Intramolecular rearrangement of epoxides generated in situ over titanium silicate molecular sieves

Article abstract of DOI:10.1006/jcat.1998.2355

Open chain unsaturated alcohols 1, having the general formula R₁R₂C=CH(CH₂)CR₁R₂OH (where R₁, R₂ = H or CH₃, and n = 1-3) and carbocyclic unsaturated alcohols of similar type have been efficiently cyclized to the corresponding hydroxytetrahydrofuran or hydroxytetrahydropyran over titanium silicate molecular sieves (TS-1 and Ti-beta), in one pot under mild liquid phase reaction conditions using dilute hydrogen peroxide as oxidant. When the hydroxy nucleophile may attack either of the activated carbon atoms of the epoxides generated in situ, to lead to a derivative of tetrahydrofuran or tetrahydropyran, the former exclusively formed. The regioselectively for such reaction is 100%. When R₁ or R₂ = CH₃, among the diasteroisomeric products trans predominates over cis. In this cyclization reaction titanium silicate epoxidizes the olefin and successively catalyzes the opening of the oxirane ring via intramolecular attack of hydroxy oxygen. Thus the behavior of titanium sites is bifunctional in nature. However, for bicyclic unsaturated alcohols, because of geometric restriction, activity of medium pore TS-1 is very low. Ti-beta synthesized by dry gel conversion has been found to be an efficient catalyst in oxidative cyclization of such bulky organic substrates as α-terpineol, isopulegol, and trans-p-menth-6-ene-2,8-diol to their corresponding tetrahydrofuranols or tetrahydropyranols with a very high regioselectivity.

Full text of DOI:10.1006/jcat.1998.2355

Journal of Catalysis 182, 349–356 (1999)
Article ID jcat.1998.2355, available online at http://www.idealibrary.com on
Intramolecular Rearrangement of Epoxides Generated in Situ
over Titanium Silicate Molecular Sieves
Asim Bhaumik and Takashi Tatsumi1
Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, Yayoi, Tokyo 113, Japan
Received July 8, 1998; revised October 26, 1998; accepted November 9, 1998
for the preparation of these compounds. For more than a
decade, titanium silicate molecular sieve, TS-1 (6), having
the medium pore MFI topology has been used as an effi-
cient, clean, and selective oxidation catalyst under liquid
phase heterogeneous reaction conditions in the presence
of dilute hydrogen peroxide (7). Until now, as an outcome
of the continuous effort to find a use for the TS-1/H2O2 sys-
tem in a new class of organic transformations, it has been
successfully employed for selective oxyfunctionalization of
alkane (8), alkene epoxidation (9), hydroxylation of aro-
matics(10), ammoximation ofcarbonyls(11), and oxidation
of amines (12) and sulfides (13). Some of these reactions
have been commercialized or tested in a large pilot plant
and the aim of the recent research is to find out their appli-
cability to other transformations. Here, we report a highly
efficient regioselective cyclization of such olefinic alcohols
over titanium silicates, under mild reaction conditions us-
ing dilute hydrogen peroxide as an oxidant. TS-1 with the
MFI structure has been very recently employed in the cy-
clization reactions for the synthesis of tetrahydrofurans and
tetrahydropyrans using dilute hydrogen peroxide as an ox-
idant (14). Because the small pore size of this molecular
sieve limits its application to molecules with kinetic diam-
Open chain unsaturated alcohols 1, having the general formula
==
R1R2C CH(CH2)nCR1R2OH (whereR1, R2 = H or CH3, and n = 1–
3) and carbocyclic unsaturated alcohols of similar type have been
efficiently cyclized to the corresponding hydroxytetrahydrofuran
or hydroxytetrahydropyran over titanium silicate molecular sieves
(TS-1 and Ti-beta), in one pot under mild liquid phase reaction
conditions using dilute hydrogen peroxide as oxidant. When the hy-
droxy nucleophile may attack either of the activated carbon atoms
of the epoxides generated in situ, to lead to a derivative of tetrahy-
drofuran or tetrahydropyran, the former exclusively formed. The
regioselectively for such reaction is 100%. When R1 or R2 = CH3,
among the diasteroisomeric products trans predominates over cis.
