Ruthenium-catalyzed alkyne-propargyl alcohol addition. An asymmetric total synthesis of (+)-alpha-kainic acid.
A novel route to the neuroexcitatory amino acid, kainic acid, is developed. The key concept derives from a ruthenium-catalyzed cycloisomerization of a tethered alkyne-propargyl alcohol to form a cyclic 2-vinyl-1-acyl compound. A single stereocenter introduced by an asymmetric reduction of a ketone sets the stage for all the other stereocenters. A novel 1,6-addition of silyl cuprate serves to install a hydroxyl group at the diene termines. [reaction: see text]
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA. bmtrost@stanford.edu
Rudd
Michael T
MT
D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D018690:Excitatory Amino Acid Agonists / Q000138:chemical synthesis; D007608:Kainic Acid / Q000138:chemical synthesis*; D007659:Ketones / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D010084:Oxidation-Reduction; D020005:Propanols / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism
D000480:Alkynes; D018690:Excitatory Amino Acid Agonists; D007659:Ketones; D009942:Organometallic Compounds; D020005:Propanols; D012428:Ruthenium; C028255:propargyl alcohol; D007608:Kainic Acid