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

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

References

• 1 Williams RM. Synthesis of Optically Active α-Amino Acids   Pergamon Press; Oxford: 1989. 
• 2 For a review of asymmetric syntheses of arylglycines see: Williams RM. Hendrix JA. Chem. Rev.  1992,  92:  889 
• 3 Watkins J. Collingridge G. Trends Pharm. Sci.  1994,  15:  333 
• 4a Bendingfield JS. Kemp MC. Jane DE. Tse HW. Roberts PJ. Watkins JC. Br. J. Pharmacol.  1995,  116:  3323 
• 4b Sekiyama N. Hayashi Y. Nakanishi S. Jane DE. Tse HW. Birse EF. Watkins JC. Br J Pharmacol.  1996,  117:  1493 
• 4c Hayashi Y. Sekiyama N. Nakanishi S. Jane DE. Sunter DC. Birse EF. Udvarhelyi PM. Watkins JC. J. Neurosci.  1994,  14:  3370 
• 5a Evans DA. Britton TC. Dorow RL. Dellaria JF. J. Am. Chem. Soc.  1986,  108:  6395 
• 5b Evans DA. Britton TC. Dorow RL. Dellaria JF. Tetrahedron  1988,  44:  5525 
• 6 Caron M. Carlier PR. Sharpless KB. J. Org. Chem.  1988,  53:  5185 
• 7 Williams RM. Hendrix JA. J. Org. Chem.  1990,  55:  3723 
• 8 Endo A. Kan T. Fukuyama T. Synlett  1999,  1103 
• For the first report of the iminolactone 4 see:
• 9a Tohma S. Endo A. Kan T. Fukuyama T. Synlett  2001,  1179 
• 9b and for its application to the total synthesis of ecteinascidin 743, see: Endo A. Yanagisawa A. Abe M. Tohma S. Kan T. Fukuyama T. J. Am. Chem. Soc.  2002,  124:  6552 
• 10a During the course of this investigation the preparation of the iminolactone B from phenylglycinol A and reaction with a Grignard reagent was reported: Harwood LM. Tyler SNG. Anslow AS. MacGlip ID. Drew MGB. Tetrahedron: Asymmetry  1997,  8:  4007 
• 10b Similar iminolactones were prepared from 2-substituted oxazolines see: Shafer CM. Molinski TF. J. Org. Chem.  1996,  61:  2044 
• 10c For its application to Mannich-type reactions see: Chen Y.-J. Lei F. Liu L. Wang D. Tetrahedron  2003,  59:  7609 
• 11a For preparation of the phenol 5a see: Fukuyama T. Sachleben RA. J. Am. Chem. Soc.  1982,  104:  4957 
• 11b

  For preparation of phenols 5b see: ref. 6

• 13 Petasis NA. Goodman A. Zavialov IA. Tetrahedron  1997,  48:  16463 
• 14a Ishiyama T. Miyaura N. J. Synth. Org. Chem., Jpn.  1999,  57:  503 
• 14b Ishiyama T. Miyaura N. J. Organomet. Chem.  2000,  611:  392 
• 2-Hydroxypyridine is a weak acid (pKa 11.7), used for the conversion of aliphatic esters to the corresponding amides, see:
• 16a Openshaw HT. Whittaker N. J. Chem. Soc. (C)  1969,  89 
• 16b Kametani T. Kanaya N. Ihara M. J. Chem. Soc., Perkin Trans. 1  1981,  959 
• 16c Jagers E. Steglich W. Angew. Chem., Int. Ed. Engl.  1981,  20:  1016 
• 16d Raduchel B. Tetrahedron Lett.  1983,  24:  3229 
• 16e Hoffmann RW. Eudesfelder A. Liebigs Ann. Chem.  1986,  1823 
• 18 Davies SG, Polywka MEC, and Sanganee HJ. inventors; US  005801249A. Alternatively compound 2 can be prepared from d-phenyl-glycine methyl ester hydrochloride by direct treatment with MeMgI in Et₂O in moderate yield (41% from methyl ester hydrochloride):

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 [phone]; E-mail: [e-mail]].

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).