A practical asymmetric synthesis of LTD4 antagonist

The asymmetric synthesis of L-699,392, a leukotriene antagonist, is reported. The main framework of the molecule is formed via a Heck reaction. The introduction of the asymmetric center was accomplished by the chiral reduction of prochiral ketone using B-chlorodiisopinocampheylborane. A very high asymmetric amplification was observed in which 95% ee product can be obtained from 70% optically pure a-pinene. A new reagent, which is prepared in situ from methylmagnesium chloride and lithiumhexamethyldisilazide, is used to convert the methyl ester to the methyl ketone in one step with essentially no impurities formed under the reaction conditions.