In this cyclization reaction titanium silicate epoxidizes the olefin
and successively catalyzes the opening of the oxirane ring via in-
tramolecular attack of hydroxy oxygen. Thus the behavior of tita-
nium sites is bifunctional in nature. However, for bicyclic unsatu-
rated alcohols, because of geometric restriction, activity of medium
pore TS-1 is very low. Ti-beta synthesized by dry gel conversion
has been found to be an efficient catalyst in oxidative cyclization of
such bulky organic substrates as -terpineol, isopulegol, and trans-
p-menth-6-ene-2,8-diol to their corresponding tetrahydrofuranols
c
or tetrahydropyranols with a very high regioselectivity.
1999
Academic Press
Key Words: TS-1; Ti–Al-beta; cyclization; tetrahydrofuran; tetra-
hydropyran.
˚
eters less than 5.5 A, large pore Ti–Al-beta synthesized by
the dry gel conversion (DGC) method (15, 16) has been
employed for the synthesis of bulky bicyclic compounds,
which cannot diffuse through the MFI pores. These molec-
ular sieves with the BEA structure having pores approx.
INTRODUCTION
The widespread occurrence of substituted tetrahydro-
furan and tetrahydropyran rings in many classes of natu-
ral products have made them valuable building blocks for
the synthesis of various biologically active organic target
molecules (1). Thus, finding a new method for the synthesis
of these oxacyclic compounds is an important area of re-
search. A convenient route for the stereoselective synthe-
sis of these compounds involves an electrophilic activation
of the double bond (2, 3) in 1 followed by an intramolec-
ular nucleophilic attack of the oxygen atom of the termi-
nal hydroxyl group. Ring closure of substituted 4-penten-
1-oxy and 5-hexen-1-oxy radicals (4, 5) is also a useful tool
˚
7.0 A in diameter allow the diffusion of the chosen bulky
reactants and products through their channels. The double
bond of olefinic alcohols was activated to the corresponding
unstable epoxy alcohols by the electrophilic attack of the
titanium hydroperoxo oxygen over TS-1 or Ti-beta. This in
turn can easily undergo cyclization by the intramolecular
attack of the hydroxy moiety present in the molecule to the
activated carbon atom of the epoxy ring.
EXPERIMENTAL
1 To whom correspondence should be addressed. Fax: 81-3-5800-6825.
E-mail: tatsumi@catal.t.u-tokyo.ac.jp.
TS-1 used in the present study was synthesized by
modifying the standard literature procedure (6, 7). In a
349
0021-9517/99 $30.00
c
Copyright
1999 by Academic Press
All rights of reproduction in any form reserved.

350
BHAUMIK AND TATSUMI
typical synthesis 42 g tetraethyl orthosilicate was hy-
drolyzed with 67.7 g tetrapropyl ammonium hydroxyde
RESULTS AND DISCUSSION
(20% aqueous, Aldrich) with vigorous stirring for 1 h. Then Cyclization of Open Chain Unsaturated Alcohols
2.26 g tetrabutyl orthotitanate dissolved in 10 g isopropyl
In Table 1 conversion and product selectivities of the cy-
alcohol was added dropwise with vigorous stirring. After
clization of various unsaturated alcohols are reported. It is
2 h continuous stirring, 54 g water was added into the re-
pertinent to mention that H2O2 conversion in all the cases
sulting clear liquid and the mixture was heated in a tum-
is above 98% . Thus for clarity these data are not given in
bling autoclave at 443 K for 24 h. After crystallization,
Table 1.
