Transformation of Amino Acids into Nonracemic 1-(Heteroaryl)ethanamines by the Enamino Ketone Methodology

• Published in: Helvetica chimica acta Vol. 89; no. 1; pp. 30 - 44
• Main Authors: Pirc, Samo, Bevk, David, Golobič, Amalija, Stanovnik, Branko, Svete, Jurij
• Format: Journal Article
• Language: English
• Published: Zürich WILEY-VCH Verlag 01.01.2006; WILEY‐VCH Verlag; Wiley
• Subjects: Amines; Amines, chiral; Amino acids; Chemistry; Chemistry, Multidisciplinary; chiral; Cylization recations; enamino; Ethanamines; Ketones; Ketones, enamino; Physical Sciences; Science & Technology; CATALYTIC BORANE REDUCTIONS; HETEROCYCLES; ACHIRAL KETONES; CYCLOADDITIONS; STEREOSELECTIVE-SYNTHESIS; ENANTIOSELECTIVE ADDITION; APLYSINOPSIN ANALOGS; DERIVATIVES; SOLUTION-PHASE SYNTHESIS; 3-(DIMETHYLAMINO)PROPENOATES
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/hlca.200690010

N‐Protected L‐phenylalanines 1a,b were transformed, via the corresponding Weinreb amides 2 and ethynyl ketones 3, into chiral enamino ketones 4 (Scheme 1). Similarly, L‐threonine 6 was transformed in four steps into the enamino ketone 10. Cyclocondensations of 4 and 10 with pyrazolamines 11, benzenecarboximidamide (12), and hydrazine derivatives 18 afforded N‐protected 1‐heteroaryl‐2‐phenylethanamines 15a–e, 16, 17, and 21a–k and 1‐heteroaryl‐1‐aminopropan‐2‐ols 23a,b in good yields (Schemes 2 and 3). Finally, deprotection by catalytic hydrogenation furnished free amines 22a–g and 24a,b (Scheme 3).