Aldehydes double oxidation

Physical and Chemical Properties. The (F)- and (Z)-isomers of cinnamaldehyde are both known. (F)-Cinnamaldehyde [14371-10-9] is generally produced commercially and its properties are given in Table 2. Cinnamaldehyde undergoes reactions that are typical of an a,P-unsaturated aromatic aldehyde. Slow oxidation to cinnamic acid is observed upon exposure to air. This process can be accelerated in the presence of transition-metal catalysts such as cobalt acetate (28). Under more vigorous conditions with either nitric or chromic acid, cleavage at the double bond occurs to afford benzoic acid. Epoxidation of cinnamaldehyde via a conjugate addition mechanism is observed upon treatment with a salt of /-butyl hydroperoxide (29). 

New functional groups can arise as a result of oxidation of the compounds mentioned above. For example, the oxidation of a thiol yields a disulfide (R-S-S-R). Double oxidation of a primary alcohol (R-CH2-OH) gives rise initially to an aldehyde (R-C(O)-H), and then to a carboxylic acid (R-C(O)-OH). In contrast, the oxidation of a secondary alcohol yields a ketone (R-C(O)-R). The carbonyl group (C=0) is characteristic of aldehydes and ketones. 

The unsaturated 3a-acetoxy-17-formyl-16-etiocholen-lip-ol-18-one lip,18-lactol is hydrogenated in the presence of palladium catalyst to saturate the 16,17-double bond, and then saturated aldehyde are oxidized by treatment with chromic oxide in pyridine to give 3a-acetoxy-lip-ol-18-one-pregnane lip,18-lactone 17-carboxylic acid. 

Barton oxidation was the key to form the 1,2-diketone 341 in surprisingly high yield, in order to close the five-membered ring (Scheme 38). The conditions chosen for the deprotection of the aldehyde, mercuric oxide and boron trifluoride etherate, at room temperature, immediately led to aldol 342. After protection of the newly formed secondary alcohol as a benzoate, the diketone was fragmented quantitatively with excess sodium hypochlorite. Cyclization of the generated diacid 343 to the desired dilactone 344 proved very difficult. After a variety of methods failed, the use of lead tetraacetate (203), precedented by work performed within the stmcmre determination of picrotoxinin (1), was spectacularly successful (204). In 99% yield, the simultaneous formation of both lactones was achieved. EIcb reaction with an excess of tertiary amine removed the benzoate of 344 and the double bond formed was epoxidized with peracid affording p-oxirane 104 stereoselectively. Treatment of... 

The nature of the products obtained is dependent on the choice of oxidant, the structure suirounding the double bond, the reaction conditions, and the woik-up procedures. In general, if the double-bonded carbon is tertiary, then ketones or secondary alcohols can be easily obtained. However, if the carbon is secondary, the products will be primary alcohols, aldehydes or, most likely, carboxylic acids. Because they are very susceptible to further oxidation, the most chfficult of these products to obtain are the aldehydes. Selective oxidants and mild conditions are required to produce good yields. 

The (3-methyl homoallylic alcohol moiety of both anti- and 5yn-configurations is a characteristic structural element of a number of macrolides and polyether antibiotics. Reactions of crotylmetal (2-butenylmetal) reagents with carbonyl substrates provide access to acyclic stereo- and enantioselective syntheses of p-methyl homoallylic alcohols. The alkene moiety of these alcohols can be further elaborated into aldehydes by oxidative cleavage of the double bond, leading to aldol-type products. 

Oxidations. Alcohols undergo rapid oxidation when exposed to PhI(0Ac)2-Alj03 (with microwave irradiation) or PhlCOAc) with catalytic amount of TEMPO. The latter procedure is mild and selective. Primary alcohols can be converted to aldehydes without oxidizing secondary alcohols. (Z)-Allylic alcohols give (Z)-enals, 1,3-diols afford 3-ketols, and cholesterol is oxidized to the 5-en-one without migration of the double bond. Tertiary cyclopropanols fragment to release carboxylic acid and alkene moieties. ... 