the product was centrifuged and washed several times to
3-buten-1-ol. Cyclization of the simplest molecule of
this series, 3-buten-1-ol, occurs at room temperature over
TS-1/H2O2 system. In solvent 2-butanol the reaction rate is
slow and it takes 18 h to reach a yield of 82% , 3-hydroxy-
tetrahydrofuran 2 being the sole product (Scheme 1). How-
ever, in the presence of water as the dispersion medium
(solid catalyst, aqueous H2O2, and organic substrate ini-
tially form three distinct phases) (17) reaction proceeds at
a faster rate (94% conversion after 6 h) with selectivity to-
ward 2 decreasing to 76% . In this case an oxirane ring open-
ing via attack of external H2O molecules of the medium
competes with the intramolecular cyclization process, lead-
ing to dihydroxylation (1,2,4-butanetriol, 24% selectivity).
Interestingly, increasing the reaction temperature to 333 K
in the latter case decreases the yield of 2 to 2.5% with se-
lective dihydroxylation (18). Unlike for the phenylsulfenyl
chloride system (3), the cyclization of 3-butene-1-ol is quite
efficient over the present TS-1/H2O2 system (14). Another
important aspect of the TS-1 catalyzed cyclization is that,
unlike radical addition reaction, the products are hydroxy-
substituted oxacyclic compounds.
make it free of occluded alkali. Then it was dried and
calcined at 823 K for 12 h. The calcined TS-1 material
thus obtained was thoroughly characterized through XRD,
surface area measurements, and FTIR and UV–Vis spec-
troscopies. Ti–Al-beta was synthesized by the recently de-
veloped DGC method (16) using TEAOH as a structure
directing agent. Typically, Ti–Al-beta was synthesized ac-
cording to the following procedure: 0.58 g tetrabutyl or-
thotitanate (97 wt% Kanto) was first added to 4.0 g dis-
tilled water, and to the resulting suspension was added 2.0 g
H2O2 (31 wt% , MGC) after 1 h. The mixture was stirred for
1 h, leading to solution A containing peroxide titanate. So-
lution B was prepared by dissolving 0.0124 g anhydrous
NaAlO2 (Koso) and 0.015 g of NaOH (96 wt% , Koso) in
8.0 g TEAOH (40 wt% in water, Alfa) at room tempera-
ture with stirring for 1 h. Then 3.0 g fumed silica (Aerosil-
200, Nippon Aerosil) was added under vigorous stirring. A
clear homogeneous solution obtained after 2 h was heated
to 353 K and dried while stirring. When the gel became
dry, it was ground into fine powder (chemical composi-
tion: SiO2 :TiO2 :Al2O3 :Na2O : TEAOH = 304 : 10 : 0.46 :
1.55 : 132.5) and transferred into a Teflon beaker situated
in a Teflon-lined special autoclave (16) where water (5.0 g)
as a source of steam was poured into the bottom. The crys-
tallization was carried out in steam first at 403 K for 96 h,
and subsequently at 448 K for 18 h under autogeneous
pressure. The recovered product (6.8 g, Si/Ti = 31.5, Si/Al =
156, Si/Na = 136) was washed with distilled water, dried at
308 K for 12 h, and calcined at 793 K for 10 h in the flow of
air.
