Diastereodivergent Hydroxyfluorination of Cyclic and Acyclic Allylic Amines: Synthesis of 4‑Deoxy-4-fluorophytosphingosines

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 HBF4·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 BF4– 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 BF4– 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.