Asymmetric synthesis of chiral diols by the catalytic enantioselective dialkylation of tere-, iso-, and phthalaldehydes and by a catalytic enantioselective autoinductive reaction

Absolute Autocatalytic Amplification Under Heterogenous Conditions Involving Subsequent Hydride Transfer and Hemiacetal Intermediate.

“…Chiral hemiacetals have been observed in intramolecular condensation of Zn-alkoxides as a result of a monoalkylation of dialdehyde with Et2Zn. [19] Further oxidation of hemiacetal would lead to the corresponding chiral ester. [20] More recent work revealed an intra-and intermolecular Claisen-Tishchenko catalyzed by metallic zinc, although achiral.…”

Enantioselective dialkylation of 1,2-phthalicdicarboxaldehyde

“…8,9 Under more forcing conditions, using the (1S,2R)-PHONE catalyst in the presence of Ti(O-iPr) 4 , the corresponding diol was formed, but although the enantiomeric purity of the C 2 -symmetric isomer was high (e.e. 92%) the meso diastereoisomer was the one formed in excess 8 (dl/meso ratio 9/91). This makes this route very unattractive from a synthetic point of view because the minor dl-isomer is the chiral target molecule.…”

“…Recently, this methodology has been applied to the synthesis of C 2 -symmetric diols derived from terephthaldehyde and isophthaldehyde using (1S,2R)-DBNE 1 or (1S,2R)-PHONE as catalyst precursors. 8 When 1,2-phthalicdicarboxaldehyde is used as the substrate, lactol 4 (see Scheme 1) is the major product, as a result of the in situ cyclization of the monoethylated alcohol. 8,9 Under more forcing conditions, using the (1S,2R)-PHONE catalyst in the presence of Ti(O-iPr) 4 , the corresponding diol was formed, but although the enantiomeric purity of the C 2 -symmetric isomer was high (e.e.…”

“…8 When 1,2-phthalicdicarboxaldehyde is used as the substrate, lactol 4 (see Scheme 1) is the major product, as a result of the in situ cyclization of the monoethylated alcohol. 8,9 Under more forcing conditions, using the (1S,2R)-PHONE catalyst in the presence of Ti(O-iPr) 4 , the corresponding diol was formed, but although the enantiomeric purity of the C 2 -symmetric isomer was high (e.e. 92%) the meso diastereoisomer was the one formed in excess 8 (dl/meso ratio 9/91).…”

“…The only product isolated after acidic work-up of these reaction mixtures was lactol 4, a phenomenon also observed by other authors. 8 Based on the above-mentioned observations, a twostep, one-pot procedure for the synthesis of diol 5 was developed (see Scheme 2). The first step involves the enantioselective addition of Et 2 Zn to 1,2-phthalicdicarboxaldehyde to give the EtZn-alkoxy derivative 4b.…”