Ketones P-hydroxy

The ester and catalj st are usually employed in equimoleciilar amounts. With R =CjHs (phenyl propionate), the products are o- and p-propiophenol with R = CH3 (phenyl acetate), o- and p-hydroxyacetophenone are formed. The nature of the product is influenced by the structure of the ester, by the temperature, the solvent and the amount of aluminium chloride used generally, low reaction temperatures favour the formation of p-hydroxy ketones. It is usually possible to separate the two hydroxy ketones by fractional distillation under diminished pressure through an efficient fractionating column or by steam distillation the ortho compounds, being chelated, are more volatile in steam It may be mentioned that Clemmensen reduction (compare Section IV,6) of the hj droxy ketones affords an excellent route to the substituted phenols. 

Dehydration of the intermediate p-alkoxy- or p-hydroxy ketone can also serve to drive the reaction to the right. 

AJdoJ Condensation -Aldol condensation Initially give p-hydroxy ketones which under certain conditions readily eliminated to give a,p-unsaturated carbonyls. 

The reaction of diketosulfides with 1,2-dicarbonyl compounds other than glyoxal is often not efficient for the direct preparation of thiophenes. For example, the reaction of diketothiophene 24 and benzil or biacetyl reportedly gave only glycols as products. The elimination of water from the P-hydroxy ketones was not as efficient as in the case of the glyoxal series. Fortunately, the mixture of diastereomers of compounds 25 and 26 could be converted to their corresponding thiophenes by an additional dehydration step with thionyl chloride and pyridine. 

The rather unsclective formation of certain anti-p-hydroxy ketones from E)-cnolates (see above) also underlines the low (E)-anti correlation. 

The crude adduct is dissolved in 20 mL of ( H, ()H and stirred with 10 mL of a pH 7 buffer soln and 10 mL of 30% H,02 for 2 24 h at 20-80X. Alter the reaction is complete (TLC monitoring), the mixture is extracted with Et20, and the orgauic layer dried over MgSO,. The resulting p-hydroxy ketones are purified by distillation. 

In theory, the chiral center can be anywhere in the molecule, but in practice, reasonable diastereoselectivity is most often achieved when it is in the a position. For examples of high diastereoselectivity when the chiral center is further away, especially in reduction of P-hydroxy ketones, see Narasaka, K. Pai, F. Tetrahedron, 1984, 40, 2233 Hassine, B.B. Gorsane, M. Pecher, J. Martin, R.H. Bull. Soc. Chim. Belg., 1985, 94, 597 Bloch, R. Gilbert, L. Girard, C. Tetrahedron Lett., 1988, 53, 1021 Evans, D.A. Chapman, K.T. Carreira, E.M. J. Am. Chem. Soc., 1988, 110, 3560. 

P-Hydroxy ketones can be prepared by treating the silyl ethers (53) of a,p-epoxy alcohols with TiCU- ... 

Ij ample Compound (21) is a P-hydroxy ketone. Disconnect ion of the usual bond reveals two molecules of onone (22), disconnected in turn to two molecules of acetone,... 

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). 

The 1,3-dipolar addition to terminal alkenes of nitrile oxides, generated from nitromethylene derivatives of bicycloheptane, provides 9,ll-ethano-13,15-isoxazolinoprostanoids, PGH analogs, with alkyl, phenyl, or additional heterocyclic fragment in the oo-chain (461). Chemical transformations of 9,11-ethano-13,15-isoxazolinoprostanoids furnish prostanoids with bifunctional fragments of P-hydroxyketone and a-aminoalcohol in the oo-chain. The reaction of P-hydroxy ketones with methanesulfonyl chloride gives rise to prostanoids with an enone component in the oo-chain. 9,ll-Ethano-16-thiaprostanoids have been prepared, for the first time, by nucleophilic addition of thiols to the polarized double bond in the oo-chain. The 1,3-dipolar addition to terminal alkenes of nitrile oxides, generated from nitromethylene derivatives of bicycloheptane provides 9,ll-ethano-13,15-isoxazolinoprostanoids with an alkyl, phenyl, or additional heterocyclic fragment in the oo-chain (462). 

Therefore, acyclic and monocyclic nitroso acetals are convenient precursors of functionalized p-hydroxy ketones and y-aniino alcohols (see Reference 403). 

