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.

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

References

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<A NAME="RG12505ST-10I">10i</A> 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 

<A NAME="RG12505ST-10J">10j</A> 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

<A NAME="RG12505ST-11">11</A> 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

<A NAME="RG12505ST-12">12</A>

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

<A NAME="RG12505ST-13">13</A>

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.

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Aldehydes 1a-c and 1f: see ref. 3c.

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<A NAME="RG12505ST-16F">16f</A> Aldehyde 1k: Ito A. Takahashi R. Baba Y. Chem. Pharm. Bull.  1975,  23:  3081 

<A NAME="RG12505ST-16G">16g</A> Aldehyde 1l: Dondoni A. Perrone D. Org. Synth.  2000,  77:  64