1
Chemicals from Alkynes with Palladium Catalysts
Rafael Chinchilla* and Carmen Nájera*
Departamento de Química Orgánica, Facultad de Ciencias,
and Instituto de Síntesis Orgánica (ISO),
Universidad de Alicante, Apartado 99, 03080 Alicante, Spain
Contents
1. Introduction
2. Chemicals by Palladium-Catalyzed Intermolecular Additions to Alkynes
2.1. Carbocycles
2.2. Heterocycles
2.3. Vinyl Arenes
2.4. Acrylic Acids, Esters and Amides
2.5. Ketones
2.6. Allyl and Vinyl Ethers
2.7. Imines, Enamines and Allylamines
2.8. Vinyl Sulfides and Selenides
2.9. Vinyl Phosphines, Phosphine Oxides, Phosphinates and
Phosphonates
3. Chemicals by Palladium-Catalyzed Intramolecular Additions to Alkynes
3.1. Carbocycles
3.2 Heterocycles
4. Chemicals by Palladium-Catalyzed Oxidation of Alkynes
4.1. 1,2-Diketones
4.2. Esters
4.3. Furans
5. Olefins by Palladium-Catalyzed Reduction of Alkynes
6. Chemicals by Palladium-Catalyzed C-C Coupling Reactions of Alkynes
6.1. Alkynylated Arenes
6.2. Alkynylated Heterocycles
6.3. 1,3-Enynes
6.4. 1,3-Diynes
6.5. Ynones
6.6. Ynoates and Ynamides
7. Conclusions
8. Acknowledgments
9. References
* To whom correspondence should be addressed. Phone: +34 965903548. Fax: +34 965903549. E-
mail: chinchilla@ua.es; cnajera@ua.es. URL: www.ua.es/dqorg
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1. Introduction
The carbon-carbon triple bond of alkynes is one of the basic functional groups, its
reactions belonging to the foundations of organic chemistry. In the past decades,
acetylene chemistry has experienced a renaissance due to, not only its occurrence in
molecules in the frontiers of organic chemistry such as biochemistry or material
sciences, but also as building blocks or versatile intermediates for the synthesis of a vast
array of chemicals.
1
This boost to the alkyne chemistry has been fueled mainly by the
development of new synthetic methodologies based on transition metal catalysis, a field
where palladium always occupies a leading position.
This review presents an overview of the use of alkynes as starting materials for the
preparation of compounds, using procedures carried out under palladium catalysis.
Many different reactions leading to many different chemicals could be included in such
a review, and trying to cover all possibilities and particularities in a fully comprehensive
way would be an overwhelming task. Thus, this review will present coverage of the
main palladium-catalyzed reactions of alkynes leading to different chemical
compounds, ordered by reaction type and chemical class. The ‘alkynes’ involved as
starting materials in this review will only be those containing H or C-substituted
carbon-carbon triple bonds. Therefore, palladium-catalyzed couplings involving alkynyl
metals or other non-strictly considered alkyne-hydrocarbons, such as 1-haloalkynes,
will be excluded. A summary of the transformations considered in this review is shown
in Table 1. Only ‘direct’ reactions of alkynes will be shown, the preliminary
transformation of the acetylene into an intermediate followed by a palladium-promoted
conversion being not considered, as well as multi-step processes such as hydro/carbo-
metalation-coupling sequences. When previous reviews of a particular palladium-
catalyzed topic exist, significant or relevant methodologies, as well as the most recent
examples will be presented.
3
Table 1. Summary of the palladium-catalyzed transformations of alkynes presented in this review.
Alkyne + Other component
Reaction type
Product
R
2
R
1
R
1
, R
2
= Alkyl,
Ar. Het
+
X
Z
X = Cl, Br, I; Z = OH, NH
2
,
NHR, CO
2
R, CONHR
Intermolecular addition
Heterocycles
R
1
R
2
R
1
, R
2
= H, Alkyl, Ar, CO
2
R, COR
+
ArX (X = H, Hal, B(OH)
2
, N
2
+
X
-
)
R
1
Ar
R
2
Vinyl arenes
R
R = Alkyl, Ar, Het
+
CO, NuH (Nu = OH, RO, NR
2
) R
O
Nu
R
O
Nu
Acrylic acids, esters and amides
R
1
R
2
R
1
, R
2
= H, Alkyl
R
1
O
R
2
Ketones
+
H
2
O
R
1
R
2
R
1
= Alkyl, Aryl; R
2
= H, Alkyl, Aryl
+ NuH (Nu = OR, NR
2
)
R
1
R
2
Nu
Allyl ethers and amines
R
1
R = Alkyl, Ar, Het
+
XH [X = R
2
S, R
2
Se, R
2
P(O).
