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Synthesis 2010(20): 3545-3555  
DOI: 10.1055/s-0030-1257938
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

First General Route to Substituted α-Arylamino-α′-chloropropan-2-ones by Oxidation of N-Protected Aminohalohydrins: The Importance of Disrupting Hydrogen Bond Networks

Vittorio Pacea, Álvaro Cortés Cabrerab, María Fernándeza, José V. Sinisterraa,c, Andrés R. Alcántara*a
a Organic and Pharmaceutical Chemistry Department, Biotransformations Group, Faculty of Pharmacy, Complutense University of Madrid, Pza. Ramón y Cajal s/n, 28040 Madrid, Spain
Fax: +34(91)3941822; e-Mail: andresr@farm.ucm.es;
b Bioinformatics Unit, Center for Molecular Biology ‘Severo Ochoa’, C/Nicolás Cabrera 1, Autónoma University Campus, 28049 Madrid, Spain
c Industrial Biotransformations Service, Scientific Park of Madrid, C/ Santiago Grisolía 2, 28760 Tres Cantos, Madrid, Spain
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Publication History

Received 8 June 2010
Publication Date:
30 July 2010 (online)

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Abstract

The presence of a network of intra- and intermolecular hydrogen bonds in β-arylamino alcohols, confirmed by both IR spectroscopy and computer modeling, inhibits their oxidation to the corresponding α-amino ketones. A straightforward protocol, including highly regioselective protection (as carbamates) and subsequent oxidation with Dess-Martin periodinane, affords near quantitative yields of the desired N-protected ketones, which upon mild treatment with iodotrimethylsilane leads to a series of differently functionalized α-arylamino-α′-chloro ketones.

Key words

amino alcohols - amino ketones - oxidation - protecting groups - hydrogen bonding

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Janssen, C. L.; Nielsen, I. B.; Leininger, M. L.; Valeev, E. F.; Kenny, J. P.; Seidl, E. T. The Massively Parallel Quantum Chemistry Program (MPQC), Version 2.3.1, Sandia National Laboratories, Livermore, CA, USA, 2008.