Titanocene-catalyzed reductive epoxide opening: The quest for novel hydrogen atom donors

Article abstract of DOI:10.1055/s-2004-831207

Novel hydrogen atom donors for the reductive titanocene-catalyzed epoxide opening are presented. While the potentially attractive cyclopentadienes gave only moderate yields of the desired alcohols, substituted, nontoxic, and commercially available 1,4-cyclohexadienes, e.g. γ-terpinene, in combination with more elaborate catalysts gave better or similar results than the much more expensive and carcinogenic 1,4-cyclohexadiene. In the practically important reactions of Sharpless epoxides and their derivatives excellent levels of regioselectivity for the epoxide opening could be obtained. The toxic and unpleasant to handle tert-butyl thiol could be replaced while increasing the yields of the desired products.

Full text of DOI:10.1055/s-2004-831207

PAPER
2567
Titanocene-Catalyzed Reductive Epoxide Opening: The Quest for Novel
Hydrogen Atom Donors
T
itanocene-Cataly
n
zedReductiv
d
e
Epoxide
O
r
pening eas Gansäuer,* Andriy Barchuk, Doris Fielenbach
Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität, Gerhard Domagk Str.1, 53121 Bonn,
Germany
Fax +49(228)734760; E-mail: andreas@gansaeuer.de
Received 5 May 2004; revised 23 June 2004
dide,3 that has been used with excellent success over the
Abstract: Novel hydrogen atom donors for the reductive ti-
last two decades, because reductive trapping of radicals
tanocene-catalyzed epoxide opening are presented. While the po-
tentially attractive cyclopentadienes gave only moderate yields of
the desired alcohols, substituted, nontoxic, and commercially avail-
by samarium diiodide is rather efficient.4 A practical dis-
advantage of samarium diiodide is constituted by the high
able 1,4-cyclohexadienes, e.g. g-terpinene, in combination with price of the metal (870 € per mol) that renders large scale
more elaborate catalysts gave better or similar results than the much
applications unattractive. This point is of major impor-
more expensive and carcinogenic 1,4-cyclohexadiene. In the practi-
tance especially when compared to the catalytic condi-
cally important reactions of Sharpless epoxides and their deriva-
tions described below that use the much cheaper metal
tives excellent levels of regioselectivity for the epoxide opening
powders manganese (ca. 7 € per mol) and zinc (ca. 3 € per
mol) as stoichiometric reductants.
could be obtained. The toxic and unpleasant to handle tert-butyl thi-
ol could be replaced while increasing the yields of the desired prod-
ucts.
A convenient and attractive alternative to samarium diio-
dide-induced reactions is constituted by opening of readi-
ly available epoxides5 mediated through electron-transfer
from titanocene(III) chloride as introduced by Nugent and
RajanBabu.6 The b-titanoxy radicals generated with ex-
cellent regioselectivity are usually fairly unreactive to-
wards a reduction by a second equivalent of the titanocene
reagent and can thus be utilized in a number of applica-
tions unusual for radical chemistry.7,8 This feature can
also be exploited in the hydrogen atom transfer from 1,4-
cyclohexadiene that is quite slow9 for radical reduction to
obtain alcohols from epoxides.6 This limits the usefulness
of the reagent. An example can be found in the more dif-
ficult but preparatively highly pertinent cases of the re-
duction of Sharpless epoxides and their derivatives to 1,2-
or 1,3-diols, respectively, when more reactive reductants,
e.g. tert-butyl thiol that is toxic and foul smelling, have to
be used.6c,d
Key words: epoxides, titanium, reductive ring opening, H-atom
donors, g-terpinene
Over the past three decades, radicals have been increas-
ingly utilized as reactive intermediates in organic synthe-
sis.1 Their ease of generation, high functional group
tolerance and predictable behavior in many transforma-
tions has led to numerous developments of novel methods
for the efficient formation of C–C and C–H bonds. How-
ever, limitations also exist. In this context, one of the more
demanding problems is constituted by the efficient and
environmentally safe reduction of carbon centered radi-
cals through hydrogen atom donors.2 Although excellent
results in radical chain reactions have been achieved by
using stannanes or silanes as reductants in chain reac-
tions,1 the toxicity and/or sensitivity of the reagents com-
bined with their high prices can render large scale
applications unattractive. Also, from a fundamental point
of view hydrogen atom abstraction ought to be a kinetical-
ly favorable process in order to maintain a fast chain prop-
agation.
