Temperature-dependent isomerisation versus net fragmentation of secondary allylic alcohols with Grubbs' catalyst

Article abstract of DOI:10.1016/S0040-4039(01)00449-X

Secondary allylic alcohols with 10 mol% of Grubbs catalyst in refluxing toluene/1,2-dichloroethane undergo isomerisation to ethyl ketones whereas with 100 mol% of Grubbs catalyst at room temperature, a net fragmentation reaction with the loss of a carbon atom occurs, to provide a methyl ketone. Probable mechanisms are described.

Full text of DOI:10.1016/S0040-4039(01)00449-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3633–3636
Temperature-dependent isomerisation versus net fragmentation of
secondary allylic alcohols with Grubbs’ catalyst
Mukund K. Gurjar* and Pedduri Yakambram
National Chemical Laboratory, Pune 411 008, India
Received 23 November 2000; revised 1 February 2001; accepted 15 March 2001
Abstract—Secondary allylic alcohols with 10 mol% of Grubbs catalyst in refluxing toluene/1,2-dichloroethane undergo isomerisa-
tion to ethyl ketones whereas with 100 mol% of Grubbs catalyst at room temperature, a net fragmentation reaction with the loss
of a carbon atom occurs, to provide a methyl ketone. Probable mechanisms are described. © 2001 Elsevier Science Ltd. All rights
reserved.
Ring-closing metathesis (RCM) is widely being used in
organic synthesis for the construction of medium to
large ring structures. Among the two most widely used
analysis, structure 5 was proposed for the new product.
It was apparent that compound 5 was formed as a
result of intramolecular hydrogen-transfer isomerisa-
tion of 4 (Scheme 1). Similar isomerisation was also
noticed at lower temperature with dichloroethane under
reflux. Isomerisation of allylic alcohols to ketones using
catalytic amounts of ruthenium complexes has been
1
catalysts, namely Grubbs’ ruthenium alkylidene catalyst
2
3
1
and Schrock’s molybdenum alkylidene catalyst 2, 1
is undoubtedly more exploited because of its inherent
characteristic properties, particularly functional group
compatibility, tolerance to many solvent systems, air
and moisture insensitivity, and thermal stability even in
7
reported previously.
4
refluxing toluene.
In the absence of catalyst 1, compound 4, in refluxing
toluene, did not furnish compound 5. The presence of a
Cross-coupling metathesis, an emerging area of
research whereby two symmetrical or non-symmetrical
olefins combine to form open-chain olefinic com-
5
pounds, has received relatively less attention. As a part
6
of our interest in HIV protease inhibitors, we sought
to develop a simple approach to construct 1,6-diphenyl-
2
,5-dihydroxy-hex-3-ene (3) by cross-coupling metathe-
Scheme 1.
sis of 4-phenyl-1-buten-3-ol (4) using 1. Compound 4
was prepared by vinyl magnesium bromide addition to
phenyl acetaldehyde. Treatment of 4 with 10 mol% of 1
in refluxing toluene gave a product that did not con-
form with the expected product 3. However, based on
1
13
H NMR, C NMR, IR spectroscopy and elemental
*
0
Corresponding author.
Scheme 2.
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00449-X

3
634
M. K. Gurjar, P. Yakambram / Tetrahedron Letters 42 (2001) 3633–3636
It seems that at higher temperature the process of
hydrogen transfer precedes the cyclo-reversion reaction
of metallocyclobutane leading to isomerisation. Final
b-elimination from metallo intermediates I and II pro-
ceeds via CꢀC cleavage, followed by hydride transfer
from ruthenium species, led to ethyl ketone as the
product and regeneration of catalyst 1 (path B). Path B
was supported by the detection of the enone-derivative
1
as a minor component. For example, the 500 MHz H
NMR spectrum of the reaction product shown in
entries 1, 2, 5 and 8 revealed, apart from major signals
of ethyl ketone derivative, the characteristic resonances
due to an enone functionality (CH ꢁCHꢀCꢁO) between
2
5
.77 and 5.88 ppm (double-doublet) and at 6.2 ppm
(
multiplet) distinctly different from the values observed
Scheme 3.
for the precursor. Path A essentially endorses the mech-
anism proposed by Hoye and Zhao to explain the loss
of one carbon atom and the decomposition of catalyst
9
8
free alcohol group was essential for the isomerisation
because, under the above conditions, the O-benzyl
derivative 6 was found to be inert (Scheme 2).
1
leading to a methyl ketone derivative.
Table 1 indicates that a large number of allylic alcohols
Our results were contrary to the observations recently
reported by Hoye and Zhao who noticed that a sec-
ondary allylic alcohol undergoes a net fragmentation
reaction with 100 mol% of 1 at room temperature,
leading to a methyl ketone, with the loss of one carbon
atom (Scheme 3).
can be isomerised in the presence of a catalytic amount
9
11
of 1
to provide the isomerised products (ethyl
13
ketones) and many protecting groups survived the
transformation. The lack of reaction for entries 9 and
10 was attributed to steric factors.
In summary, this communication, for the first time,
deals with studies on net fragmentation with stoichio-
metric amounts of Grubbs’ catalyst and isomerisation
with the more usual catalytic amounts of Grubbs’
catalyst of secondary allylic alcohols and has examined
their temperature dependence.
We also carried out the fragmentation reaction on
substrates 7 and 9 with 100 mol% of 1 at room temper-
ature and, indeed, observed the formation of methyl
ketones 8 and 10 with the loss of a carbon atom. Based
on the above observation, we proposed two hypotheti-
cal mechanistic pathways to explain the net fragmenta-
tion reaction (path A) and hydrogen-transfer
isomerisation reaction (path B), since the conventional
Acknowledgements
2
mechanism involving h complexation of an alkene,
followed by hydrogen transfer to the metal to form an
P.Y. would like to thank the CSIR (New Delhi) for
financial assistance in the form of a Junior Research
Fellowship.
3
10
h intermediate, is tedious for the present transforma-
tion (Scheme 4).
Scheme 4.

M. K. Gurjar, P. Yakambram / Tetrahedron Letters 42 (2001) 3633–3636
3635
Table 1.
Entry
1
Allylic alcohol
Time (h)
2
Solventa
Product
Yield (%)
7012a
A/B
2
3
2
3
A
8012a
A/B
6712b
4
5
4
2
A/B
6712c
B
70
6
7
8
1
1
B
B
B
8112d
5212e
–
24
–
–
9
24
B
–
a
A is 1,2-dichloroethane; B is toluene.
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