Asymmetric PTC Alkylation of Glycine Imines: Variation of the Imine Ester Moiety

Abstract

Studies into the enantioselective phase-transfer alkylation of a series of glycine imine esters are presented. Using a quaternary ammonium salt catalyst derived from α-methyl-naphthylamine, high enantioselectivities were obtained in reactions involving imines containing tert-butyl, benzhydryl, and benzyl esters. In contrast, a quaternary ammonium salt catalyst derived from dihydrocinchonidine gave highest enantioselectivities with tert-butyl and ethyl esters. Application of the benzhydryl ester alkylation in the preparation of a differentially protected aspartic acid derivative is also presented.

amino acids - asymmetric alkylation - phase-transfer catalysis - quaternary ammonium salts

References

For recent reviews covering phase-transfer alkylation of glycine imines see:

1a Maruoka K. Ooi T. Chem. Rev.  2003,  103:  3013 

1b O’Donnell MJ. Aldrichimica Acta  2001,  34:  3 

2a Lygo B. Allbutt B. James SR. Tetrahedron Lett.  2003,  44:  5629 

2b Lygo B. Andrews BI. Crosby J. Peterson JA. Tetrahedron Lett.  2002,  43:  8015 

2c Lygo B. Humphreys LD. Tetrahedron Lett.  2002,  43:  6677 

2d Lygo B. Crosby J. Peterson JA. Tetrahedron  2001,  57:  6447 

2e Lygo B. Crosby J. Lowdon TR. Peterson JA. Wainwright PG. Tetrahedron  2001,  57:  2403 

2f Lygo B. Crosby J. Lowdon TR. Wainwright PG. Tetrahedron  2001,  57:  2391 

2g Lygo B. Crosby J. Peterson JA. Tetrahedron Lett.  1999,  40:  1385 

2h Lygo B. Wainwright PG. Tetrahedron Lett.  1997,  38:  8595 

For examples of asymmetric PTC alkylation of glycine imines other than tert-butyl ester ^1a see ref. ¹ and:

3a Ooi T. Tayama E. Maruoka K. Angew. Chem. Int. Ed.  2003,  42:  579 ; amides

3b Mazon P. Chinchilla R. Najera C. Guillena G. Kreiter R. Gebbink . R JMK. van Koten G. Tetrahedron: Asymmetry  2002,  13:  2181 ; iso-propyl ester

3c Vyskocil S. Meca L. Tislerova I. Cisarova I. Polasek M. Harutyunyan SR. Belokon YN. Stead RMJ. Farrugia L. Lockhart SC. Mitchell WL. Kocovsky P. Chem.-Eur. J.  2002,  8:  4633 ; Ni salt of PBP imine

For leading references to asymmetric PTC alkylations of glycine imine^1a not covered in ref.¹ and ref.², see:

4a Ooi T. Kameda M. Maruoka K. J. Am. Chem. Soc.  2003,  125:  5139 

4b Mase N. Ohno T. Hoshikawa N. Ohishi K. Morimoto H. Yoda H. Takabe K. Tetrahedron Lett.  2003,  44:  4073 

4c Park HG. Jeong BS. Yoo MS. Lee JH. Park BS. Kim MJ. Jew SS. Tetrahedron Lett.  2003,  44:  3497 

4d Thierry B. Plaquevent JC. Cahard D. Tetrahedron: Asymmetry  2003,  14:  1671 

4e Danelli T. Annunziata R. Benaglia M. Cinquini M. Cozzi F. Tocco G. Tetrahedron: Asymmetry  2003,  14:  461 

4f Okino T. Takemoto Y. Org. Lett.  2001,  3:  1515 

4g Chen G. Deng Y. Gong L. Mi A. Cui X. Jiang Y. Choi MCK. Chan ASC. Tetrahedron: Asymmetry  2001,  12:  1567 

4h O’Donnell MJ. Delgado F. Dominguez E. de Blas J. Scott WL. Tetrahedron: Asymmetry  2001,  12:  821 

See for example ref.^4a and:

5a Kim S. Lee J. Lee T. Park HG. Kim D. Org. Lett.  2003,  5:  2703 

5b Armstrong A. Scutt JN. Org. Lett.  2003,  5:  2331 

5c Lygo B. Andrews BI. Tetrahedron Lett.  2003,  44:  4499 

5d Boisnard S. Carbonnelle A.-C. Zhu J. Org. Lett.  2001,  3:  2061 

5e Lygo B. Tetrahedron Lett.  1999,  40:  1389 

6 O’Donnell MJ. Polt RL. J. Org. Chem.  1982,  47:  2663 

For examples that illustrate of the utility of this see:

