, 1:3).
Menthol 2d was obtained as a crystalline solid 0.087 g,
84% yield).
Method B. 86% Yield. 1H and 13C NMR data were identical
with those of a sample obtained via method A.
4.3.10. 5-Hydroxypentylacetate 2i. Method A. Ether±
petroleum ether, 2:1), 77% yield, liquid. Its spectroscopic
data were in perfect agreement with those described in the
literature.26
Method B. 94% Yield.
4.3.11. 5-t-Butyldimethylsilyloxypentan-1-ol 2j. Method
A. Ether±petroleum ether, 2:1), 22% yield, oil. Its spectro-
scopic data were in accordance with those reported in the
literature.27
4.4.3. Reaction of iodine 30.4 equiv.) with the prenyl
ether 1l: isolation of the intermediates. To a solution of
1l 0.2 g, 6.94 mmol) in 6 mL of CH2Cl2, cooled to 08C, was
added iodine 0.071 g, 0.4 equiv.).The reaction was allowed
to warm up to room temperature and stirred for 2 h. After an
usual work-up, the residue was puri®ed by ¯ash chroma-
tography on silica gel. Elution with ether±petroleum ether
1:2) gave 4-[3-methyl-2-butenyl)oxy]propylphenol 7 as an
oil 0.04 g, 26%). 1H NMR: 1.68 s, 3H, CH3), 1.74 s, 3H,
CH3), 1.88 m, 2H, CH2±CH2OPre), 2.63 t, 2H, Jˆ6.5 Hz,
CH2Ar), 3.46 t, 2H, Jˆ6.5 Hz, CH2OPre), 3.99 d, 2H,
Method B. 2j was separated from 3-methyl-1-butenal by
¯ash chromatography ether±petroleum ether, 2:1), 80% yield.
4.3.12. 5-t-Butyldiphenylsilyloxypentan-1-ol 2k. Method
A. Ether±petroleum ether, 1:1), 70% yield, oil. Its spectro-
scopic data were identical with those described in the
literature.28

Á
J.-M. Vatele / Tetrahedron 58 32002) 5689±5698
5697
Jˆ6.9 Hz, CH2±CHvC), 5.39 brt, 1H, Jˆ6.9 Hz,
CHvCMe2), 5.87 s, 1H, OH), 6.75 d, 2H, Jˆ8.5 Hz,
Ar), 7.03 d, 2H, Jˆ8.5 Hz, Ar). 13C NMR: 18.1, 25.8,
31.49, 31.52, 67.3, 69.4, 115.3 2C), 121.0, 129.5 2C),
133.8, 137.2, 153.9. Anal. calcd for C14H20O2: C, 76.33,
H, 9.15. Found: C, 76.10, H, 9.21. Pursuing the elution
with ether±petroleum ether 1:1) gave ®rst compounds 2l
and the iodo 4 ratio 7:3) as an unseparable mixture
0.018 g) and then zanthoxylol 6 0.03 g, 2%).
Jˆ9.78 Hz, CHvCH-Ar), 6.30 d, 1H, Jˆ9.80 Hz,
CHvCH-Ar), 6.72 d, 1H, Jˆ8.2 Hz, Ar), 6.84 1H, Jˆ
2.1 Hz, Ar), 6.96 dd, 1H, Jˆ2.1 and 8.1 Hz, Ar). 13C
NMR: 28.0 2C), 38.4, 63.8, 76.2, 116.4, 121.3, 122.3,
126.8, 129.5, 130.6, 131.0, 151.6.14
4.4.7. 1-Iodo-5-iodomethyl-2,2,4-trimethyl-4-cyclohexene
11 from 1d. Prenyl ether cleavage of 1d was effected on
0.45 g 2 mmol). After an usual work-up, the residue was
puri®ed by chromatography on silica gel, eluant petroleum
ether, to give 11 as a yellow oil 0.06 g, 7%). 1H NMR: 0.99
s, 3H, CH3), 1.04 s, 3H, CH3), 1.58 s, 3H, CH3), 1.92 d,
1H, Jˆ18.5 Hz, CHa±CH CH3)2), 2.04 d, 1H, Jˆ18.5 Hz,
CHb±CH CH3)2), 2.94 m, 2H, CH2±CHI), 3.86 d, 1H,
Jˆ9.2 Hz, CHaI), 3.92 d, 1H, Jˆ9.2 Hz, CHbI), 4.33 dd,
1H, Jˆ6 and 8.3 Hz, CHI). 13C NMR: 8.0, 18.2, 25.2, 30.0,
35.1, 40.1, 44.3, 44.5, 126.3, 132.3.
4.4.4. Formation of the iodo 4 from phenol 7. To a solu-
tion of 7 0.04 g, 0.18 mmol) in 2 mL of CH2Cl2 was added
iodine 0.046 g, 1 equiv.). The reaction mixture was stirred
for 1 h at room temperature and worked-up as usual.
Chromatography of the residue on silica gel ether±petro-
leum ether, 1:1) afforded 4 as a yellow oil 0.025 g, 40%).
