Asymmetric catalysis / Allylic alkylation / 1-Methyl-5-(1Ј-methylpent-2Ј-ynyl)barbituric acid / Palladium catalysts / Chiral phosphane imine ligands / Methohexital / Anesthetic dose Allylation of 1-methyl-5-(1Ј-methylpent-2Ј-ynyl)barbituric
Chiral phosphane imine ligands are a successful class of compounds, synthesized by Schiff base condensation of (2-acid (MBS) with allyl acetate using in situ catalysts of palladium(II) acetylacetonate and chiral phosphane imine formylphenyl)diphenylphosphane with optically active primary amines. The most efficient ligands have a ligands resulted in the enantioselective formation of 5-allyl-1-methyl-5-(1Ј-methylpent-2Ј-ynyl)barbituric acid (Metho-hydroxymethyl and a bulky alkyl substituent at the asymmetric centre in the imine part, e.g. the L-iso-leucinol hexital), an important anesthetic drug. Both, MBS and Methohexital contain two stereogenic carbon atoms. In MBS, and the L-tert-leucinol derivatives 5 and 7. In the Pdcatalyzed allylation of MBS a kinetic resolution and the effect the asymmetric centre in the barbiturate system is labile due to enolization. The asymmetric centre in the hexyne side of the enantioselective catalyst interplay, the contributions of which are separated. For MBS the best stereoselectivity chain is stable and racemic. The two asymmetric centres of Methohexital are stable and give rise to four stereoisomers, factor of the kinetic resolution s = k R /k S was 2.6 and 83 % "ee" were achieved. The corresponding values for two diastereomeric racemates. An analysis of the isomers of MBS and Methohexital was established on the basis of 1 H Methohexital were s = 3.5 and 80 % ee in the α-dl pair. For 10 mixtures of Methohexital stereoisomers the anesthetic NMR and, in particular, GC including a base-line separation of the four stereoisomers of Methohexital. The doses for rats were determined. With 9.1 mg/kg body weight of the animal the sample obtained from the catalysis with the stereoselectivity of the allylation is difficult to control, because the new quaternary asymmetric centre in the D-α-phenylglycinol derivative 8 gave a much lower anesthetic dose than the widely used narcotic barbiturate ring of Methohexital is formed within the nucleophile, attacking the η 3 -allyl ligand of the catalyst from Brevimytal ® Natrium, the sodium salt of the α-dl racemate of Methohexital, with 13.0 mg/kg body weight. the side opposite to the palladium atom. Classical optically active ligands, such as diop or norphos, give only 2-6 % ee.
the synthesis of 5-allyl-1-methyl-5-(1Ј-methylpent-2Ј-ynyl)-[ ] Part 124: Ref. [1]