Axially chiral hemiaminals from nonracemic α-amino acid derivatives (thiohydantoins): Synthesis and isomer identification

Stable, nonracemic axially chiral hemiaminals (O,N-hemiacetals) have been synthesized stereoselectively from lithium aluminum hydride (LiAlH₄) reductions of nonracemic 5-methyl- and 5-isopropyl-3-(o-aryl)-2-thioydantoins in tetrahydrofuran (THF) at room temperature in 10 min. Predominantly S -configured hemiaminals at C-4 of the heterocyclic ring were produced from the S-configured thiohydantoins at C-5 (by 80% when the C5 substituent is methyl and by 97% when it is isopropyl). The configuration at C-5 was retained during the reduction reaction. The stereochemical outcome of the axially chiral hemiaminals resulted from their conformational preferences.