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Enantioselective Synthesis of ?-Fluoro Amines via ?-Amino ?-Fluoro Nitroalkanes and a Traceless Activating Group Strategy.

ABSTRACT: Preparation of a range of enantioenriched ?-fluoro amines (?,?-disubstituted) is described in which the nitrogen and fluorine atoms are attached to sp3-hybridized carbons. The key finding is a chiral bifunctional Brønsted acid/base catalyst that can deliver ?-amino-?-fluoro nitroalkanes with high enantio- and diastereoselection. A denitration step renders the nitro group "traceless" and delivers secondary, tertiary, or vinyl alkyl fluorides embedded within a vicinal fluoro amine functional group. A synthesis of each possible stereoisomer of a ?-fluoro lanicemine illustrates the potential ease with which fluorinated small molecules relevant to neuroscience drug development can be prepared in a stereochemically comprehensive manner.

SUBMITTER: Vara BA

PROVIDER: S-EPMC5453840 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Enantioselective Synthesis of β-Fluoro Amines via β-Amino α-Fluoro Nitroalkanes and a Traceless Activating Group Strategy.

Vara Brandon A BA Johnston Jeffrey N JN

Journal of the American Chemical Society 20161017 42

Preparation of a range of enantioenriched β-fluoro amines (α,β-disubstituted) is described in which the nitrogen and fluorine atoms are attached to sp<sup>3</sup>-hybridized carbons. The key finding is a chiral bifunctional Brønsted acid/base catalyst that can deliver β-amino-α-fluoro nitroalkanes with high enantio- and diastereoselection. A denitration step renders the nitro group "traceless" and delivers secondary, tertiary, or vinyl alkyl fluorides embedded within a vicinal fluoro amine funct ...[more]

PMID: 27749040

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