Ketones, periodate oxidation

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. ... 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

Bis-hydrazide-containing molecules also can be used to activate soluble polymeric sub-stances-containing aldehyde groups. For instance, dextran may be periodate oxidized to create numerous formyl functionalities on each molecule. Subsequent reaction with a homobifunctional hydrazide in large excess results in a hydrazide-activated polymer having multivalent-binding capability toward aldehydes or ketones (Chapter 25, Section 2.2). Insoluble support matrices suitable for affinity chromatography have been activated in a similar fashion to create the hydrazide derivative (O Shannessy and Wilchek, 1990). 

The hydrazide derivative of AMCA can be used to modify aldehyde- or ketone-containing molecules, including cytosine residues using the bisulfite activation procedure described in Chapter 27, Section 2.1. AMCA-hydrazide reacts with these target groups to form hydrazone bonds (Figure 9.26). Carbohydrates and glycoconjugates can be labeled specifically at their polysaccharide portion if the required aldehydes are first formed by periodate oxidation or another such method (Chapter 1, Section 4.4). 

Hydrazide derivatives also may be prepared from a periodate-oxidized dextran polymer or from a carboxyl-containing dextran derivative by reaction with te-hydrazidc compounds (Chapter 4, Section 8). A hydrazide terminal spacer provides reactivity toward aldehyde- or ketone-containing molecules. Thus, the hydrazide-dextran polymer can be used to conjugate specifically glycoproteins or other polysaccharide-containing molecules after they have been oxidized with periodate to form aldehydes (Chapter 1, Section 4.4). 

Perfiuoroolefins, 0-substituted, from a-trifluoromethyl ketones, 48,119 Periodate oxidation of thioanisole, 46, 78... 

Periodate oxidation involves the simultaneous oxidation and cleavage of carbon to carbon bonds that have adjacent free hydroxyl groups or an aldehyde or ketone group adjacent to a hydroxyl group. The action of periodic acid is represented by the following equation ... 

An alternative approach to the synthesis of isocoumarins which probably proceeds through the intermediacy of 2-carboxybenzyl ketones is based on the oxidative cleavage of indan-1-ones (76JCS(P1)1438). Although ozonolysis of the silyl enol ether (505) leads to the 2-hydroxy-2-methylindan-l-one (506), periodate oxidation of which gives the isocoumarin, a more convenient and direct route involves ozonolysis of the enol trifluoroacetate (Scheme 182). This synthesis is especially attractive for the preparation of isotopically labelled isocoumarins, since the precursors of the indanones, arylpropanoic acids or acrylophenones, are readily available bearing labels at specific sites. 

Thus, (-)-frontalin 19 (Scheme 4), pheromone of Dentroctonus Frontalis bark beetle, was obtained from the methyl ketone 12 through the intermediacy of the adduct 20, that was obtained as the sole transformation product by reaction with 4-methyl-pent-4-enylmagnesium bromide in THF. The latter material, once O-benzy-lated, with acid hydrolysis yielded 22, and was then converted into 23 by periodate oxidation, followed by NaBH reduction. 

A special category of ethers are trimethylsilyl ethers. Trimethylsilyl ethers of primary alcohols, on treatment with Jones reagent, give acids [590]. On treatment with A-bromosuccinimide under irradiation, trimethylsilyl ethers yield esters [744]. Secondary alkyl trimethylsilyl ethers are converted into ketones by oxidation with both reagents [590, 744, 981]. Oxidation with Jones reagent is regiospecific the 2-ferf-butyldimethylsilyl 11-Krf-butyldiphenylsilyl ether of 2,11-dodecanediol is oxidized only in the sterically less hindered position [590]. Trimethylsilyl ethers of tertiary alcohols are degraded by periodic acid to carboxylic acids with shorter chains [755] (equations 336-339). 

An oxidative Prins cyelization forming a six-membered ring system takes place when the bicyclo[3.2.1]oct-7-ene system is treated with pyridinium chlorochromate. The tricyclic ketone 5 is isolated in 67% yield and can then be converted into natural products of the seychellene type18. A similar cyelization building a seychellene precursor has been described19. Sodium periodate oxidation of the diol leads spontaneously to the tricyclic carbon skeleton 6 giving a 3 1 mixture of stereoisomers. 

Chiral amines. Synthesis of chiral amines from ketones through reductive amination with (-(-)- or (-)-norephedrine requires selective C-N bond cleavage. Sacrificial dissection of the chiron by periodate oxidation completes the operation. 

Bessonova and Yunusov (76) isolated folisine Ci5H]7N04 mp 236-237° [ In —123° (MeOH) from H. foliosum and established structure 90 for the alkaloid by spectroscopic studies and by periodate oxidation to ketone 91. Dubinidine methiodide was converted into folisine by reaction with pyridine. 

The carbonyl stretching frequency of aldehydes and ketones is found at 1730-1665 cm For example, the acyclic form of some aldoses and ketoses (in a lyophili-zate of the equilibrium mixture of mutarotation) produces a very weak band (Tipson and Isbell, 1962) at 1718 cm . Kuhn (1950) attributed the band at 1613 cm exhibited by periodate-oxidized methyl a-D-glucopyranoside to aldehydic carbonyl. Periodate-oxidized cellulose has only a very weak band (Rowen et ai, 1951), and exists mainly as the hemialdal —CH(OH)—O—CH(OH)— (Spedding, 1960), formed by hydration of two aldehyde groups per oxidized residue. 

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