This relative persistence of the radicals is even more pro-
nounced under the catalytic conditions10 that we have de-
vised to introduce the concept of reagent control to these
reactions.10,11 A number of unusual radical reactions could
also be realized in this manner.12
Especially the last limitation does not necessarily apply to
radical chemistry mediated or catalyzed by electron-trans-
fer. Because no chain reaction needs to be maintained rel-
atively slow transformations can be realized if the radicals
generated are not reduced by a second equivalent of the
reductant too swiftly. In this undesired scenario an orga-
nometallic species is generated and the typical radical re-
activity cannot be exploited. This is often the case with the
most popular electron-transfer reagent samarium diio-
To exploit this relative persistence, we decided to investi-
gate substituted 1,4-cyclohexadienes and other reagents
hitherto unexplored as hydrogen atom donors for our
model substrate 1 as shown in Scheme 1. Our choice of
these compounds was based on their low bond dissocia-
tion energies. The potential hydrogen atom donors are
shown in Figure 1.
The results of the studies are summarized in Table 1.
We initially checked the reaction in the absence of any ex-
ternal hydrogen atom donors to exclude any unexpected
reaction pathways (entry 1). Even in this case some of the
desired product 2 was obtained (<22% in combination
with 3 and another unknown impurity) at most under these
SYNTHESIS 2004, No. 15, pp 2567–2573
Advanced online publication: 02.09.2004
DOI: 10.1055/s-2004-831207; Art ID: T05104SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
4

2568
A. Gansäuer et al.
PAPER
OH
the weak C–H bond (77 kcal/mol). Presumably this is due
to a hindered attack for sterical reasons.
Titanocene
Coll⋅HCl,
O
Mn,
Ph
Ph
Cyclopentadienes were chosen as potential reducing re-
agents because of the low C–H bond strength (BDE = ca.
80 kcal/mol)14 and the generation of the stabilized cyclo-
pentadienyl radical after hydrogen atom abstraction. The
formation of this intermediate is of potential relevance for
the development of hydrogen atom donor catalysts. After
reduction of the cyclopentadienyl radical to the anion and
protonation in the acidic reaction medium would result in
regeneration of the cyclopentadiene as hydrogen atom do-
nor catalyst. Unfortunately, the results summarized in en-
tries 3 and 4 suggest that hydrogen atom transfer is not
very efficient (32% of desired product at most) for reasons
not fully understood yet.
H–Atom–Donor
1
2
identified side products
OH
OH
Cl
Ph
Ph
3
4
Scheme 1 Test system for the optimization of epoxide reduction
(Coll·HCl = 2,4,6-collidinium hydrochloride).
The 1,4-cyclohexadienes gave satisfying results. Interest-
ingly, the additional steric demand of the two substituents
in g-terpinene (8) (entry 6) did not result in any deteriora-
tion of the yield of 2 (84%). We were pleasantly surprised
by this finding since the titanocene-catalyzed epoxide
opening is usually fairly sensitive towards steric crowd-
ing. While the overall driving force when using the hexa-
dienes is constituted by the second H-atom transfer, the
first transfer is slower and thus rate determining. Conse-
quently the use of overstoichiometric amounts of the red-
ucant is required.
5
6
7
H
8
9
10
The practical importance of these results is substantial.
Since g-terpinene is less toxic and substantially cheaper
(about 25 €/mol) than 1,4-cyclohexadiene (about 220 €/
mol), that is a cancer suspect agent, it will certainly re-
place 1,4-cyclohexadiene in day-to-day use. We have also
established that unreacted 8 can be recovered from the re-
action mixture in combination with p-cymene, the product
of hydrogen atom abstraction, quantitatively. If desired
this mixture can be transformed into 8 by reduction.
