Synthesis of fused bicyclic medium-ring lactones via Claisen rearrangement

Métodos de preparação de lactonas de anel médio

“…O rearranjo de ceteno-acetais vinil-e alquenil-substituídos, preparados in situ a partir de fenil seleno-acetais ou de carbonatos, vem sendo bastante explorado na síntese de lactonas de anel mé-dio, pelo grupo de Holmes e Burton [93][94][95][96][97][98] . Em 1997, foi relatada 93 a síntese assimétrica da (+)-laurencina, um éter cíclico de 8 membros.…”

“…Esta estratégia também foi aplicada com sucesso na síntese de lactonas bicíclicas 95 , conforme exemplos mostrados no Esquema 43.…”

Synthesis of (+)‐Obtusenyne

“…This strategy has successfully been employed in the synthesis of (+)-laurencin [6] and in the preparation of fused bicyclic mediumring ethers and lactones. [7] To test the scope of this Claisen rearrangement/methylenation methodology in the synthesis of other marine-ether natural products we selected (+)-obtusenyne as our synthetic target. [8] (+)-Obtusenyne ((+)-1) was independently isolated from L. obtusa by Imre [9] and Fenical and Clardy [10] and their respective co-workers.…”

“…We have used dimethyl titanocene [55,56] for the methylenation of numerous medium-ring lactones and chlorine-containing substrates. [6,7,48] However, exposure of the lactone (À)-52 to dimethyl titanocene in toluene at reflux provided the desired enol ether (À)-53 in rather low yield (17 %). Fortunately methylenation of the lactone (À)-52 could be achieved in good yield on treatment with the Tebbe reagent in THF at À50 8C (Scheme 12).…”

“…We have achieved monoprotection of 1,3-diols by cleavage of the corresponding p-methoxybenzylidene acetals with diisobutylaluminium hydride (see earlier). [6,7] Unfortunately, attempted regioselective cleavage of the acetal (À)-56 with diisobutylaluminium hydride only furnished the desired primary alcohol ((À)-69 see Scheme 17) in low yield (17 %); the primary silicon protecting group in (À)-56 was found to be labile under the reaction conditions, resulting in a poor yield of the desired primary alcohol. Subsequently, an orthogonal protection-deprotection strategy was employed to furnish the desired primary alcohol (À)-69 in good overall yield.…”