anti-Selective enolboration–aldolization of propanoic acid

The Enediolate Chemistry of Free Carboxylic Acids

“…Applying similar reagent, dicyclohexylbromoborane/triethylamine, Ramachandran group successfully enolized propanoic acid for aldol reaction with aldehydes affording anti-hydroxy acids selectively in high yields (Scheme 13B). [28] The diastereoselectivity was dependent on the aldehyde sterics and electronics. When benzaldehyde was used as substrate, the corresponding product was obtained in 92% yield, and the diastereoselectivity (syn:anti = 14 : 86) slightly improved compared with the previous example using dicyclopentylboryltriflate/DPEA (syn:anti = 20 : 80).…”

Diastereoselective synthesis of anti -3-hydroxy-2-trifluoromethyl carboxylic acids

“…However, the yield of aldol products was very poor (30%, Table 3, entry 5), very similar to the enolization-aldolization of the hydrocarbon analog in THF. 9 Improved yield was realized by warming the reaction from À78°C to À40°C and extending the reaction time to 3 h each, for the enolization and aldolization (Condition E, Table 3, entry 6).…”

“…9 The use of haloboranes has positive advantages over boron triflates during the bicarbonate workup and purification of the aldol, in that triflic acid contamination can be circumvented. The reaction afforded antihydroxy acids selectively in very high yields.…”

“…In contrast, the same protocol was instrumental in providing up to 97% anti-diastereoselectivity (ds) for the hydrocarbon analog. 9 A systematic investigation was begun in search of the conditions for exclusive syn-or anti-diastereoselection during the aldol reaction of 1. The boron reagent, solvent, and reaction temperature were all targeted to achieve the goal ( Table 1).…”

Chemoselective Boron-Catalyzed Nucleophilic Activation of Carboxylic Acids for Mannich-Type Reactions

“…We began our study inspired by the pioneering work of Evans, who used unsaturated diborondiolates, generated from propionic acid, 2 equiv of R 2 BOTf (R = n -butyl or cyclohexyl), and i Pr 2 NEt at 0 °C, in aldol reactions with benzaldehyde at −78 °C. The corresponding aldol adducts were obtained in high yield and moderate diastereoselectivity (87% yield, syn / anti = 35/65–20/80).…”