Ring fission of chiral cyclic acetals plus intramolecular [4 + 2] cycloaddition: a sequential access to medium-size lactones. Application to the synthesis of carbasugars

Abstract

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.

A fully enzymatic esterification/transesterification sequence for the preparation of symmetrical and unsymmetrical trehalose diacyl conjugates

“…Lipase mediated transesterifications are dramatically improved when the starting ester is derived from vinyl or 2,2,2-trifluoroethyl moieties for instance. Among them we have chosen to work on 2,2,2-trifluoroethyl esters due to the availability 2,2,2-trifluoroethanol and their common use as acyl donor in enzymatic 13,[32][33][34] and non-enzymatic 35 transesterification reactions. These esters are classically prepared by reaction of 2,2,2-trifluoroethanol on activated carboxylic acid derivative such as acyl chloride or anhydride, or using Steglich esterification conditions (DCC/DMAP).…”

High pressure in organic chemistry on the way to miniaturization

“…101 More examples of Diels-Alder reactions affected by high pressure, when catalysts are involved, are summarized in several papers. [102][103][104][105][106][107][108][109] Other researchers have used high pressure for the synthesis of Diels-Alder cycloadducts in a regio-and stereoselective manner. 85,99,106,[110][111][112][113][114][115][116] In solid phase organic synthesis, high pressure conditions eliminate the need for stirring and heating, which can damage the resin, and also eliminate the use of a catalyst, which may deposit residues in the polymeric matrix.…”

Desymmetrization of a meso-Allylic Acetal by Enantioselective Conjugate Elimination

“…When applied to cyclic acetals, this reaction afforded a diene prolonged by an hydroxyalkyl chain (Scheme ) . We took advantage of this functional bonus by quenching directly the intermediate alkoxide with acryloyl chloride for instance.…”