Enantioselective synthesis of methyl-5(R)-fluorohept-6-ynoate

The asymmetric synthesis of propargylic fluorides, (+)-6 and (+)-3 with ee’s >95%, is reported. The first key step involves an asymmetric transfer hydrogenation of the propargylic ketone 11, using Noyori’s catalyst, to give alcohol (+)-10. The second important step is the highly stereoselective DAST mediated fluorination of the propargylic alcohol (−)-5. The ee determinations were performed using both NMR in chiral solvents and chiral GC. These propargylic fluorides appear to be useful intermediates in the preparation of fluorinated analogues of bioactive chiral molecules.

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tert-Butyl[(3(R)-fluorohept-1-yn-7-yl)oxy]dimethylsilaneC14H28FOSiEe: 96%[α]D21=+3.0 (c 1.00, CHCl3)Absolute configuration: R

Methyl 5 (R)-fluorohept-6-ynoateC8H11FO2Ee: 96%[α]D21=+14.5 (c 0.44, CHCl3).Absolute configuration: R