Chiral linker. Part 4: Diastereoselective addition of RZnX to α-keto esters using m-hydrobenzoin derived chiral auxiliaries in solution and on solid support and their application in the stereoselective synthesis of frontalin

Two recently reported, m-hydrobenzoin derived open chain chiral auxiliaries, which were developed for application in either solution or immobilized on a solid support, were tested in the diastereoselective addition of RZnX to their corresponding phenylglyoxylates and pyruvates, respectively, resulting in diastereoisomeric excesses of up to >98% de. The optimized procedure was applied in the stereoselective synthesis of frontalin, the aggregation pheromone of pine bark beetles of the Dendroctonus family, by the use of both the solution phase and the polymer supported chiral auxiliary.

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2-Oxophenylacetic acid, (1R,2S)-2-(2-methoxyethoxy)-1,2-diphenylethyl esterC20H22O5Ee = >98%[α]D20=-2.4 (c 0.99, CH2Cl2)Source of chirality: [2R-(2α,3aα,4β,7β,7aα)]-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-olAbsolute configuration: (1R,2S)

Oxophenylacetic acid, (1R,2S)-2-(2-methoxyethoxy)-1,2-diphenylethyl esterC25H24O5Ee = >98%[α]D20=+18.6 (c 0.71, CH2Cl2)Source of chirality: [2R-(2α,3aα,4β,7β,7aα)]-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-olAbsolute configuration: (1R,2S)