Highly efficient and regioselective cyclization catalyzed by titanium silicate-1
Asim Bhaumik† and Takashi Tatsumi
Engineering Research Institute, The University of Tokyo, Yayoi, Tokyo 113, Japan
Highly regioselective cyclization of 3,4, 4,5 and 5,6 unsatu-
rated alcohols to tetrahydrofuranols and tetrahydropyranols
is reported using the TS-1–H O system for the first time.
2 2
2 2
1-ol is relatively efficient in the present TS-1–H O system.
Another important aspect of the TS-1 catalyzed cyclization is
that, unlike the radical addition reaction, the products are
hydroxy-substituted oxacyclic compounds.
Since the discovery of the titanium silicate molecular sieve,
The tetrahydrofuran derivative 2-methyl-4-hydroxytetra-
hydrofuran 2 (trans:cis ratio 70:30) was formed from (±)-pent-
4-en-2-ol in acetone (80% yield at room temperature after 18 h).
In water at room temperature, the selectivity for 2 drops to 70%,
with a trans:cis ratio of 67:33 after 12 h. At higher temperature
in a water dispersion medium the dihydroxylation product
predominates in a manner similar to that for but-3-en-1-ol.
Interestingly, here also the intermediate epoxide is highly
reactive and undergoes very rapid oxirane ring opening via
either intramolecular cyclization or hydrolysis. However, using
butan-2-ol as solvent 2 forms as the sole product in 84% yield
(trans:cis ratio 72:28). The high trans selectivity among the
diastereomers of 2 may be due to the higher stability of the
transition state at the active site.
1
TS-1, and its use in liquid phase heterogeneous oxidation
2
catalysis in the presence of dilute hydrogen peroxide, it has
been the subject of tremendous research activity to establish its
applicability to various organic transformations.3–7
Substituted tetrahydrofuran and tetrahydropyran rings are
common in many natural products, and thus play an important
role as building blocks for the synthesis of various biologically
8
active organic target molecules. Hence, new methods for the
synthesis of these oxacyclic compounds have long been sought.
A strategy involving electrophilic activation of the double
bond9 in pent-4-en-1-ol or hex-5-en-1-ol followed by intra-
molecular nucleophilic attack of the oxygen atom of the
hydroxy group offers a convenient route for the stereoselective
synthesis of these compounds. Ring closure of substituted pent-
,10
The cyclization of pent-4-en-1-ol occurred regioselectively
to the 5-exo product tetrahydrofuran-2-methanol 3. Attack of
the hydroxy nucleophile definitely does not take place at the
other carbon atom of the intermediate oxirane ring. Irrespective
of the reaction medium (butan-2-ol, acetone or water), 3 was
exclusively obtained in 98–99% yield. This is interesting, since
4
-en-1-yloxy and hex-5-en-1-yloxy radicals11,12 is also of
notable synthetic utility. Here, we report a highly efficient
regioselective cyclization of such olefinic alcohols over TS-1,
under mild reaction conditions using dilute hydrogen peroxide
as oxidant. A similar oxidative cyclization (bifunctional
behavior, epoxidation followed by acid catalyzed cyclization)
was observed in the oxidation of linalool13 over Al-Ti-Beta and
Al-Ti-MCM-41, where the acidity at the Al sites was responsi-
ble for the cyclization.
9
2,4,6,6-tetrabromocyclohexa-2,4-dienone-induced cyclization
leads to a mixture of tetrahydopyran to tetrahydrofuran in the
ratio 3:1. In water at high temperature (333 K) no dihydroxyl-
ation product is formed. Although theoretical calculations on
1
1
TS-1 used in the present study was synthesized by the
the transition state energies for the pent-4-en-1-yloxyl radical
indicates that the 5-exo product is strongly favored, and in the
TS-1–H system oxidation is believed to occur via titanium
1
standard literature procedure and thoroughly characterized via
X-ray diffraction and FT-IR and UV-VIS spectroscopy. The
liquid phase reaction was carried out in a two-necked glass
2 2
O
15
hydroperoxo species 4 (Scheme 2) and is thus essentially ionic
in nature. Restricted geometry inside the TS-1 channel (MFI
topology with intersecting 10-membered rings of 5.3 3 5.6 and
2
reactor fitted with a water condenser under an N atmosphere at
the required temperature (298 and 333 K) with vigorous stirring.
In a typical reaction the following constituents were employed:
3
21
5.1 3 5.5 Å pore diameters and 0.10 cm g internal void
volume helps in bending the chain) might play a crucial role in
the regioselectivity of the cyclization. The decreasing trend for
the ratio of tetrahydropyran to tetrahydrofuran from mesopor-
ous MCM-41 to large pore Beta13 followed by exclusive
formation of tetrahydrofuran rings over medium pore TS-1
supports the above proposition.
substrate (0.02 mol), aq. H
O
2 2
(0.02 mol, 30 wt%), catalyst
(
TS-1, Si/Ti = 27, 20 wt% with respect to the substrate),
acetone (10 g), butan-2-ol or H
2
O (in a three phase system). At
various reaction times products were analyzed via capillary gas
chromatography (Shimatzu 14 A, OV-1 and Chiraldex G-TA
with Flame Ionization Detector). Products were identified via
GC retention times and GC–MS using authentic reference
samples. When authentic samples were unavailable identifica-
OH
1
tion was performed via H NMR spectroscopy.
Cyclization of the simplest molecule in this series, but-3-en-
-ol, occurs at room temperature using the TS-1–H O system.
2 2
In butan-2-ol the reaction rate is slow and it takes 18 h to reach
a yield of 82%, 3-hydroxytetrahydrofuran 1 being the sole
product (Scheme 1). However, in the presence of water as the
OH
O
1
1
(82%)
HO
HO
+
2 2
dispersion medium (solid catalyst, aq. H O and organic
substrate initially forms three distinct phases) reaction proceeds
at a faster rate (93.6% conversion after 6 h). Selectivity towards
HO
OH
O
Major
O
Minor
1
decreases to 75.5%. In this case oxirane ring opening via
attack of external H O molecules from the medium competes
with intramolecular cyclization, leading to dihydroxylation
butane-1,2,4-triol, selectivity 24.5%). Interestingly, increasing
the reaction temperature to 333 K in the latter case decreases the
2
(80–85%)
2
(
O
2
CH OH
14
3 (99%)
yield of 1 to 2.5% with selective dihydroxylation. Unlike the
benzenesulfenyl chloride system,10 the cyclization of but-3-en-
Scheme 1
Chem. Commun., 1998
463