4-Fluoro and 4-Hydroxy Pyrrolidine-thioxotetrahydropyrimidinones: Organocatalysts for Green Asymmetric Transformations in Brine

Abstract

The synthesis of both trans- and cis-diastereomers of pyrrolidinine-thioxotetrahydropyrimidinone bearing either a fluorine or a hydroxyl group was accomplished. The new compounds were tested for their catalytic properties in a variety of asymmetric organic transformations and compared with the first generation catalyst. It was found that the new catalysts could efficiently catalyze the reactions in brine, without the use of organic solvent, and by employing an almost stoichiometric amount of reagents. Thus, the products were isolated by simple extractions, avoiding the use of chromatography in excellent yields, diastereoselectivities, and enantioselectivities.

Green Asymmetric Organocatalysis

“…Kokotos et al. applied novel 4‐fluoropyrrolidine–thioxotetrahydropyrimidinone catalyst C98 to this reaction, which was conducted in brine . The best results were achieved with respect to reaction yield and diastereoselectivity.…”

Organocatalyzed Synthesis of [3.2.1] Bicyclooctanes

“…They observed that 1,4-cyclohexadienone with catalyst 16 with phenylnitrodiene gave the corresponding bicyclic compound in 48% yield, excellent diastereoselectivity (dr > 99:1) and a 97% ee [40]. …”

Recent Advances in Asymmetric Organocatalyzed Conjugate Additions to Nitroalkenes

“…Not only aromatic nitroalkenes with electron-withdrawing and electron-donating substituents were suitable electrophiles, but also some aliphatic nitroalkenes and aromatic nitrodienes were successfully used as Michael acceptors. The use of brine and the possibility of reducing the reagent ratio to almost stoichiometric values by using catalyst 52 made this protocol green and effective [ 80 ].…”