Figure 1 Hydrogen atom donors shown in this study (compounds 5
and 6 as a mixture of isomers).
Table 1 Opening of 1 to Afford 2 in THF in the Presence of 10
mol% Cp2TiCl2
Entry
H-Atom Donor
Yield (%)
<22
<22
32
1
2
3
4
5
6
7
8
–
Increasing the steric demand of the substituents even fur-
ther in 9 and 10 resulted in only a slight decrease in isolat-
ed yields of 2. In these cases larger amounts of the
chlorohydrin 4 (2% with 7 and 8, 15% with 9, 7% with
10), formed through acid initiated epoxide opening
through an SN1 reaction, were produced as a result of the
decreased efficiency of the catalytic cycle. Still, this find-
ing is of great potential relevance for the evolution of
enantiomerically pure hydrogen atom donors for enan-
tioselective radical reduction. We are currently pursuing
this goal.
Ph3CH
5
6
30
7
8810c
84
8
9
69
10
66
To establish the scope and limitation of g-terpinene as hy-
drogen atom donor a number of epoxides were reduced
and the results compared to the reactions using 1,4-cyclo-
hexadiene as shown in Table 2. Gratifyingly, in all cases
examined 8 performed similar to or even superior than 7
except for entry 6. It was found, however, that when per-
forming this reaction in the presence of 8 on a 10 mmol
scale with a 0.2 M concentration instead of the usual 0.1
M concentration the yield of 20 increased from 69 to 84%.
conditions. It seems, however, that this product results
from trapping of the radical by a second equivalent of
Cp2TiCl and concomitant protonation of the Ti–C bond or
b-hydride elimination.13 The presence of 3 renders hydro-
gen atom transfer from THF unlikely. Some amount of
compound 4 was also formed through acid initiated ep-
oxide opening. The finding, that addition of Ph3CH (entry
2) lead to essentially the same results suggests that this
compound did not act as a hydrogen atom donor despite
Another important question in the reductive epoxide
opening concerns the use of more complex titanocene cat-
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Titanocene-Catalyzed Reductive Epoxide Opening
2569
Table 3 Comparison of Different Catalysts in the Opening of 1 to
Give 2
Table 2 Comparison of 1,4-Cyclohexadiene (7) and g-Terpinene (8)
as Hydrogen Atom Donors
Entry
Catalyst
21
H-Atom Donor Yield (%)
Entry Substrate
Product
Yield (%) 7/8
8810c/84
1
2
3
4
5
6
7
8
7
8
8
7
7
8
7
8
72
72
43
55
21
24
83
85
1
2
1
2
21
72/82
t-BuO2C CO2t-Bu
t-BuO2C CO2t-Bu
22
O
OH
23
11
13
12
3
4
5
6
7210c/69
6910c/78
5810c/73
87/69a
O
OH
24
( )9
( )9
24
14
O
OH
25
PivO ( )
9
PivO ( )
9
25
15
16
OH
O
sible explanation could be that reductive trapping of the b-
titanoxy radicals is efficiently suppressed by this bulky ar-
rangement while maintaining a pocket wide enough for
substrate binding. Brintzinger’s complex 24 performed
poorly. It seems that adding three substituents to the cy-
clopentadienyl ligand shuts down the reactivity almost
completely. Curiously, 8 performed better than or similar
to 7 in all cases. An even more stunning example for the
superiority of 8 is shown in Scheme 2 where an almost
quantitative yield of the desired product 20 was obtained.
In this case the reagent combination 25/8 is even superior
to Cp2TiCl2/7, the sterically least hindered combination
(87%, Table 2, entry 6). However, in the cases of the
chiral catalysts, 2 was obtained in racemic form. This in-
dicates that a dual approach employing chiral hydrogen
atom donors and catalysts is necessary for enantioselec-
tive reduction that is currently pursued in our group.
