Efficient entry to the [2.2.2]-diazabicyclic ring system via diastereoselective domino reaction sequence

Organic Letters
Kaila A MargreyJonathan R Scheerer

Abstract

A domino reaction sequence involving aldol condensation, alkene isomerization, and intramolecular hetero-Diels-Alder cycloaddition for the synthesis of [2.2.2]-diazabicyclic structures is reported. 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 nonenolizable aldehyde substrates (nine examples total). Progress toward the synthesis of malbrancheamide B, a protypical member of the [2.2.2]-diazabicyclic natural product family, is also disclosed.

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Citations

Dec 13, 2012·Magnetic Resonance in Chemistry : MRC·Shivani Mahajan, Inder Pal Singh
Jan 31, 2013·The Journal of Organic Chemistry·Stephen W Laws, Jonathan R Scheerer
Jan 31, 2014·Organic Letters·Kaila A MargreyJonathan R Scheerer

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