Cycloadditions

Cycloadditions, which include the Diels-Alder, ene, and Alder-Bong reactions, are important single-step, ring-forming reactions in organic synthesis. These transformations usually require harsh conditions (high pressures and temperatures) and long reaction times. Diels-Alder cycloadditions were the first reaction types to be examined in conjunction with microwave irradiation.209-236,262 Giguere et al. showed one of the first examples of a microwave-induced Diels-Alder reaction in 1986 (Scheme 42).3 Irradiating anthracene and dimethyl fumarate in a multi-mode instrument at 600 W gave a complete reaction in 10 minutes compared to 72 hours with conventional heating.

Scheme 42

Majetich and Hicks have also shown successful Diels-Alder reactions.223 Both of the transformations shown in Schemes 43 and 44 were executed in DMF or in solvent-free conditions.

Scheme 43

Scheme 44

Microwave heating has also been used extensively in heterocyclic Diels-Alder reactions.224-236,263 These reactions are very important in synthetic chemistry, as they enable the synthesis of biologically significant nitrogen-, sulfur-, and oxygen-containing rings, which are usually difficult to achieve by standard methodology. Avalos et al. reacted 1,2-diaza-1,3-butadienes with diethyl azodicarboxylate (DEAD) to form functionalized tetrazines (Scheme 45).224 Under conventional heating, these reactions take 30 days for completion, whereas with microwave irradiation, they were performed in 15 minutes.

Scheme 45

The ene reaction is a reaction between and alkene and an enophile (analogous to a dienophile in a Diels-Alder reaction). A new C–C bond is formed, and the position of the original double bond shifts through a cyclic transition state. Intramolecular reactions are entropically more favorable, but they still require long reaction times to complete. One example of an intramolecular ene reaction is shown in Scheme 46.3 With microwave irradiation, this solvent-free reaction only took 15 minutes compared to 12 hours with conventional methods.

Scheme 46

The Alder-Bong reaction is another interesting cycloaddition reaction. In this particular reaction, an ene reaction is followed by an intramolecular Diels-Alder reaction. The Diels-Alder reaction proceeds rapidly, thus the intermediates formed from the ene reaction cannot be isolated. Scheme 47 shows a reaction between 1,4-cyclohexadiene and diethyl acetylene dicarboxylate.237 With conventional heating methods, this reaction takes 40 hours to complete. With microwave irradiation, it proceeds in 20 minutes, solvent-free.

Scheme 47

Instruments

Discover 2.0

Microwave Synthesizer

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