As shown in Scheme 1, the hydroxy nucleophile has two
probabilities for intramolecular attack to the activated car-
bon atoms of intermediate epoxide. Path 1, the exo adduct
TABLE 1
Cyclization of Various Unsaturated Alcohols over TS-1a
Product selectivity (% )
The liquid phase reaction was carried out in a two-necked
glass reactor fitted with a water condenser under inert N2
atmosphere at the required temperature (298 or 333 K)
with vigorous stirring. In a typical reaction the following
constituents were employed: 0.02 mol substrate, 0.02 mol
H2O2 (30 wt% aqueous), catalyst (TS-1, Si/Ti = 29) 20 wt%
with respect to the substrate, 10 g acetone, 2-butanol, or
H2O (in the three phase system). At various reaction times
products were analyzed by a capillary gas chromatograph
(Shimadzu 14 A, OV-1 Chiraldex G-TA columns with flame
ionization detectors). Products were identified through GC
retention times and GC-MS splitting patterns of the au-
thentic samples. When authentic samples were unavail-
Solvent/ Time Conv. Cyclized
medium
Substrate
(h) (mol% ) productb
Others
3-Buten-1-ol
H2O
2-Butanol 18
) 4-Penten-2-ol H2O
Acetone
6
94.0
82.0
85.4
80.1
84.0
98.0
96.5
92.0
90.0
76.0 (2)
100 (2)
70.0 (3)
87.7 (3)
100 (3)
100 (7)
100 (7)
100 (9)
100 (10)
24.0
—
30.0
12.3
—
—
—
—
—
(
12
18
2-Butanol 24
H2O
4-Penten-1-olc
3
4
4
6
Acetone
cis-4-Hexen-1-olc Acetone
5-Hexen-1-olc
Acetone
a Substrate : H2O2 = 1 : 1; catalyst TS-1 (20 wt% with respect to the sub-
strate); temperature = 298 K unless otherwise stated.
b Formula of the corresponding product (as shown in the schemes) is
given in parentheses.
1
able, identification was made through H NMR spectro-
scopy.
c Reactions were carried out at 333 K.

INTRAMOLECULAR REARRANGEMENT OF EPOXIDES
351
the intermediate epoxide is highly reactive and undergoes
a very rapid oxirane ring opening either via intramolecular
cyclization or hydrolysis. However, when using 2-butanol as
solvent, 3 forms as the sole product in 84% yield (trans : cis
ratio 72 : 28). High trans selectivity between the diasteri-
omers of 3 may be due to the higher stability of transition
state at the active site. Scheme 2 compares the reaction se-
quences of ( ) 4-penten-2-ol at 298 and 333 K using water
as the dispersion medium.
4-penten-1-ol. In Scheme 3, the oxidative cyclization of
4-penten-1-ol 5 over TS-1/H2O2 is illustrated. Titanium hy-
droperoxide 4 is the proposed intermediate (19–21) gen-
erated in situ when titanium silicates come in contact with
dilute aqueous hydrogen peroxide. As shown in Scheme 3, 6
is the proposed reaction intermediate. The cyclization of 4-
penten-1-ol occurred regioselectively to the 5-exo product
tetrahydro-2-furanmethanol 7. The corresponding tetrahy-
dropyran regioisomer of7 (i.e., 8, supposed to form via endo
attack of the hydroxy nucleophile to the activated terminal
carbon atom of the epoxide intermediate 6) does not form
at all. This is quite interesting, since 2,4,4,6-tetrabromo-1,5-
cyclohexadienone (2) induced cyclization leads to a mixture
of tetrahydopyran and tetrahydrofuran at a mole ratio of
3 : 1. Reaction medium has no effect; in 2-butanol, acetone,
and water, 7 was exclusively obtained in 98–99% yield. In
water at high temperature (333K) no dihydroxylation prod-
uct is formed.
SCHEME 1. Different open chain unsaturated alcohols, reaction
pathways, and cyclized products.
from the epoxide of 3-buten-1-ol, leads to the very unstable
4-membered ring compound. Thus it cannot form under the
present reaction conditions. Path 2, the endo adduct, leads
to the stable 5-membered tetrahydrofuran ring. Thus it is
the only cyclized product in case of 3-buten-1-ol. However,
as the endo product proceeds via terminal attack, for which
transition state carbocation is not very stable, increasing
reaction temperature from 298 to 333 K leads to the pre-
dominant dihydroxylation product when water is used as
the dispersion medium.
