N-Iodosuccinimide-Promoted Selective Construction of Cyclopropyl and Dihydrofuranyl Spirooxindoles from Alkylidene Oxindoles and Annular β-Dicarbonyl Compounds

An efficient N-iodosuccinimide-promoted cyclization of readily available alkylidene oxindoles with annular β-dicarbonyl compounds has been demonstrated. With five-membered cyclic β-dicarbonyl compounds as the starting materials, a series of cyclopropyl oxindoles can be obtained in good to excellent yields, whereas it almost quantitatively affords dihydrofuranyl spirooxindoles when six- or seven-membered cyclic β-dicarbonyl compounds are employed. This protocol provides a new alternative to the practical synthesis of structurally diverse spirooxindoles.

A Practical Synthesis of Macrocyclic Schiff Base Bearing Hydroxyethyl Pendants Utilizing Solubility Discrepancies

Six macrocyclic Schiff bases bearing hydroxyethyl pendants have been synthesized in high yields via [2 + 2] condensation between the rigid dialdehydes and 2-[bis(2-aminoethyl)amino]ethanol or 1-[bis(2-aminoethyl)amino]-2-propanol at 0 oC for 12 hours in the CH3CN/H2O mixture. Solubility discrepancies between macrocyclic products and raw materials in selected solvents enable a facile separation and high yields, avoiding any intractable chromatographic purification. This straightforward synthetic protocol provides a relatively facile resolution with potential widespread applications for the synthesis of Schiff bases.

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

A simple and efficient method for α-brominating lactones that affords α-bromolactones under mild conditions using tetraalkylammonium hydroxide (R4N+OH−) as a base was developed. Lactones are ring-opened with Br2 and a substoichiometric amount of PBr3, leading to good yields of the corresponding α-bromocarboxylic acids. Subsequent intramolecular cyclization over 1 h using a two-phase system (H2O/CHCl3) containing R4N+OH− afforded α-bromo lactones in good yields. This method can be applied at the 10 mmol scale using simple operations. α-Bromo-δ-valerolactone, which is extremely reactive and difficult to isolate, could be isolated and stored in a freezer for about one week using the developed method. Optimizing the solvent for environmentally friendly large-scale syntheses revealed that methyl ethyl ketone (MEK) was as effective. In addition, in situ-generated α-bromo-δ-valerolactone was directly converted into a sulfur-substituted functional lactone without difficulty by reacting it with a sulfur nucleophile in one pot without isolation. This new bromination system is expected to facilitate the industrial use of α-bromolactones as important intermediates.

Development of a Practical Synthesis of the 8-FDC Fragment of OPC-167832

A concise and practical synthesis has been developed to provide the 8-fluoro-5-hydroxy-3,4-diydrocarbostyril (8-FDC) fragment of OPC-167832 in 41 % yield and in > 99 % purity over 4 steps from 3-amino-4-fluorophenol. The key feature of this process is the development of a telescoped one pot synthesis of the quinolone via a chemoselective amidation and easier product isolation without the need for a column chromatography.