4.4.5. 3-[4-Hydroxy-3-33-methyl-2-butenyl)phenyl]-1-pro-
panol 6 3zanthoxylol). To a solution of the iodo 4 0.056 g,
0.16 mmol) in 2 mL of ethanol was added powdered zinc
0.02 g, 2 equiv.). The suspension was re¯uxed for 1 h,
cooled down and evaporated to dryness. The residue was
chromatographed on silica gel to give 6 as an oil 0.031 g,
88% yield). IR ®lm): 3340, 1660 cm21. 1H NMR: 1.62 brs,
1H, CH2OH), 1.78 s, 6H, 2 CH3), 1.87 m, 1H, CH2±
CH2OH), 2.62 t, 2H, Jˆ7.2 Hz, CH2±CH2±CH2OH),
3.34 d, 2H, Jˆ7.1 Hz, CH2±CHvCMe2), 3.69 t, 2H,
Jˆ6.5 Hz, CH2OH), 5.33 brt, 1H, Jˆ7.1 Hz, CHvCMe2),
5.48 s, 1H, OH), 6.72 d, 1H, Jˆ8.3 Hz, Ar), 6.92 d, 1H,
Jˆ8.3 Hz, Ar), 6.94 brs, 1H, Ar).10c 13C NMR: 17.9, 25.8,
29.7, 31.3, 34.5, 62.5, 115.6, 122.1, 127.0, 127.2, 129.9,
133.8, 134.3, 152.5.
References
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2. a) Rudinger, J. Pure Appl. Chem. 1963, 7, 335±362.
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8121±8124.
4.4.6. Synthesis of 6-32-hydroxyethyl)-2,2-dimethyl-2H-
1-benzopyran 10 from 8. Diprenyl ether of 2- 4-hydroxy-
phenyl)ethanol, compound 8, was prepared according to the
5. a) Lu, R. J.; Liu, D.; Giese, R. W. Tetrahedron Lett. 2000, 41,
2817±2819. b) Yadav, J. S.; Subba Reddy, B. V.; Srinivasa
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1
procedure described for 1l in 95% yield. H NMR: 1.68 s,
3H, CH3), 1.76 s, 6H, CH3), 1.81 s, 3H, CH3), 2.86 t,
2H, Jˆ7.4 Hz, CH2±CH2OPre), 3.61 t, 2H, Jˆ7.4 Hz,
CH2OPre), 3.99 d, 2H, Jˆ6.9 Hz, CH2±CHvC), 4.50 d,
2H, Jˆ6.7 Hz, PhOCH2±CHvC), 5.37 brt, 1H, Jˆ6.9 Hz,
CHvCMe2), 5.51 brt, 1H, Jˆ6.7 Hz, CHvCMe2), 6.86 d,
2H, Jˆ8.6 Hz, Ar), 7.15 d, 2H, Jˆ8.6 Hz, Ar). Trans-
formation of 8 to 9, in the presence of iodine, was affected
according to the same procedure described for 4 oil, 55%
yield). 1H NMR: 1.48 s, 3H, CH3), 1.56 s, 3H, CH3), 2.77
t, 2H, Jˆ6.6 Hz, CH2±CH2OH), 3.43 d, 1H, Jˆ8.4 Hz,
CHa±CHI), 3.44 d, 1H, Jˆ6.5 Hz, CHb±CHI), 3.80 t,
2H, Jˆ6.6 Hz, CH2OH), 4.40 dd, 1H, Jˆ6.4 and 8.3 Hz,
CHI), 6.75 d, 1H, Jˆ8.3 Hz, Ar), 6.86 brd, 1H, Ar), 7.0
dd, 1H, Jˆ1.9 and 8.3 Hz). 13C NMR: 23.8, 27.7, 32.6,
36.8, 38.3, 63.9, 76.5, 117.6, 120.5, 128.6, 129.0, 130.4,
151.5. The dehydroiodination of 9 was effected by heating
a solution of 10 0.1 g, 0.3 mmol), in 2 mL of toluene at
808C for 4 h in the presence of 4 drops of DBU. The pre-
cipitate formed was ®ltered and the ®ltrate was washed with
1N HCl solution, water, a saturated NaHCO3 solution, water
again. The organic phase was dried Na2SO4), evaporated to
dryness and the residue was puri®ed by ¯ash chroma-
tography on silica gel CH2Cl2±MeOH, 99:1) to give 10
Á
6. a) Vatele, J. M. Synlett 2001, 1989±1991. b) Vatele, J. M.
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Marchelli, R.; Bochi, V. Gazz. Chim. Ital. 1975, 105, 1253±
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1
as a yellow oil 0.057 g, 93% yield). H NMR: 1.33 s, 1H,
OH), 1.43 s, 6H, 2CH3), 2.76 t, 2H, Jˆ6.57 Hz, CH2±
CH2OH), 3.80 t, 2H, Jˆ6.55 Hz, CH2OH), 5.64 d, 1H,

Á
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5698
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scopic data in accord with those described in the literature
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Á
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