Synthesis of medium-ring lactones via tandem methylenation/Claisen rearrangement of cyclic carbonates

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.…”

“…O grupo também relatou seus estudos sobre a reação seqüencial de olefinação/rearranjo de Claisen de carbonatos cíclicos 96,97 . A olefinação de carbonatos cíclicos de 6 e 7 membros, promovida pelo dimetiltitanoceno, levou à geração in situ dos respectivos ceteno-acetais, os quais, por sua vez, forneceram lactonas de 8 e 9 membros, através do rearranjo sigmatrópico [3,3] (Esquema 44).…”

Synthesis of (+)‐Obtusenyne

“…We have previously developed a highly efficient synthesis of nine-membered lactones from 2-deoxy-d-ribose and we decided to use this methodology for our second-generation approach to obtusenyne and for further model studies. [48,49] In part, this decision was taken because of the time-consuming kinetic resolution of the racemic epoxide (AE )-6 discussed above. The use of 2-deoxy-dribose as a starting material would ultimately give rise to a synthesis of non-natural (À)-obtusenyne ent-1; however, we pursued this synthetic route knowing that a number of efficient preparations of 2-deoxy-l-ribose have been reported, which would subsequently allow the synthesis of the natural enantiomer of 1.…”

“…The differentially protected lactone 43 would be prepared by the Claisen rearrangement of the ketene acetal 44 derived from the corresponding selenoxides which would, in turn, be available from 2-deoxy-d-ribose (45). We have previously reported the preparation of the chlorolactone (À)-42 [48] from 45, in which we had introduced the chlorine atom prior to medium-ring lactone formation. However, this route was not amenable to the production of gram quantities of the lactone (À)-42.…”

“…An efficient synthesis of the bis-tert-butyldiphenylsilylprotected lactone, corresponding to 43, from 45, has previously been disclosed [48,49] and the synthesis of the differentially protected lactone (À)-43 closely followed this route (Scheme 11).…”