Carbon-nitrogen bond formation conjugate addition

Reactions of organomagnesium compounds with nitroso or nitro compounds are often complicated, and not useful in synthesis, or only represented by isolated examples. One exception to this generalization involves conjugate addition to a,[3-unsaturated and aromatic nitro compounds (see Section 4.2), and two others lead to the formation of carbon-nitrogen bonds. 

The formation of asymmetric carbon-carbon and carbon-heteroatom bonds by lithiation-substitution at a carbon adjacent to nitrogen can be accomplished by deprotonations or des-tannylations, followed by reaction with electrophiles. Apphcations of these sequences for amine elaboration are summarized for reactions controlled by chiral hgands and chiral auxiliaries. Notable features include syntheses of alkaloids, the ability to make both enantiomers with a single chiral ligand and diastereoselective and enantioselective conjugate additions with benzylic and allylic lithiation intermediates. The sequences are classified, where information is available, in terms of stereocontrol in the lithiation or substitution step. 

In addition to solvolysis and nitrenium ion formation, Af-aLkoxy-A-chloroamides (2) also undergo bimolecular reactions with nucleophiles at nitrogen. Not only is the configuration destabilized by the anomeric effect, it also parallels that of a-halo ketones, where halogen on an sp carbon is activated towards reactions by the adjacent carbonyl. This rate-enhancing effect on 8 /2 processes at carbon is well-known, and has been attributed to conjugation of the p-orbital on carbon with the carbonyl jr-bond in the S 2 transition state stabilization of ionic character at the central carbon as outlined by Pross as weU as electrostatic attraction to the carbonyl carbon. The transition states are also affected by the nature of the nucleophile. ... 

---