Multicatalytic processes using diverse transition metals for the synthesis of alkenes

Article abstract of DOI:10.1021/ja0472681

A series of cascade processes for the synthesis of alkenes from alcohols is described. Each individual step is catalyzed with a specific transition metal complex. The oxidation-methylenation one-pot procedure took place in the presence of a palladium and a rhodium catalyst to produce the desired terminal alkenes in high yields. A methylenation-ring-closing metathesis allowed the synthesis of cyclic alkenes from carbonyl derivatives, using the second-generation metathesis catalyst. Finally, an oxidation-methylenation-RCM process that involves up to three different transition metal catalysts in the same vessel is presented. Copyright

Full text of DOI:10.1021/ja0472681

Published on Web 08/21/2004
Multicatalytic Processes Using Diverse Transition Metals for the Synthesis of
Alkenes
He´le`ne Lebel* and Vale´rie Paquet
De´partement de chimie, UniVersite´ de Montre´al, C.P. 6128, Succursale Centre-Ville,
Montre´al, Que´bec, Canada, H3C 3J7
Received May 10, 2004; E-mail: lebelhe@chimie.umontreal.ca
Table 1. One-Pot Palladium-Catalyzed Oxidation and
Rhodium-Catalyzed Methylenation Reaction
A number of useful transition metal-catalyzed processes have
been developed over the years.1 Although those denote a significant
improvement by minimizing the amount of the required reagents,
a traditional step-by-step approach in which each intermediate needs
to be purified is generally required. The development of a
multicatalytic process, which mimics the biosynthesis in living cells,
would greatly enhance the efficiency of organic synthesis. Not only
would such a process eliminate intermediate recovery steps, but it
also would considerably decrease the amount of generated waste,
a particularly important concern in industrial process chemistry.2
Many examples of cascades using biocatalysts are described in the
literature.3 In addition, the combination of enzymes and metal
catalysts has been reported to be a powerful strategy in dynamic
kinetic resolution.4 In contrast, one-pot procedures that utilize more
than one metal complexes to catalyze independent reactions are
scarce.5,6 The development of this approach would greatly expand
the possibilities in multicatalytic processes since the number of
reported transition metal-catalyzed reactions is constantly growing.1
In this communication, we present the first example of a cascade
process that involves up to three different transition metal catalysts
in the same vessel.
Our interest in de novo synthesis of alkenes prompted us to study
the development of a new catalytic one-pot process for the
conversion of alcohols into alkenes. The isolation and purification
of the potentially unstable aldehyde intermediate is then avoided.
Indeed, a number a stoichiometric one-pot oxidation-olefination
procedures have been developed over the years.7 Those procedures
were typically restricted to benzylic, allylic, and primary alcohols
and involved the use of an excess of the phosphorus ylide, which
is usually derived from carboxymethylenephosphonium salts. We
decided to focus our attention on the palladium-catalyzed aerobic
oxidation of alcohols, recently reported by Sigman and co-workers,8
in combination with the rhodium-catalyzed methylenation of
carbonyl derivatives developed in our group.9,10
a Isolated yield. bIn parantheses, literature yield9a for step-by-step
procedure. Ref 7c.
c
Treatment of the alcohol with 2.5 mol % palladium catalyst 111
and 5 mol % tetrabutylammonium acetate under an atmosphere of
oxygen led to the formation of the corresponding carbonyl
derivative, either an aldehyde or a ketone. The reaction mixture
was then submitted to the methylenation reaction conditions, in
the presence of Wilkinson’s catalyst (2), triphenylphosphine,
2-propanol, and trimethylsilyldiazomethane in 1,4-dioxane (Table
1). Not only was there no deleterious interaction between the two
transition metal catalysts during the methylenation, but also the
isolated yields for the corresponding terminal alkenes were superior
to those obtained with the step-by-step procedure. This cascade
process is compatible with both primary aliphatic and benzylic
alcohols, which provide the corresponding terminal alkenes 4 and
6, respectively, in good yields (entries 1 and 2).
This is the first example of a successful one-pot process that
involves ketone intermediates. A four-reaction sequence was also
achieved with diol 15, which was converted to the corresponding
diene 14 with 54% yield, indicating that each individual step
afforded more than 80% yield (entry 7).
Metathesis reactions of terminal alkenes have been established
as a powerful synthetic method to produce stereodefined substituted
alkenes.12 The development of a cascade process in which a
carbonyl derivative is converted to a diene, which then undergoes
a metathesis reaction, will further improve the efficiency of this
method.13 The mildness of our rhodium-catalyzed methylenation
of carbonyl derivatives prompted us to study a one-pot methyl-
enation-methasis procedure to produce functionalized alkenes. A
number of issues needed to be addressed, in particular the
compatibility of both catalysts, and the compatibility of the
Moreover, this one-pot procedure could be used for the synthesis
of 2,2-disubstituted alkenes from secondary alcohols (entries 3-6).
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C O M M U N I C A T I O N S
Table 2. One-Pot Methylenation-Ring Closing Metathesis
Reaction
In conclusion, we have devised a series of one-pot procedures
that combined various transition metal catalysts to achieve a highly
efficient synthesis of alkenes from alcohols.
Acknowledgment. This research was supported by NSERC
(Canada), the Canadian Foundation for Innovation, Boehringer
Ingelheim (Canada) Lte´e, Merck Frosst Canada, and the Universite´
de Montre´al. V.P. thanks Boehringer Ingelheim (Canada) Lte´e for
a graduate scholarship.
Supporting Information Available: Characterization data for new
compounds and experimental procedures. This material is available free
of charge via the Internet at http://pubs.acs.org.
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a Conditions A: PPh3; additive ) AlCl3. B: DPPBE (17); additive )
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