Practical asymmetric synthetic route to 4,4,4‐trifluoro‐3‐hydroxybutyrate: Head‐to‐tail and head‐to‐head crystallizations through double and single hydrogen bonds of hetero‐ and homochiral 4,4,4‐trifluoro‐3‐hydroxybutyrophenones

Abstract

A practical asymmetric synthetic route to 4,4,4-trifluoro-3-hydroxybutyrophenone and the butyric acid phenyl ester is described using heterochiral crystallization through double hydrogen bonding assembly in head-to-tail fashion and sequential Baeyer-Villiger oxidation reaction by trifluoroperacetic acid.

Intermolecular-medium and intramolecular-weak hydrogen bonding chains in the crystals of chiral trifluoromethylated amino alcohols

“…Thus, it cannot be purified optically by a simple recrystallization. A diastereomeric recrystallization or a chromatographic method is needed for its optical purification [7,8].…”

Chiral bifunctional thiourea-catalyzed enantioselective aldol reaction of trifluoroacetaldehyde hemiacetal with aromatic ketones

“…However, only several limited reports involved the asymmetric aldol condensation of trifluoroacetaldehyde and derivatives with ketones. Mikami et al presented the asymmetric aldol reaction of ketone-derived vinyl ethers or silyl enol ethers with trifluoroacetaldehyde catalyzed by a chiral binaphthol-derived titanium catalyst [13][14][15]. Funabiki and coworkers developed another asymmetric transformation of chiral ketimines with easily handling trifluoroacetaldehyde ethyl hemiacetal instead of trifluoroacetaldehyde gas [16][17][18][19].…”

“…Among the solvents tested, CH 2 Cl 2 was found to be the best with respect to catalytic activity and asymmetric induction. Subsequently, a preliminary screen of additives was carried out (Table 1, entries [11][12][13][14][15][16]. No reaction occurred in the presence of molecular sieves.…”

“…Surprisingly, no reaction was observed in the reaction of 1-naphthyl methyl ketone 2h with trifluoroacetaldehyde methyl hemiacetal ( Table 2, entries 11 vs. 4). The stereogenic center of 4,4,4-trifluoro-1-phenyl-3-hydroxy-1-butanones (3a), which was generated by 1a-catalyzed asymmetric aldol condensation of trifluoroacetaldehyde hemiacetal with 2a, was determined to be R by the comparison to the reported values such as the optical rotation and the retention time of HPLC using a chiral stationary phase [15][16][17][18][19]. The absolute stereochemistry of other products 3b-j was assigned on the basis of analogy with 3a studies.…”

“…The absolute configuration was assigned according to Refs. [15][16][17][18][19]. c 20 mol% of 1a was used.…”