Chemistry Reference
In-Depth Information
by microwave techniques [126] and sometimes with
high regio- and enantioselectivities [127,128].
Palladium and its complexes and salts can catalyse
a range of transformations, including oxidation,
hydrogenation and rearrangement, but one of the
most useful applications of the metal is for activation
of C-H bonds towards coupling reactions. The Heck
reaction, which involves C-C coupling of an aryl or
vinyl halide with an alkene in the presence of palla-
dium derivatives, has been the subject of intensive
study [129]. Synthetic transformations of terminal
alkynes via homo- or heterocouplings of the Glaser,
Eglington or Chodkiewicz-Cadiot type have at-
tracted interest as well [130-136].
Stille coupling involves the use of tin reactants.
Tin is both toxic and difficult to remove. In an
elegant extension of the pioneering work of Horvath,
which has been reviewed [137], Curran and co-
workers prepared fluorous tin reactants that facili-
tated Stille reactions and enabled the convenient
isolation and separation of products afterwards
[138]. Probably owing to the low solubility of
fluorine-containing compounds in organic solvents,
the reactions normally required about 1 day at 80°C.
However, with microwave heating they were com-
pleted within minutes [139].
Typically, the Pd species for Heck couplings are
homogeneous catalysts that are stabilised by air-sen-
sitive ligands and present economic and environ-
mental problems regarding separation, regeneration
and reuse [140,141]. These difficulties can be
minimised with heterogeneous catalysts that are
more easily recoverable from the reaction mixture.
A catalyst consisting of palladium metal deposited on
porous glass tubing was developed for C-C coupling
reactions [91]. It was used for reactions conducted
continuously or batchwise and could be reused
several times for repeat or different reactions. Reac-
tions were performed in the presence of air, with
either conventional heating or under microwave
irradiation in the MBR [64,91].
Coupling of aryl halides with terminal acetylenes
affords internal alkynes [130-136]. Typically, high
amounts of catalyst (1-5 mol.% Pd) and co-addition
of copper salts (also 1-5 mol.% in Cu) are needed,
thus diminishing the industrial viability of such pro-
cedures [140,141]. With palladium on porous glass,
copper salts or activating ligands were not necessary
and direct coupling of terminal acetylenes occurred
readily. In contrast with Heck reactions involving
halogen-containing reactants (usually aryl bromides
or iodides), homocoupling of terminal acetylenes
occurred readily [91] and with excellent atom
economy [142,143].
Advantages of palladium on porous glass included
ease of manufacture, mechanical strength and
obviation of air- and temperature-sensitive ligands.
Depending on the specific application, the catalyst
also showed thermal stability and resistance to
organic solvents. On occasions it was reused for
repeat or different reactions. Turnover numbers of
the order of 15 000 were achieved for Heck reactions
in high-temperature water (with either Et
3
N or
NaOAc as base). However, some of the support dis-
solved and an alternative material may be advanta-
geous for such conditions.
Other workers have explored analogous catalysts,
although not in microwave systems. Tonks
et al
.
investigated Heck reactions with palladium com-
plexes in ethylene glycol on porous glass beads
[144]. More recently, Clark and co-workers devel-
oped a Pd catalyst supported on a chemically modi-
fied mesoporous silica gel [145]. The metal did not
leach out and the catalyst could be reused at least
five times without a significant decrease in activity.
Turnover numbers were in excess of 2000. These
studies indicate the scope for further linking of
microwave technology and catalysis to develop new
clean processes.
9 Enzymatic Processes
Enzymes now are used widely in organic synthesis
to effect enantioselective chemical transformations
at moderate temperatures under relatively neutral
conditions. Microwave heating is attractive in that
regard, particularly with thermally stable enzymes
available through recombinant DNA technology and
immobilised on solid supports [7]. Carillo-Munoz
et
al
. resolved racemic 1-phenylethanol by selective
transesterification of isopropenyl acetate to leave
the
S
-isomer. They also transesterified racemic 1-
phenylethyl valerate enantioselectively to liberate
the
R
-isomer [146]. Model reactions of natural
hydrolytic processes brought about by phosphodi-
esterases and cellulases also have been investigated
and it was concluded that there was no particular
rate enhancement under microwave conditions
[147]. Parker
et al
. studied the rate of an enzyme-
catalysed esterification in organic solvent and found
