Regioselective Reduction of NAD+ Models with [Cp*Rh(bpy)H]+: Structure-Activity Relationships and Mechanistic Aspects in the Formation of the 1,4-NADH Derivatives

The hydride transfer mechanism of the NAD+ model compound 1 to its 1,4-NADH derivative 3 [Eq. (1)] is proposed to be a consequence of the critical role of the carbonyl group of the amide to coordinate to the ring-slipped η5- to η3-Cp*Rh metal center of the catalyst [Cp*Rh(bpy)H]+, prepared in situ from 2, while a steric effect of a substituent in the 3 position, for example, C(O)NEt2, was found to totally inhibit this regioselective reduction. bpy=2,2′-bipyridine, Cp*=C5Me5, OTf=trifluoromethanesulfanate.