Base-Promoted Rearrangement of 1,5-Dibromopentacyclo[5.3.0.02,5.03,9.04,8]decane-6,10-dione: Easy Entry of a Novel Cage System, 10-Oxa-9-oxopentacyclo[5.3.0.02,4.03,6.05,8]decane

Abstract

The Diels-Alder dimerization of 2-bromo-2,4-cyclopentadienone ethylene acetal (2) gave endo-2,7-dibromodicyclopentadiene-1,8-dione 1,8-bis (ethylene acetal) (3) as a minor product in a 4.5% yield. Ultraviolet irradiation of 5 led to dimerization product 7. Deacetalization was accomplished by treating with concentrated sulfuric acid to give 1,5-dibromopentacyclo[5.3.0.02,5.03,9.04,8]decane-6,10-dione (9). Compound 9 was converted into a new cage system, 10-oxa-9-oxopentacyclo[5.3.0.02,4.03,6.05,8]decane, in a high yield by treating with 5% aqueous potassium hydroxide at 80 °C.

Pilot-Scale Production of Dimethyl 1,4-Cubanedicarboxylate

“…Indeed, this sequence was demonstrated enabling the isolation of the bisketal 10 in high purity and in good overall yields of ∼80% (see Supporting Information). In this work, no attempt was made to remove the minor stereoisomer of 10 , 14 , that is also produced during this process . Finally, it is worth noting that the first (i.e., fastest) dehydobromination is that which gives the dibromide 15 , and that this reaction proceeds rapidly at ambient temperatures.…”

Wie der Würfel wirkt

“…6) Sie nutzten die Reaktivität von Cyclobutadien-Eisen-Tricarbonyl in Gegenwart bromierter Chinone, die das tricyclische Molekül (6) durch eine Diels-Alder-Reaktion liefern. Die [2+2]-Cycloaddition unter photochemischen Bedingungen ergibt die C2-symmetrische Verbindung (7). Sie wird unter basischen Bedingungen einer Favorskii-Umlagerung unterzogen, wobei (8) in 80 % Ausbeute entsteht (Abbildung 2B).…”

“…Die Methode für den Zugang zu 1,2-Dicarbonylcubanen geht von der Monosäure (9) aus und nutzt eine dirigierende Metallierungsstrategie. 7) Die Umwandlung von (9) in das entsprechende Amid (10) ermöglicht, mit TMP-Basen zu β-metallieren. Elektrophiles Abfangen der dabei entstehenden Spezies mit CO 2 liefert (11) in 12 % Ausbeute (Abbildung 2C).…”

Cubanes in Medicinal Chemistry

“…Access to 1,2-disubstituted cubanes occurs through neighboring group participation, namely, using the ortho -lithiation approach (Scheme ). Lithiation of amide 104 , simply derived from acid 11 and a variety of amines with LiTMP, affords lithiated intermediate 105 that can be treated with an electrophile, e.g., CO 2 to afford the 2-substituted acid 106 . Originally the diisopropyl amide (R = i Pr) was used, which requires aggressive conditions to further manipulate (e.g., LiAlH 4 followed by DMDO for conversion to a carboxylic acid), but other amide examples also exist .…”

“…The authors then converted 117 into 110 following their procedures for the 1,4-disubstituted series, though again no details were provided. Utilizing 118 , which is obtained as a minor byproduct (4.5%) from the debromination and dimerization of 5 , conditions for the formation of 110 were provided. These involved a ring contraction to 119 , followed by deprotection to 120 , which then allows for a second ring contraction to give 110 .…”