Tandem olefin metathesis/hydrogenation at ambient temperature: Activation of ruthenium carbene complexes by addition of hydrides

Article abstract of DOI:10.1039/b303441k

Sodium hydride activates ruthenium carbene complexes to catalyze hydrogenation reactions subsequent to ring closing olefin metathesis. Under these conditions, hydrogenation of cyclopentenols proceeds smoothly at ambient temperature and under 1 atm of hydrogen in toluene. An alternative protocol was developed that involves the formation of hydrogen in situ by reaction of excess sodium hydride with protic functional groups and water.

Full text of DOI:10.1039/b303441k

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Tandem olefin metathesis/hydrogenation at ambient temperature:
activation of ruthenium carbene complexes by addition of hydrides
Bernd Schmidt* and Michael Pohler
Universität Dortmund, Fachbereich Chemie, Organische Chemie, D-44227 Dortmund, Germany.
E-mail: bschmidt@chemie.uni-dortmund.de; Fax: (ϩ49) 231 7555363;
Tel: (ϩ49) 231 7553850;
Received 28th March 2003, Accepted 2nd June 2003
First published as an Advance Article on the web 16th June 2003
Sodium hydride activates ruthenium carbene complexes to catalyze hydrogenation reactions subsequent to ring
closing olefin metathesis. Under these conditions, hydrogenation of cyclopentenols proceeds smoothly at ambient
temperature and under 1 atm of hydrogen in toluene. An alternative protocol was developed that involves the
formation of hydrogen in situ by reaction of excess sodium hydride with protic functional groups and water.
Introduction
Results and discussion
Hydrogenation of C–C-double bonds resulting from olefin
metathesis reactions1 is an important issue in organic synthesis
directed towards target molecules. While this transformation is
normally achieved in a two-step procedure using palladium on
charcoal as a hydrogenation catalyst,2 some attempts have
recently been made to improve the overall efficiency of these
transformations by using tandem catalysis. One approach
involves the use of two distinct catalysts. In the field of olefin
metathesis this approach has been investigated by Grigg et al.
for metathesis/Heck-reaction sequences3 and very recently by
Cossy et al. for metathesis/PtO2-catalyzed hydrogenation reac-
tions.4 Alternatively, olefin metathesis catalysts A or B (Fig. 1)
can be activated to mediate a non-metathesis transformation
by changing the reaction conditions upon completion of the
metathesis reaction.
We have chosen diallyl carbinols 1 and diallyl ethers 4 as meta-
thesis precursors for the project described in this contribution.
Both give five-membered rings 2 and 5, respectively, by ring
closing metathesis (Scheme 1).
Scheme 1 Reagents and conditions: i, B (1.1–2.9 mol%), CH2Cl2, 20 ЊC
(68%–92%) (cf. Table 1); ii, A (2.0 mol%), CH2Cl2, 20 ЊC, cf. ref. 8,10.
Five-membered carba- or oxacycles are normally hydro-
genated at relatively low pressures of 1 atm6b While ring closing
metathesis of diallyl ethers 4 is smoothly catalyzed by the first
generation Grubbs’ catalyst A (Fig. 1),10 we experienced serious
difficulties for the ring closing metathesis of diallyl carbinols 1
with catalyst A: comparatively high catalyst loadings of 5 to
8 mol% and elevated temperatures (refluxing toluene) over a
relatively long period of time are required. Unidentified by-
products, probably resulting from competing double bond
isomerization reactions, were often observed under these
conditions.11 Diallyl carbinol 1a turned out to be particularly
unreactive, as no ring closing metathesis (RCM) product 2a
could be isolated from the reaction mixture when 5 mol% of A
was used. In contrast, complete conversion was observed with
1.1 mol% of second generation catalyst B within two hours
at 20 ЊC (Table 1). Generally, quantitative conversion and
good isolated yields of cyclopentenols 2a–e were obtained using
1.1 to 2.9 mol% of B at ambient temperature (Scheme 1 and
Table 1). After we found conditions that allow smooth and
rapid conversion of diallyl carbinols to the corresponding
cyclopentenols, different additives were screened for their
potential to activate the metathesis catalyst for hydrogenation
reactions. To this end, 1a was converted to the metathesis
product 2a in the presence of approximately 1.5 mol% of B
under an argon atmosphere. After TLC indicated complete
consumption of the starting material, additives as indicated in
Table 2 were added to the reaction mixture which was then
exposed to an atmosphere of hydrogen (1 atm) for 16 hours.
Fig. 1 First (A) and second (B) generation Grubbs’ catalyst.
Thus, it was demonstrated by Grubbs and co-workers that
exposure of olefin metathesis reactions to a hydrogen atmos-
phere at elevated temperatures induces the conversion of
the ruthenium carbene species to RuHCl(H2)(PCy3)2,5 which
is an effective hydrogenation catalyst.6 Tandem ring closing
metathesis/double bond migration reactions via an in situ
generated ruthenium hydride species have recently been
published by Snapper and co-workers7 and by one of us.8 While
Snapper and co-workers achieved activation of the meta-
thesis catalyst for double bond migration reactions using
an atmosphere of hydrogen diluted with nitrogen, we were
able to demonstrate that ruthenium carbene complexes can
be efficiently activated to promote double bond migration
reactions by addition of hydride donor reagents in an
aprotic solvent such as toluene. To the best of our know-
ledge, this method of activation was hitherto unknown for
ruthenium carbene complexes.9 In this contribution we des-
cribe that our method of activation also allows ring closing
metathesis and ruthenium-catalyzed hydrogenation to be
coupled in ‘tandem’. In contrast to previously described RCM-
hydrogenation tandem reactions our method does not require
elevated temperatures.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 5 1 2 – 2 5 1 7
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
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Table 1 RCM of diallyl carbinols with catalyst Ba
(entry 2, Table 2). Other inorganic hydrides proved to be signifi-
cantly less effective: while addition of LiAlH4 gives a ratio
of hydrogenated and non-hydrogenated product of 2 : 1 after
16 hours (entry 3, Table 2), less than 5% of 3a was obtained
using CaH2 as an additive (entry 4, Table 2). We applied the
optimum protocol found for the conversion of 1a to 3a to a
variety of other diallyl carbinols. The results are summarized in
Table 3.
