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Synthesis 2004(6): 909-917  
DOI: 10.1055/s-2004-815980
PAPER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Nucleophilic Addition with a New Chiral Template and Its Application to the Synthesis of Optically Active α-Arylglycine Derivatives

Shigemitsu Tohmaa, Kentaro Rikimarua, Atsushi Endoa, Keiko Shimamotob, Toshiyuki Kana, Tohru Fukuyama*a
a Graduate School of Pharmaceutical Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Japan
Fax: +81(3)58028694; e-Mail: fukuyama@mol.f.u-tokyo.ac.jp;
b Suntory Institute for Bioorganic Research, Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618, Japan
Weitere Informationen

Publikationsverlauf

Received 19 January 2004
Publikationsdatum:
19. Februar 2004 (online)

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Abstract

Mannich-type reaction of phenols with iminolactone 4, readily prepared from commercially available phenylglycine, proceeded with high stereoselectivity to give α-arylglycine derivatives. The reaction was also applicable to other electron-rich aromatic compounds, arylboronic acids and other nucleophiles. Additionally, several Lewis acid-promoted addition reactions with iminolactone 4 were accomplished efficiently. These adducts could be converted readily to the corresponding optically active α-amino acid derivatives.

Key words

Mannich-type reaction - iminolactone - phenols - electron-rich aromatics - arylboronic acids - hydroxyphenylglycines - amino acids - α-arylglycines

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12

Compound 7 was prepared from 6a by treatment with MsCl and Et3N in 85% yield. X-ray crystallographic data for the structure reported in this paper have been deposited with the Cambridge Crystallographic Date Base (Deposition No. 162231). Copies of the data can be obtained free of charge on application to the CCDC 12 Union Road, Cambridge CB21EZ UK [fax +44 (1223)336333; E-mail: deposit@ccdc.cam.ac.uk].

15

Unfortunately the hydroxyphenylglycines 17a-c had no agonist and antagonist activity in mGluR1-5. Detailed experimental procedures and results of the assay will be reported elsewhere.

17

(S)- or (R)-Phenylglycine methyl ester hydrochloride was purchased from Aldrich Inc. Free methyl ester 1 is easily obtained by treatment with gaseous ammonia in CH2Cl2, followed by filtration, and evaporation. Alternatively (S)- or (R)-phenylglycine can be converted to the methyl ester using SOCl2 in MeOH (see also ref.18).