(
) 4-penten-2-ol. The tetrahydrofuran derivative 2-
methyl-4-hydroxy-tetrahydrofuran 3 (trans : cis ratio 70 :
30) is formed from ( ) 4-penten-2-ol when acetone is used
as solvent (80% yield at room temperature after 18 h re-
action time). In a water medium at room temperature, se-
lectivity for 3 (Scheme 2) drops to 70% with trans : cis ratio
of 67 : 33 after 12 h. At higher temperature in a water dis-
persion medium dihydroxylation product predominates in
a similar manner to 3-buten-1-ol. Interestingly, here also
SCHEME 2. Reaction pathways for the oxidation of 4-penten-2-ol
over TS-1/H2O2.

352
BHAUMIK AND TATSUMI
which may not diffuse easily through the MFI pore: the
TS-1/H2O2/acetone system gives rise to only 30% conver-
sion at 333 K after 4 h reflux. Large pore Ti–Al-beta
(BEA structure with 12-membered rings of pore open-
˚
ing 6.9 7.4 A, Si/Ti = 31.5, Si/Al = 156) synthesized by the
DGC method improves the conversion drastically to 90%
after 4 h reaction time at 333 K under identical conditions.
Scheme 4 illustrates the reaction pathways. The protonated
form of the epoxide formed from 11, i.e., 12, leads to a
secondary carbocation, which undergoes CH3 shift, pro-
ducing the corresponding rearranged ketone 13 via a stabi-
lized carbocation. Otherwise 12 gives a stable tertiary car-
bocation, which is converted to the ketone 14 via H shift.
These ketones are obtained (13 : 14 = 65 : 35) at 40% selec-
tivity. The rest (60% selectivity) was the cyclized product
2-(1-hydroxy-1-methylethyl)-5-methyl-tetrahydrofuran 15.
Here also high regioselectivity for the trans diasteriomer
(trans : cis = 70 : 30) is obtained. Over TS-1 the product dis-
tribution remained almost the same with a slightly higher
trans : cis ratio (75 : 25) of 15. Despite the higher stability for
the intermediate carbocation, the tetrahydropyran deriva-
tive 5-hydroxy-2,2,6-trimethyltetrahydropyran 16 formed
in a very low yield (6.5% , Scheme 4), indicating the high
preference for the 5-exo product in the present cyclization
system inside the zeolite pores. Thus there is a decreasing
tendency toward the formation of 6-membered oxacyclices
over 5-membered ones in the presence of microporous ti-
tanium silicates.
SCHEME 3. Possible reaction pathway for the oxidation of 4-penten-
1-ol.
Cis-4-hexen-1-ol. One possible explanation for the 5-
exo product formation from 4-penten-1-ol is the acidic na-
ture of TS-1, apart from higher stability of 5-membered
oxacycles over the 6-membered one. If the oxirane ring
opening follows SN1 pathways (involving initial protona-
tion), a more preferential attack would be onto the more
substituted carbon atom; the hydroxyl group would attack
preferentially at the more substituted carbon atom due
to the greater stability of the corresponding carbocation.
On the contrary, alkyl group substitution at C5 does not
cause any change in the regioselectivity of cyclization as ob-
served for cis-4-hexen-1-ol. Between the two possibilities
of the intermediate oxirane ring opening the 5-exo prod-
uct, tetrahydro-2-furan-1-ethanol 9 (Scheme 1), forms ex-
clusively in 92% yield in acetone at 333 K. The 6-endo prod-
uct, 2-methyl-3-hydroxytetrahydropyran, does not form at
all, although it would have been formed via a more sta-
ble carbocation intermediate. As shown in Scheme 3 for 5,
the titanium hydroperoxo species here protonates the inter-
mediate epoxide and thus activates it for the nucleophilic
attack of the OH groups at C4.
Corma et al. (22) have reported the oxidation of
linalool to cyclic ethers catalyzed by Ti–Al-beta and
5-hexen-1-ol. In the case of 5-hexen-1-ol (n = 3 and R1,
R2 = H), where two products, either tetrahydropyran or
its 7-membered regioisomer tetrahydrohomopyran deriva-
tive, are possible, tetrahydro-2-pyranmethanol 10 only
forms in 90% yield in acetone at 333 K (Scheme 1). Here
the exo attack prevails to give 6-membered tetrahydropy-
ran rather than the corresponding 7-membered regioiso-
mer, which can form via endo attack.