Entry
1
Starting material
RCM product
B (mol%)
Yield
92%
1.1 mol%
Remarkably, the protocol works well with substoichiometric
amounts of NaH for all substrates containing only a tertiary
alcohol, which is not readily deprotonated at ambient temper-
ature.12 For substrates 1d and 1e containing secondary alcohol
groups, a large excess of NaH is required to achieve hydro-
genation, presumably because the secondary hydroxy function
is deprotonated faster than reaction of the ruthenium species
with the hydride occurs.
Application of our protocol to diallyl ethers 4 gives tetra-
hydrofurans 6 in good overall yield. We examined three
examples 4a, b and c. Surprisingly, for the 3-methoxy derivative
4b the hydrogenation step fails. In this case, the corresponding
dihydrofuran 5b was isolated. The reasons for this result are
unclear. In the case of 4-methoxy substituted derivative 6c a
trace (approximately 5%) of the corresponding double bond
migration product 7c could be detected from the 1H NMR
spectrum of the crude reaction product (Scheme 3).
2
3
4
2.0 mol%
2.7 mol%
2.9 mol%
68%
89%
74%
5
1.9 mol%
78%
a For reaction conditions see legend to Scheme 1.
Table 2 Screening of hydride additivesa
Amount
of additive
(mol%)
Ratio
2a : 3a
Entry
B (mol%)
Additive
1
2
3
4
1.7
1.7
1.5
1.6
None
NaH
LiAlH4
CaH2
—
14
13
13
>95 : 5
<5 : 95
1 : 2
>95 : 5
Scheme 3 Reagents and conditions: B (2.0 mol%), toluene, 20 ЊC until 4
is completely consumed, then add NaH (13 mol%), H2 (3 bar), 20 ЊC, 16
hours.
a See Scheme 2.
Finally, we investigated the possibility of using an excess of
sodium hydride not only to activate the catalyst for hydro-
genation reactions, but also as a source for hydrogen. Thus, the
hydrogen required for the C–C-double bond hydrogenation step
was generated in situ by the reaction of excess NaH with protic
functional groups or with water. After completion of the olefin
metathesis step (normally two hours), three to four equivalents
of NaH were added to the reaction mixture and the vessel was
stoppered tightly. During this period, the catalyst was activated
for the hydrogenation step and molecular hydrogen was formed
by deprotonation of the secondary alcohol functions. To make
sure that enough hydrogen was present to achieve complete
conversion, additional water was added after one hour. Using
this protocol, substrates 1d and 1e were smoothly converted to
cyclopentanols 3d and 3e, respectively (Scheme 4). Extension of
After this time the ratio of hydrogenated product 3a and
primary metathesis product 2a was determined by NMR-spec-
troscopy of the crude reaction mixture. The results are summar-
ized in Scheme 2 and Table 2.
Scheme 2 Reagents and conditions: i, B (1.5–1.7 mol%), toluene, 20 ЊC,
2 hours, then add additive, H2, 20 ЊC, 16 hours (cf. Table 1).
The result described in entry 1 clearly demonstrates that
exposure of an olefin metathesis reaction mixture to an atmos-
phere of hydrogen at ambient temperature does not activate the
ruthenium carbene species for hydrogenation reactions. Under
these conditions, the primary RCM product 2a is exclusively
formed. The hydrogenated product 3a could not be detected by
H-NMR-spectroscopy of the crude reaction mixture. In sharp
contrast, under otherwise identical conditions, the addition of
14 mol% of NaH (used as a dispersion in mineral oil) prior to
exposure of the reaction mixture to hydrogen leads to complete
conversion of the metathesis product 2a to the cyclopentanol 3a
Scheme 4 Reagents and conditions: i, B (2.0 mol%), toluene, 20 ЊC;
then add NaH (4.0 eq.), 1 h, 20 ЊC; then add water (30 eq.), 16 hours.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 5 1 2 – 2 5 1 7
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Table 3 Sequential RCM/hydrogenation of diallyl carbinolsa
Entry
1
Diallyl carbinol
B (mol%)
Cylopentanol
NaH (mol%)
14
Yield of 3
1.7
92%
2
3
2.7
2.0
28
81%
81%
300
4
5
2.5
2.0
300
38
55%
61%
6
7
2.0
2.0
17
42
81%
78%
a Reagents and conditions: B, toluene, 20 ЊC until 1 is completely consumed, then add indicated amount of NaH, H2 (1 bar), 20 ЊC, 16 hours.
this protocol to other substrates without secondary hydroxy
functions will be investigated in due course.
an internal standard. Coupling constants are given in Hz. 13C
NMR spectra were recorded at 100 MHz or at 125 MHz in
CDCl3 with CDCl3 (δ = 77.0 ppm) as an internal standard. The
number of coupled protons was analyzed by APT experiments
and is denoted by a number in parentheses following the chem-
ical shift value. IR spectra were recorded as films on NaCl or
KBr plates. The peak intensities are defined as strong (s),
medium (m) or weak (w). Mass spectra were obtained at 70 eV.
The ruthenium catalyst B was prepared following a literature
procedure.13 Preparation and ring closing metathesis of diallyl
ethers 4 have been described previously.10
In conclusion, we describe a method to activate ruthenium
carbene complexes to catalyze hydrogenation reactions sub-
sequent to the olefin metathesis step. In contrast to previous
reports in the literature, we achieved formation of a ruthenium
hydride species by treatment of the reaction mixture with
catalytic amounts of inorganic hydrides, with NaH giving the
best results. Products resulting from double bond migration
reactions could only be detected in one example in trace
amounts. This finding is quite remarkable, because we used
toluene as a solvent in all experiments. Aromatic solvents
have previously been described in the literature to facilitate
General procedure for the preparation of diallyl carbinols 1
ruthenium-catalyzed double bond migration reactions.6b
A
A solution of allyl magnesium bromide (2.5 eq., c 1.0) in ether
was added to a solution of the corresponding ester (1.0 eq.) in
ether (c 0.5) at 0 ЊC. The reaction mixture was poured onto
aqueous NH4Cl solution, the organic layer was separated and
the aqueous layer was extracted with ether. The combined
organic extracts were dried with MgSO4, filtered, and evapor-
ated. The residue was purified by distillation or flash chromato-
graphy on silica. For the preparation of 1b, 1d and 1e, 4.0 eq. of
the allyl Grignard solution were required.
possible explanation why competing double bond migration is
not a problem in our studies might be that our protocol does
not require elevated temperatures.
