DOI: 10.1002/chem.201102584
Synthesis of a,b-Unsaturated Ketones by Pd-Catalyzed Decarboxylative
AHCTUNGTRENNUNG llylation of a-Oxocarboxylates
Nuria Rodrꢀguez, Filipe Manjolinho, Matthias F. Grꢁnberg, and Lukas J. Gooßen*[a]
Within recent years, the field of decarboxylative allylation
reactions has undergone tremendous development, with in-
novative contributions that have attracted considerable at-
tention within the chemical community.[1] The foundations
for this area were laid by Carroll in 1940 with his report that
allyl b-oxocarboxylates extrude carbon dioxide to give g,d-
unsaturated alkyl ketones when heated in the presence of a
base.[2] In the 1980s, palladium-catalyzed versions of this
transformation that proceed under neutral conditions were
discovered by Saegusa[3] and Tsuji (Scheme 1, top).[4] This
these species normally precludes their use in organic synthe-
sis. Instead, synthetic equivalents to acyl anions usually have
to be generated within multistep procedures, for example,
through umpolung of aldehydes by reaction with dithiols
and subsequent deprotonation with strong bases.[10]
a-Oxocarboxylic acid are attractive sources of acyl anions
as they are stable and easy to access.[11] Some derivatives
serve as intermediates in the synthesis of a-amino acids and
are commercially available. Others are accessible by double
carbonylations of aryl halides with CO using Pd,[12] Co,[13] or
Cu catalysts,[14] by Friedel–Crafts acylations with oxalyl
chlorides,[15] additions of arylmetal reagents to oxalates,[16] or
oxidations of acetophenones.[17]
We herein report the Pd/phosphine-catalyzed decarboxy-
lative allylation of allyl a-oxocarboxylates as the first exam-
ple of a decarboxylative allylation involving destabilized
carbon nucleophiles (see Scheme 1, bottom). This reaction
provides an expedient synthetic entry to a,b-unsaturated ke-
tones as privileged structures in biologically active natural
products.[18] Such compounds are traditionally synthesized,
for example, by using aldol condensations, Meyer–Schuster
rearrangement of propargylic alcohols,[19] or the hydroacyla-
tion of alkynes.[20]
In the course of our work on redox-neutral decarboxyla-
tive cross-couplings of aryl and vinyl halides with bimetallic
catalysts,[21] we successively extended the substrate scope
from heterocyclic and ortho-substituted benzoic acids[22] to
nonactivated aromatic carboxylic acids[23] and finally to a-
imino-[24] and a-oxocarboxylic acids.[25] a-Oxocarboxylate
salts proved to be particularly unreactive, extruding CO2
only at 1708C within the coordination sphere of special
copper catalysts. Oxidative decarboxylative couplings of a-
oxocarboxylatic acids proceed at lower temperatures, but
these reactions involve stable electrophilic rather than labile
nucleophilic acyl intermediates.[26]
As can be seen in Scheme 2, the targeted decarboxylative
allylation would have to proceed through a different mecha-
nism than bimetallic decarboxylative cross-coupling reac-
tions.[1] Coordination and subsequent oxidative addition of
the substrate to a Pd0 precursor (A) lead to the formation of
covalent or ionic p-allyl-Pd-carboxylate complexes (B). Our
initial plan was to tune the ligand environment of palladium
complex A in a way that the next step, an extrusion of CO2
with formation of the acyl p-allyl-Pd complex C, would
become possible. Reductive elimination would then give the
allyl ketone 2, which can be expected to rapidly isomerize
Scheme 1. Decarboxylative allylation of carbon nucleophiles.
concept was decisively advanced by Tunge[5] and Stoltz.[6]
For example, Tunge et al. reported an asymmetric decarbox-
ylative allylation of ketone enolates.[5] Stoltz et al. utilized
decarboxylative allylations as the key step in enantioselec-
tive syntheses of complex target molecules such as (À)-cyan-
thiwigin F, (+)-carissone and (+)-cassiol. In all these cases,
the carbon nucleophiles generated in the decarboxylation
step of the allylation process are highly stabilized carban-
ions,[3] that is, enolates, benzyl, a-iminoyl,[7] a-cyano-,[3] a-
sulfonyl-,[8] nitronate-,[9] or nitrotolyl-anions.[5d]
Another major step in the development of this reaction
class would undoubtedly be its extension to carboxylates for
which the decarboxylation step would lead to non-stabilized
or even destabilized carbon nucleophiles. Examples of the
latter are acyl anions, generated by extrusion of carbon di-
oxide from a-oxocarboxylates. The proverbial instability of
[a] Dr. N. Rodrꢀguez, F. Manjolinho, M. F. Grꢁnberg,
Prof. Dr. L. J. Gooßen
Department of Chemistry, University of Kaiserslautern
Erwin-Schrçdinger-Strasse 54, 67663 Kaiserslautern (Germany)
Fax : (+49)631-205-3921
Supporting information for this article is available on the WWW
13688
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Chem. Eur. J. 2011, 17, 13688 – 13691