(
) 6-methyl-5-heptene-2-ol. The nature of the inter-
mediate epoxide formed plays a crucial role in the fi-
nal product distribution. This is examplified by the reac-
tion of bulky ( ) 6-methyl-5-heptene-2-ol, 11 (Scheme 4),
SCHEME 4. Reaction pathways for the oxidation of 6-methyl-5-
heptene-2-ol over Ti-beta.

INTRAMOLECULAR REARRANGEMENT OF EPOXIDES
353
Ti–Al–MCM-41. Here acidity associated with framework
Al was considered to be responsible for the cyclization af-
ter initial epoxidation of the double bond. It is noteworthy
that TS-1 with neutral framework structure also catalyzes
the cyclization of such unsaturated alcohols under mild liq-
uid phase reaction conditions in the presence of hydrogen
peroxide. Ti–Al-beta used for the present study is Na-form.
So the acidity associated with the catalysis in the cycliza-
tion step could be attributed to that generated at the Ti
sites rather than that of Al sites.
Cyclization of Carbocyclic Unsaturated Alcohols
-terpineol. TS-1/H2O2 system used for the cyclization
of open chain unsaturated alcohols shows poor activity in
the case of unsaturated alcohol containing carbocyclic ring.
Table 2 illustrates the results of oxidative cyclization of
-terpineol, isopulegol, and trans-p-menth-6-ene-2,8-diol.
For -terpineol over a TS-1/H2O2 system a conversion of
13% with very poor selectivity for cyclized product (Table 1,
5th column) was observed. In the case of -terpineol over
Ti–Al-beta (synthesized by the DGC method) the yield of
product 17 (Scheme 5) is 50% (with 23% other product mix-
ture including 16% uncyclized epoxide) vis-a`-vis 7.6% over
Ti–Al-beta (at 313 K after 8 h using t-butyl hydroperoxide,
TBHP, as an oxidant in CH2Cl2 solvent) synthesized accord-
ing to the hydrothermal synthesis method (23). Here it is
pertinent to mention that since Ti–Al-beta synthesized by
the DGC method is more hydrophobic (24), dilute aqueous
H2O2 is a more suitable oxidant in the present case whereas
for hydrothermally synthesized Ti–Al-beta (relatively hy-
drophilic) TBHP is the best oxidant. In Scheme 5 the
probable pathway for -terpineol oxidation is shown. In
this bicyclic system, 6-endo product 17 (bicycle consist-
ing of two 6-membered rings) predominantly forms over
the exo product (5- and 7-membered rings). This may be
due to the fact there is less strain in the former case.
However, unlike the open chain system, here the hydroxy
nucleophile may face more strain in an intramolecular
SCHEME 5. Oxidative cyclization of -terpineol over Ti-beta.
attack because of the restricted geometry of the carbocy-
cle. Hence, the epoxide intermediate is considerably more
stable than that of the molecule at the transition state for
intramolecular attack. This explains the observation of in-
termediate epoxide after the reaction as described above.
Isopulegol. In Scheme 6 the pathways for oxidative
cyclization of isopulegol are shown. Only 18 formed as the
major product from isopulegol. The cyclized product 18 is
an endo product; a corresponding exo attack would have
given rise to a very unstable 4-membered oxirane. The
unstable epoxide intermediate undergoes dihydroxylation
to the corresponding triol 19 to a considerable extent.
Results of oxidative cyclization on this unsaturated alcohol
containing one carbocyclic ring over Ti–Al-beta/H2O2
is in close agreement to that obtained in the case of an
open system (3-buten-1-ol and 4-penten-2-ol). As shown
in Table 2, the selectivity for triol in this case is high, which
may be due to the more open structure of the initially
formed epoxide. However, in this case acetone is used as
a solvent, which is unlikely to favor dihydroxylation as
observed in other substrates.
