Resolution of nitrogen-centered chiral tetraalkylammonium salts: application to [1,2] Stevens rearrangements with N-to-C chirality transmission

The resolution of N-chiral, amino acid-derived quaternary ammonium salts is demonstrated by using chiral BINOL as a complexing agent. Determination of the enantiopurities and absolute configurations of the resolved N-chiral tetraalkylammonium salts are described. The [1,2] Stevens rearrangement of N-chiral ammonium salts is shown to proceed with N-to-C chirality transmission to afford optically active 3-substituted morpholin-2-one derivatives.

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(R)-N-(tert-Butoxycarbonylmethyl)-N-(2-hydroxyethyl)-N-methyl-N-(2-methylbenzyl)ammonium bromideC17H28BrNO3Ee = 94%[α]58926=+13.3 (c 1.00, EtOH)Source of chirality: resolutionAbsolute configuration: (R)

(R)-N-(2-Hydroxyethyl)-N-(methoxycarbonylmethyl)-N-methyl-N-(2-methylbenzyl)ammonium bromideC14H22BrNO3Ee >95%[α]58924=+10.3 (c 1.00, EtOH)Source of chirality: resolutionAbsolute configuration: (R)

(S)-4-Methyl-3-(2-methylbenzyl)morpholin-2-oneC13H17NO2Ee = 60%[α]58922=+4.0 (c 1.00, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)