Experimental
General
All experiments were conducted in dry reaction vessels under
an atmosphere of dry argon. Solvents were purified by standard
procedures. 1H NMR spectra were recorded at 400 MHz,
500 MHz or 600 MHz in CDCl3 with CHCl3 (δ = 7.24 ppm) as
4-tert-Butyl-hepta-1,6-dien-4-ol (1a)
Obtained from ethyl pivaloate (5.00 g, 38.4 mmol) as a colour-
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 5 1 2 – 2 5 1 7
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less liquid that was purified by flash chromatography (TLC:
cyclohexane–MTBE 5 : 1 (v/v), Rf = 0.6). Yield 5.30 g, 82%.
Analytical data are identical with those reported in the
literature.14a
CDCl ) δ 7.29–7.43 (10H, Ph), 5.82–5.92 (2H, CH᎐CH ),
᎐
3 2
5.11 (dm, 1H, J = 10.2, –CH᎐CH ), 5.07 (dm, 1H, J = 9.2,
᎐
2
–CH᎐CH ), 5.06 (dm, 1H, J = 17.2, –CH᎐CH ), 5.02 (dm, 1H,
᎐
᎐
2
2
J = 17.2, –CH᎐CH ), 4.46 (d, 1H, J = 11.5, –OCHHPh), 4.36 (s,
᎐
2
1H, –CHOBn), 4.26 (d, 1H, J = 11.5, –OCHHPh), 2.48 (dd, 1H,
J = 14.2, 7.5, –CHHCH᎐), 2.34 (s, 1H, OH ), 2.23–2.29 (2H,
2-Allyl-pent-4-ene-1,2-diol (1b)
᎐
–CH –CH᎐), 2.04 (dd, 1H, J = 14.2, 8.0, –CHHCH᎐). 13C
᎐
᎐
2
Obtained from butyl glycolate (3.96 g, 30.0 mmol) as a colour-
less liquid that was purified by flash chromatography (TLC:
cyclohexane–MTBE 1 : 1 (v/v), Rf = 0.2). Yield 2.20 g, 52%.
Analytical data are identical with those reported in the
literature.14b
NMR (125 MHz, CDCl3) δ 138.0 (0), 137.5 (0), 134.1 (1), 133.8
(1), 128.8 (1), 128.4 (1), 128.1 (1), 128.0 (1), 127.9 (1), 127.7 (1),
118.2 (2), 118.1 (2), 84.6 (1), 75.7 (0), 71.0 (2), 40.5 (2), 40.0 (2).
IR (neat, NaCl) ν/cmϪ1 3546w, 3028s, 1066s, 914m. MS (EI) m/z
(%) 223 (Mϩ Ϫ1, 1), 207 (6), 141 (44), 71 (100), 57 (69). Found:
C, 81.1%; H, 7.9%. C21H24O2 requires C, 81.8%; H, 7.8%.
4-Benzyloxymethyl-hepta-1,6-dien-4-ol (1c)
4-Phenyl-hepta-1,6-dien-4-ol (1g)
Obtained from diallyl carbinol 1b (1.00 g, 7.0 mmol) by treat-
ment with NaH (0.38 g of a 60% dispersion in mineral oil,
9.4 mmol) and benzyl bromide (0.50 mL, 7.5 mmol) in THF
(20 mL) as a colourless liquid that was purified by flash chrom-
atography (TLC: cyclohexane–MTBE 2 : 1 (v/v), Rf = 0.8). Yield
0.80 g, 50%.14c 1H NMR (500 MHz, CDCl3) δ 7.42–7.28 (5H,
Obtained from ethyl benzoate (2.90 g, 18.5 mmol) as a colour-
less liquid that was purified by flash chromatography (TLC:
cyclohexane–MTBE 5 : 1 (v/v), Rf = 0.7). Yield 2.60 g, 75%.
Analytical data are identical with those reported in the
literature.14f
Ph), 5.86 (dddd, 2H, J = 17.0, 10.5, 7.3, 7.3, –CH᎐CH ), 5.12 (d,
᎐
2
2H, J = 10.5, –CH᎐CH ), 5.10 (d, 2H, J = 17.0, –CH᎐CH ), 4.56
᎐
᎐
2
2
4-(1-Ethyl-hexyl)-hepta-1,6-dien-4-ol (1h)
(s, 2H, –OCH2Ph), 3.35 (s, 2H, –CH2OBn), 2.37–2.27 (5H,
–CH CH᎐, –OH ). 13C NMR (100 MHz, CDCl3) δ 138.0 (0),
Obtained from 2-ethyl-heptanoic acid methyl ester (0.72 g,
4.2 mmol) as a colourless liquid that was purified by flash
chromatography (TLC: cyclohexane–MTBE 5 : 1 (v/v), Rf =
᎐
2
133.5 (1), 128.3 (1), 127.7 (1), 127.6, (1), 118.4 (2), 74.9 (2), 73.4
(2), 73.2 (0), 41.3 (2).
