Synthesis of [2.2.2]-diazabicyclic ring systems
AssigneeCollege of William and Mary
InventorJonathan R. Scheerer
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Abstract
Herein we describe compositions and methods for the synthesis of [2.2.2]-diazabicyclic structures comprising a domino reaction sequence involving aldol condensation, alkene isomerization, and intramolecular hetero-Diels-Alder cycloaddition. Excellent diastereofacial control during the cycloaddition is enforced with a removable chiral phenyl aminal diketopiperazine substituent. The reaction sequence rapidly generates molecular complexity and is competent with both enolizable and non-enolizable aldehyde substrates. This method provides an efficient route to [2.2.2]-diazabicyclic structures, common to bioactive prenylated indole alkaloids such as the brevianamides and stephacidins.
Claims9
A process for preparing [2.2.2.]-diazabicyclic structures comprising:
- reacting a diketopiperazine, an aldehyde, and a substituted unsaturated hydrocarbon under basic conditions to perform a three-step reaction sequence comprising the following sequential steps:
- A) performing an aldol condensation,
- B) performing an alkene isomerization, and
- C) performing a Diels-Alder cycloaddition to form a [2.2.2.]-diazabicyclic structure;
- wherein said sequential aldol condensation, alkene isomerization, and Diels-Alder cycloaddition are performed in one reaction vessel without purification and isolation of the products between the sequential reaction steps.
Dependencies are inferred from the claim text.