Microwave-heated carbonylations

Palladium-catalysed coupling reactions under carbon monoxide have been extensively used in traditional medicinal chemistry72. Despite this, these crucial transformations have hardly been employed in combinatorial chemistry. These shortcomings have recently been recognised and a series of microwave-heated carbonylative transformations with solid or liquid CO-sources have been reported. 

Acylsulfonamides have important applications as carboxylic add bioisosteres in medidnal chemistry. Thus, it was of great interest to examine sulfonamides as nudeophiles in microwave-heated carbonylations. Starting from the conditions reported for the hydrazidocarbonylations, it was revealed that by simply changing the solvent from THF to 1,4-dioxane, aryl iodides and primary sulfonamides were... 

Another example of a one-pot indole synthesis, which proceeds through a Heck carbonylation and a Suzuki coupling, is shown below. The reaction conditions are similar to the previous example however microwave heating is employed [174] (Scheme 6.54). 

Mejla-Oneto and Padwa have explored intramolecular [3+2] cycloaddition reactions of push-pull dipoles across heteroaromatic jr-systems induced by microwave irradiation [465]. The push-pull dipoles were generated from the rhodium(II)-cata-lyzed reaction of a diazo imide precursor containing a tethered heteroaromatic ring. In the example shown in Scheme 6.276, microwave heating of a solution of the diazo imide precursor in dry benzene in the presence of a catalytic amount of rhodium I) pivalate and 4 A molecular sieves for 2 h at 70 °C produced a transient cyclic carbonyl ylide dipole, which spontaneously underwent cydoaddition across the tethered benzofuran Jt-system to form a pentacyclic structure related to alkaloids of the vindoline type. 

Gordon used a household microwave oven for the transfer hydrogenation of benz-aldehyde with (carbonyl)-chlorohydridotris-(triphenylphosphine)ruthenium(II) as catalyst and formic acid as hydrogen donor (Eq. 11.43) [61]. An improvement in the average catalytic activity from 280 to 6700 turnovers h-1 was achieved when the traditional reflux conditions were replaced by microwave heating. 

Scheme 2.29 depicts two of the first examples of microwave-assisted carbonylation reactions7. In these reactions, the temperature controls the rate of the CO release. Thus, during heating at 150°C in sealed vessels, carbon monoxide was smoothly emitted from the molybdenum carbonyl complex into the reaction mixture (Fig. 2.1, Profile A). As a result, aryl iodides and bromides underwent efficient amino carbonylation with non-hindered, aliphatic, primary and secondary amines in only 15 min, using Herrmann s palladacycle as pre-catalyst7 (Scheme 2.29). In contrast, at a reaction temperature of 210°C, carbon monoxide was liberated almost instantaneously (Fig. 2.1, Profile B).

The synthesis of the pyrazino[l,2-a]indole nucleus (64)/(65) was attained by intramolecular cyclization of several 2-carbonyl-1-propargylindoles (63) in the presence of ammonia. The reaction conditions were optimized using microwave heating and a... 

In addition, supported reagents have been demonstrated to be effective under reaction conditions when either thermal or microwave heating - is employed. They have also been utilised in traditional batch synthesis, stop-flow methods and continuous flow processes. ° However, one caveat is that the immobilisation of reagents can change their reactivity. For example, polymer-supported borohydride selectively reduces a,P-unsaturated carbonyl compounds to the a,P-unsaturated alcohoF in contrast to the behaviour of the solution-phase counterpart, which additionally causes double bond reduction. 

Selected Transition Metal Carbonyl Complexes Prepared by Microwave Heating... 

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