α-Arylation of Cyclic Amines by Aryl Transfer in Lithiated Ureas

Abstract

Treatment with base of N¢-aryl urea derivatives of hetero-or carbocyclic amines with benzylic nitrogen atoms promotes rearrangement with transfer of the aryl ring from N to C, giving rise to a-arylated products.

Modern Aspects of the Smiles Rearrangement

“…Subsequently, α‐pyridylation of chiral amines was also reported using this method . The reaction was also applied to cyclic amines; secondary amines (tetrahydroisoquinoline) readily underwent aryl migration under standard conditions whereas addition of DMPU was required to affect benzylic lithiation for the more hindered tertiary amines …”

“…[51] The reaction was also appliedt oc yclic amines;s econdary amines (tetrahydroisoquinoline) readily underwent aryl migration under standard conditions whereas additiono fD MPU was required to affect benzylic lithiation for the more hindered tertiary amines. [52] Ad eprotonation, rearrangement cascade sequence was demonstrated with N-allyl ureas 121 (Scheme 36). [53] Initial Claydenr earrangement of 121 gave 122,w ith the double bond moving into conjugation after as econd lithiation/protonation.P alladium-catalyzedN -arylation formed urea 123, which underwent stereoselective deprotonation with ac hiral lithium amine, then asecond nitrogen-to-carbona ryl migration to give diaryl allyl amines 124 with excellent enantiomeric ratio.…”