Study On Asymmetric Syntheses Of Chiral Acyloin Flavor Compounds

2-Hydroxy-5-methyl-3-hexanone and3-hydroxy-4-phenyl-2-butanone are importantacyloin chiral flavor compounds, which naturally occur in volatile components of manyfood and drinks and are used in various flavor formulations. Very few methods aboutasymmetric syntheses of these two flavors have been reported at present and the odorcharacteristics are still unknown. Optically active2-hydroxy-5-methyl-3-hexanone and3-hydroxy-4-phenyl-2-butanone were prepared by Shi’s asymmetric epoxidation andSharpless asymmetric dihydroxylation.The preparing methods of racemic and optically active2-hydroxy-5-methyl-3-hexanone were studied starting from5-methyl-3-hexanone through the oxidation of theintermediate silyl enol ether.5-methyl-3-hexanone was obtained in about68%yield byoxidizing5-methyl-3-hexanol with pyridium chlorochromate, which was synthesized byGrignard reaction of isovaleraldehyde with ethylmagnesium bromide in about80%yield.5-Methyl-3-hexanone was converted to the intermediate silyl enol ether through thereaction with Me3SiCl at the presence of base. The effects of various bases, such astriethylamine, lithium diisopropylamide, sodium bis(trimethylsilyl)amide (NaHMDS) andlithium diphenylamide, on regioselectivity and stereoselectivity during the formation ofsilyl enol ether were investigated. The results indicated that5-methyl-3-hexanone wasdeprotonated with NaHMDS in n-hexane with the highest regioselectivity. The ratio of thedesired product5-methyl-3-hexen-3-yl trimethylsilyl ether to the by-product5-methyl-2-hexen-3-yl trimethylsilyl ether reached7/1and the ratio of (E)-5-methyl-3-hexen-3-yl trimethylsilyl ether to the (Z)-isomer was7.5/1. The obtained silylenol ether was oxidized with m-chloroperoxybenzoic acid to give racemic2-hydroxy-5-methyl-3-hexanone in about77%yield. The products with the same absoluteconfiguration were obtained when the silyl enol ether was oxidized by Sharplessdihydroxylation reagent AD-mix-and AD-mix-. The fomer gave the product in about69.2%yield with15.7%ee, while the latter in about76.9%yield with75.6%ee. The silylenol ether was oxidized by Shi’s catalyst derived from D-fructose to produce the product inabout54%yield with74.6%ee with the same configuration as the Sharplessdihydroxylation method; while Shi’s catalyst derived from L-fructose gave the product inabout50%yield with72.8%ee with the opposite configuration. The absolute configurationof the products was tentatively assigned according to the Sharpless AD face selection rule. The product obtained by the catalyst from D-fructose was assigned to be R and L-fructosegave (S)-isomer.The preparing methods of racemic and optically active3-hydroxy-4-phenyl-2-butanone were studied starting from4-phenyl-2-butanone through the oxidation of theintermediate silyl enol ether.4-Phenyl-2-butanone was converted to the intermediate silylenol ether through the reaction with Me3SiI at the presence of hexamethyldisilazane. Theobtained silyl enol ether was oxidized with m-chloroperoxybenzoic acid to give racemic3-hydroxy-4-phenyl-2-butanone in about71%yield. The products were obtained with theopposite absolute configuration when the silyl enol ether was oxidized by Sharplessdihydroxylation reagent AD-mix-and AD-mix-. The fomer gave the product in about91%yield with62%ee, while the latter in about85%yield with80%ee. The silyl enolether was oxidized by Shi’s catalyst derived from D-fructose to produce the product inabout78%yield with76%ee with the same configuration as AD-mix-. The absoluteconfiguration of the products was tentatively assigned according to the Sharpless AD faceselection rule. The product obtained by AD-mix-and the catalyst from D-fructose wasassigned to be R.The odor properties of optically active3-hydroxy-4-phenyl-2-butanone wereevaluated by GC/O.(R)-3-hydroxy-4-phenyl-2-butanone presented a weak fruity and greenodor, no matter how it was prepared by Shi’s AE or Sharpless AD. By contrast,(S)-3-hydroxy-4-phenyl-2-butanone had a strong caramel, sweet and floral aroma, whichdisplayed stronger odor intensity than (R)-isomer. The results indicated that twoenantiomers had different organoleptic properties.