Diastereodivergent hydroxyfluorination of cyclic and acyclic allylic amines

Synthesis of 4-deoxy-4-fluorophytosphingosines

Alexander J. Cresswell, Stephen G. Davies, James A. Lee, Melloney J. Morris, Paul M. Roberts, James E. Thomson

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

A diastereodivergent hydroxyfluorination protocol enabling the direct conversion of some conformationally biased allylic amines to the corresponding diastereoisomeric amino fluorohydrins has been developed. Sequential treatment of a conformationally biased allylic amine with 2 equiv of HBF 4·OEt2 followed by m-CPBA promotes epoxidation of the olefin on the face proximal to the amino group under hydrogen-bonded direction from the in situ formed ammonium ion. Regioselective and stereospecific epoxide ring-opening by transfer of fluoride from a BF 4- ion (an SN2-type process at the carbon atom distal to the ammonium moiety) then occurs in situ to give the corresponding amino fluorohydrin. Alternatively, an analogous reaction using 20 equiv of HBF4·OEt2 results in preferential epoxidation of the opposite face of the olefin, which is followed by regioselective and stereospecific epoxide ring-opening by transfer of fluoride from a BF 4- ion (an SN2-type process at the carbon atom distal to the ammonium moiety). The synthetic utility of this methodology is demonstrated via its application to a synthesis of 4-deoxy-4-fluoro-l-xylo- phytosphingosine and 4-deoxy-4-fluoro-l-lyxo-phytosphingosine, each in five steps from Garner's aldehyde.

Original languageEnglish
Pages (from-to)7262-7281
Number of pages20
JournalJournal of Organic Chemistry
Volume77
Issue number17
DOIs
Publication statusPublished - 7 Sep 2012

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Ammonium Compounds
Amines
Epoxidation
Epoxy Compounds
Alkenes
Ions
Fluorides
Carbon
Atoms
Aldehydes
Hydrogen
4-deoxy-4-fluorophytosphingosine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Diastereodivergent hydroxyfluorination of cyclic and acyclic allylic amines : Synthesis of 4-deoxy-4-fluorophytosphingosines. / Cresswell, Alexander J.; Davies, Stephen G.; Lee, James A.; Morris, Melloney J.; Roberts, Paul M.; Thomson, James E.

In: Journal of Organic Chemistry, Vol. 77, No. 17, 07.09.2012, p. 7262-7281.

Research output: Contribution to journalArticle

Cresswell, Alexander J. ; Davies, Stephen G. ; Lee, James A. ; Morris, Melloney J. ; Roberts, Paul M. ; Thomson, James E. / Diastereodivergent hydroxyfluorination of cyclic and acyclic allylic amines : Synthesis of 4-deoxy-4-fluorophytosphingosines. In: Journal of Organic Chemistry. 2012 ; Vol. 77, No. 17. pp. 7262-7281.
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