Design and Synthesis of New Chiral Amino Alcohols and Their Application in the Asymmetric Borane Reduction of Prochiral Ketones
|Keywords||asymmetric reduction prochiral ketones β-amino alcohol C2-symmetric reversal of stereoselectivity|
Catalytic asymmetric synthesis is a hot field in modern organic synthesis,which creates good fortunes to enantiomerically pure chiral drugs and other materials. Optically active secondary alcohols are chiral ligands for enantioselectivity synthesis and important precursors of many chiral drugs,natural products and functional materials.Asymmetric borane reduction of prochiral ketones is a good process to the synthesis of enantiomerically enriched secondary alcohols.Herein we mainly discuss the design of four series of chialβ-amino alcohols and their application to the asymmetric borane reduction ofprochiral ketones.（1）Three chiral ligands I-5（a-b）and I-8 have been synthesized from camphor in three steps.They have no asymmetric induction when applied in the borane reduction of prochiral ketones.（2）C2-symmetricβ-amino alcohol ligandⅡ-8 was prepared in several steps from commercially available natural amino acid L-proline and applied in the asymmetric borane reduction of prochiral ketones.When the catalyst loading was 1 mol%, enantiomeric excess of up to 94.5%was observed in refluxing toluene.Although our catalystⅡ-8 did not provided as high enantioselectivity as that of A,the chiral induction of catalystⅡ-8 seemed to be identical or higher than that of catalyst B, which indicated that the structural changes were of advantage to some extent.（3）A series of C2-symmetric chiralβ-amino alcoholsⅢ-6 andⅢ-10（a-d）were synthesized in several steps from natural amino acids,and applied in the asymmetric borane reduction of prochiral ketones.The catalytic activity ofⅢ-6 was better thanⅢ-10（a-d）.When the catalyst loading was 10 mol%,ee of up to 85%was obtained in refluxing THF.The unusual temperature dependent reversal of stereoselectivity was observed.（R）-1-phenylethanol was obtained in up to 67%ee in refluxing THF. （S）-1-phenylethanol was obtained in up to 19%ee in toluene at 0℃.（4）A series of C2-symmetric chiralβ-amino alcoholsⅣ-5（a-c）were synthesized in several steps from natural amino acid L-proline,and applied in the asymmetric borane reduction of prochiral ketones.The unusual temperature dependent reversal of stereochemistry was also observed.When the catalyst loading was 10 mol%, （R）-1-phenylethanol was obtained in up to 78%ee in refluxing toluene,while （S）-1-phenylethanol was obtained in up to 30%ee in toluene at room temperature.