Ring fission of chiral cyclic acetals plus intramolecular [4 + 2] cycloaddition: a sequential access to medium-size lactones. Application to the synthesis of carbasugars.
A set of alpha,beta-unsaturated cyclic acetals were reacted with t-butyllithium in THF. A conjugate elimination took place, triggering a ketal ring cleavage when two eq. of TMEDA were added to the medium. The lithium alcoholate thus obtained could be trapped in situ by 2,2,2-trifluoroethyl acrylate. The resulting acryloyl (1Z,3E)-dienyl ether was then submitted to an intramolecular Diels-Alder cycloaddition under high pressure (12 kbar, 50 degrees C). Depending on the structure of the linkage between the diene and the acrylate, the expected ("fused") lactones were obtained with total endo- or exo-selectivities and high to complete diastereoselectivities. A remarkable inversion of selectivity, from endo to exo, with respect to the stereochemical elements of the tether could be observed in these cases. A five step diastereoselective transformation of two of the resulting nine-membered ring lactones into modified carbasugars was finally achieved in 23% overall yield.
Lemiègre
Loïc
L
Laboratoire des Fonctions Azotées & Oxygénées Complexes, IRCOF, UMR 6014 CNRS, Université de Rouen, 76821, Mont St Aignan Cedex, France.
Stevens
Richard L
RL
Combret
Jean-Claude
JC
Maddaluno
Jacques
J
D000080:Acetals / Q000737:chemistry*; D002241:Carbohydrates / Q000138:chemical synthesis*; D003500:Cyclization; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D013237:Stereoisomerism
D000080:Acetals; D002241:Carbohydrates; D007783:Lactones