Synthesis of novel optically pure quinolyl-β-amino alcohol derivatives from 2-amino thiophenol and chiral α-acetylenic ketones and their IBX-mediated oxidative cleavage to N-Boc quinolyl carboxamides

• Published in: Tetrahedron: asymmetry 2001-07, Vol.12 (13), p.1851-1863
• Main Authors: Cabarrocas, Gemma, Ventura, Montserrat, Maestro, Miguel, Mahı́a, José, Villalgordo, José M.
• Format: Article
• Language: English
• ISSN: 0957-4166; 1362-511X
• DOI: 10.1016/S0957-4166(01)00308-1

A methodology directed toward the stereoselective synthesis of novel quinolyl glycines is presented. This strategy is based on the cyclocondensation reaction between 2-amino thiophenol 4 and chiral acetylenic ketones of the type 3 containing a latent α-amino acid functionality. The initially formed benzo[ b][1,4]thiazepine derivatives 5, readily undergo sulphur extrusion in refluxing toluene to yield the corresponding 2,4-disubstituted quinolines 6. Subsequent oxazolidine ring opening followed by in situ re-protection of the amino group afforded the corresponding quinolyl-β-amino alcohols 8a– 8f in enantiomerically pure form and good overall yields. The derivatives 8 are in principle suitable precursors for the synthesis of novel optically pure quinolyl glycines through oxidation of the alcohol side chain. However, these amino alcohol derivatives 8, did not afford the expected quinolyl glycines 10 using numerous oxidising agents and reaction conditions. Instead, by reacting 8 with the mild oxidising reagent IBX 11, an oxidative CC cleavage leading to the N-Boc quinolyl carboxamides 12 took place. Graphic