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A new method for the asymmetric synthesis of 1‐substituted tetrahydroisoquinolines is presented. It is based on stereoselective addition reactions of organometallic compounds to the intermediate N‐acyliminium ion 6, which is provided with an N‐acyl group as a chiral auxiliary. In addition reactions with organomagnesium and organozinc reagents diastereoselectivities from 70:30 to 95:5 (for 7/8) were observed with the zinc reagents in general leading to markedly improved stereoselectivities. By catalytic hydrogenation of 7 and 8 and after removal of the chiral auxiliary the target compounds 11 and 12 were obtained. The enantiomerically pure 11c–g and 12c–g (ee > 99 %), 1‐aryl‐tetrahydroisoquinolines, were evaluated for their affinity to the PCP [1‐(1‐phenylcyclohexyl)piperidine] binding site of the NMDA (N‐methyl D‐aspartate) receptor. In each case the enantiomers 11 exhibited a higher affinity than those of 12, with the potencies of the enantiomers differing by a factor of 4 (11/12g) to 27 (11/12c). The absolute configuration of the more potent enantiomers 11 is in accordance with the stereochemical requirement found for FR115427 (3) which is a close analogue.

[reaction: see text] A new method for the synthesis of beta-amino acids based on 2,3-dihydropyridones as starting materials is presented. Conversions of 2,3-dihydropyridones with NaIO4 and subsequently with base gave the corresponding beta-amino acids in a one-pot procedure. The reactions have been monitored by 1H NMR indicating that the beta-amino acids were formed in quantitative yields mostly. This method appears to be of broad scope, as 2-substituted 2,3-dihydropyridones are easily accessible via N-acyliminium ions generated from 4-methoxypyridine.

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