Scope and limitations of the nitro-Mannich reaction for the stereoselective synthesis of 1,2-diamines

DIAGRAM The acetic acid-promoted addition of lithium nitropropanate and the Lewis acid-catalyzed [Sc-(OTf)(3), Cu(OTf)(2), or Ti(OiPr)(4)] addition of trimethylsilyl nitropropanate to a rang of heteroaromatic and simple aliphatic aldimines gave anti-rich (similar to3-19:1) beta-nitroamines in > 95 % yields as the kinetic products. It was found that a nonpolar N-imine protecting group was essential for reactivity with the o-methoxybenzyl (OMB) group giving better selectivities and yields than p-methoxybenzyl (PMB) or p-methoxyphenyl (PMP) in the Lewis acid-catalyzed addition reactions. Reduction with SmI2, treatment with COCl2, followed by OMB deprotection gave diastereomerically pure cis-imidazolidinones in 55-79 % overall yield from imine. Preliminary results have shown that acetic acid can catalyze the reaction of N-OMB-benzylideneamine with nitropropane, used as solvent.. to give the thermodynamically more stable syn-beta-nitroamine product.