Direct Stereoselective Synthesis of Enantiomerically Pure anti-β-Amino Alcohols

GASTON SILVEIRA-DORTA, OSVALDO J. DONADEL, VÍCTOR S. MARTÍN AND JOSÉ M. PADRÓN

JOURNAL OF ORGANIC CHEMISTRY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2014 vol. 79 p. 6775 - 6782

0022-3263

Enantiomerically pure anti-β-amino alcohols were synthesized from optically pure α-(N,N-dibenzylamino)benzyl esters, derived from α-amino acids, by the sequential reduction to aldehyde with DIBAL-H at −78 °C and subsequent in situ addition of Grignard reagents. Besides anti-β-amino alcohols, anti-2-amino-1,3- and anti-3-amino-1,4-diols were obtained in good yields (60−95%) and excellent stereoselectivity (de > 95%). Our technique is compatible with free hydroxyl groups present in the substrate. To demonstrate the versatility of the method, spisulosine and sphinganine were synthesized in two steps from the appropriate N,N-dibenzyl-L-aminobenzyl ester in 42% and 45% yield, respectively. ABSTRACT: Enantiomerically pure anti-β-amino alcohols were synthesized from optically pure α-(N,N-dibenzylamino)benzyl esters, derived from α-amino acids, by the sequential reduction to aldehyde with DIBAL-H at −78 °C and subsequent in situ addition of Grignard reagents. Besides anti-β-amino alcohols, anti-2-amino-1,3-diols and anti-3-amino-1,4-diols were obtained in good yields (60−95%) and excellent stereoselectivity (de > 95%). Our technique is compatible with free hydroxyl groups present in the substrate. To demonstrate the versatility of the method, spisulosine and sphinganine were synthesized in two steps from the appropriate N,N-dibenzyl-L-aminobenzyl ester in 42% and 45% yield, respectively.