1
0.7). Yield 0.67 g, 70%. H NMR (500 MHz, CDCl3) δ 5.85
(dddd, 2H, J = 17.4, 10.2, 7.3, 7.3, –CH᎐CH ), 5.11 (dm, 2H,
2-Allyl-1-phenyl-pent-4-ene-1,2-diol (1d)
᎐
2
J = 10.3, –CH᎐CH ), 5.09 (dm, 2H, J = 17.6, –CH᎐CH ), 2.29
᎐
᎐
2
2
Obtained from rac-methyl mandelate (2.00 g, 12.0 mmol) as a
colourless solid, mp 52 ЊC, that was purified by flash chromato-
graphy (TLC: cyclohexane–MTBE 1 : 1 (v/v), Rf = 0.5). Yield
2.30 g, 89%.14d 1H NMR (500 MHz, CDCl3) δ 7.41–7.28 (5H,
Ph), 5.92 (dddd, 1H, J = 17.0, 10.2, 7.5, 7.5, –CH᎐CH ), 5.81
(dddd, 1H, J = 17.2, 10.0, 7.3, 7.3, –CH᎐CH ), 5.18 (d, 1H,
(ddm, 2H, J = 14.1, 7.5, –CHHCH᎐), 2.19 (ddm, 2H, J = 14.1,
᎐
7.5, –CHHCH᎐), 1.60 (m, 1H, CH), 1.52 (m, 1H, CHH ), 1.47
᎐
(s, 1H, OH ), 1.38 (m, 1H, CHH ), 1.12–1.31 (8H, CHH ), 0.93
(t, 3H, J = 7.5, –CH3), 0.86 (t, 3H, J = 7.2, –CH3). 13C NMR
(125 MHz, CDCl3) δ 134.3 (1), 118.4 (2), 76.3 (0), 47.5 (1), 41.5
(2), 41.4 (2), 32.6 (2), 30.1 (2), 29.3 (2), 23.1 (2), 22.6 (2), 14.1
(3), 13.9 (3). IR (neat, NaCl) ν/cmϪ1 3535m, 2965s, 2926s,
1456m, 909m. MS (EI) m/z (%) 223 (Mϩ Ϫ1, < 5), 141 (45), 71
(100). Found: C, 80.3%; H, 12.7%. C15H28O requires C, 80.3%;
H, 12.6%.
᎐
2
᎐
2
J = 10.0, –CH᎐CH ), 5.15 (d, 1H, J = 17.0, –CH᎐CH ), 5.10 (d,
᎐
᎐
2
2
1H, J = 10.2, –CH᎐CH ), 5.03 (d, 1H, J = 17.2, –CH᎐CH ), 4.61
᎐
᎐
2
2
(s, 1H, –OCHPh), 2.65 (br s, 1H, –OH ), 2.42 (dd, 1H, J = 14.2,
7.5, –CHHCH᎐), 2.30–2.20 (3H, –OH, –CHHCH᎐), 1.98 (dd,
᎐
᎐
1H, J = 14.2, 7.4, –CHHCH᎐). 13C NMR (125 MHz, CDCl3)
᎐
δ 139.9 (0), 133.6 (1), 133.5 (1), 128.0 (1), 127.9 (1), 127.7 (1),
119.0 (2), 118.9 (2), 77.5 (1), 75.7 (0), 40.4 (2), 39.4 (2). IR (disc,
KBr) ν/cmϪ1 3443s, 3074m, 1639m, 1027s, 915s, 703s. MS (EI)
General procedure for the preparation of cyclopentenols 2
The corresponding metathesis precursor 1 was dissolved in dry
CH2Cl2 (c 0.3–0.5) and ruthenium complex B (1.1 mol%–
2.9 mol%) was added. The mixture was stirred until the start-
ing material was fully consumed as indicated by TLC. The
solvent was evaporated, and the residue was purified by flash
chromatography or by Kugelrohr distillation.
m/z (%) 115 (25, Mϩ Ϫ CH CH᎐CH ), 69 (87), 41 (100). Found:
᎐
2
2
C, 76.5%; H, 8.4%. C14H18O2 requires C, 77.0%; H, 8.3%.
(S )-3-Allyl-hex-5-ene-2,3-diol (1e)
Obtained from (S)-ethyl lactate (10.0 g, 84.7 mmol) as a colour-
less liquid that was purified by flash chromatography (TLC:
cyclohexane–MTBE 1 : 1 (v/v), Rf = 0.3). Yield 11.4 g, 86%.14e
1-tert-Butyl-cyclopent-3-enol (2a)
[α]2D0 ϩ23.6Њ (c 2.0 in CH2Cl2). H NMR (600 MHz, CDCl3)
Obtained from 1a (1.00 g, 5.9 mmol) and B (54 mg, 1.1 mol%)
as a colourless liquid after Kugelrohr distillation (25 ЊC,
0.5 mbar). TLC: cyclohexane–MTBE 5 : 1 (v/v), Rf = 0.4). Yield
0.77 g (92%). 1H NMR (500 MHz, CDCl3) δ 5.67 (s, 2H,
1
δ 5.93–5.83 (2H, –CH᎐CH ), 5.18–5.08 (4H, –CH᎐CH ), 3.71
᎐
᎐
2
2
(q, 1H, J = 6.4, –OCHCH3), 2.39 (dd, 1H, J = 14.2, 7.3, –CHH–),
2.34 (dd, 1H, J = 14.2, 7.3, –CHH–), 2.25 (dd, 1H, J = 14.2,
7.3, –CHH–), 2.15 (dd, 1H, J = 14.2, 7.3, –CHH–), 2.04 (br s,
2H, –OH ), 1.17 (d, 3H, J = 6.4, –CH3). 13C NMR (125 MHz,
CDCl3) δ 133.6 (1), 133.5 (1), 118.8 (2), 118.5 (2), 75.4 (0), 71.6
(1), 40.9 (2), 38.9 (2), 16.9 (3). IR (disc, KBr) ν/cmϪ1 3473s,
3076s, 2979s, 1640s, 1047s, 914s. MS (EI) m/z (%) 218 (Mϩ, 2),
131 (35), 108 (74), 69 (100). Found: C, 68.8%; H, 10.5%.
C9H16O2 requires C, 69.2%; H, 10.3%.
–CH᎐), 2.67 (d, 2H, J = 16.5, –CHH–), 2.13 (d, 2H, J = 16.5,
᎐
t
–CHH–), 1.51 (s, 1H, –OH ), 0.92 (s, 9H, Bu). 13C NMR (125
MHz, CDCl3) δ 128.6 (1), 86.5 (0), 43.1 (2), 36.4 (0), 25.7 (3). IR
(neat, NaCl) ν/cmϪ1 3476w, 2918m, 1439w, 1063w. MS (EI) m/z
(%) 139 (Mϩ Ϫ1, < 5), 123 (95), 83 (70), 57 (100). Found: C,
76.8%; H, 11.5%. C9H16O requires C, 77.1%; H, 11.5%.
