A-Hydroxymethyl ketones

Hydrogenolysis of the isoxazoline ring with Ra-Ni in the presence of hydrogen results in conversion to a hydroxymethyl ketone (Scheme 4.142).540... 

Isoflavanones.1 A synthesis of these products from a poly hydroxy desoxy-benzoin such as 2 involves conversion of the nonhydrogen-bonded hydroxyl group to the protected ether by reaction with 1 and K2C03 in acetone at 25°. Further reaction with 1 at 60-70° gives an a-hydroxymethyl ketone 3 in 85-95% yield. This product cyclizes to the isoflavanone 4 in the presence of Na2C03. The final step involves deprotection of the ethoxymethyl group to give 5 (92-94% yield). 

In a synthesis of the natural insecticide ajugarin-IV (4),4 the butenolide portion was prepared from the acid chloride 3 in two steps. Reaction with tris(lrimethylsilyloxy)ethylene (8, 523 9, 512)5 led to a hydroxymethyl ketone, which on reaction with 1 was converted into the butenolide 4. In this series, 1 was vastly Kupcrior to the alternative Wittig-Horner reagent 2. 

Aldol-type reactions.1 Reaction of lithium enolates with SEM chloride results in a-hydroxymethyl ketones protected as the P-trimethylsilylethyl ethers, which can undergo deprotection with Bu4NF or TFA. Yields are in the range of 55-80%. 

In contrast to (diacetoxyiodo)benzene, [bis(trifluoroacetoxy)iodo]benzene, (BTI) reacts in aqueous solvents with both terminal and non-terminal alkynes affording eventually a-hydroxyketones and 1,2-diketones, respectively. The primary reaction of terminal alkynes leads to the formation of alkynyl phenyliodonium salts, which are not isolable under the experimental conditions but have been prepared by other routes (Section 9.1.3) these are hydrolysed in situ to a-hydroxymethyl ketones, through the intermediacy of their O-tri fluoroacetates, which sometimes may be isolated as by-products. 

BTI is suitable for the direct hydroxylation of ketones. Aliphatic, aromatic and heterocyclic ketones in acetonitrile-water and trifluoroacetic acid afforded a-hydroxymethyl ketones (in the range of 70%), whereas a-methylene ketones, such as propiophenone, gave less satisfactory yields. 

Anhydrous reagent is particularly advantageous in the trapping of regiospecifically generated enolates in the preparation of a-hydroxymethyl ketones (6, 264-267). 

Esters of a-hydroxymethyl ketones are formed by heating diazoketones with organic acids. The crude diazoketones prepared from acyl halides and diazomethane may be used. The over-all yields of acetoxy ketones, ArCOCHjO,CCHj, from benzoyl and /3-naphthoyl chlorides are 55% and 72%, respectively. ... 

From the first course of reaction we obtain the completely polarized form of a ketone (LIV) and from the second a hydroxymethyl ketone (LV). Since ketones are extremely reactive molecules they would be expected to combine at once with the solvent employed to give the products shown in equation 21. 

Sodium hydroxide a-Metkylene ketones from ketones via a-hydroxymethyl ketones 9.4,621 NaOH... 

HYDROXY-(3-KETO ESTERS Titanium(lV) chloride. a-HYDROXYMETHYL KETONES Formaldehyde. 

Hydroxy-2-methylcyclohexanone, 214 a-Hydroxymethyl ketones, 264-266 p-Hydroxymethylphenylboronic acid, 194 N-Hydroxy-5-norbornene-endo-2,3-... 

A Claisen-type condensation of ethyl retinoate (24) with the a-hydroxymethyl ketone (641) in the presence of lithium amide in tetrahydrofuran led to the enolized diketone (642), which when treated with an acid, underwent cyclization to give the butenolide (643) (Ito et aL, 1979b). 

Dihydroxyalkanoic acids can be prepared by Lewis acid-catalysed condensations between aldehydes and tris(trimethylsiloxy)ethylene (Scheme 6). This approach, previously used to synthesize a-hydroxymethyl-ketones from acid chlorides, gives yields of 58—82% (five examples) and is non-stereoselective. 

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