TABLE 2
Cyclization Reaction over Ti–Al-Betaa
Product selectivity (% )
Conv.
Cyclized
Substrate
-Terpineolb
-Terpineol
Isopulegol
(mol% ) product Epoxide Triol Others
17.8
73.4
53.7
90.0
26.8
68.4
61.4
95.0
60.3
21.8
6.6
—
—
28.3
—
12.9
9.8
3.7
5.0
trans-p-Menth-6-ene-2,8-diol. Oxidation of trans-p-me-
nth-6-ene-2,8-diolin the presence ofan acetone and CH2Cl2
solvent mixture (used to avoid the phase seperation) leads
to a very high selectivity for the cyclized product 20 (90%
conversion after 6 h reaction time at 333 K). The reac-
tion pathway is shown in Scheme 7. The selectivity toward
cyclization is as high as 95% . Among the diastereomers the
trans-p-Menth-6-ene-
2,8-diol
—
a Reaction conditions: catalyst (Si/Ti = 31.5, Si/Al = 156); reaction
time = 4–6 h; substrate : H2O2 : acetone or acetone/dichloromethane
(1 :1) = 1 :1 :5; temperature = 333 K.
b Catalyst TS-1 (Si/Ti = 29).

354
BHAUMIK AND TATSUMI
FIG. 1. Effect of temperature on selectivities in the oxidation of 3-
butan-1-ol.
cyclization is favored at low temperatures only. In Fig. 1
the kinetics of oxidative cyclization for 3-buten-1-ol is
shown. Curves a and a0 correspond to the selectivities for
3-hydroxytetrahydrofuran and 1,2,4-butanetriol, respec-
tively, at 298 K. Curves b and b0 correspond to the same
at 333 K. As seen from the figure, increasing the tem-
perature from 298 to 333 K results in the dihydroxyla-
tion products being predominant. From the figure it is
clear that the selectivity loss of 3-hydroxytetrahydrofuran
does not correspond to the gain in selectivity for 1,2,4-
butantriol, indicating that the triol formed mainly from the
intermediate epoxide directly rather than via hydrolysis of
3-hydroxytetrahydrofuran.
SCHEME 6. Oxidative cyclization of isopulegol over Ti-beta.
selectivity ratio is 86 : 14 (cis-dihydroxy vs trans-dihydroxy).
Intermediate epoxide undergoes dihydroxylation to pro-
duce the corresponding diol 21 to some extent (8.0% selec-
tivity).
Effect of Temperature
For 3-buten-1-ol and 4-penten-2-ol, where there is no
possibility of exo attack in the intermediate epoxide, as
this would give rise to unstable 4-membered oxacycles,
Mechanistic Aspects
Although theoretical calculation on the transition state
energies for 4-penten-1-oxyl radical (4) indicates the 5-exo
product is strongly favored, in the TS-1/H2O2 system oxi-
dation is believed to occur through titanium hydroperoxo
species 4 (19, 20) (Scheme 3) and thus to be essentially ionic
in nature. It is noteworthy that a different type of coordina-
tion of alcohol has been proposed recently (21). Restricted
geometry inside the TS-1 channel (the MFI topology with
˚
intersecting 10-membered rings of 5.3 5.6 and 5.1 5.5 A
pore diameters and 0.10 cm3/g internal void volume helps
in bending the chain) might play a crucial role in the re-
gioselective cyclization. The decreasing trend of the ratio
of tetrahydropyrans to tetrahydrofurans from mesoporous
MCM-41 (internal void volume very high, 0.95 cm3/g) to
large pore beta (22) followed by exclusive formation of
tetrahydrofuran rings over medium pore TS-1 supports the
above proposition.
In the oxidative cyclization (bifunctional behavior, epox-
idation followed by acid catalyzed cyclization) observed
SCHEME 7. Cyclization pathway for trans-p-menth-6-ene-2,8-diol.

