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

Abstract

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).