Nitro-Mannich reaction/lactamization

Additions of stabilized carbanions to imines and hydrazones, respectively, have been used to initiate domino 1,2-addition/cyclization reactions. Thus, as described by Benetti and coworkers, 2-subshtuted 3-nitropyrrolidines are accessible via a nitro-Mannich (aza-Henry)/SN-type process [165]. Enders research group established a 1,2-addition/lactamization sequence using their well-known SAMP/ RAMP-hydrazones 2-308 and lithiated o-toluamides 2-307 as substrates to afford the lactams 2-309 in excellent diastereoselectivity (Scheme 2.72) [166]. These compounds can be further transformed into valuable, almost enantiopure, dihydro-2H-isoquinolin-l-ones, as well as dihydro- and tetrahydroisoquinolines. 

In addition, a four-component domino Michael/nitro-Mannich/lactamization reaction was recently developed by Dixon et al. [286]. It occurred between a... 

Scheme 14.13 Dixon s synthesis of manzamine A (82) via domino nitro-Mannich reac-tion/lactamization and reductive nitro-Mannich domino reaction.

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