Carbon-nitrogen bond formation electrophilic amination

Formation of Carbon-Nitrogen Bonds A ring closure of this type will most often involve either the attack of an electrolytically formed nucleophile (hydroxylamine, amine, or hydrazine) on an electrophilic center (existing or potential carbonyl, cyano, nitro, or nitroso group) or a reaction between a nucleophile and an electrolytically generated electrophilic center (e.g., nitroso group or carbonium ion). 

All animating reagents dealt with in this chapter are listed here references to their preparation are found in the section on Experimental Conditions. Stereochemistry is discussed in the relevant sections of Scope and Limitations. The term animation refers to the formation of a carbon-nitrogen bond, not just to the introduction of an amine group. For a quantum Monte Carlo study of electrophilic animation reagents see ref. 51. 

This methodology is also an important and potentially valuable method for C—N bond formation using the amination of carbon nucleophiles with electrophilic nitrogen transfer reagents (Scheme 1) Amination of ordinary carbanions and a-carbanion derived from carbonyl compounds and nitriles provides an important method for the synthesis of amines and a-amino carbonyl compounds and nitriles", respectively. For this purpose, a number of electrophilic amination reagents, which are synthetic equivalents of the R2N+ synthon, have been developed and the synthetic potential of electrophilic amination of carbon nucleophiles has been studied in detail . ... 

Amines are generally prepared by nucleophilic amination, which is a coupling of carbon electrophiles with a nucleophilic amination reagent, NR2, and Ni and Pd catalyzed reaction of aryl halides with arylamines (Hartwig-Buchwald amination) . Thus, the direct C—N bond formation between carbon nucleophiles and electrophilic nitrogen functionality R2N+ constitutes an example of the umpolung methodology. 

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. 

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