ROP(O)R', ROP(O)H, R
2
P(O)]
R
1
X
R
1
X
Vinyl sulfides, selenides, phosphines,
phosphine oxides and phosphonates
Intramolecular addition
R
XH
R = H, Alkyl, Ar, Het
X = CZ
2
, NH, NR, OH, CO, CO
2
Carbocycles and heterocycles
R
2
R
1
R
1
, R
2
= Alkyl, Ar. Het
Oxidation
R
1
R
2
O
O
1,2-Diketones
R
CO
2
Me
Methyl esters
R
2
R
1
R
1
, R
2
= H, Alkyl, Ar, Het
Reduction
R
1
+
oxidant
+
H
2
(or hydrogen donor)
R
2
R
1
R
2
Alkenes
C-C Coupling
R
1
R
1
= Alkyl, Ar, Het
+ X-R
2
R
2
= Alkenyl, Ar, Het
X = Cl, Br, I, OTs
R
2
(Het)
R
1
Alkynes and 1,3-enynes
or H-Het
R
1
R
1
+
R
1
, R
2
= Alkyl, Ar, Het
or
R
2
X
R
1
(R
2
)
R
1
1,3-Diynes
R
1
+
R
1
, R
2
= Alkyl, Ar, Het
R
2
COCl (or CO + R
2
Hal)
O
R
2
(Nu)
R
1
CO + NuH (Nu = OR, NR
2
2
)
Ynones, ynoates and ynamides
R
1
R
1
= Alkyl, Ar
+
ArNH
2
or HNR
2
2
R
1
N
Ar
or
R
1
NR
2
2
Imines and enamines
R
2
R
1
R
1
, R
2
= H, Alkyl, Ar
Aromatics and polyaromatics
(or +
o
-TfOC
6
H
4
SiMe
3
or + ArH)
Section
2.1
2.2
2.3
2.4
2.5
2.7
2.6, 2.7
2.8, 2.9
3.1, 3.2
4.1, 4.2
5
6.1, 6.2,
6.3
6.4
6.5, 6.6
X = Br, I
4
2. Chemicals by Palladium-Catalyzed Intermolecular Additions to
Alkynes
The formal intermolecular addition reaction involving only the carbon atoms of
an alkyne system is an approach which can lead directly to the synthesis of carbocyclic
systems, a process which can be achieved under palladium-catalysis. In addition, the
palladium-catalyzed intermolecular annulation of alkynes with halogenated heteroatom-
bearing systems is also a formal addition to alkynes which leads to heterocycles. Other
intermolecular additions to alkynes can be achieved under palladium-catalysis, as
hydroarylation, hydrocarbonylation or the addition of heteroatomic nucleophiles to
alkynes, a practical way of preparing a large variety of alkene-bearing chemicals, once
the adequate regio- and stereocontrol are achieved. This section will present examples
of carbocycles and heterocycles obtained by all these approaches, as well as a survey of
chemicals obtained by palladium-catalyzed intermolecular addition of C, N, O, S, Se
and P nucleophiles to alkynes.
2.1. Carbocycles
The transition metal-catalyzed conversion of internal and terminal alkynes to
substituted benzene derivatives by a cyclotrimerization process is an old procedure
which has also been achieved using palladium species as catalysts.
2
The process has
been traditionally considered to occur via coordination of two alkyne moieties to the
metal, coupling reaction giving a metallacyclopentadiene, and further insertion or
addition of an alkyne to the metallacycle giving a six-carbon metalacycle which forms
the benzene ring after reductive elimination.
2
Thus PdCl
2
3
and PdCl
2
(PhCN)
2
4
catalyze
the cyclotrimerization of alkynes to benzene derivatives, the yields generally depending
on the alkyne substituents, as regioisomers are normally obtained in the case of
unsymmetrical acetylenes. However, it has been shown that the addition of CuCl
2
(200
mol%) to the reaction mixture, not only increases the yield of the process, as discovered
in the case of the PdCl
2
-catalyzed cyclotrimerization of oct-4-yne to give 1,2,3,4,5,6-
hexapropylbenzene,
5
but also induces regiospecificity in the process. Thus,
unsymmetrical alkynes, such as oct-1-yne, where cyclotrimerized regiospecifically to
benzene derivatives such as 1 under PdCl
2
catalysis (6 mol%) in the presence of CuCl
2
5
and a mixture of n-butanol/benzene as solvent at 40 ºC (Scheme 1),
6
diphenylacetylene
affording no reaction. In addition, the presence of carbon dioxide was found to favor
this PdCl
2
-catalyzed/CuCl
2
-assisted process when performed in water.
7
Moreover, the
reaction has also been carried out in supercritical carbon dioxide.
8
The palladium-catalyzed cyclotrimerization was also applied to strained
cycloalkynes.
9
For instance, Pd(PPh
3
)
4
(10 mol%) catalyzed the cyclotrimerization of
cyclohexyne (3), generated in situ by a fluoride-induced β-elimination in
trimethylsilylated triflate 2, to dodecahydrotriphenylene 4 in 64% yield (Scheme 2), but
subjecting cyclopentyne to the same conditions failed to afford isolable amounts of the
cyclotrimer.
10
3
4
Pd(PPh
3
)
4
(10 mol%)
CsF, MeCN, 20 ºC
(64%)
SiMe
3
OTf
2
Scheme 2
This cyclotrimerization reaction can also be performed using non-soluble
palladium reagents as catalysts. Thus, the transformation of acetylene into benzene
11
has been catalyzed by alumina-supported palladium
12
and Pd(111) single crystals.
13
In
addition, the trimerization of alkynes has also been achieved using 10% Pd/C as catalyst
in the presence of trimethylsilyl chloride, which is suggested to form highly dispersed
