10.1002/ejoc.200901283
The study investigates the development of highly efficient aminal–pyrrolidine organocatalysts for the α-functionalization of carbonyl compounds. Researchers synthesized a series of catalysts by substituting the 4-position of hydroxyproline with a phenol group and incorporating an aminal on the 2-position. These catalysts demonstrated excellent enantiocontrol in the α-functionalization of a wide range of linear and branched aldehydes and ketones, including Michael additions to ethenediyl disulfones or nitrostyrene and α-amination. The introduction of a 4-phenoxy group on the pyrrolidine ring further enhanced the steric hindrance, leading to improved reactivity and selectivity. The catalysts achieved enantioselectivities up to 98.5% with low catalyst loadings (down to 1 mol-%) and turnover frequencies (TOFs) of up to 1000 h–1. The study highlights the modular nature of these catalysts, allowing for tunability by changing the diamine substituent, and their potential for industrial applications due to their high efficiency and selectivity in various organocatalytic reactions.
10.1016/j.tetlet.2013.02.029
The research presents an innovative and efficient method for the asymmetric synthesis of (?)-venlafaxine, an antidepressant drug. The purpose of this study was to develop a practical and environmentally friendly approach to synthesize (?)-venlafaxine using an organocatalyst derived from L-proline, overcoming the limitations of previous methods that either used expensive, environmentally hazardous catalysts or resulted in significant material loss. The synthesis strategy involved several key steps: an asymmetric organocatalytic Michael addition of cyclohexanone to nitrostyrene using the L-proline-based catalyst to form the core structure, followed by selective reductions and transformations to introduce the tertiary hydroxyl group and the N,N-dimethyl group. The final product, (?)-venlafaxine, was obtained with high enantiomeric purity (≥99% ee) and in good yield (60%). The key chemicals used included L-proline for the organocatalyst, nitrostyrene synthesized from anisaldehyde and nitromethane, and various reagents for selective reductions and functional group transformations such as NaBH4, NiCl2·6H2O, benzyl chloroformate (Cbz-Cl), and lithium aluminum hydride. The study concludes that this method provides a concise and efficient route to synthesize (?)-venlafaxine from readily available starting materials, and by using different enantiomers of the proline-based catalyst, both enantiomers of venlafaxine can be accessed without material loss. This approach not only enhances the practicality of venlafaxine synthesis but also aligns with green chemistry principles by avoiding the use of hazardous catalysts.
10.1016/j.tetasy.2008.09.030
The research investigates the development of a new and easy synthesis of chiral bifunctional organic catalysts obtained by combining (S)-t-leucine derivatives with (1R,2R)-trans-1,2-diamino-cyclohexane. Acetylacetone (also known as 2,4-pentanedione) is a β-diketone with the molecular formula C5H8O2. It is a colorless liquid with a characteristic odor and is commonly used as a ligand in coordination chemistry and as a precursor in organic synthesis. In this study, acetylacetone serves as the nucleophile in the model reaction. Nitrostyrene is an aromatic compound with a nitro group attached to a styrene backbone. The specific isomer used in this research is trans-b-nitrostyrene, which has the nitro group and the vinyl group in a trans configuration. The molecular formula for nitrostyrene is C8H7NO2. In the context of this study, nitrostyrene acts as the electrophile in the model reaction.