1-Hydroxymethyl-cyclopent-3-enol 2b
4-(Benzyloxy-phenyl-methyl)-hepta-1,6-dien-4-ol (1f)
Obtained from 1b (1.97 g, 13.9 mmol) and B (236 mg,
2.0 mol%) as a colourless liquid after flash chromatography
on silica (TLC: cyclohexane–MTBE 1 : 1 (v/v), Rf = 0.1). Yield
1.07 g (68%). 1H NMR (400 MHz, CDCl3) δ 5.60 (s, 2H,
Obtained from diallyl carbinol 1d (1.10 g, 5.0 mmol) by treat-
ment with NaH (0.40 g of a 60% dispersion in mineral oil,
10.0 mmol) and benzyl bromide (0.70 mL, 6.0 mmol) in THF
(30 mL) as a colourless liquid that was purified by flash chrom-
atography (TLC: cyclohexane–MTBE 2 : 1 (v/v), Rf = 0.6). Yield
1.00 g, 69%. [α]2D0 ϩ39.9Њ (c 0.9 in CH2Cl2). 1H NMR (500 MHz,
–CH᎐), 3.81 (br s, 1H, –OH ), 3.64 (br s, 1H, –OH ), 3.51 (s, 2H,
᎐
–CH2OH), 2.42 (d, 2H, J = 16.1, –CHH–), 2.31 (d, 2H, J = 16.1,
–CHH–). 13C NMR (100 MHz, CDCl3) δ 128.2 (1), 81.5 (0),
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 5 1 2 – 2 5 1 7
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69.0 (2), 43.7 (2). IR (neat, NaCl) ν/cmϪ1 3385m, 2927m, 1432w,
1107m. MS (EI) m/z (%) 114 (Mϩ, < 5), 96 (20), 83 (95), 79 (30),
55 (100). Found: C, 62.8%; H, 8.8%. C6H10O2 requires C, 63.1%;
H, 8.8%.
0.3 mbar). TLC: cyclohexane–MTBE 5 : 1 (v/v), Rf = 0.4. Yield
0.46 g (92%). Analytical data are identical with those reported
in the literature.15a
1-Benzyloxymethyl-cyclopentanol 3c
1-Benzyloxymethyl-cyclopent-3-enol 2c
Obtained from 1c (0.40 g, 1.7 mmol) and B (40 mg, 2.7 mol%)
as a colourless liquid after flash chromatography on silica
(TLC: cyclohexane–MTBE 2 : 1 (v/v), Rf = 0.6). Yield 0.29 g
(81%). 13C NMR (125 MHz, CDCl3) δ 138.2 (0), 128.3 (1), 127.6
(1), 127.5 (1), 81.5 (0), 77.1 (2), 73.4 (2), 37.2 (2), 24.1 (2). Other
analytical data are identical with those reported in the
literature.15b
Obtained from 1c (0.40 g, 1.7 mmol) and B (40 mg, 2.7 mol%)
as a colourless liquid after flash chromatography on silica
(TLC: cyclohexane–MTBE 2 : 1 (v/v), Rf = 0.6). Yield 0.31 g
(89%). 1H NMR (500 MHz, CDCl3) δ 7.30–7.38 (5H, Ph), 5.65
(s, 2H, –CH᎐), 4.58 (s, 2H, –OCH Ph), 3.47 (s, 2H, –CH OBn),
᎐
2
2
2.70 (s, 1H, –OH ), 2.49 (d, 2H, J = 16.2, –CHH–), 2.42 (d, 2H,
J = 16.2, –CHH–). 13C NMR (125 MHz, CDCl3) δ 138.0 (0),
128.4 (1), 128.2 (1), 127.7 (1), 127.6 (1), 80.3 (0), 76.7 (2), 73.4
(2), 44.3 (2). IR (neat, NaCl) ν/cmϪ1 3441w, 2856m, 1453w,
1098s. MS (EI) m/z (%) 204 (Mϩ, 3), 91 (100), 83 (55). Found: C,
76.3%; H, 8.0%. C13H16O2 requires C, 76.4%; H, 7.9%.
1-(Hydroxy-phenyl-methyl)-cyclopentanol 3d
Obtained from 1d (0.57 g, 2.6 mmol) and B (44 mg, 2.0 mol%)
as a colourless solid, mp = 75 ЊC, after flash chromatography on
silica (TLC: cyclohexane–MTBE 1 : 1 (v/v), Rf = 0.3). Yield 0.29
g (81%).15c 1H NMR (500 MHz, CDCl3) δ 7.39 (d, 2H, J = 7.3,
Ph), 7.34 (dd, 2H, J = 7.3, 7.3, Ph), 7.30 (t, 1H, J = 7.3, Ph), 4.61
(s, 1H, –CHOH–), 2.20 (br s, 2H, –OH ), 1.88–1.71 (4H,
–CHH ), 1.68–1.52 (3H, –CHH–), 1.30 (m, 1H, –CHH–). 13C
NMR (125 MHz, CDCl3) δ 141.0 (0), 128.0 (1), 127.8 (1), 127.3
(1), 84.8 (0), 79.6 (2), 37.5 (2), 36.0 (2), 23.6 (2), 23.6 (2). IR
(neat, NaCl) ν/cmϪ1 3417s, 3317s, 2965m, 2869m, 1452m,
1041m, 702m. MS (EI) m/z (%) 192 (Mϩ, 2), 108 (100), 85 (48).
Found: C, 74.6%; H, 8.2%. C12H16O2 requires C, 75.0%; H,
8.4%.
1-(Hydroxy-phenyl-methyl)-cyclopent-3-enol 2d
Obtained from 1d (0.16 g, 0.7 mmol) and B (18 mg, 2.9 mol%)
as a colourless solid after flash chromatography on silica (TLC:
cyclohexane–MTBE 1 : 1 (v/v), Rf = 0.3). Yield 0.14 g (89%).
