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Workup of Hydrogenation Product. The corresponding solutions of 2-acetamide or -benzamido-3-hetarylpropanoic acids after hydrogenation were evaporated to dryness, and one of the following procedures was used to isolate the hydrogenation product.A. In the cases of 2-acetamide3-(3-pyridyl)propanoic acid (7a) and 2-acetamido-3-(3-quinolyl)propanoic acid (6a) the residue was dissolved in water and separated from the insoluble catalyst by filtration. Evaporation to dryness afforded the product, yields were essentially 100% except for the slowest reactions (time 21440 min).B. In the cases of 2-benzamide3-(2-thienyl)propanoic acid (lb), 2-benzamido-3-(2-furyl)propanoic acid (3b), 2-benzamido-3-[ 1methylpyrrol-2-yl]propanoic acid (4b), 2-benzamido-3-(3-indoly1)propanoic acid (5b), 2-benzamido-3-(3-pyridyl)propanoic acid (7b), 2-benzamido-3-(3-quinoly1)propanoic acid (6b), and 2-benzamido-3-(3-thienyl)propanoic acid (2b), the residue was dissolved in 0.5 N sodium hydroxide and separated from the insoluble catalyst by filtration. The filtrate was acidified with dilute hydrochloric acid and the precipitate filtered and dried, giving the desired product.C. In the cases of 2-acetamide3-(2-thienyl)propanoic acid (la), 2-acetamido-3-(2-furyl)propanoic acid (3a), and 2-acetamido-3-(3-indolyl)propanoic acid (5a), the residue was dissolved in 0.5 N sodium hydroxide and separated from the insoluble catalyst by filtration. The filtrate was acidified with dilute hydrochloric acid and extracted with diethyl ether. The ethereal extract was dried and evaporated to dryness to afford the product.Acknowledgment. This research was made possible by the generous financial support of the Comisidn Asesora de Investigacidn Cientifica y TBcnica. We are grateful to Prof. Ernest L. Eliel for his criticism and helpful suggestions for the preparation of this manuscript. We are indebted to Mme. M. F. Grenier (University of Pau, France) for her help and advice with regard to the NMR measurements.Registry No. la,

The utilization of natural amino acids as a source of chirality for the preparation of various enantiomerically enriched compounds has been reviewed recently"]. We have reported that tetrahydroisoquinolines, via their N-iminomethyl derivatives (i.e. as formamidine derivatives), are metalated and alkylated to give l-alkyltetrahydroisoquinolines in good while enantioselective alkylations via chiral formamidines provide these products in high enantiomeric excessE4]. These enantioselective alkylations were performed using the disilyl ethers of (1S,2S)-(+)-2-amino-l-phenyl-1,3-propanediol, whose availability and stability posed some technical problems. We now report that the tert-butyl ether 8d of valinol 8a can not only be conveniently prepared, but also leads to higher enantioselectivity than the propanediol derivative when transformed into the formamidine 9. By simple exchange between the isoquinolines 1 or 2 and 9, the chiral formamidines 3a or 3b are obtained in 70-90% yield'']. Metalation with lithium diisopropylamide (for 3a) and tert-butyllithium (for 3b) gave the lithiated formamidines, which were alkylated with alkyl halides and then hydrazinolyzed to remove the iminomethyl group@'. The high efficiency of this process is outlined in Table 1. The enantiomeric excesses of 4 were determined by chiral-column HPLC analysis, as developed by Pirkle, and applied to chiral N-heterocycles and other amine~[~.*I. The optical rotations in Table