TsO ( )
9
TsO ( )
9
17
18
OH
O
t-Bu
t-Bu
19
20
a Ratio of trans:cis = 82:18; 83:17.
alysts than Cp2TiCl2, because the performance of the reac-
tion should also depend on the proper choice of the
electron-transfer catalyst. We have recently demonstrated
that complexes with an open configuration perform dis-
tinctly superior to the ones with a closed configuration in
C–C bond forming reactions concerning both yields and
diastereoselectivities.15 As shown in Table 3, the same
trend was observed with the complexes depicted in
Figure 2 for the reduction of simple epoxides.
10 mol% 25,
Mn, Coll⋅HCl,
8,
O
OH
t-Bu
t-Bu
95%, dr = 86:14
20
19
TiCl2
TiCl2
TiCl2
)
2
)
2
)
2
Scheme 2 Opening of 19 in the presence of 10 mol% 25 and 8.
21
23
22
Amongst the preparatively most useful epoxides are
Sharpless epoxides21 and their derivatives. This is mainly
due to the ease of their preparation in high enantiomeric
purity. Methods for their regioselective opening by hy-
dride reagents (DIBALH and RedAl®) have been estab-
lished.22 However, the functional group tolerance in these
transformations is not high and milder methods are still
desirable. We have therefore applied our method to the
opening of Sharpless epoxides and their derivatives to in-
vestigate the regioselectivity of epoxide opening under
catalytic conditions. The results are summarized in
Scheme 3.
Cl
Cl
Ti
TiCl2
)
2
24
25
Figure 2 Titanocene complexes used in this study.
In accordance, complex 2216 with a closed configuration
gave a low 43% yield of 2 (entry 3). The complexes 21,17
23,18 24,19 and 2520 with open configurations gave better
results. The tert-butyl substitution seems to result in a
ligand too bulky for an efficient reaction (entry 4). It is in-
teresting to note that Kagan’s complex 2520 performs best,
even though its ligands are sterically demanding. A plau-
Gratifyingly, the opening of the unprotected 2,3-epoxy al-
cohol 26 proceeded to give the 1,3-diol 27 with essentially
complete regioselectivity (>97:<3 by 1H NMR) with both
catalysts investigated. In line with the previous results,
Kagan’ s complex 25 and 8 performed distinctly superior
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2570
A. Gansäuer et al.
PAPER
OH
tive catalysis. Moreover, the method is also applicable to
the highly selective opening of Sharpless epoxides to 1,3-
diols and their sulfonate esters to derivatized 1,2-diols in
good yields.
O
OH
OH
( )6
( )6
27
26
10 mol% Cp2TiCl2, Zn,
59%
76%
Coll·HCl, 7
All reactions were performed in oven-dried (100 °C) glassware un-
der argon. THF was freshly distilled from LiAlH4 or K. Et2O was
freshly distilled from Na/K. CH2Cl2 was freshly distilled from
CaH2. Products were purified by flash chromatography23 on Mach-
erey-Nagel silica gel 60 and Merck silica gel 50 (eluents given in
brackets; MTBE refers to tert-butyl methyl ether, CH to cyclohex-
ane and PE to petrol ether, 30–60 °C fractions). Yields refer to ana-
lytically pure samples. Isomer ratios were determined from suitable
1H NMR integrals of cleanly separated signals.
10 mol% 25, Zn,
Coll⋅HCl, 8
OSO2R
( )2
OH
O
29
OSO2R
( )2
OH
28
NMR: Bruker AMX 300, AM 400, DRX 500, Varian XR 200, and
MERCURY 300 HFCP; 1H NMR: tetramethylsilane (0.00 ppm) in
the indicated solvent, benzene-d6 (7.15 ppm) and CHCl3 (7.26 ppm)
as internal standard in the same solvent; 13C NMR: tetramethylsi-
lane (0.00 ppm) in the indicated solvent or CDCl3 (77.16 ppm) and
benzene-d6 (128.06 ppm) as internal standards in the same solvent;
integrals in accord with assignments, coupling constants are mea-
sured in Hz. An asterisk (*) indicates the signals of the minor dia-
stereomer. The word ‘both’ indicates overlapping signals for two
diastereoisomers. Combustion analyses: Mrs. Martens, Kekulé-In-
stitut für Organische Chemie und Biochemie, Universität Bonn. IR
spectra: Perkin Elmer 1600 series FT-IR, PARAGON 1000, and
1620 as KBr pellets or as neat films on NaCl and KBr plates.
