Scope and limitations of the nitro-Mannich reaction for the stereoselective synthesis of 1,2-diamines.
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 range of heteroaromatic and simple aliphatic aldimines gave anti-rich (approximately 3-19:1) 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.
Anderson
James C
JC
School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, United Kingdom. j.anderson@nottingham.ac.uk
Blake
Alexander J
AJ
Howell
Gareth P
GP
Wilson
Claire
C