7a Mitchell SA. Pratt MR. Hruby VJ. Polt R. J. Org. Chem.  2001,  66:  2327 

7b Tilley JW. Sarabu R. Wagner R. Mulkerins K. J. Org. Chem.  1990,  55:  906 

7c Felix AM. Heimer EP. Lambros TJ. Tzougraki C. Meienhofer J. J. Org. Chem.  1978,  43:  4194 

8 O’Donnell MJ. Sennett WD. Wu S. J. Am. Chem. Soc.  1989,  111:  2353 

9

Representative Procedure: A solution of salt ent-4 (1.2 mg, 1 mol%) and imine 1b (50 mg, 0.12 mmol) in toluene (4 mL) was cooled to 0 °C, degassed, and placed under an argon atmosphere. tert-Butyl bromoacetate (22 µL, 0.14 mmol) was added followed by degassed 15 M aq KOH (1mL). The resulting mixture stirred at 1500 rpm for 45 min, then diluted with H₂O (5 mL) and extracted with EtOAc (3 × 4 mL). The combined organic extracts were dried (MgSO₄) and concentrated under reduced pressure. Residual tert-butyl bromoacetate was removed under vacuum (1 mm Hg, r.t.) to afford imine 2b′′′ as a colourless oil (64 mg, 100%, 86% ee). ¹H NMR (400 MHz, CDCl₃): δ = 7.62-7.60 (2 H, m, ArH), 7.41-7.23 (16 H, m, ArH), 7.16-7.13 (2 H, m, ArH), 6.89 (1 H, s, OCHPh₂), 4.58 (1 H, dd, J = 7.5, 5.5 Hz, H-2), 2.99 (1 H, dd, J = 15.5, 5.5 Hz, H-3a), 2.85 (1 H, dd, J = 15.5, 7.5 Hz, H-3b), 1.35 (9H, s, t-Bu). ¹³C NMR (100 MHz, CDCl₃): δ = 171.8 (C), 170.0 (C), 139.9 (C), 139.9 (C), 139.6 (C), 136.0 (C), 130.5 (CH), 129.0 (CH), 128.8 (CH), 128.5 (CH), 128.0 (CH), 128.0 (CH), 127.9 (CH), 127.4 (CH), 127.1 (CH), 80.8 (C), 77.5 (CH), 62.3 (CH), 39.5 (CH₂), 28.1 (CH₃). HPLC: Chiralpak AD column (150 × 2.1 mm), hexane/i-propanol (97.5/2.5), 0.2 mL/min, R_t = 13.9 min (R)-isomer, 18.8 min (S)-isomer.
Imine 2b′′′ (38 mg) was then dissolved in THF (1 mL) and treated with 15% aq citric acid (1 mL). The resulting solution was stirred at r.t. for 3 h, then washed with Et₂O (3 × 2 mL). The aqueous layer was basified (sat. aq K₂CO₃) and extracted with CHCl₃ (3 × 5 mL). The combined organic extracts were dried (MgSO₄) and concentrated under reduced pressure to afford amine 5 as a colourless oil (22 mg, 85%). ¹H NMR (400 MHz, CDCl₃): δ = 7.36-7.27 (10 H, m, ArH), 6.92 (1 H, s, OCHPh₂), 3.84 (1 H, dd, J = 6.5, 4.5 Hz, H-2), 2.80 (1 H, dd, J = 16.5, 4.5 Hz, H-3a), 2.72
(1 H, dd, J = 16.5, 6.5 Hz, H-3b), 1.88 (2 H, s, broad, NH₂), 1.38 (9 H, s, t-Bu). ¹³C NMR (100 MHz, CDCl₃): δ = 173.5 (C), 170.3 (C), 139.8 (C), 128.6 (CH), 128.6 (CH), 128.2 (CH), 128.1 (CH), 127.2 (CH), 127.2 (CH), 81.5 (C), 77.8 (CH), 51.6 (CH), 39.8 (CH₂), 28.1 (CH₃)

10 Corey EJ. Xu F. Noe MC. J. Am. Chem. Soc.  1997,  119:  12414