Pergamon Tetrahedron Letters 39 (1998) 5323-5326 TETRAHEDRON LETTERS A Novel Chromium Trioxide Catalyzed Oxidation of Primary Alcohols to the Carboxylic Acids Mangzhu Zhao*, Jing Li, Zhiguo Song, Richard Desmond, David M. Tschaen, Edward J. J. Grabowski and Paul J. Reider Process Research Department, Merck Research laboratories, Merck & Co. Inc., P.O. Box 2000, Rahway, NJ 07065, USA Received 10 April 1998; revised 5 May 1998; accepted 7 May 1998 Abstract A novel CrO~ catalyzed oxidation of primary alcohols to the carboxylic acids is reported. The oxidation proceeds smoothly with only 1-2 tool % of CrO 3 and 2.5 equivalents of H~IO 6 in wet MeCN to give the carboxylic acids in excellent yield. No significant racemization is observed for alcohols with adjacent chiral centers. Secondary alcohols are cleanly oxidized to ketones. © 1998Elsevier ScienceLtd. All rights reserved. Keywords: chromium;catalysis; oxidation; alcohols Oxidation is a fundamental transformation in organic synthesis and there are numerous methods reported in the literature [1]. However, direct conversion of primary alcohols to the corresponding carboxylic acids is still a challenge especially in the presence of other functional groups. There are only a few commonly used methods for this transformation including CrO/H2SO, [2], RuCI~I~IO, [3] and TEMPO/NaC10 [4]. A two- step process involving Swern oxidation [5] followed by oxidation of the resulting aldehyde with NaC102 [6] is another option. However, all of these methods have limitations and disadvantages, and new oxidation methods are still desired. Herein, we report a very facile oxidation of primary alcohols to the carboxylic acids using periodic acid (HsIO~) as the stoichiometric oxidant and only a catalytic amount of CrO 3 [7a]. Although chromium catalyzed oxidation of secondary alcohols has been reported [7h, c] a similar version for the oxidation of primary alcohols to the carboxylic acids is not known. In our initial investigations, we found that some primary alcohols can be oxidized to the acids in aqueous acetonitrile (v/v -lid with HrIO6 and 5 mol % CrO 3. We observed conversions as high as 72% but additional H~IO 6 failed to push the reaction to completion. The reaction mixture also gradually turned greenish indicating generation of Cr(III) species that failed to turn over to Cr(VI). Nevertheless, these experiments proved that a catalytic process was viable. 0040-4039/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved. PII: S0040-4039(98)00987-3