Hydroxy ketones, alkylation oxidation

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). 

Primary alkyl halides (chlorides, bromides, and iodides) can be oxidized to aldehydes easily and in good yields with dimethyl sulfoxide.311 Tosyl esters of primary alcohols can be similarly converted to aldehydes,312 and epoxides313 give a-hydroxy ketones or aldehydes.314 The reaction with tosyl esters is an indirect way of oxidizing primary alcohols to aldehydes (9-3). This type of oxidation can also be carried out without isolation of an intermediate ester The alcohol is treated with dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC),315 and anhydrous phosphoric acid.316 In this way a primary alcohol can be converted to the aldehyde with no carboxylic acid being produced. 

The cycloaddition of a nitrile oxide with a chiral allylic ether affords an isoxazoline with selectivity for the pre/-isomer. This selectivity increases with the size of the alkyl substituent and is insensitive to the size of the allyl oxygen substituent. However, allyl alcohols tend to form the / ar/ isomcr preferentially, although the selectivity is often low.427"434 The product of dipolar cycloadditions based on nitrile oxides, the isoxazoline moiety, can be converted into a large variety of functional groups under relatively mild conditions.3 Among other products, the addition can be used to prepare P-hydroxy ketones (Scheme 26.17).435 The isoxazoline moiety can be used to control the relative stereochemistry through chelation control.436,437... 

Hydrolysis of alkylated products and carbonyl compound adducts derived from a-lithiated DHF and DHP with 2 M HC1 in THF at room temperature gave y- and 5-hydroxy ketones, respectively824,865 (Scheme 162). Jones oxidation generated keto acids866,887 and when the R substituent bears an hydroxy group, cyclization occurred in the presence of pyridinium tosylate (PPTS) in CH2C12 or HC1 in ether to provide spiroketals875,883,894,901. 

Esters have been prepared in 63-73% yields from several simple cycloalkyl and aryl alkyl ketones by reaction at room temperature with per-benzoic acid. The larger radical of the ketone appears as the alcohol fragment of the ester. Cyclic ketones are oxidized by potassium persulfate and sulfuric acid to esters from which o>-hydroxy aliphatic esters are obtained upon hydrolysis and reesterification. Peracetic acid in acetic anhydride converts salicylaldehyde to o-hydroxyphenyl formate (88%). ... 

A variation that is more of an acyl addition (16-25) involves the reaction of an allylic alcohol with benzaldehyde. With a ruthenium catalyst and in an ionic liquid, the C=C unit reacts with the aldehyde, with concomitant oxidation of the allylic alcohol unit, to give a p-hydroxy ketone, PhCHO - -C=C—CH(OH)R PhCH(OH) CH(Me)COR. In another variation, formate esters add to alkenes using a ruthenium catalyst to give an alkyl ester via a formylation process. 

OL Hydroxy ketones. This hypervalent iodine reagent oxidizes terminal alkyl-or arylalkynes to a-hydroxy ketones (equation I). Of greater interest, it oxidizes ethynylcarbinols to a,a -dihydroxy ketones. ... 

Samarium diiodide when coupled with irradiation is a very reactive reducing reagent with respect to alkyl chlorides, whose oxidation potential is higher than those of the corresponding bromides and iodides. When such a reduction of an alkyl chloride was attempted under CO pressure [60], an unsymmetrical ketone was obtained, comprised of two molecules of alkyl chloride and two molecules of carbon monoxide. An a-hydroxy ketone, obtained via the dimerization of acylsa-marium, is a likely precursor of the final product. 

Dicarbonyl compounds can be cleaved oxidatively using peracids this protocol has been used to prepare cyclopropanecarboxylic acids from a dicyclopropylethanedione, e.g. 2 from 1 and several 2-cyclopropyl-2-oxoacetic acids. " An appropriately substituted 1,3-diketone has also been converted to a cyclopropanecarboxylic acid by basic hydrolysis. When a hydroxy group is attached p to the carbonyl group of an alkyl cyclopropyl ketone, periodate oxidation afforded a similar acid in quantitative yield. ... 

Alkylation of carbonyl compounds and derivatives. The 02/Co(OAc)2-Mn(OAc)2 system is useful to accomplish a-alkylation of ketones with 1-alkenes. Acetals also add to acrylic esters under O2 in the presence of catalytic amounts of Co(OAc)2 and A-hydroxyphthalimide to afford a-hydroxy-y-oxo ester acetals. The adducts of methyl vinyl ketone suffer oxidative degradation in situ. 

Controlled oxidation of the a-pinenes with potassium permanganate leads to the enantiomeric 2-hydroxy-3-pinanones 38 29-31, while under forcing conditions, ring cleavage occurs, leading to cyclobutane derivatives 39. The hydroxy ketones 38 are useful auxiliaries forming imines with benzylic amines or glycine esters which can be alkylated enantioselectively via the enolates (Sections D.l. 1.1.1.3.2., D. 1.1.1.4.1. and D.I.5.2.4.). 

The bis-alkyne side chain was synthesized as outlined in Scheme 64. Hy-drazone 300 was alkylated, followed by hydrolysis, to give a-hydroxy ketone 301, which was converted to oxazolone by treatment with trichloroacetyl isocyanate. The oxazolyl triflate 302, prepared by reaction of the oxazolone with triflic anhydride, was coupled with alkyne 213 under Sonogashira conditions as reported by Panek [118], followed by deprotection of MPM and oxidation, to furnish the side chain precursor bisalkynyloxazole 299. 

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