Hydroxy ketones conversion

Huonnations with DAST proceed with high chemoselectivity In general, under very mild reaction conditions usually required for the replacement of hydroxyl groups, other functional groups, including phenolic hydroxyl groups [112], remain intact This provides a method for selective conversion of hydroxy esters [95 97] (Table 6), hydroxy ketones [120, 121], hydroxy lactones [722, 123], hydroxy lactams [124] and hydroxy nitriles [725] into fluoro esters, fluoro ketones, fluoro lactones, fluoro lactams, and fluoro nitnles, respectively (equations 60-63)... 

Stork s elegant use of a protected cyanohydrin function in the synthesis of PGF2a (2) is also noteworthy. The electron-withdrawing cyano substituent in intermediate 21 (Scheme 7) confers nucleophilic potential to C-9 and permits the construction of the saturated cyclopentane nucleus of PGF2a (2) through intramolecular alkylation. In addition, the C-9 cyanohydrin function contained within 40 is stable under the acidic conditions used to accomplish the conversion of 39 to 40 (see Scheme 7), and it thus provides suitable protection for an otherwise labile /J-hydroxy ketone. 

In a similar way. ft-keto imide 19 undergoes stereodivergenl aldol reactions. Thus, conversion of 19 into the tin enolate, and subsequent addition of aldehydes, give predominantly the diastereomers 20. On the other hand, hydroxy ketones 21 are the main products when the chlorotitanium enolate of 19 is reacted with aldehydes53. ... 

A different method for the conversion of ketones to a-hydroxy ketones consists of treating the enolate with a 2-sulfonyloxaziridine (such as 15). This is not a free-radical process the following mechanism is likely ... 

Primary nitro compounds are good precursors for preparing nitriles and nitrile oxides (Eq. 6.31). The conversion of nitro compounds into nitrile oxides affords an important tool for the synthesis of complex natural products. Nitrile oxides are reactive 1,3-dipoles that form isoxazolines or isoxazoles by the reaction with alkenes or alky nes, respectively. The products are also important precursors for various substrates such as P-amino alcohols, P-hydroxy ketones, P-hydroxy nitriles, and P-hydroxy acids (Scheme 6.3). Many good reviews concerning nitrile oxides in organic synthesis exist some of them are listed here.50-56 Applications of organic synthesis using nitrile oxides are discussed in Section 8.2.2. 

The conversion of isoxazolines to P-hydroxy ketones can be carried out by H2 in the presence of Raney Ni under various conditions 91 The reaction proceeds cleanly with complete stereospecificity (Eq. 8.62). 

Literature search showed the dihydro-chromandione motif in 53, or other related system, is relatively unknown and/or under-investigated, and the proposed conjugate reduction to this system was unprecedented. Fortuitously, our attempt employed NaBH4 in MeOH at 0 °C, and while a new spot was rapidly produced, the conversion was slow. When the solution was warmed to ambient temperature and additional aliquots of NaBH4 were added, a mixture of diketone 55 and hydroxy ketone 56 was isolated. In subsequent trials, 55 could be reduced cleanly to 56 especially at elevated temperatures. 

A further example of the trapping of the in situ generated silyl enol ether from the reduction of an enone is the conversion of an enone into an a-hydroxy ketone via oxidation of the silyl enol ether (Eq. 286).465... 

Oxidative cleavage of the terminal double bond of 49 by ozonolysis to the aldehyde followed by permanganate oxidation to the acid and esterification with diazomethane produced the methyl ester 50. Dieckmann cyclisation of 50, following the procedure developed in Holton s laboratory (LDA, THF, -78 °C, 0.5 h, then HOAc, THF), gave the enol ester 5J in 93% yield (90% conversion). Decarbomethoxylation of 5J. was carried out by temporarily protection of the secondary alcohol (p-TsOH, 2-methoxypropene, 100%), and heating the resulting compound 52 with PhSK in DMF, at 86 °C (3 h) to provide 53a or, after an acidic workup, the hydroxy ketone 53b. 92% yield. 

Conversion of 4-hydroxy ketones into 4-halo ketones... 

