Synthesis of Chiral Chromenes
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The enantioselective synthesis of monosubstituted benzopyran derivatives, known as chromenes, is presented. Exhibiting a wide variety of biological activities, such as bronchodilation and minimizing the effects of tachycardia, this structural unit is found in many important pharmaceutical agents. In order to induce asymmetry in the achiral starting material, we use the inexpensive yet powerful enzyme oxynitrilase, which we isolate from a commercial grade bag of raw almonds. The novel palladium catalyzed chiral shift reaction transfers the stereocenter from the a carbon to the γ carbon, while preserving stereochemical configuration. This step, followed by the Grubbs catalyzed ring-closing metathesis, produces the respective chromene. In total, five chromenes have been successfully synthesized, three enzyme direct and two enzyme indirect. The enzyme indirect chromenes require an additional synthetic step in which the hydroxy ester undergoes a Grubbs catalyzed cross metathesis with a desired ligand. Each produced chromene was characterized with NMR and GCMS analysis.