Synthesis 2017; 49(17): 3874-3884
DOI: 10.1055/s-0036-1590812
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© Georg Thieme Verlag Stuttgart · New York

Formation of Bicyclic Cyclopentenone Derivatives by Robinson-Type Annulation of Cyclic β-Oxoesters Containing a 1,4-Diketone Moiety

Irina Geibel
Institut für Chemie, Carl von Ossietzky Universität Oldenburg, 26111 Oldenburg, Germany   Email: jens.christoffers@uol.de
,
Christoph Kahrs
Institut für Chemie, Carl von Ossietzky Universität Oldenburg, 26111 Oldenburg, Germany   Email: jens.christoffers@uol.de
,
Jens Christoffers*
Institut für Chemie, Carl von Ossietzky Universität Oldenburg, 26111 Oldenburg, Germany   Email: jens.christoffers@uol.de
› Author Affiliations
Further Information

Publication History

Received: 03 May 2017

Accepted: 31 May 2017

Publication Date:
25 July 2017 (online)


Abstract

Robinson-type cyclopentannulations of cyclic β-oxoesters possessing a 1,4-diketone moiety are accomplished under four different Brønsted basic reaction conditions. Using pyrrolidine/acetic acid in DMSO, an oxohexahydrocyclopenta[a]indene (42%) and an N-Boc-protected oxohexahydrocyclopenta[c]pyridine derivative (62%) are obtained with retention of the ester moieties. The latter compound defines an interesting new scaffold for medicinal chemistry with three positions allowing further derivatizations. The use of KOtBu in DMSO or NaH in toluene leads to cyclopentene derivatives with either partial ester saponification and decarboxylation or displacement of the ester moiety within the carbon skeleton. With aqueous KOH, the cyclopentannulations are successful in almost all cases, but with the ester moieties cleaved off. The respective bicyclic and tricyclic products are obtained in good to excellent yields. The 1,4-diketone starting materials are prepared by cerium-catalyzed oxidative coupling of β-oxoesters with isopropenyl acetate. Alternatively, a two-step sequence consisting of α-propargylation followed by palladium-catalyzed alkyne hydration is used.

Supporting Information

 
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