Highly diastereoselective Mannich-type reaction of titanium enolate derived from 2′-hydroxypropiophenone

Mannich-type addition of the titanium enolate derived from 2′-hydroxypropiophenone to N-tosylimines provided the corresponding β-aminoketones in good to excellent yields (60%–90%) and with >99 : <1 anti diastereoselectivity. A model for synthesis of anti β-aminoketone as a predominant isomer based on the titanium enolate has been developed. High anti selectivity is not independent of the electron-donating and electron-withdrawing groups on the phenyl ring of the N-tosylimines. Noteworthy is the observation that the influence of a second Lewis acid on the Mannich-type reaction based on the titanium enolate is opposite to that obtained from other titanium enolates reported. A reasonable mechanism has been proposed to explain the high anti diastereoselectivity and the effect of a second Lewis acid on yield.