Aminol Pharm: Asymmetric Syntheses and Utilization of Chiral, Non-Racemic Amino Acids

Date & time

1–2pm 11 March 2014

Location

Rm 3.105, Craig Wing, Building 138

Speakers

Professor Bakthan Singaram

Contacts

 Gavin Perri
 61 2 61252391

Enantiomerically pure β-amino alcohols play important roles both in the treatment of a wide variety of human disorders and as chiral auxiliaries in organic syntheses. There are a few methods available for the synthesis of non-racemic amino alcohols from amino acids and by resolution procedures. However, the amino acid route is limited by the high cost and lack of availability of unnatural amino acids. As part of our comprehensive investigation of the hydroboration of functionalized alkenes, such as enamines and enol-ethers, we have developed several methods for the direct synthesis of β-amino alcohols from enamines derived from aldehydes, ketones and chiral terpene ketones. We have also found that enantiomerically pure epoxides, such as styrene oxide, react with primary and secondary lithium amides to give a single enantio- and regio-isomeric β-amino alcohol in essentially quantitative yields. Asymmetric reduction of 2-amino acetophenones using Ipc2BCl also affords β-amino alcohols in very high enantiomeric purity. A series of chiral β-amino alcohols were also synthesized from terpene epoxides and amines in the presence of a catalytic amount of water. These chiral, non-racemic, β-amino alcohols were systematically evaluated as potential chiral directors in various asymmetric transformations, such as asymmetric carbonyl addition reactions, asymmetric Barbier reaction. Amino alcohols can also be used for asymmetric reductions. However, we have achieved high enantioselectivities for the reduction of a series of ketones using the inexpensive and mild reducing agent NaBH4 and our chiral Lewis acid, TarB-NO2. This easily prepared tartaric acid based reagent combines a Lewis acid with carboxylic acid in a single bifunctional reagent. When combined with NaBH4, the resulting chiral acyloxyborohydride mediates the reductions aromatic ketones and haloalkylaryl ketones to provide the product alocohols and epoxides, respectively, in enantiomeric excess of 93-98%. Several aliphatic ketones were also reduced with moderate to excellent enantioselectivity. A unique mechanism is provided with supporting calculations for the proposed active species and transition state. This talk will trace major developments, largely in our own research program, which led from the asymmetric hydroboration-oxidation of enamines to the present time where we have several reagents, methods and applications based on chiral β-amino alcohols and TarB-X reagent for asymmetric synthesis in organic chemistry.
 

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