OSO2R
( )2
30
a R = 2,4,6-(iPr)3-Ph
29 : 62%
30 : 4%
Cp2TiCl2, Zn,
Coll⋅HCl, 8
b R = 4-Me-Ph
Cp2TiCl2, Zn,
Coll⋅HCl, 7
66%
29:30 = 92:8
Scheme 3 Reductive opening of Sharpless epoxides and their sulfo-
The following compounds were prepared according to published
procedures or have already been described in the literature: 1,24 5,25
6,26 9,27 13,10c 15,10c 17,10c 19,28 26,29 28a.30 Compound 10 was ob-
tained from 2-endo-phenylbornane31 by modified Birch reduction.32
Besides 10 the product contained 50% of the starting material. Col-
lidine hydrochloride was dried prior to use by gentle heating under
vacuum.
nate esters.
than Cp2TiCl2 and 7, giving the 1,3-diol in a yield of 76%.
In a similar system Nugent and RajanBabu’s stoichiomet-
ric reaction employing tert-butyl thiol, gave a regioselec-
tivity of 95:5 in favor of the 1,3-diol, which was obtained
in 69% yield. Through the use of g-terpinene as hydrogen
atom donor the utilization of the unpleasantly smelling
tert-butyl thiol in the stoichiometric reaction could be
avoided without problems. Our method therefore seems
clearly superior for practical use.
2-Methyl-4-phenylbutan-1-ol (2)33 (Table 1, entry 6)
A mixture of Cp2TiCl2 (25 mg, 0.1 mmol), Mn (82 mg, 1.5 mmol),
collidine hydrochloride (236 mg, 1.5 mmol), 8 (0.69 mL, 4.3 mmol)
and 1 (171 mg, 1.056 mmol) in THF (10 mL) was stirred for 24 h at
r.t. The reaction mixture was treated with MTBE (50 mL) and fil-
tered. The filtrate was washed with H2O (30 mL), 1 N HCl (30 mL),
H2O (30 mL), aq sat. Na2CO3 (30 mL), H2O (30 mL). The organic
layer was dried (MgSO4) and evaporated under reduced pressure.
Purification by SiO2 flash chromatography (7% EtOAc, 93% CH)
afforded 2 as a colorless oil (145 mg, 84%).
Regioselectivity of epoxide opening could be almost com-
pletely reversed by employing the epoxides’ sulfonate es-
ters as starting materials. It turned out that a small but
noticeable dependence of regioselectivity in favor of the
1,2-diol derivatives 29 was observed when the steric bulk
of the sulfonate was changed. Employing the bulky 2,4,6-
trisisopropylbenzenesulfonate 29a a higher and prepara-
tively useful selectivity of 94:6 was observed compared to
the tosylate 29b (91:9). Curiously, electronic effects
turned out to be less important. The brosylate resulted in
a slightly decreased regioselectivity of 89:11.
Table 1, entry 3: Compound 2 (52 mg, 32%) was obtained via the
same procedure starting from 1 (162 mg, 1 mmol) and 5 (610 mg, 5
mmol).
Table 1, entry 4: Compound 2 (51 mg, 30%) was obtained via the
same procedure starting from 1 (170 mg, 1.049 mmol) and 6 (1155
mg, 5 mmol).
Table 1, entry 7: Compound 2 (116 mg, 69%) was obtained via the
same procedure starting from 1 (166 mg, 1.025 mmol) and 9 (787
mg, 4.8 mmol).
In the stoichiometric reaction the use of silylated Sharp-
less epoxides has been reported to yield the 1,2-deriva-
tives with a selectivity (91:9)6d similar to the one observed
in our system.
