Practical Synthesis of Natural Amino Acid Derivatives: Hf(OTf)₄-Catalyzed Mannich-Type Reaction of Ketene Silyl Acetals or Enol Silyl Ethers with N,O-Acetals as a Glycine Cation Equivalent

Abstract

The authors demonstrated the Hf(OTf)₄-catalyzed Mannich-type reaction of an enol silyl ether and a ketene silyl acetal with an N,O-acetal leading to the preparation of amino acid derivatives. In particular, use of the N,O-acetal having a bis(trimethylsilyl)amino group directly produced N-unprotected aspartic acid derivatives after a standard aqueous workup.

Key words

Mannich-type reaction - N,O-acetal - amino acid - hafnium triflate

References and Notes

• 1a Nájera C. Sansano JM. Chem. Rev.  2007,  107:  4584 
• 1b Taggi AE. Hafez AM. Lectka T. Acc. Chem. Res.  2003,  36:  10 
• 1c Arend M. Westermann B. Risch N. Angew. Chem. Int. Ed.  1998,  37:  1044 
• 1d Williams RM. Hendrix JA. Chem. Rev.  1992,  92:  889 
• 1e α-Amino Acid Synthesis, In Tetrahedron   O’Donnell MJ. Tetrahedron Symposia in Print, Elsevier; Amsterdam: . 
• 1f Wagner I. Musso H. Angew. Chem., Int. Ed. Engl.  1983,  22:  816 
• 2a Kano T. Hato Y. Yamamoto A. Maruoka K. Tetrahedron  2008,  64:  1197 
• 2b Dziedzic P. Cordova A. Tetrahedron: Asymmetry  2007,  18:  1033 
• 2c Jacobsen MF. Ionita L. Skrydstrup T. J. Org. Chem.  2004,  69:  4792 
• 2d Janczuk A. Zhang W. Xie W. Lou S. Cheng J. Wang PG. Tetrahedron Lett.  2002,  43:  4271 
• 2e Johannsen M. Chem. Commun.  1999,  2233 
• 2f Manabe K. Oyamada H. Sugita K. Kobayashi S. J. Org. Chem.  1999,  64:  8054 
• 2g Hagiwara E. Fujii A. Sodeoka M. J. Am. Chem. Soc.  1998,  120:  2474 
• 2h Colvin EW. McGarry D. Nugent MJ. Tetrahedron  1988,  44:  4157 
• 2i Fiaud J.-C. Kagan HB. Tetrahedron Lett.  1970,  11:  1813 
• 3a Janey JM. Hsiao Y. Armstrong JD. J. Org. Chem.  2006,  71:  390 
• 3b Ferraris D. Young B. Dudding T. William J. Drury I. Lectka T. Tetrahedron  1999,  55:  8869 
• 3c Ferraris D. Dudding T. Young B. Drury WJ. Lectka T. J. Org. Chem.  1999,  64:  2168 
• 3d Kobayashi S. Ishitani H. Komiyama S. Oniciu DC. Katritzky AR. Tetrahedron Lett.  1996,  37:  3731 
• 3e Tsukamoto T. Kitazume T. Chem. Lett.  1992,  21:  1377 
• 3f Okano K. Morimoto T. Sekiya M. Chem. Pharm. Bull.  1985,  33:  2228 
• 3g Okano K. Morimoto T. Sekiya M. J. Chem. Soc., Chem. Commun.  1984,  883 
• 3h Ben-Ishai D. Sataty I. Bernstein Z. Tetrahedron  1976,  32:  1571 
• 3i Zoller U. Ben-Ishai D. Tetrahedron  1975,  31:  863 
• 4 Sugiura M. Mori C. Hirano K. Kobayashi S. Can. J. Chem.  2005,  83:  937 
• 5a Sakai N. Asano J. Shimano Y. Konakahara T. Tetrahedron  2008,  64:  9208 
• 5b Sakai N. Asano J. Shimano Y. Konakahara T. Synlett  2007,  2675 
• 5c Sakai N. Hirasawa M. Hamajima T. Konakahara T. J. Org. Chem.  2003,  68:  483 
• 5d Sakai N. Hamajima T. Konakahara T. Tetrahedron Lett.  2002,  43:  4821 
• Selected papers for metal-promoted Mannich-type reaction using carbon nucleophiles and N,O-acetals, see:
• 6a Huguenot F. Brigaud T. J. Org. Chem.  2006,  71:  2159 
• 6b DeNinno MP. Eller C. Etienne JB. J. Org. Chem.  2001,  66:  6988 
• 6c Loh T.-P. Liung SBKW. Tan K.-L. Wei L.-L. Tetrahedron  2000,  56:  3227 
• 6d Heaney H. Papageorgiou G. Wilkins RF. J. Chem. Soc., Chem. Commun.  1988,  1161 
• 6e Shono T. Tsubata K. Okinaga N. J. Org. Chem.  1984,  49:  1056 
• 6f Hosomi A. Iijima S. Sakurai H. Tetrahedron Lett.  1982,  23:  547 
• Selected papers for formation of a primary amino group by hydrolytic cleavage of an N-Si bond, see:
• 10a Gong Y. Kato K. Kimoto H. Bull. Chem. Soc. Jpn.  2002,  75:  2637 
• 10b Gong Y. Kato K. J. Fluorine Chem.  2001,  108:  83 
• 10c Tanino K. Takahashi M. Murayama K. Kuwajima I. J. Org. Chem.  1992,  57:  7009 
• 10d Bestmann HJ. Wölfel G. Angew. Chem., Int. Ed. Engl.  1984,  23:  53 
• 10e Morimoto T. Takahashi T. Sekiya M. J. Chem. Soc., Chem. Commun.  1984,  794 