1
Mp 91 ЊC. H NMR (400 MHz, CDCl3) δ 7.29–7.41 (5H, Ph),
5.67 (m, 1H, –CH᎐), 5.61 (m, 1H, –CH᎐), 4.68 (s, 1H, –CHPh),
᎐
᎐
2.80 (ddd, 1H, J = 17.0, 2.0, 1.8, –CHH–), 2.59 (ddd, 1H,
J = 17.2, 2.0, 1.8, –CHH–), 2.51 (s, 1H, –OH), 2.40 (dd, 1H,
J = 17.0, 1.8, –CHH–), 2.05 (dm, 1H, J = 17.2, –CHH–), 1.60 (s,
1H, –OH ). 13C NMR (125 MHz, CDCl3) δ 140.6 (0), 128.4 (1),
128.2 (1), 128.2 (1), 128.0 (1), 127.5 (1), 86.8 (0), 79.1 (1), 45.0
(2), 43.5 (2). IR (disc, KBr) ν/cmϪ1 3436s, 3289m, 3059w, 2901w,
1281m, 1019s. MS (EI) m/z (%) 173 (Mϩ Ϫ 17, 100), 156 (25),
108 (85), 79 (50). Found: C, 75.5%; H, 7.3%. C12H14O2 requires
C, 75.8%; H, 7.4%.
(S )-1-(1-Hydroxy-ethyl)-cyclopentanol 3e
Obtained from 1e (0.53 g, 3.4 mmol) and B (72 mg, 2.5 mol%)
as a colourless liquid after Kugelrohr distillation (0.4 mbar,
40 ЊC). TLC: cyclohexane–MTBE 1 : 1 (v/v), Rf = 0.2. Yield
0.24 g (55%). [α]2D0 Ϫ2.3Њ (c 1.5 in CH2Cl2). Other analytical data
are identical with those reported in the literature.15d
(S )-1-(1-Hydroxy-ethyl)-cyclopent-3-enol 2e
(S )-1-(Benzyloxy-phenyl-methyl)-cyclopentanol 3f
Obtained from 1e (0.50 g, 3.2 mmol) and B (51 mg, 1.9 mol%)
as a colourless liquid after Kugelrohr distillation (75 ЊC oven
temperature, 0.3 mbar). TLC: cyclohexane–MTBE 1 : 1 (v/v),
Obtained from 1f (0.40 g, 1.3 mmol) and B (23 mg, 2.0 mol%)
as a colourless liquid after flash chromatography on silica
(TLC: cyclohexane–MTBE 2 : 1 (v/v), Rf = 0.4). Yield 0.22 g
Rf = 0.2. Yield 0.32 g (78%). [α]2D0 Ϫ3.4Њ (c 2.7 in CH2Cl2). H
1
(61%). [α]2D0 ϩ65.5Њ (c 2.0 in CH2Cl2). H NMR (500 MHz,
1
NMR (400 MHz, CDCl ) δ 5.68–5.63 (2H, –CH᎐), 3.71 (q, 1H,
᎐
3
J = 6.3, –CHOH), 2.85 (br s, 2H, –OH ), 2.50 (d, 1H, J = 16.0,
–CHH–), 2.47 (d, 1H, J = 16.0, –CHH–), 2.33 (d, 1H, J = 16.0,
–CHH–), 2.19 (d, 1H, J = 16.0, –CHH–), 1.12 (d, 3H, J = 6.3,
–CH3). 13C NMR (125 MHz, CDCl3) δ 128.5 (1), 128.3 (1), 83.5
(0), 73.1 (1), 45.2 (2), 42.4 (2), 17.8 (3). IR (neat, NaCl) ν/cmϪ1
3408s, 2939m, 1454w, 1058w. MS (EI) m/z (%) 128 (Mϩ, < 5), 83
(100), 82 (60), 55 (50). Found: C, 65.3%; H, 9.2%. C7H12O2
requires C, 65.6%; H, 9.4%.
CDCl3) δ 7.30–7.43 (10H, Ph), 4.54 (d, 1H, J = 11.7, CHH–Ph),
4.31 (s, 1H, CH–OH), 4.28 (d, 1H, J = 11.7, CHH–Ph), 2.16 (s,
1H, OH ), 1.50–1.80 (8H, –CH2–CH2–). 13C NMR (125 MHz,
CDCl3) δ 138.4 (0), 138.2 (0), 128.4 (0), 128.3 (0), 128.0 (0),
127.8 (0), 127.8 (0), 127.6 (1), 86.2 (1), 84.2 (0), 70.7 (2), 37.4 (2),
35.7 (2), 23.5 (2). IR (neat, NaCl) ν/cmϪ1 2961m, 2869m, 1495w,
1453m, 1066s. MS (EI) m/z (%) 282 (Mϩ, < 5), 198 (20), 107
(85), 91 (100), 79 (45), 77(25). Found: C, 80.4%; H, 7.5%.
C19H22O2 requires C, 80.8%; H, 7.8%.
General procedure for the sequential RCM-hydrogenation
reaction with hydrogen
1-Phenyl-cyclopentanol 3g
The corresponding metathesis precursor 1 was dissolved in dry
toluene (c 0.3–0.5) and ruthenium complex B (1.7 mol%–
2.7 mol%) was added. The mixture was stirred until the start-
ing material was fully consumed as indicated by TLC. NaH
(14 mol%–300 mol%, 60%-dispersion in mineral oil) was added
and the argon atmosphere was replaced by an atmosphere of
hydrogen. Stirring was continued under an atmosphere of
hydrogen for 16 hours. After this time, the reaction mixture was
diluted with ether, washed with water, dried with MgSO4,
filtered and the solvents were evaporated. The dark residue
was purified by flash chromatography on silica or Kugelrohr
distillation.
