Grignard reagents Beckmann rearrangement

Pathway 2 of Scheme 9 corresponds to one of the most interesting developments in the Beckmann rearrangement chemistry. By trapping of the electrophilic intermediate with a nucleophile (Nu ) other than water, an imine derivative 227 is produced that may be used for further transformations. Carbon or heteroatom nucleophiles have been used to trap the nitrilium intermediate. Reducing agents promote the amine formation. More than one nucleophile may be added (for example, two different Grignard reagents can be introduced at the electrophilic carbon atom). Some of the most used transformations are condensed in Scheme 11. 

Grignard reagents may themselves be used to induce the Beckmann rearrangement, trapping the reactive intermediate. A new and highly efficient one-step synthesis of 2-arylated 1-benzocines 440 by a Beckmann rearrangement was recently devised (equation 187). 

BECKMANN REARRANGEMENT Grignard reagents. Phosphorus(V) oxide-Hexamcthyldisiloxane. Silica. Trialkylaluminum. 

Beckmann rearrangement.3 Reaction of oxime sulfonates with simple Grignard reagents in dry toluene at —78° results in imines, which can be reduced to a-alkylamincs or alkylated with allylic or propargylic Grignard reagents to furnish a,a-diulkylnmincs. 

Imidoyl iodides. Reaction of oxime mesylates (or carbonates) of ketones with (C2H5)2A11 effects Beckmann rearrangement to imidoyl iodides, which can be directly alkylated with Grignard reagents and then reduced (DIBAH) to a-alkylated amines. Examples ... 

Treatment of benzaldehyde oxime ether (166) with butyllithium (pentane/-10 C) demonstrates the complexity of the reaction (Scheme 32) as the desired alkoxyamine (167 R = Bu) is accompanied by other oxime-derived side products" (entry 1, Table 12). Selectivity is reagent/solvent dependent as allyl Grignard (ether)," allylzinc bromide (THF)," and butyllithium (THF)" treatment produce predominantly amine (171 R = allyl) (the Beckmann rearrangement derived product), alkoxyamine (167 R = allyl) (the oxime addition product) and ketone (169 R = Bu) (the nitrile-derived pro ct), respectively (entries 2-4, Table 12). 

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