Primary alcohols, chemoselectivity

The compound NaBH4 in the presence of Me2N=CHCl" Cl" reduces carboxylic acids to primary alcohols chemoselectively in the presence of halide, ester, and nitrile groups Fujisawa, T. Mori, T. Sato, T. Chem. Lett., 1983, 835. 

The highly efficient catalytic system for the chemoselective transfer hydrogenation of aldehydes was reported by Xiao et al. [52]. This system consisted of [Cp IrCl2]2 (1), a diamine and HCOONa, and worked on water and in air. A wide range of aromatic aldehydes were reduced to the corresponding primary alcohols in a highly chemoselective manner some representative examples are summarized in Table 5.9. 

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

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. 

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

Chemoselective primary alcohol oxidation of the 1,5-diol 849 followed by in situ cyclization and lactol oxidation to afford 3,6-dihydropyran-2-one 850 is achieved using catalytic TEMPO in the presence of NCS (Equation 342) <20050L1853>. 

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. 

A zirconium complex, bis(cyclopenta(Uenyl)zirconium(IV) hydride will function as a catalyst for the chemoselective Oppenauer oxidation of primary alcohols in the presence of a hydrogen acceptor (cyclohexanone, benzaldehyde or benzophenone). This method appears to be of some value, since it also allows for the selective monooxidation of primary (and secondary) diols (Scheme 3). 1,2-Diols are not cleaved under these conditions and retro-aldol reactions appear not to be a problem. 

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). 

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. 

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