A catalytic asymmetric synthesis of 5,5-dimethylproline

The methyl ester derivative of commercially available N-acetyl-allylglycine readily undergoes cross-metathesis with 2-methylbut-2-ene and ruthenium–alkylidene catalyst to afford the prenylglycine derivative. Acid-catalysed cyclisation then affords 5,5-dimethylproline in near quantitative yield and enantioselectivity.

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5,5-DimethylprolineC7H13NO2Ee = 98%Source of chirality: asymmetric synthesis[α]D22=-50.2 (c 1.01, H2O)

5,5-Dimethylproline hydrochlorideC7H13NO2·HClEe = 98%Source of chirality: asymmetric synthesis[α]D22=+49.7 (c 0.75, H2O)

(2S)-Methyl 2N-acetylamino-5-methylhex-4-enoateC10H17NO3Ee = 100%Source of chirality: asymmetric synthesisBaseline resolution via chiral GC[α]D22=+58.2 (c 0.79, CHCl3)