Table 1, entry 8: Compound 2 (115 mg, 66%) was obtained via the
same procedure starting from 1 (172 mg, 1.062 mmol) and 10
(1.036 mg, 4.8 mmol).
In summary, we have devised a simple economically and
ecologically benign system for the highly regioselective
epoxide opening that employs the cheap and nontoxic g-
terpinene as hydrogen atom donor. Because substituted
cyclohexadienes and titanocenes can also be used with
good success our method offers potential for enantioselec-
3,4-Epoxycyclopentane-1,1-dicarboxylic Acid Di-tert-butyl Es-
ter (11)
Cyclopent-3-ene-1,1-dicarboxylic acid di-tert-butyl ester34 (1.34 g,
5 mmol) was reacted with m-chloroperbenzoic acid (1.86 g, 70%
solid mixture, 7.5 mmol) in CH2Cl2 (30 mL) at 0 °C. After stirring
for 4 h, the white mixture was poured into MTBE (50 mL) and the
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Titanocene-Catalyzed Reductive Epoxide Opening
2571
MTBE layer was washed with 2 N NaOH (2 × 50 mL). The organic
layer was dried (MgSO4) and evaporated under reduced pressure.
Purification by SiO2 flash chromatography (8% EtOAc, 92% CH)
afforded the desired product as a colorless oil (1.184 g, 84%);
mp 66–67 °C; Rf 0.1.
forded the desired product as a colorless oil (148 mg, 87%,
trans:cis = 82:18).
B. Following the procedure for the preparation of 2, compound 18
(168 mg, 1 mmol) was reacted with 8 (0.690 mL, 4.3 mmol). Puri-
fication by SiO2 flash chromatography (6% EtOAc, 94% CH) af-
forded the desired product as a colorless oil (117 mg, 69%,
trans:cis = 83:17).
IR (KBr): 2980, 1725, 1460, 1370, 1272, 1153, 1091, 967, 847, 763
cm–1.
1H NMR (400 MHz, CDCl3): d = 3.45 (s, 2 H), 2.88 (d, J = 14.5 Hz,
2 H), 2.09 (d, J = 14.5 Hz, 2 H), 1.44 (s, 9 H), 1.40 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 170.5, 169.9, 81.9, 80.9, 57.5,
55.7, 35.7, 27.9, 27.8.
C. Reaction on 10 mmol scale at 0.2 M concentration in THF. Com-
pound 18 (1.680 g, 10 mmol), Cp2TiCl2 (250 mg, 1.0 mmol), Mn
(820 mg, 15 mmol), Coll·HCl (2.360 g, 15 mmol), and 8 (6.9 mL,
43 mmol) were reacted in THF (50 mL). Purification by SiO2 flash
chromatography (6% EtOAc, 94% CH) afforded the desired prod-
uct as a colorless oil (1.432 g, 84%, trans:cis = 82:18).
Anal. Calcd for C15H24O5 (284.35): C, 63.36; H, 8.51. Found: C,
63.34; H, 8.43.
D. Following the procedure for the preparation of 2, compound 18
(168 mg, 1 mmol) was reacted with 8 (0.690 mL, 4.3 mmol) and 25
(52.6 mg, 0.1 mmol). Purification by SiO2 flash chromatography
(6% EtOAc, 94% CH) afforded the desired product as a colorless oil
(166 mg, 95%, trans:cis = 86:14); Rf 0.1.
1H NMR (400 MHz, CDCl3): d = 3.64 (d, J = 7.6 Hz, 2 H)*, 3.44
(d, J = 6.3 Hz, 2 H), 1.81–1.68 (m, 4 H) both, 1.52–1.25 (m, 4 H)
both, 1.02–0.80 (m, 6 H) both, 0.85 (s, 9 H), 0.83 (s, 9 H)*.
3-Hydroxycyclopentane-1,1-dicarboxylic Acid Di-tert-butyl Es-
ter (12) (Table 2, entry 2)
A: Following the procedure for the preparation of 2, compound 11
(284 mg, 1 mmol) was reacted with 7 (0.410 mL, 4.3 mmol). Puri-
fication by SiO2 flash chromatography (8% EtOAc, 92% CH) af-
forded the desired product as a colorless oil (205 mg, 72%).
