A Direct and Efficient Stereoconservative Procedure for the Selective Oxidation of N-Protected β-Amino Alcohols

Abstract

An efficient, very simple and eco-friendly procedure has been developed for the synthesis of highly enantioenriched α-amino aldehydes by IBX-mediated oxidation of the corresponding β-amino alcohols. The procedure has been applied to a wide range of ­substrates with different side chains and protecting groups showing that the final aldehydes can be obtained in very high yields and with no racemization at the stereogenic center present in the starting compounds.

Key words

amino aldehydes - amino alcohols - oxidations - iodine - green chemistry

References

• For some reviews see:
• 1a Gryko D. Chalko J. Jurczak J. Chirality  2003,  15:  514 
• 1b Alcaide B. Almendros P. Chem. Soc. Rev.  2001,  30:  226 
• 1c Liang X. Andersch J. Bols M. J. Chem. Soc., Perkin Trans. 1  2001,  2136 
• 1d Reetz MT. Chem. Rev.  1999,  99:  1121 
• 1e Jurczak J. Golebiowski A. Chem. Rev.  1989,  89:  149 
• 2a Palomo C. Oiarbide M. Garcia JM. Gonzalez A. Pazos R. Odriozola JM. Bañuelos P. Tello M. Linden A. J. Org. Chem.  2004,  69:  4126 
• 2b Falorni M. Giacomelli G. Porcheddu A. Taddei M. J. Org. Chem.  1999,  64:  8962 
• 2c Dondoni A. Perrone D. Semola T. Synthesis  1995,  181 
• 2d Zlatoidsky P. Helv. Chim. Acta  1994,  77:  150 
• 2e Ho TP. Ngu K. J. Org. Chem.  1993,  58:  2313 
• 2f Maeda H. Maki T. Ohmori H. Tetrahedron Lett.  1992,  33:  1347 
• 3a Wen JJ. Crews CM. Tetrahedron: Asymmetry  1998,  9:  1855 
• 3b Paris M. Pothion C. Heitz A. Martinez J. Fehrentz J.-A. Tetrahedron Lett.  1998,  39:  1341 
• 3c Fehrentz J.-A. Castro B. Synthesis  1983,  676 
• 4 Douat C. Heitz A. Martinez J. Fehrentz J.-A. Tetrahedron Lett.  2000,  41:  37 
• 5 Zlatoidsky P. Tetrahedron Lett.  1995,  36:  7281 
• 6a Drag M. Latajka R. Gumienna-Kontecka E. Kozlowski H. Kafarski P. Tetrahedron: Asymmetry  2003,  14:  1837 
• 6b De Luca L. Giacomelli G. Porcheddu A. J. Org. Chem.  2001,  66:  7907 
• 6c Lee K.-Y. Kim Y.-H. Park M.-S. Oh C.-Y. Ham W.-H. J. Org. Chem.  1999,  64:  9450 
• 6d Veeresa G. Datta A. Tetrahedron Lett.  1998,  39:  3069 
• 6e Jayashinge L.-R. Datta A. Ali SM. Zygmunt J. VanderVelde DG. Georg GI. J. Med. Chem.  1994,  37:  2981 
• 6f Denis J.-N. Correa A. Greene AE. J. Org. Chem.  1991,  56:  6939 
• 7a De Luca L. Giacomelli G. Porcheddu A. Org. Lett.  2001,  3:  3041 
• 7b Jurczak J. Gryko D. Kobrzycka E. Gruza H. Prokopowicz P. Tetrahedron  1998,  54:  6051 
• 7c Leanna MR. Sowin TJ. Morton HE. Tetrahedron Lett.  1992,  33:  5029 
• 8a Wroblewski AE. Piotrowska DG. Tetrahedron: Asymmetry  2002,  13:  2509 
• 8b Myers AG. Zhong B. Movassaghi M. Kung DW. Lanman BA. Kwon S. Tetrahedron Lett.  2000,  41:  1359 
• Reviews:
• 9a Zhdankin VV. Stang PJ. Chem. Rev.  2002,  102:  2523 
• 9b Nicolaou KC. Baran PS. Angew. Chem. Int. Ed.  2002,  41:  2678 
• 9c Wirth T. Angew. Chem. Int. Ed.  2001,  40:  2812 