The best results with respect to the enantiomeric excess (ee) of the resulting 2-hydroxy ketones were obtained with meta-substituted benzaldehydes. When these substrates were used, the ee increased to more than 99%, indicating that the steric demand and electronic properties of the substituent play a decisive role in both conversion rate and ee (Table 2.2.7.3, entries 2-4). Ortho-substituted benzalde-... 

The reduction of /1-hydroxy ketones with a tetramethylammonium triace-toxyborohydride-anhydrous acetic acid system yielded the anti diols via the transition state (TA). The stereochemistry of the 1,3-diols was assigned by using H NMR coupling constants after their conversion to the corresponding cyclic acetonide. 

Chlorodifluoromethylketones underwent aldol reactions (Eq. 124) via zinc enolates, to afford good yields of a,a-difluoro-/ -hydroxy ketones, in a study by the Kyoto group [327]. Copper(I) or silver salt catalysis was essential and boron-trifluoride additive appeared to exert a key role in the conversion to the enolate. Earlier [328], chlorodifluoromethyl ketones had been converted to the di-fluoroenoxy silanes by the action of zinc in the presence of chlorotrimethyl silane. A difluoroenoxy silane was used by McCarthy and co-workers [329] to synthesise a kynureninase inhibitor (Eq. 125) Lewis acid-mediated reaction with a chloroglycinate installed the key carbon-carbon bond. 

While a maximum conversion of only approximately 25% of the polymer s repeating units can be obtained in solution, prolonged exposure times also result in a significant decrease in the molecular weight of polymer VI as some degradation also occurs with the liberation of phenol. The mechanism for this degradation is likely to resemble that proposed by Hiraoka and others (25,26) for the radiolysis of PMMA. The 13C NMR spectrum of the polymeric photoproduct shows clearly that the polymer contains a majority of unreacted starting phenyl methacrylate units with also some o-hydroxy ketone units. 

Permanganate oxidations may be used for the direct conversion of olefins to a-hydroxy ketones and 1,2-diketones in moderate yields usually under acidic conditions.562"566... 

Kinetic Resolution of a Racemic Ketone. Kinetic resolution is a process by which one of the enantiomeric constituents of a racemate is more readily transformed into a product than the other (63b). For example, in the presence of an (/ )-BINAP-Ru catalyst, the S enantiomer of the a-hydroxy ketone is hydrogenated 64 times faster than R enantiomer, and, after 50.5% conversion, both the syn 1,2-diol and unreacted R hydroxy ketone are obtained in high ee (Scheme 61). 

Selective oxidation of sec -alcohols.1 The final steps in a synthesis of spec-tinomycin (3), an aminocyclitol antibiotic, involved a selective oxidation of one of three alcohol groups of 1 to provide 2, which furnishes 3 on deprotection (H2/Pd/ C, 90% yield). This oxidation can be carried out by conversion to a tributyltin ether followed by NBS oxidation to an a-hydroxy ketone in 80% yield (crude). Alternatively, reaction with Bu2SnO provides a stannylidene acetal, which is also oxidized by NBS to 2 in high yield. 

The initial experiments discussed in this section were performed without oxygen in the gas phase. Figures la and lb show conversion of i and selectivity towards 2 and 3 as a function of time, respectively. Initially, the conversion (65%) as well as the selectivity were stable. However, after 6 hours on stream the catalyst started to be deactivated. The decrease in conversion was accompanied by a decrease in selectivity towards the unsaturated diketone 2 and an increase in that for the saturated diketone 3. The ratio of the hydroxy ketone isomers 1 and 4 was not influenced by the deactivation. 

An impressive new route to enantiopure syn- and anti- 1,2-diols involves sequential diastereoselective DIBAL reduction of oxalyl-di(/V-iucthyl-/V-methoxyainide) following conversion to a corresponding intermediate / -keto sulfoxide a route that involved control of both reductions by the chiral sulfoxide auxiliary.253 Comparison of / -hydroxy ketone systems with die y-sulfoxide-/ -keto systems used here showed this to be die first example of such asymmetric induction by a y-sulfoxide substituent. 

Starting meso-diol Conversion (%) Product hydroxy ketone ee (%)... 

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