Redox isomerization of allylic alcohols and amides using Grubbs' catalyst

Article abstract of DOI:10.1081/SCC-120015704

Commercially available Grubbs' catalyst was found to catalyze the redox isomerization of allylic alcohols and amides under mild conditions.

Full text of DOI:10.1081/SCC-120015704

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Redox Isomerization of Allylic Alcohols and Amides
Using Grubbs’ Catalyst
E. S. Greenwood a , P. J. Parsons a c & M. J. Young b
a The Chemical Laboratories , School of Chemistry, Physics & Environmental Science ,
University of Sussex , Falmer, Brighton, East Sussex, UK
b PR&D , Astra Zeneca , Severn Road, Hallen, Bristol, UK
c The Chemical Laboratories , School of Chemistry, Physics & Environmental Science ,
University of Sussex , Falmer, Brighton, East Sussex, BN1 9QJ, UK
Published online: 21 Aug 2006.
To cite this article: E. S. Greenwood , P. J. Parsons & M. J. Young (2003) Redox Isomerization of Allylic Alcohols and Amides
Using Grubbs’ Catalyst, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 33:2, 223-228, DOI: 10.1081/SCC-120015704
To link to this article: http://dx.doi.org/10.1081/SCC-120015704
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 2, pp. 223–228, 2003
Redox Isomerization of Allylic Alcohols and
Amides Using Grubbs’ Catalyst
E. S. Greenwood,1 P. J. Parsons,1, and M. J. Young2
*
1The Chemical Laboratories, School of Chemistry, Physics &
Environmental Science, University of Sussex,
Falmer, Brighton, East Sussex, UK
2PR&D, Astra Zeneca, Severn Road,
Hallen, Bristol, UK
ABSTRACT
Commercially available Grubbs’ catalyst was found to catalyze the
redox isomerization of allylic alcohols and amides under mild
conditions.
Key Words: Redox isomerization; Allylic alcohol; Allylic amide;
Grubbs’ catalyst.
*Correspondence: P. J. Parsons, The Chemical Laboratories, School of
Chemistry, Physics & Environmental Science, University of Sussex, Falmer,
Brighton, East Sussex, BN1 9QJ, UK. Fax: þ44(0)1273 677196; E-mail:
P.J.Parsons@sussex.ac.uk or afp2@york.ac.uk.
223
DOI: 10.1081/SCC-120015704
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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224
Greenwood,Parsons,and Young
The use of cross metathesis catalysts in organic synthesis has esca-
lated dramatically over the past decade, due predominantly to the use of
Grubbs’ ruthenium based catalysts 1 and 2.[1] The commercial availability,
stability, and tolerance of a wide range of functional groups has made the
ruthenium benzylidene catalyst (1) the reagent of choice in all but the
most hindered of cross metathesis reactions.
Unrelated studies by Trost and Kulawiec[2] have concentrated on
chemoselective, ruthenium-catalyzed redox isomerization of allylic alco-
hols. Early work focused on the bidentate co-ordinator Cp(Ph3P)2RuCl
(3) as a catalyst, in the presence of triethylammonium hexafluorate,
which effected clean isomerization of mono- and 1,1-disubstituted allylic
alcohols in good to excellent yields. 1,2-Disubstituted olefins required
significantly longer reaction times and gave lower yields. Tri-substituted
olefinic substrates showed little or no reactivity.
Enhanced reactivity was observed with the indenyl analogue (4),
which gave significant rate increases with cyclic and highly substituted
olefins.
Studies into base-catalyzed ruthenium isomerization reactions have
been conducted by Backvall and Andreasson,[3] using either
RuCl2(PPh3)2 (5) of [RuCl2( p-cymene)]2 (6). The addition of either potas-
sium carbonate or Et3NHPF6 causes a dramatic rate increase and affords
reasonable yields with cyclic olefins. The dimetallic species (7), which
can itself serve as a base, led to rapid reactions without the addition of
extra base.

