Sarett oxidation

CrOs-pyridine complex The oxidation of alcohols to aldehydes and ketones with CrOs in the presence of pyridine solvent is known as the Sarett oxidation. Sarett used the CrOs-pyridine complex in the synthesis of steroids. Although primary alcohols give poor yield, benzylic, allylic and secondary alcohols give good yields with Sarett reagent. 

Snatzke has found that a solution prepared from chromium trioxide and dimethylformamide with a small amount of sulfuric acid has similar chemical properties as the Sarett reagent. It is useful with acid sensitive compounds and oxidation occurs at such a moderate rate that selective oxidations are often possible. Although the position allylic to a A -double bond is not attacked, the 3-hydroxy-A -system cannot be oxidized satisfactorily to the cor-... 

Dipyridiue-chromium(VI) oxide2 was introduced as an oxidant for the conversion of acid-sensitive alcohols to carbonyl compounds by Poos, Arth, Beyler, and Sarett.3 The complex, dispersed in pyridine, smoothly converts secondary alcohols to ketones, but oxidations of primary alcohols to aldehydes are capricious.4 In 1968, Collins, Hess, and Frank found that anhydrous dipyridine-chromium(VI) oxide is moderately soluble in chlorinated hydrocarbons and chose dichloro-methane as the solvent.5 By this modification, primary and secondary alcohols were oxidized to aldehydes and ketones in yields of 87-98%. Subsequently Dauben, Lorber, and Fullerton showed that dichloro-methane solutions of the complex are also useful for accomplishing allylic oxidations.6... 

Therefore, nine steps or synthetic operations are necessary in the conessine synthesis for isomerising the cir-B/C decalin system to trans-hIC, a transformation that in the cortisone synthesis is accomplished without any extra step, since it takes place spontaneously in the oxidation step, which, in turn, is necessary to introduce the second angular methyl group and build up ring D of cortisone in a stereoselective manner. Better correlation amongst different synthetic operations would be difficult to find in more recent synthesis of similar complexity and magnitude than that of Sarett. 

The Collins/Sarett oxidation (chromium trioxide-pyridine complex), and Corey s PCC (pyridinium chlorochromate) and PDC (pyridinium dichromate) oxidations follow a similar pathway as the Jones oxidation. All these oxidants have a chromium (VI), normally yellow, which is reduced to Cr(IV), often green. 

Similar to the Dakin-West procedure previously mentioned, the Henry nitro-aldol condensation reaction is most widely used to synthesize trifluoromethyl ketones, although there are many examples of a,a-difluoroalkyl ketones synthesized by this method (Table 6)JU 12271 The method for a,a-difluoroalkyl and trifluoromethyl ketone synthesis is identical except for the final oxidation although fluoroalkyl and a,a-difluoroalkyl ketones are easily oxidized by the Sarett method (Cr03/pyridine),[12 the corresponding trifluoromethyl ketones can only be oxidized under basic conditions (0.3 M NaOH) with KMn04Jul Also, in some of the syntheses of a,a-difluoroalkyl ketones, the nitro alcohol intermediate was protected by si-lylation with /ert-butylchlorodimethylsilane. The silyl group was later removed by TosOH prior to oxidation. The full details of this method are given in Section 15.1.4.3.2. 

A 62.5% yield of the desired ketone with no epimerization at the ot-position is obtained, employing catalytic TPAP as oxidant. Other oxidizing conditions, including Collins, Sarett, Oppenauer and Swern oxidations, as well as PCC, fail to deliver an acceptable yield of... 

Because you can easily further oxidize aldehydes to carboxylic acids, you can only employ mild oxidizing agents and conditions in the formation of aldehydes. Typical mild oxidizing agents include manganese dioxide (MnO), Sarett-Collins reagent (CrO,—(CSHSN)2), and pyridinium chlorochromate (PCC),... 

Oxidation of veatchine (48) with Sarett reagent gave veatchinone (53), which, when reduced with NaBD4 in CH3OH, afforded an epimeric mixture of (54) and (55). This mixture was acetylated with acetic anhydride in pyridine and the acetates, (56) and (57), were separated by preparative-scale t.l.c. Treatment of (56) with 10% HC1 and re-acetylation gave (58). The 13C n.m.r. data indicated that there was no deuterium present at C-16 in (58) therefore, this rearrangement did not take place by a 15 —> 16 hydride shift. 

Sarett and coworkers discovered that the complex (1) prepared by the addition of chromium(VI) oxide to pyridine (CAUTION—reverse order of addition may cause the mixture to inflame) is an efficient oxidizing agent for the preparation of ketones from secondary alcohols. The reagent, as prepared by Sarett, is moderately soluble in pyridine, but is only sparingly soluble in standard organic solvents. Thus the normal procedure is to add a solution of the dcohol in pyridine to three equivalents of the complex, also in pyrictoe. This procedure is also useful for the preparation of aromatic and a, -unsaturated aldehydes, but the use of pyridine as solvent prohibits the oxidation of volatile, saturated primary alcohols. ... 

The mechanism of the Sarett oxidation, Collins oxidation, with Corey s PCC and with PDC, follows a similar mechanism as shown in Scheme 7.1. The alcohol reacts with CrOs to give a chromate ester. Either a base (Py) removes a proton from the chromate ester to give an oxidized product (aldehyde or ketone) and HCrOs" or a proton is transferred by the intramolecular mechanism to give an aldehyde or ketone and H2Cr03. 

This solid is obtained by dissolving CrOs in a minimum of water, adding pyridine, and collecting the precipitate. PDC is probably present in Sarett and Cornforth oxidants. Unlike pyridinium chlorochromate, it is nearly neutral. 

Oxidation of akohois. The oxidation of alcohols with the reagent is conducted in methylene chloride with a sixfold molar excess of oxidant. The oxidation usually proceeds to completion in 3 -13 min. at 23°. The reagent is particularly recommended for oxidation of primary alcohols to aldehydes in this case use of the Sarett reagent (1,145 -146 2,74-75) usually gives low yields. Thus 1-heptanol can be oxidized by the Collins reagent in methylene chloride to l-heptanal in 70-84% yield. 

Sarett oxidation. Oxidation of primary and secondary alcohols to aldehydes and ketones by means of Cr03-pyridine complex. 

Prepared by passing phosgene into a solution of trichloroethanol in benzene-diethylaniline, this stable chloroformate acylates hydroxyl and amino groups in pyridine at room temperature or under Schotten-Baumann conditions (1-3).1 The protective group is removed by treatment with zinc dust in methanol. The group is stable to the conditions of Sarett and of Jones oxidations, to dioxane-HCl, to CF3-... 

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