Synthesis of the antiepileptic (R)-Stiripentol by a combination of lipase catalyzed resolution and alkene metathesis

The enantiopure (ee >99%) antiepileptic (R)-(+)-Stiripentol has been stereoselectively synthesized via cross metathesis of 5-vinylbenzo[d][1,3]dioxole 1 and (R)-(+)-4,4-dimethylpent-1-en-3-ol (R)-(+)-2. A novel one-pot two-step pathway for the synthesis of 5-vinylbenzo[d][1,3]dioxole 1 starting from 3,4-dihydroxycinnamic acid has been introduced. A lipase catalyzed kinetic resolution access to enantiopure (R)-(+)-4,4-dimethylpent-1-en-3-ol (R)-(+)-2 (ee >99%) has also been developed.

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(R)-(+)-4,4-Dimethylpent-1-en-3-yl butyrateC11H20O2(ee >99%)[α]D20=+5.1 (c 10 CHCl3)Absolute configuration: (R)

(R)-(+)-4,4-Dimethylpent-1-en-3-olC7H14O(ee >99%)[α]D20=+8.3 (c 10 CHCl3)Absolute configuration: (R)