INTRAMOLECULAR REARRANGEMENT OF EPOXIDES
CONCLUSIONS
355
in the oxidation of linalool (22) over Ti–Al-beta and Ti–
Al–MCM-41 the acidity at the Al sites was responsible
for the oxirane ring opening leading to cyclized product.
Since TS-1 employed here contains no Al (tetraethyl or-
thosilicate used as Si source is absolutely free of Al), the
protonic character of the titanium hydroperoxo species 4
seems to promote the cyclization. In the transition state of
the acid-catalyzed SN2 cleavage of the oxirane ring, bond
breaking proceeds faster than bond making, and carbon
has acquired a considerable positive charge. Thus the re-
action has considerable SN1 character and the nucleophilic
attack is easy to occur at the crowded carbon atom that
can best accommodate the positive charge. However, for
3-buten-1-ol and ( ) 4-penten-2-ol, the attack of the OH
group on such a carbon leading to the 4-membered ring is
unfavorable. The attack on the less crowded carbon occurs
instead. At high temperatures the attack of water predom-
inates over the attack of the intramolecular OH group. In
contrast, for 4-penten-1-ol the attack of the OH group on
the crowded carbon to produce 7 is favorable, excluding
the occurrence of dihydroxylation even at high tempera-
ture.
In the case of products 2 and 3, where dihydroxylation
product predominates at higher temperature in the wa-
ter medium, the lower stability of the endo adduct can
be accounted for according to the Baldwin rule (25). For
them the exo adduct is very unstable, as it would lead to
4-membered oxacycles, and dihydroxylation is the most fa-
vored pathway at higher temperature. In contrast, for the
substrates of formula 1, having n = 2, a favorable exo adduct
leads to 5-membered oxacyles and having n = 3, a favorable
exo adduct leads to 6-membered oxacycles following the
Baldwin rule. Restricted geometry inside the zeolite pore
further assists these processes. Interestingly, no intermedi-
ate epoxide is detected either while studying the kinetics
of various constituents of the reaction mixture in the open
chain unsaturated alcoholsbyGC, indicatingthat TS-1cata-
lyzed the present cyclization process at a very fast rate and
ring closure takes place inside the cages of the zeolite im-
mediately after the epoxidation.
In the presence of aqueous H2O2, TS-1 generates ti-
tanium hydroperoxo species 4, which not only efficiently
epoxydizes the double bond of the unsaturated alcohols
of type 1 but also catalyzes the oxirane ring opening via in-
tramolecular attack of hydroxy nucleophile, leading to oxa-
cyclic ring formation. The reaction sequence indicates that
when there is a choice between hydroxytetrahydrofuran
and tetrahydropyran, the former exclusively formed under
the present reaction conditions. However, when there is no
possibility of smaller oxacycles other than the 6-membered
one, hydroxytetrahydropyran forms exclusively. Large pore
titanium silicate Ti-beta synthesized by the DGC method
effectively catalyzes the oxidation of bulky unsaturated al-
cohols to the corresponding bicyclic compounds with high
selectivity. Because the number of acid sites of this mate-
rial is very low and pure titanium silicate TS-1 also cata-
lyzes this type of cyclization, it is believed that the titanium
sites are solely responsible for this reaction. The nature of
the substituent groups present in the intermediate epoxide
plays a crucial role in guiding the final product selectivities.
The lower stability of 12 in turn may be responsible for the
formation of hydroxytetrahydropyran (6-endo product) in
this case to a considerable extent, which is not observed in
other examples of open chain unsaturated alcohols, studied
here. More open structured carbocyclic unsaturated alco-
hols, where endo attack is the only possibility of cyclization,
lead to considerable dihydroxylation product even in the
presence of a reactant amount of water.
ACKNOWLEDGMENT
A.B. thanks the Japan Society for the Promotion of Science (JSPS) for
a postdoctoral fellowship.
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