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Redox Isomerization Using Grubbs’ Catalyst
225
While recently studying the cross metathesis of allylic alcohols using
Grubbs’ catalyst (1) we observed that the allylic alcohol had undergone
redox isomerization to the corresponding saturated ketone. A range of
allylic substrates were then subjected to the same conditions, the results
of which are shown in Table 1.
Concurrent studies within the group observed a similar redox iso-
merization when Grubbs’ catalyst (1) was used in the ring-closing metath-
esis of N-allyl acrylamide (8). In this instance the production of the amide
(8) as its tert-butyl carbamate (10) allowed the reaction to proceed,
although in disappointing yield (Sch. 1).
Recourse to the literature revealed only one other instance of ruthe-
nium-catalyzed allylic isomerization using Grubbs’ catalyst, by Tori
et al.[4] Previous studies on ruthenium-catalyzed allylic isomerization
(vide supra) have postulated the initial formation of a bis-coordinated
allyl alcohol complex (13) as the facile ionization of ruthenium complexes
[(1) !(12)] is well documented.[5] The ruthenium alkoxide (13) is then
able to undergo b-hydrogen insertion to give the coordinated enone (14).
Table 1.
Entry Starting Material Reaction Conditions
Product
Yielda
>98%
1
2
3
DCM, reflux,
4 mol% catalyst
DCM, reflux,
4 mol% catalyst
>98%
43%
DCM, reflux,
4 mol% catalyst
4
5
DCM, reflux,
4 mol% catalyst
No reaction
No reaction
DCM, reflux,
4 mol% catalyst
aBased on isolated product.

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226
Greenwood,Parsons,and Young
Scheme 1.
Scheme 2.

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Redox Isomerization Using Grubbs’ Catalyst
227
Transfer of the ruthenium hydride to the enone system gives 15, proto-
nation of which generates the saturated ketone and reforms the catalytic
species. A similar mechanism would account for both the allyl alcohol
and amide isomerizations (Sch. 2).
To summarize, we wish to report that 1 can catalyze the redox
isomerization of simple allylic alcohols and amides under mild
conditions without the use of acid or base catalysis. Simple straight chain
mono-substituted allylilc alcohols were found to readily undergo the
transformation in quantitative yields (Entries 1 and 2) while the redox
isomerization of allylic alcohols with di-substituted alkenes was found to
be more sluggish (Entries 3 and 4). Attempts to break conjugation in the
molecule by the isomerization of an allylic alcohol were unsuccessful.
Amide isomerization took significantly longer reaction times.
TYPICAL REACTIONS CONDITIONS
To a stirred solution of Grubbs’ catalyst (4 mol%) in dichloro-
methane (0.5 M) was added the allylic species and the reaction mixture
refluxed until TLC analysis indicated no remaining starting material. The
reaction mixture was concentrated under reduced pressure and purified
by flash column chromatography.
ACKNOWLEDGMENTS
We wish to thank AstraZeneca for providing funding for MJY
and ‘The Royal Commission for the Exhibition of 1851’ for funding a
fellowship for ESG.
REFERENCES
1. For recent reviews on olefin metathesis see: (a) Schuster, M.;
Blechart, S. Olefin metathesis in organic chemistry. Angew. Chem.
Int. Ed. (Engl.) 1997, 36 (19), 2037–2056; (b) Grubbs, R.H.; Chang, S.
Recent advances in olefin metathesis and its application in organic
synthesis. Tetrahedron 1998, 54 (18), 4413–4450; (c) Armstrong, S.K.
Ring closing diene metathesis in organic synthesis. J. Chem. Soc.,
Perkin I 1998, (2), 371–388.

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228
Greenwood,Parsons,and Young
2. (a) Trost, B.M.; Kulawiec, R.J. A chemoselective internal redox
of allyl alcohols to saturated aldehydes or ketones. Tetrahedron
Lett. 1991, 32 (26), 3039–3042; (b) Trost, B.M.; Kulawiec, R.J.
Chemoselectivity in the ruthenium-catalyzed redox isomerization of
allyl alcohols. J. Am. Chem. Soc. 1993, 115 (5), 2027–2036.
3. Backvall, J.-E.; Andreasson, U. Ruthenium-catalyzed isomerization
of allylic alcohols to saturated ketones. Tetrahedron Lett. 1993, 34
(34), 5459–5462.
4. Nakashima, K.; Ito, R.; Sono, M.; Tori, M. Olefin metathesis reac-
tions of some aromatic dienes with ortho- and meta-disubstitution,
formation of 10-, 12-, 14-, and 17-membered cyclic compounds and
isomerization of an allylic alcohol. Heterocycles 2000, 53 (2), 301.
5. Davies, S.G.; Smallridge, A.J. The stereoselective reaction of sodium
cyanide with the cationic ruthenium vinylidene complex [(eta-5-
C5H5)(PMe3)2Ru¼C¼C(Me)Ph]þ. J. Organomet. Chem. 1990,
395 (2), C39–C41.
Received in the Netherlands December 10, 2001