In the second example27 the fungus Geotrichum candidum is used and (5)-2-methyl-y-bu-tyrolactone is directly obtained from ( )-3-(l,3-dioxolan-2-yl)-2-buten-l-ol after stereospecific double bond hydrogenation, acetal hydrolysis and aldehyde oxidation followed by spontaneous cyclization. It is interesting to note that the aldehyde is oxidized in this reaction. 

Heyns and Blazejewicz427 studied the oxidation of alcohols, in water or organic solvents, by oxygen at platinum catalysts under mild conditions. Primary alcohols gave aldehydes or carboxylic acids according to the reaction conditions secondary alcohols gave ketones. This method is especially suitable for preparation of long-chain aldehydes double bonds are not attacked. 

Aldehydes and ketones are prepared by the oxidation of primary and secondary alcohols, respectively. Aldehydes can be further oxidized to carboxylic acids, but ketones resist oxidation. Thus, aldehydes are oxidized by Tollens reagent (Ag" ) and Benedict s solution (Cu ), whereas ketones are not. A characteristic reaction of both aldehydes and ketones is the addition of hydrogen to the carbonyl double bond to form alcohols. In a reaction that is very important in sugar chemistry, an alcohol can add across the carbonyl group of an aldehyde to produce a hemiacetal. The substitution reaction of a second alcohol molecule with the hemiacetal produces an acetal. Ketones can undergo similar reactions to form hemiketals and ketals. 

Reactions of Saturated Aldehydes with NHCs via Double Oxidation... 

In 2013, the Chi group realized an NHC-catalyzed asymmetric p-functional-ization reaction of aldehydes via the transformation of saturated aldehydes to formal Michael acceptors via double oxidation. By using the catalyst derived from the chiral amino indanol triazolium salt in combination with quinone as the oxidant, the p-aryl substituted saturated aldehydes were converted to the o,p-unsaturated acyl azolium intermediates which further reacted with 1,3-dicarbonyl compounds or p-keto esters to generate the corresponding 5-lactones. It was found the use of LiCl and 4 A MS as additives was beneficial to improve the ee s of the products. Notably, the p-alkyl substituted saturated aldehydes were not viable substrates, probably due to the reduced acidity of the p-C—H bonds (Scheme 7.118). 

Detailed review of studies on the auto- and catalytic-oxidation of unsaturated aldehydes in the liquid phase may be found in [2,9], Here we just note the main specific feature of the unsaturated aldehydes oxidation, briefly cited in Section 5.2. It implies that the free-radical chain process of the aldehyde group oxidation stimulates undesirable reactions, including the copolymerization of aldehyde with oxygen through the aldehyde s double bond, and in some cases also the copolymerization of the reaction products, the unsaturated acids and peroxyacids with oxygen. The oxidation reactions of unsaturated aldehydes are defined as the multicentered chain processes with two types of reaction centers acyl monomeric and polyperoxide free radicals. 

The reactions of the saccharides are characteristic of carbonyl, alcohol, and hemiacetal groups. They include oxidation of the aldehyde to the carboxy function of aldonic acifls, double oxidation to aldaric acids, oxidative cleavage of vicinal diol units, reduction to alflitols, condensations,... 

SCHEME 25.89. SOMO-enamine activation and double oxidative C C bond formation at the a-position of aldehydes. 

Both oxides of silver, Ag20 and AgO, have been used for aldehyde oxidations. The silver]I) reagent has mainly been applied in transformations of aliphatic [83] and aromatic aldehydes [84], less so in oxidations of organometallic complexes bearing an aldehyde function [85] or a,P-unsaturated compounds [86]. Use of the silver(II) oxide is less common [70, 87], probably due to its limited availability and high cost Cyanide ions catalyze this oxidation in methanol leading to carboxylic acids (and not to esters as compared with manganese) [70]. In reactions with a,p-unsaturated aldehydes, double bond isomerizations have been observed [70]. Less common silver re-... 

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). 

---