N-Thioacyl 1,3-amino alcohols were synthesized via the ring-opening of oxiranes with thioamide dianions generated from N-benzyl thioamides and BuLi in a highly regio- and stereoselective manner. The diastereomers of N-thioacyl 1,3-amino alcohols were readily separated by column chromatography to give stereochemically defined N-thioacyl 1,3-amino alcohols. They underwent intramolecular cyclization with Bu4F and EtI to give 5,6-dihydro-4H-1,3-oxazines. The reaction was specific with anti-N-thioacyl 1,3-amino alcohols, and cis-5,6-dihydro-4H-1,3-oxazines were obtained with high efficiency, whereas the reaction of a syn-alcohol gave a thioimidate as a major product. The reduction of N-thioacyl 1,3-amino alcohols with LiAlH4gave N-alkyl 1,3-amino alcohols in high yields. The use of optically active propylene oxide as a starting material gave the corresponding oxazine and alcohols in optically pure forms.
Thioamide dianions were generated by the highly efficient reaction of N-benzyl thioamides with 2 equiv of BuLi. Alkylation, allylation, and silylation took place selectively at the carbon atom adjacent to the nitrogen atom of the thioamide dianions. Oxiranes and an aldehyde were also used as electrophiles in the reaction of thioamide dianions to form N-thioacyl 1,3- or 1,2-amino alcohols. The insertion reaction of elemental sulfur to a thioamide dianion and subsequent ethylation afforded a N-thioacyl hemithioaminal. NMR studies on the thioamide mono- and dianions derived from N-benzyl 2-methoxythiobenzamide showed a linear relationship between the chemical shifts of all carbon atoms of thioamide mono- and dianions. The results also suggested that the negative charge at the benzylic carbon atom of the dianion is not fully delocalized. The charge distribution patterns of the dianion are consistent with those of pi polarization.
Thioamides. -Thioamide dianions, like the isolable representative (XIX), are generated by reaction of N-benzyl thioamides with two equivalents of BuLi. Alkylation, allylation and silylation proceeds regioselectively at the carbon adjacent to the nitrogen atom of the dianions. By reaction of oxiranes with the dianions, ring-opening occurs. The dianion of amide (Ia) also reacts with elemental sulfur as electrophile to afford N-thioacyl hemithioaminal (XVI) as major product after addition of Et-I. In addition, NMR studies on the thioamide dianion (XIX) and its corresponding monoanion are made. The results suggest that the negative charge at the benzylic carbon atom of the dianion is not fully delocalized. -(MURAI*, T.; ASO, H.; TATEMATSU, Y.; ITOH, Y.; NIWA, H.; KATO, S.; J. Org. Chem. 68 (2003) 22, 8514-8519; Dep. Chem., Fac. Eng., Gifu Univ., Yanagido, Gifu 501-11, Japan; Eng.) -Klein 10-090 2004 Carboxylic amides
Amino alcohols Q 0240N-Thioacyl 1,3-Amino Alcohols: Synthesis via Ring-Opening of Oxiranes with Thioamide Dianions and Applications as Key Intermediates Leading to Stereochemically Defined 5,6-Dihydro-4H-1,3-oxazines and 1,3-Amino Alcohols. -The method offers a new and highly regio-and stereoselective approach to N-thioacyl 1,3-amino alcohols. They can smoothly be converted into N-alkyl 1,3-amino alcohols such as (V) and (XXI). Furthermore, the anti isomers undergo intramolecular cyclization as an efficient route to stereochemically defined 5,6-dihydro-1,3-oxazines. -(MURAI*, T.; SANO, H.; KAWAI, H.; ASO, H.; SHIBAHARA, F.; J. Org. Chem. 70 (2005) 20, 8148-8153; Dep. Chem., Fac. Eng., Gifu Univ., Yanagido, Gifu 501-11, Japan; Eng.) -Jannicke 04-065
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