7

When the similar reaction was carried out with only TMSCl (1.2 equiv), the desired Mannich-type reaction did not proceed. In addition, when the reaction was carried out with less than 10 mol% of the hafnium catalyst, e.g., 5 mol%, the product yield of 7 decreased to 80%; TfOH and TMSOTf were ineffective for the present Mannich-type reaction.

8

General Procedure for the Synthesis of N,O -Acetals 2
To a freshly distilled THF solution (100 mL), the corresponding secondary amine (24 mmol), i-Pr₂NEt (4.1 mL, 24 mmol), and methyl 2-bromo-2-methoxyacetate (11 mL, 20 mmol) were successively added, and the solution was stirred at r.t. After 2 h, the reaction was quenched by adding a sat. aq soln (2 mL) of NaHCO₃. The aqueous layer was extracted with CHCl₃, the organic phase was combined, dried over anhyd Na₂CO₃, filtered, and evaporated under reduced pressure. The crude product was distilled to give the corresponding N,O-acetals 2.
General Procedure for the Hf(OTf) ₄ -Catalyzed Mannich-Type Reaction of a Silyl Ether with an N,O -Acetal
An N,O-acetal (0.50 mmol), a silyl ether (0.60 mmol), and Hf(OTf)₄ (38.8 mg, 0.0500 mmol) were successively mixed together in CH₂Cl₂ (2 mL) at r.t. with stirring. The resulting solution was stirred until the reaction reached completion, as shown by TLC (SiO₂, hexane-EtOAc = 4:1). The reaction was quenched with a sat. aq soln (2 mL) of NaHCO₃. The combined organic layer was dried over Na₂CO₃ and evaporated under reduced pressure. The crude product was purified by SiO₂ column chromatography (hexane and hexane-EtOAc) to afford amino acid derivatives.
Spectral Data for Selected Compounds
2-(1-Piperidinyl)butanedioic Acid 1-Methyl 4-Ethyl Ester (7)
Pale yellow oil. ^¹H NMR (500 MHz, CDCl₃): δ = 1.24 (t, 3 H, J = 7 Hz), 1.39-1.42 (m, 2 H), 1.52-1.55 (m, 4 H), 2.41 (m, 2 H), 2.58-2.63 (m, 3 H), 2.81-2.86 (m, 1 H), 3.69-3.72 (m, 4 H), 4.13 (q, 2 H, J = 7 Hz). ^¹³C NMR (125 MHz, CDCl₃): δ = 14.0, 24.2, 26.3, 34.2, 50.8, 51.1, 60.3, 64.1, 171.2, 171.3. MS (EI): m/z (%) = 243 (100) [M⁺]. HRMS: m/z calcd for C₁₂H₂₁NO₄: 243.1471; found: 243.1469. 2-Diallylamino-3,3-Dimethyl-butanedioic Acid 1-Ethyl 4-Methyl Ester (15) Pale yellow oil. ^¹H NMR (500 MHz, CDCl₃): δ = 1.21 (t, 3 H, J = 7.0 Hz), 1.23 (s, 3 H), 1.26 (s, 3 H), 3.00-3.10 (m, 2 H), 3.30-3.40 (m, 2 H), 3.70 (s, 3 H), 3.83 (s, 1 H), 4.00-4.20 (m, 2 H), 5.10-5.20 (m, 4 H), 5.70-5.80 (m, 2 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 14.0, 19.9, 25.3, 45.9, 50.9, 56.4, 60.4, 66.8, 117.1, 136.4, 172.3, 177.2. MS-FAB: m/z (%) = 284 (100) [M⁺ + H]. HRMS-FAB: m/z calcd for C₁₅H₂₅NO₄: 284.1857; found: 284.1862.

9

The E/Z ratio of amino acid derivatives 3-5 is nearly in agreement with that of the starting material, enol silyl ether 1.