Catalytic decarboxylative sp-sp3 coupling

Article abstract of DOI:10.1021/ja0542688

A palladium-catalyzed 1,4-enyne synthesis was developed based the decarboxylative coupling of acetylides with allyl electrophiles. Stereochemical studies have implicated palladium-allyl-acetylides as intermediates. Thus, decarboxylative metalation was established as an environmentally benign alternative to transmetalation from alkynyl tin reagents. Copyright

Full text of DOI:10.1021/ja0542688

Published on Web 09/07/2005
Catalytic Decarboxylative sp-sp3 Coupling
Dinesh Kumar Rayabarapu and Jon A. Tunge*
Department of Chemistry, UniVersity of Kansas, 2010 Malott Hall, 1251 Wescoe Hall DriVe,
Lawrence, Kansas 66045
Received June 28, 2005; E-mail: tunge@ku.edu
Table 1. Palladium-Catalyzed Decarboxylative Coupling of
The majority of C-C bond forming cross-coupling reactions (i.e.,
Allyl-CO2-Acetylidea
Negishi, Stille, Suzuki-Miyaura, Sonogashira, Kumada) involve
three basic transformations: oxidative addition, transmetalation, and
reductive elimination.1 The transmetalation steps in many of these
reactions involve the use of toxic (Stille) or highly basic (Kumada)
reagents. In addition, the reagents required for transmetalation
necessarily produce stoichiometric quantities of unwanted byprod-
ucts. We envisioned that the transmetalation step could be
circumvented by decarboxylative metalation of carboxylic acid
derivatives (Scheme 1), where the only byproduct would be CO2.
Since carboxylic acid derivatives are ubiquitous synthetic building
blocks, the ability to access reactive organometallic species via
decarboxylation offers clear practical advantages.2
Scheme 1
Recent notable examples of the synthetic utilization of organo-
metallics generated by decarboxylation include a decarboxylative
Heck coupling,3 aldol additions,4,5 and asymmetric decarboxylative
enolate alkylations.6,7 Herein we report that propiolic acid deriva-
tives readily decarboxylate under the influence of a palladium
catalyst, and the resulting metal acetylides can be coupled with
palladium π-allyl electrophiles to afford 1,4-enynes.
To demonstrate the principle of decarboxylative coupling, the
sp-sp3 coupling of metal acetylides with allyl electrophiles was
explored.8 Previous palladium-catalyzed sp-sp3 couplings to give
1,4-enynes have focused on the formation of palladium acetylides
by transmetalation from alkynyl tin reagents.8a,b On the basis of
the model proposed above, it was expected that treatment of allylic
alkynoate 1a under conditions favorable for oxidative addition to
form π-allyl palladium intermediates would allow access to
palladium-allyl-acetylides through decarboxylation (Scheme 2).
Specifically, substrate 1a was treated with 10 mol % of Pd(PPh3)4
in toluene. Heating this solution for 2 h at 75 °C resulted in
formation of 1,4-enyne 2a in 80% yield.
a A quantity of 0.5 mmol of 1 was treated with 0.05 mmol of Pd(PPh3)4
in toluene at 75 °C. b The mass balance was dimeric product akin to 3r.
Next, we briefly examined the scope of the decarboxylative
allyl-acetylide coupling. A variety of aliphatic allyl fragments are
compatible with the decarboxylative coupling and provide 1,4-
enynes in good to high yield (Table 1). Interestingly, substrates
that are expected to give rise to 1,3-unsubstituted π-allyl palladium
intermediates require longer reaction times. For instance, cinnamyl
phenylpropiolate (1a) requires only 2 h for reaction completion,
while allyl phenylpropiolate (1c) requires 40 h to reach complete
conversion; 1,3-disubstituted allyl substrates, such as 1e, react over
a period of 8 h. Thus, the order of reactivity with respect to allyl
substitution is: monosubstituted aromatic > disubstituted >
terminally unsubstituted. This order is somewhat unusual and
suggests that the rate-limiting step of this reaction is something
Scheme 2
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10.1021/ja0542688 CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3
catalytic decarboxylation of propiolic acids. Indeed, treatment of
allyl acetates with phenyl propiolic acid and 10 mol % of Pd(PPh3)4
produced 1,4-enynes in yields similar to those obtained through
the decarboxylative coupling of allylic propiolates 1 (eq 3).
However, this approach required the addition of a stoichiometric
amount of base to avoid palladium-catalyzed decarboxylation of
the propiolic acid to the corresponding alkyne.16
other than π-allyl formation.9 In support of this hypothesis, complete
crossover is observed between 1d and 1m prior to decarboxylation
(ca. 30 min); the exchange presumably proceeds through π-allyl
palladium intermediates (Scheme 3).
A variety of acetylide reaction partners were investigated, as well.
While aromatic propiolates react smoothly, providing E-1,4-enynes
in high yield, the unsubstituted propiolate 1k produces an insepa-
rable mixture of products that does not contain 2k. Furthermore,
propiolates substituted with small aliphatic groups, such as 1r, give
the dimeric products 3 exclusively (eq 1).10 However, the allyl-
acetylide coupling is not limited to aryl acetylides, as is shown by
the formation of 1,4-enynes with 1-cyclohexenyl (2p) and TMS
substituents (2m-o). Additionally, the benzyl-protected propargylic
alcohol derivative 1q provided a good yield of coupling product.
In conclusion, we have demonstrated that palladium acetylides
are readily accessible through decarboxylation of propiolic acid
derivatives. Thus, decarboxylative metalation was established as
an alternative to the common practice of transmetalation. The
synthetic utility of decarboxylative metalation was demonstrated
by the development of a convenient sp-sp3 coupling of acetylides
with allyl electrophiles to form 1,4-enynes.
Acknowledgment. We acknowledge support of this work by
the ACS Petroleum Research Fund (39562-G1) and by the
University of Kansas.
Supporting Information Available: Spectroscopic data for
new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
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1
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