Alcohol chemoselective oxidation

A double mediatory system consisting of modified TEMPO and halide ion or metal ion was also exploited for the oxidation of alcohols [53-55]. A number of carbohydrates have been chemoselectively oxidized at the primary hydroxyl group to uronic acids [56]. 

With both building blocks 103 and 109 in hand, the total synthesis of lb was completed as shown in Scheme 17. Coupling of acid 103 and alcohol 109 under Yamaguchi conditions to give ester 110 and subsequent desilylation followed by chemoselective oxidation provided hydroxy acid 111. Lactonization of the 2-thiopyridyl ester derived from 111 in the presence of cupric bromide produced the macrodiolide 112 in 62% yield, which was finally converted to pamamycin-607 (lb) via one-pot azide reduction/double reductive AT-methylation. In summary, 36 steps were necessary to accomplish the synthesis of lb from alcohols 88 and 104, sulfone 91, ketone 93, and iodide rac-97. 

Scheme 20 Chemoselective oxidation of alcohols with (o-TolbBiC -DBU and Dess-Martin periodinane [82]...

More recently, the Noyori group described an organic solvent- and haUde-free oxidation of alcohols with aqueous H202 . The catalyst system typically consists of Na2W04 and methyltrioctylammonium hydrogen sulfate, with a substrate-to-catalyst ratio of 50-500. Secondary alcohols are converted to ketones, whereas primary alcohols, in particular substituted benzyUc ones, are oxidized to aldehydes or carboxylic acid by selecting appropriate reaction conditions This system also catalyzed the chemoselective oxidation of unsaturated alcohols, the transformation exemplified in equation 65, with a marked prevalence for the hydroxy function. 

The second synthetic approach to oidiolactone C (61) is summarized in Scheme 20. This route also commences with the ozonolysis of trans-communic acid 180. Now, when this compound was exposed to ozone in excess, keto aldehyde 187 was obtained in 76% yield. The key step in this approach was the y-lactone closure via chemoselective reduction of the lactone moiety on compound 189 through a SN2 mechanism. Compound 189 could be prepared by saponification of the corresponding methyl ester with sodium propanethiolate. Once the primary alcohol is oxidized, the completion of the synthesis of key lactone 103 only requires the allylic oxidation of the C-17 methyl with concomitant closure of the 8-lactone. This conversion was achieved with Se02 in refluxing acetic acid to give 103 in 51% yield. 

Step 1. Chemoselective oxidation of the primary alcohol (diacetoxyiodo)benzene (DIB) is the stoichiometric co-oxidant. 

Mannam S, Alamsetti SK, Sekar G (2007) Aerobic, chemoselective oxidation of alcohols to carbonyl compounds catalyzed by a DABCO-copper complex under mild conditions. Adv Synth Catal 349(14-15) 2253-2258... 

Table 26 Summary of the results obtained for the chemoselective oxidation of primary alcohols...

Chemoselective oxidation of the allylic alcohol in triol 865 with manganese dioxide followed by in situ cyclization and oxidation of the resulting 5,6-dihydropyran-2-ol provides the 5,6-dihydropyran-2-one subunit 866 of bryostatin (Equation 349) <20000L2189>. 

Figure 4.10 Chemoselective oxidation of alcohols with Cr-APO-5 in the presence of TBHP.

The chemoselective oxidation of a primary alcohol in the presence of a secondary alcohol is a somewhat more difficult task. Not only is the inherent difference in reactivity less than in the case of the selective oxidation of allylic alcohols discussed above, but most reagents will oxidize secondary alcohols somewhat more rapidly than primary alcohols. Nevertheless there are reagents which will carry out the selective oxidation of a primary alcohol to an aldehyde without oxidizing a secondary alcohol, some of which will be considered here. 

Examples of the highly chemoselective oxidation of a secondary hydroxy group have been reported using bromine in the presence of bis(tri-n-butyltin) oxide (equations 36 and 37), primary alcohols being essentially inert to this reagent mixture. ... 

Several procedures for this chemoselective oxidation utilize molybdenum-based catalysts, with either hydrogen peroxide or r-butyl hydroperoxide as the stoichiometric oxidant. These include ammonium molybdate in the presence of a ph e transfer reagent and hydrogen peroxide, which with pH control (potassium carbonate) will selectively oxidize a secondary alcohol in the presence of a primary alcohol without oxidizing alkenes. In addition hindered alcohols are oxidized in preference to less hindered ones (Scheme 18). 

Benzyltrimethylammonium tetrabromooxomolybdate will catalyze the chemoselective oxidation of secondary alcohols with r-butyl hydroperoxide as cooxidant.Remote double bonds can interfere with this oxidation, and 1,2-diols are converted into 1,2-diketones (Scheme 19). 

There are numerous reagents available for the chemoselective oxidation of polyfunctional alcohols. The most promising general type of oxidant must be that in which a mild, clean oxidizing agent e.g. t-buQ l hydroperoxide, bromine, air orN-methylmorpholineN-oxide) is used in conjunction with a reagent which will catalyze the desired selective oxidation. Mild, stoichiometric oxidants (such as periodinane). 

Sodium metiq>eriodate, NaI04, is a two-electron chemoselective oxidant and when absorbed on alumina oxidizes alcohols to carbonyl compounds and sulfides to sulfoxides without overoxidation to sul-fones. 2 Alkenic double bonds in the substrate remain intact during this oxidation. Typically reactions are performed in 95% ethanol at room temperature for a few hours and with good (85-90%) yields. 

An interesting example of this type of chemoselective oxidation has been reported with the reagent mixture derived irom (Uisopropyl sulfide and )V-chlorosuccinimide. This reagent will oxidize selectively a primary alcohol to an aldehyde at 0 C. Surprisingly, this same reagent at -78 C will oxidize selectively a secondary alcohol to the corresponding ketone (Scheme 2). Allylic and benzylic alcohols are oxidized at both temperatures. 

The oxidation of primary alcohols to the corresponding carboxylic acid or ester generally requires fairly powerful oxidants, and in most cases the issue of selectivity is dealt with by protection of other oxidiz-able functionality within the molecule. One important area in which this need not be the case is the oxidation of symmetrical and unsymmetrical diols to the corresponding lactone. The general scheme is presented in Scheme S, and relies on an initial chemoselective oxidation to the hydroxy aldehyde, which is in equilibrium with the lactol. This lactol is then oxidized to the lactone. In some cases it is possible to halt the reaction at the lactol stage, but usually the lactone is the product. Most of this section will be concerned with this type of selective oxidation. 

The chemoselective oxidation of a saturated secondary alcohol in the presence of a saturated primary alcohol is possible with a number of reagents. N-Bromosuccinimide in an aqueous organic solvent has been used to carry out this type of selective oxidation and has found use in synthesis. The value of this reagent is exemplified by its use in the synthesis of isocyanopupukeanane and in work towards a total synthesis of gelsemine (equations (32) and (33) respectively). Clearly this reagent would not be compatible with all functional groups, given the well-known reactivity of N-bromosuccinimide towards unsaturated compounds. 

The preceding section dealt specifically with the chemoselective oxidation of secondary/jprimary diols. There is a clear interest in chemoselective oxidation of secondary alcohols in the presence of other sensitive functional groups, and some of the methods available will be described briefly in this section. 

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