Obtained from 1g (0.55 g, 2.9 mmol) and B (50 mg, 2.0 mol%)
as a colourless liquid after flash chromatography on silica
(TLC: cyclohexane–MTBE 5 : 1 (v/v), Rf = 0.5). Yield 0.38 g
(81%). 13C NMR (125 MHz, CDCl3) δ 147.0 (0), 128.1 (1), 126.7
(1), 125.0 (1), 83.4 (0), 41.7 (2), 23.8 (2). Other analytical data
are identical with those reported in the literature.15e
1-(1-Ethyl-pentyl)-cyclopentanol 3h
Obtained from 1h (0.20 g, 1.2 mmol) and B (15 mg, 2.0 mol%)
as a colourless liquid after flash chromatography on silica
(TLC: cyclohexane–MTBE 5 : 1 (v/v), Rf = 0.5). Yield 0.14 g
1
(78%). H NMR (500 MHz, CDCl3) δ 1.76 (2H), 1.50–1.62
(7H), 1.40 (2H), 1.15–1.30 (8H), 1.16 (s, 1H, OH), 0.91 (t, 3H,
J = 7.3, –CH3), 0.84 (t, 3H, J = 6.9, –CH3). 13C NMR (125 MHz,
CDCl3) δ 86.2 (0), 49.3 (1), 38.7 (2), 38.7 (2), 32.5 (2), 30.6 (2),
28.8 (2), 23.8 (2), 23.8 (2), 23.6 (2), 22.6 (2), 14.1 (3), 13.4 (3). IR
1-tert-Butyl-cyclopentanol 3a
Obtained from 1a (0.59 g, 3.5 mmol) and B (50 mg, 1.7 mol%)
as a colourless liquid after Kugelrohr distillation (25 ЊC,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 5 1 2 – 2 5 1 7
2516

View Online
(neat, NaCl) ν/cmϪ1 3463w, 2959s, 2872m, 1465w. MS (EI, 70
eV) m/z (%) 198 (Mϩ, 1), 181 (1), 141 (11), 85 (100), 57 (18).
HREI-MS [Mϩ] for C13H26O calc. 198.1984 found 198.1984.
Acknowledgements
Generous support by the Deutsche Forschungsgemeinschaft,
the Fonds der Chemischen Industrie and the Fachbereich
Chemie der Universität Dortmund is gratefully acknowledged.
We thank M. Terbeck for excellent technical assistance.
2-(2-Methoxy-phenyl)-tetrahydro-furan 6a
Obtained from 4a (0.60 g, 3.0 mmol) and B (50 mg, 2.0 mol%)
as a colourless liquid after Kugelrohr distillation (140 ЊC,
0.2 mbar). TLC: cyclohexane–MTBE 10 : 1 (v/v), Rf = 0.5. A
hydrogen pressure of 3 bar was applied in this case. Yield 0.41 g
(74%).15f 1H NMR (500 MHz, CDCl3) δ 7.43 (d, 1H, J = 7.5,
Ar), 7.23 (ddd, 1H, J = 8.0, 7.5, 1.5, Ar), 6.96 (dd, 1H, J = 7.5,
7.5, Ar), 6.86 (d, 1H, J = 7.5, Ar), 5.18 (dd, 1H, J = 7.0, 7.0,
–OCHAr), 4.11 (ddd, 1H, J = 7.5, 6.7, 6.7, –OCHH–), 3.92
(ddd, 1H, J = 7.5, 7.5, 7.5, –OCHH–), 3.83 (s, 3H, –OCH3), 2.38
(m, 1H, –CHH–), 2.00–1.92 (2H, –CHH–), 1.71 (m, 1H,
–CHH–). 13C NMR (125 MHz, CDCl3) δ 157.6 (0), 133.7 (0),
129.2 (1), 127.0 (1), 121.9 (1), 111.5 (1), 77.3 (1), 70.0 (2), 56.7
(3), 34.6 (2), 27.4 (2).
References
1 Reviews: (a) S. K. Armstrong, J. Chem. Soc., Perkin Trans. 1,
1998, 371; (b) R. H. Grubbs and S. Chang, Tetrahedron, 1998,
54, 4413; (c) M. Schuster and S. Blechert, Angew. Chem., Int. Ed.,
1997, 36, 2036; (d ) A. Fürstner, Angew. Chem., Int. Ed., 2000, 39,
3013.
2 For applications in target molecule synthesis, see: (a) H. Mizutani,
M. Watanabe and T. Honda, Tetrahedron, 2002, 58, 8929; (b) M. G.
Organ, J.-L. Xu and B. N’Zemba, Tetrahedron Lett., 2002, 43, 8177;
(c) A. Fürstner, F. Jeanjean and P. Razon, Angew. Chem., Int. Ed.,
2002, 41, 2097; (d ) D. E. Williams, K. S. Craig, B. Patrick, L. M.
McHardy, R. van Soest, M. Roberge and R. J. Andersen, J. Org.
Chem., 2002, 67, 245.
3 R. Grigg, V. Sridharan and M. York, Tetrahedron Lett., 1998, 39,
4139.
2-(4-Methoxy-phenyl)-tetrahydro-furan 6c
4 (a) J. Cossy, F. C. Bargiggia and S. BouzBouz, Org. Lett., 2003, 5,
459; (b) J. Cossy, F. C. Bargiggia and S. BouzBouz, Tetrahedron
Lett., 2002, 43, 6715.
5 The mechanism of the formation of ruthenium–hydride species
from ruthenium carbene complexes and hydrogen has been
investigated: S. D. Drouin, G. P. A. Yap and D. E. Fogg, Inorg.
Chem., 2000, 39, 5412.
6 Applications to hydrogenation of ROMP or RCM products:
(a) C. W. Bielawski, J. Louie and R. H. Grubbs, J. Am. Chem. Soc.,
2000, 122, 12872; (b) J. Louie, C. W. Bielawski and R. H. Grubbs,
J. Am. Chem. Soc., 2001, 123, 11312; (c) S. D. Drouin, F. Zamanian
and D. E. Fogg, Organometallics, 2001, 20, 5495; (d ) P. Borsting
and P. Nielsen, Chem. Commun., 2002, 2140; (e) A. Fürstner and
A. Leitner, Angew. Chem., Int. Ed., 2003, 42, 308.
Obtained from 4c (0.99 g, 4.9 mmol) and B (103 mg, 2.0 mol%)
as a colourless liquid after Kugelrohr distillation (140 ЊC, 0.2
mbar). TLC: cyclohexane–MTBE 10 : 1 (v/v), Rf = 0.5. A
hydrogen pressure of 3 bar was applied in this case. Yield 0.41 g
(78%). The product contains approximately 10% of di-
hydrofuran 7c. TLC: cyclohexane–MTBE 10 : 1 (v/v), Rf = 0.8.
