Issue Date: March 28, 2005
New Actor On The Diels-Alder Stage
The use of 1-hydrazinodienes in the Diels-Alder reaction is adding a new twist to the well-studied reaction: The cycloaddition product may be driven to rearrange, according to research by Princeton University chemistry professor Erik J. Sorensen. The new reactivity offers synthetic chemists a different way to plan the use of Diels-Alder reactions in complex syntheses. It also allows construction of complex bicyclic systems from easily made building blocks.
The cycloaddition of a nitrogen-protected 1-hydrazinodiene with an olefin forms the usual Diels-Alder product, according to Sorensen. When the groups on nitrogen are removed, the Diels-Alder product rearranges. Sorensen and his coworkers believe the rearrangement is triggered by an allylic diazene intermediate, which is not isolated or even observed. The rearrangement expels a nitrogen molecule and selectively forms a new stereocenter two carbon atoms away from the carbon atom that loses N2. In this way, Sorensen has shown that stereochemically complex cyclohexenes and bicyclic systems can be accessed through the Diels-Alder reaction more easily than through alternative strategies.
Sorensen plans to apply this chemistry to the synthesis of the antifungal natural product ilicicolin H. A key step in the first total synthesis of this compound is an intramolecular Diels-Alder reaction to stereoselectively construct a trans-decalin with four stereogenic centers. Although the reaction is straightforward, the polyunsaturated substrate is laborious to prepare, he told C&EN. He hopes to replace that reaction with an intermolecular Diels-Alder step using reactants that are much easier to prepare. With postdocs Glenn M. Sammis and Eric Flamme and graduate student Hao Xie, Sorensen has laid the foundation for this alternative approach through studies with a model system.
Although 1-hydrazinodienes are easy to prepare, they have not been described in the chemical literature before. Sorensen is preparing a manuscript describing the synthesis and reactivity of the new dienes. "Our aim is to contribute a family of 1-hydrazinodienes that can benefit chemists wishing to use the Diels-Alder reaction in novel ways."
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