B. Following the procedure for the preparation of 2, compound 11
(284 mg, 1 mmol) was reacted with 8 (0.69 mL, 4.3 mmol). Purifi-
cation by SiO2 flash chromatography (8% EtOAc, 92% CH) afford-
ed the desired product as a colorless oil (234 mg, 82%); mp 52–
53 °C; Rf 0.1.
13C NMR (100 MHz, CDCl3): d = 68.9, 63.9*, 48.4 both, 40.8,
35.5*, 32.6 both, 30.1 both, 27.2, 27.6*, 26.9, 22.2*.
HRMS: m/z calcd for C11H22O: 170.1671; found: 170.1676.
Table 3, entry 1: Compound 2 (116 mg, 72%) was obtained via the
same procedure starting from 1 (159 mg, 0.981 mmol), 21 (26.3 mg,
0.1 mmol) and 7 (0.410 mL, 4.3 mmol).
IR (KBr): 3290, 2977, 1718, 1368, 1283, 1170, 1140, 1080, 1030,
964, 854, 739 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.31 (br s, 1 H), 2.29–2.14 (m, 5
H), 1.88 (dddd, 2J = 13.5 Hz, 3J = 8.5 Hz, 3J = 8.5 Hz, 3J = 5.1 Hz,
1 H), 1.74–1.67 (m, 1 H), 1.44 (s, 9 H), 1.42 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 173.1, 171.3, 81.7, 81.2, 73.4,
60.7, 43.2, 35.3, 31.8, 27.9, 27.8.
Table 3, entry 2: Compound 2 (122 mg, 72%) was obtained via the
same procedure starting from 1 (167 mg, 1.031 mmol), 21 (26.3 mg,
0.1 mmol) and 8 (0.690 mL, 4.3 mmol).
Table 3, entry 3: Compound 2 (77 mg, 43%) was obtained via the
same procedure starting from 1 (156 mg, 0.963 mmol), 22 (41.3 mg,
0.1 mmol) and 8 (0.690 mL, 4.3 mmol).
Anal. Calcd for C15H26O5 (286.36): C, 62.91; H, 9.15. Found: C,
63.05; H, 9.09.
Table 3, entry 4: Compound 2 (90 mg, 55%) was obtained via the
same procedure starting from 1 (162 mg, 1.000 mmol), 23 (30.5 mg,
0.1 mmol) and 7 (0.410 mL, 4.3 mmol).
2-Methyldodec-11-en-1-ol (14)10c (Table 2, entry 3)
Following the procedure for the preparation of 2, compound 13 (196
mg, 1 mmol) was reacted with 8 (0.69 mL, 4.3 mmol). Purification
by SiO2 flash chromatography (2% EtOAc, 98% CH) afforded the
desired product as a colorless oil [148 mg, 69% of 14, the remaining
3% (by NMR) was 2-chloro-2-methyldodec-11-en-1-ol].
Table 3, entry 5: Compound 2 (35 mg, 21%) was obtained via the
same procedure starting from 1 (167 mg, 1.031 mmol), 24 (38.3 mg,
0.1 mmol) and 7 (0.410 mL, 4.3 mmol).
Table 3, entry 6: Compound 2 (40 mg, 24%) was obtained via the
same procedure starting from 1 (165 mg, 1.019 mmol), 24 (38.3 mg,
0.1 mmol) and 8 (0.690 mL, 4.3 mmol).
2,2-Dimethylpropionic Acid (11-Hydroxy-10-methylundecyl)
Ester (16)10c (Table 2, entry 4)
Following the procedure for the preparation of 2, compound 15 (284
mg, 1 mmol) was reacted with 8 (0.69 mL, 4.3 mmol). Purification
by SiO2 flash chromatography (5% EtOAc, 95% CH) afforded the
desired product as a colorless oil (223 mg, 78%).