More recently, Doris et al. have described the reductive ring-opening of a-keto epoxides [16]. In this manner, p-hydroxy ketones can be obtained in high yields. The synthesis of enantiomerically pure compounds can easily be realized. The titanocene] 111) reagents are distinctly superior to samarium diiodide, which is also known to induce this transformation. 

Oxidation of p-hydroxy ketones. Reaction of the Corey-Kim reagent with these substrates can result in dimethylsulfonium dicarbonylmethylides in 80-98% yield. These S-ylides are desulfurized to p-diketones by zinc in acetic acid, p-... 

Homologation of ECHO to a-bromo-a, -enones.4 The initial steps of this homologation involve addition of dibromomethyllithium (1) to an aldehyde followed by oxidation of the adduct to a dibromomethyl ketone (2). The aluminum enolate of 2 undergoes an aldol reaction to provide an a-bromo-p-hydroxy ketone... 

The regiospecificity of the exclusive O-acylation [8] and O-phosphorylation [9] of P-dicarbonyl compounds (Chapter 3) also illustrates the effect of phase-transfer catalysts on the stereochemical course of reactions. Similarly, directed reduction of P-hydroxy ketones using tetramethylammonium trisacetoxyborohydride leads to the preferential formation of the anti dihydroxy system in high yield with a stereoselectivity >95% [10] (Section 11.4). 

Moderate levels of diastereomeric differentiation are observed in the additions of achiral allylboronates to P-hydroxy ketones, as exemplified in Eq. 51a. ° The major product is tentatively assigned as the anti diastereomer. Few reports describe the use of carbonyl substrates other than aldehydes and ketones, and these reactions have not led to applications. For instance, low reactivity leading... 

The catalytic asymmetric diboration of allenes provides a-substituted 2-boronyl allylic boronates of type 25 (see Eq. 32). One of them, 91, adds to ben-zaldehyde, albeit with a slight erosion of stereoselectivity (Eq. 65). The major P-hydroxy ketone stereoisomer, isolated after an oxidative work-up, originates from the putative chairlike transition structure 92. 

Chain degradation proceeds at the oxidised sites, where two different routes can be discerned. One way uses the p-hydroxy ketone functionalities introduced by the initial enzymatic attack as direct substrates in an aldolase-like scission reaction. The other way proceeds via further oxidation of this structure to a 1,3-diketone, which serves as a target structure for a hydrolase-type splitting enzyme. 

The elimination proceeds rapidly at room temperature with a catalytic amount of acid or fluoride, however, it has also been observed to occur upon distillation of the isoxazolidine (16,18). Because of the facile elimination, several procedures have been developed in which the reaction is quenched with an acidic agents, and the isoxazoline is isolated directly (108). Isoxazolines are useful in the preparation of p-hydroxy ketones and amino alcohols (138). 

As synthetic equivalents of p-hydroxy ketones and amines, isoxazolidines provide access to important synthetic building blocks. However, there have been... 

This chapter deals mainly with the 1,3-dipolar cycloaddition reactions of three 1,3-dipoles azomethine ylides, nitrile oxides, and nitrones. These three have been relatively well investigated, and examples of external reagent-mediated stereocontrolled cycloadditions of other 1,3-dipoles are quite limited. Both nitrile oxides and nitrones are 1,3-dipoles whose cycloaddition reactions with alkene dipolarophiles produce 2-isoxazolines and isoxazolidines, their dihydro derivatives. These two heterocycles have long been used as intermediates in a variety of synthetic applications because their rich functionality. When subjected to reductive cleavage of the N—O bonds of these heterocycles, for example, important building blocks such as p-hydroxy ketones (aldols), a,p-unsaturated ketones, y-amino alcohols, and so on are produced (7-12). Stereocontrolled and/or enantiocontrolled cycloadditions of nitrones are the most widely developed (6,13). Examples of enantioselective Lewis acid catalyzed 1,3-dipolar cycloadditions are summarized by J0rgensen in Chapter 12 of this book, and will not be discussed further here. 

Dipolar cycloaddition reactions between nitrile oxides and aUcenes produce 2-isoxazolines. Through reductive cleavage of the N—O bond of the 2-isoxazohnes, the resulting heterocycles can be readily transformed into a variety of important synthetic intermediates such as p-hydroxy ketones (aldols), p-hydroxy esters, a,p-unsaturated carbonyl compounds, y-amino alcohols, imino ketones and so forth (7-12). 

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