Asymmetric synthesis of β-hydroxy-β-trifluoromethylated ketones via in situ generation of trifluoroacetaldehyde and its asymmetric carbon–carbon bond formation reaction with chiral imines in aqueous media

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

“…Chemical shifts were reported in ppm down field from internal Me 4 Si. 19 F NMR (376 MHz) spectra were recorded on a Bruker ARX400 instrument in CDCl 3 solutions using CFCl 3 as the internal standard. HPLC analyses were carried out on a Hewlett Packard Model HP 1200 instrument.…”

“…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]. In addition, several research groups also disclosed the asymmetric aldol condensations of (a)cyclo alkyl ketones with trifluoroacetaldehyde hemiacetal by the use of chiral organocatalysts [20][21][22][23].…”

“…The water might accelerate the reaction by facilitating the interconversion of the different intermediates of the catalytic cycle. Further optimization of temperature, the loading of the additive and the catalyst was finished (Table 1, entries [17][18][19][20][21][22][23][24][25]. The good results were attained when 15 mol% of thiourea 1a and 5 mol% of H 2 O were employed at room temperature.…”

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

“…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.…”