Analytical data of 6c are identical with those reported in the
literature.15f 1H NMR data of 7c were obtained from the mix-
1
ture: H NMR (500 MHz, CDCl3) δ 7.28 (d, 2H, J = 8.5, Ar),
6.85 (d, 2H, J = 8.5, Ar), 6.40 (ddd, 1H, J = 2.5, 2.5, 2.5, –OCH᎐
᎐
CH–), 5.45 (dd, 1H, J = 10.5, 8.5, –OCH(Ar)–), 4.94 (ddd, 1H,
J = 2.5, 2.5, 2.5, –OCH᎐CH–), 3.72 (s, 3H, –OCH ), 3.01 (dddd,
᎐
3
7 A. E. Sutton, B. A. Seigal, D. F. Finnegan and M. L. Snapper, J. Am.
Chem. Soc., 2002, 124, 13390.
8 B. Schmidt, Eur. J. Org. Chem., 2003, 816.
1H, J = 15.1, 10.5, 2.5, 2.5, –OCH(Ar)CHH–), 2.59 (dddd, 1H,
J = 15.1, 8.5, 2.5, 2.5, –OCH(Ar)CHH–).
9 Recently,
a study describing the formation of a ruthenium–
General procedure for the sequential RCM-hydrogenation
reaction with in situ generated hydrogen
carbonylhydride complex by alcoholysis of ruthenium carbene
complexes appeared: M. B. Dinger and J. C. Mol, Organometallics,
2003, 22, 1089 . A ruthenium hydride complex has previously been
described as a by-product in the synthesis of catalysts for olefin
metathesis: A. Fürstner, L. Ackermann, B. Gabor, R. Goddard,
C. W. Lehmann, R. Mynott, F. Stelzer and O. R. Thiel, Chem. Eur.
J., 2001, 7, 3236.
The corresponding metathesis precursor 1 was dissolved in dry
toluene (c 0.3–0.5) and ruthenium complex B (2.0 mol%) was
added. The mixture was stirred until the starting material was
fully consumed as indicated by TLC. NaH (4 eq.) was added
and the reaction vessel was stoppered immediately (Caution:
gas evolution !). Stirring at ambient temperature was continued
for 1 hour. After this time water (30 eq.) was added rapidly
(Caution: vigorous gas evolution!) and the reaction vessel was
stoppered immediately. Stirring was continued for 16 hours at
ambient temperature. The mixture was diluted with water,
extracted with ethyl acetate (in the case of diols) or MTBE. The
combined organic layers were dried with MgSO4, filtered and
the solvents were evaporated. The residue was purified by flash
chromatography.
10 B. Schmidt and H. Wildemann, Eur. J. Org. Chem., 2000, 3145.
11 B. Schmidt and H. Wildemann, J. Chem. Soc., Perkin Trans. 1, 2002,
1050 . It has previously been reported that diallyl carbinols show
comparatively low reactivity in RCM with catalyst A: D. L. J. Clive
and H. Cheng, Chem. Commun., 2001, 605.
12 B. Schmidt and M. Westhus, Tetrahedron, 2000, 56, 2421.
13 M. Scholl, S. Ding, C. W. Lee and R. H. Grubbs, Org. Lett., 1999, 1,
953.
14 (a) R. L. Snowden, S. M. Linder, B. L. Müller and K. H. Schulte,
Helv. Chim. Acta, 1987, 70, 1858; (b) J. Barluenga, J. Florez and
M. Yus, J. Chem. Soc., Perkin Trans. 1, 1983, 3019; (c) V. J. Bryan
and T.-H. Chan, Tetrahedron Lett., 1997, 38, 6493; (d ) H. L. Yale,
E. J. Pribyl, W. Braker, J. Bernstein and W. A. Lott, J. Am. Chem.
Soc., 1950, 72, 3716; (e) D. J. Wallace, P. G. Bulger, D. J. Kennedy,
M. S. Ashwood, I. F. Cottrell and U.-H. Dolling, Synlett, 2001, 357;
( f ) C. Kashima, X. C. Huang, Y. Harada and A. Hosomi, J. Org.
Chem., 1993, 58, 793.
15 (a) H.-J. Schneider, N. Nguyen-Ba and F. Thomas, Tetrahedron,
1982, 38, 2327; (b) T. Imamoto, T. Hatajima, N. Takiyama,
T. Takeyama, Y. Kamiya and T. Yoshizawa, J. Chem. Soc., Perkin
Trans. 1, 1991, 3127; (c) V. Nyzam, C. Belaud, F. Zammattio and
J. Villieras, Bull. Soc. Chim. Fr., 1997, 134, 583; (d ) P. Le Gendre,
T. Braun, C. Bruneau and P. H. Dixneuf, J. Org. Chem., 1996, 61,
8453; (e) S. Celebi, D. A. Modarelli, S. Leyva and M. S. Platz, J. Am.
Chem. Soc., 1993, 115, 8613; ( f ) A. Inoue, H. Shinokubo and
K. Ochima, Synlett, 1999, 1582.
1-(Hydroxy-phenyl-methyl)-cyclopentanol 3d
Obtained from 1d (0.21 g, 0.9 mmol) and B (29 mg, 3.6 mol%)
as a colourless solid, mp = 75 ЊC, after flash chromatography on
silica (eluent cyclohexane–ethyl acetate 3 : 1 (v/v)). Yield 0.14 g
(78%).
(S )-1-(1-Hydroxy-ethyl)-cyclopentanol 3e
Obtained from 1e (0.38 g, 2.5 mmol) and B (51 mg, 2.4 mol%)
as a colourless liquid after Kugelrohr distillation (0.4 mbar,
40 ЊC). Yield 0.24 g (74%).
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 5 1 2 – 2 5 1 7
2517