10.1021/op500386g
The study outlines an efficient and practical synthesis process for ramelteon, a sedative-hypnotic drug used for treating insomnia. The novel synthesis involves the use of acetonitrile as a nucleophilic reagent to add to 4,5-dibromo-1,2,6,7-tetrahydro-8H-indeno[5,4b]furan-8-one, followed by a catalytic hydrogenation step that合并了debromination, dehydration, olefin reduction, and cyano reduction into one operation, resulting in the ethylamine compound. The process utilizes dibenzoyl-L-tartaric acid for salt formation and as a resolution agent, leading to the target compound ramelteon with an overall yield nearly double that of existing methods. The study emphasizes the avoidance of the traditional Wittig-Horner reaction, simplifying the synthesis with cost-effective reagents and reduced reaction steps.
10.1039/a809715a
The researchers synthesized various SuperQuat auxiliaries, including 5,5-dimethyl and 5,5-diphenyl derivatives, and compared their performance in enolate alkylation reactions. They found that the 4-isopropyl-5,5-dimethyl SuperQuat provided superior results, achieving high yields and excellent diastereoselectivities. This was attributed to the geminal dimethyl groups at the 5-C position, which suppressed endocyclic cleavage pathways and improved the stability and reactivity of the enolates. The study concluded that the 5,5-dimethyl-4-isopropyloxazolidin-2-one is an effective chiral auxiliary for asymmetric enolate alkylations, offering a robust alternative to the Evans' auxiliary for large-scale synthesis. Key chemicals used in the process included n-butyllithium, propionyl chloride, benzyl bromide, and various α-amino acids for the synthesis of the SuperQuat auxiliaries.