• See:
• 10a Moore JD. Finney NS. Org. Lett.  2002,  4:  3001 
• See also:
• 10b Moorthy JN. Singhal N. Venkatakrishnan P. Tetrahedron Lett.  2004,  45:  5419 
• 10c Yadav JS. Reddy BVS. Basak AK. Narsaiah AV. Tetrahedron  2004,  60:  2131 
• 10d Liu Z. Chen Z.-C. Zheng Q.-G. Org. Lett.  2003,  5:  3321 
• 10e Surenda K. Krishnaveni NS. Reddy MA. Nageswar YVD. Rao KR. J. Org. Chem.  2003,  68:  2058 
• 10f Karthikeyan G. Perumal PT. Synlett  2003,  2249 
• 10g Bose DS. Gurjar SMK. Tetrahedron Lett.  1997,  38:  5839 
• 10h de Munari S. Frigerio M. Santagostino M. J. Org. Chem.  1996,  61:  9272 
• 10i A polymer-supported IBX-derived reagent has also been applied in the oxidation of alcohols: Sorg G. Mengel A. Jung G. Rademann J. Angew. Chem. Int. Ed.  2001,  40:  4395 
• 10j For an overview of the use of IBX in other oxidative transformations see: Nicolaou KC. Mathison CJN. Montagnon T. J. Am. Chem. Soc.  2004,  126:  5192 ; and references therein
• 11 IBX can explode on impact or heating at high temperatures: Plumb JB. Harper DJ. Chem. Eng. News  1990,  68 (29):  3 ; in our hands, using IBX at temperatures between 20 °C and 90 °C, no hazards have been experienced
• 14 For a review see: Liang X. Andersch J. Bols M. J. Chem. Soc., Perkin Trans. 1  2001,  2136 
• 15a Dondoni A. Perrone D. Org. Synth.  2000,  77:  64 
• 15b Meffre P. Durand P. Branquet E. Le Goffic F. Synth. Commun.  1994,  24:  2147 
• Aldehydes 1a-c and 1f: see ref. 3c.
• 16a For aldehydes 1d and 1g see: Morita T. Nagasawa Y. Yahiro S. Matsunaga H. Kunieda T. Org. Lett.  2001,  3:  897 
• 16b Aldehyde 1e: Dondoni A. Merchan FL. Merino P. Rojo I. Tejero T. Synthesis  1996,  641 
• 16c Aldehyde 1h: Sibi MP. Christensen JW. J. Org. Chem.  1999,  64:  6434 
• 16d Aldehyde 1i: Kang M. Park J. Konradi AW. Pedersen SF. J. Org. Chem.  1996,  61:  5528 
• 16e Aldehyde 1j: Wen JJ. Crews CM. Tetrahedron: Asymmetry  1998,  9:  1855 
• 16f Aldehyde 1k: Ito A. Takahashi R. Baba Y. Chem. Pharm. Bull.  1975,  23:  3081 
• 16g Aldehyde 1l: Dondoni A. Perrone D. Org. Synth.  2000,  77:  64 

12

Representative Experimental Procedure. IBX (2.40 g, 8.57 mmol) was added to a solution of the β-amino alcohol 5a (0.50 g, 2.86 mmol) in EtOAc (40 mL) and the mixture was refluxed for 2 h opened to the atmosphere. The mixture was cooled to r.t., filtered and the solvent was removed under reduced pressure to afford α-amino aldehyde 1a pure as its ¹H NMR spectrum indicated. For correct characterization purposes, the crude mixture was purified by short path flash column chromatography (hexanes-EtOAc, 8:2) affording pure product as a white solid (0.44 g, 2.54 mmol, 89% yield). All spectral data of compounds 1a-l were in agreement with those previously reported.¹⁶

13

N-Boc-phenylglycinal is known to racemize under basic conditions (see ref. 8a) and during flash chromatography purification on SiO₂ (ref. 1e) but in our hands we have not observed racemization at all.