Table 3, entry 7: Compound 2 (138 mg, 83%) was obtained via the
same procedure starting from 1 (165 mg, 1.019 mmol), 25 (52.6 mg,
0.1 mmol) and 7 (0.410 mL, 4.3 mmol).
Table 3, entry 8: Compound 2 (137 mg, 85%) was obtained via the
same procedure starting from 1 (160 mg, 0.988 mmol), 25 (52.6 mg,
0.1 mmol) and 8 (0.690 mL, 4.3 mmol).
Toluene-4-sulfonic Acid (11-Hydroxy-10-methylundecyl) Ester
(18)10c (Table 2, entry 5)
1,3-Decanediol (27)35
Following the procedure for the preparation of 2, compound 17 (354
mg, 1 mmol) was reacted with 8 (0.69 mL, 4.3 mmol). Purification
by SiO2 flash chromatography (6% EtOAc, 94% CH) afforded the
desired product as a colorless oil [271 mg, 73% of 18, the remaining
3% (by NMR) was toluene-4-sulfonic acid (10-chloro-11-hydroxy-
10-methylundecyl) ester].
A. Adapting the same procedure, starting with Cp2TiCl2 (25 mg, 0.1
mol), Zn (98 mg, 1.5 mmol), coll·HCl (236 mg, 1.5 mmol), 26 (172
mg, 1.0 mmol) and 7 (0.48 mL, 4.8 mmol), compound 2735 (103 mg,
59%) was obtained after SiO2 flash chromatography (32% EtOAc,
68% CH).
B. Adapting the same procedure, starting with 25 (27 mg, 0.05 mol),
Zn (49 mg, 0.75 mmol), coll·HCl (118 mg, 0.75 mmol) and 8 (0.35
mL, 2.2 mmol), compound 27 (62 mg, 76%) was obtained after
SiO2 flash chromatography (32% EtOAc, 68% CH).
cis- and trans-(4-tert-Butylcyclohexyl)methanol (20) (Table 2,
entry 6)
A. Following the procedure for the preparation of 2, compound 18
(168 mg, 1 mmol) was reacted with 7 (0.410 mL, 4.3 mmol). Puri-
fication by SiO2 flash chromatography (6% EtOAc, 94% CH) af-
Synthesis 2004, No. 15, 2567–2573 © Thieme Stuttgart · New York

2572
A. Gansäuer et al.
PAPER
2,4,6-Triisopropylbenzenesulfonic Acid 3-Propyloxiranylmeth-
yl Ester (28a)
Acknowledgment
To a solution of 3-propyloxiranylmethanol36 (1.16g, 10 mmol) in
CH2Cl2 (50 mL) was added pyridine (1.61 mL, 20 mmol) and 2,4,6-
triisopropylsulfonyl chloride (3.83 g, 15 mmol) at 0 °C. After stir-
ring for 18 h at r.t., H2O (50 mL) was added and the mixture was
poured onto Et2O (50 mL). The organic phase was washed with aq
HCl (2 N, 2 × 30 mL) and brine (30 mL). After removing the vola-
tiles in vacuum, the crude was purified by SiO2 flash chromatogra-
phy (5% EtOAc, 95% CH) to yield 28a (0.89 g, 23%) as a colorless
solid; mp 38–41 °C; Rf 0.4 (CH–EtOAc, 90:10).
We thank the Deutsche Forschungsgemeinschaft (Ga 619/2-1, Ger-
hard Hess-Programm) and the Fonds der Chemischen Industrie
(Dozentenstipendium to A. G. and Sachbeihilfen) for continued fi-
nancial support of our work.
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30a
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Toluene-4-sulfonic Acid (2-Hydroxyhexyl) Ester (29b)37
Adapting the same procedure, starting with Cp2TiCl2 (25 mg, 0.10
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Synthesis 2004, No. 15, 2567–2573 © Thieme Stuttgart · New York

PAPER
Titanocene-Catalyzed Reductive Epoxide Opening
2573
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Synthesis 2004, No. 15, 2567–2573 © Thieme Stuttgart · New York