Oxidation of Enals

Electrophilic acyl azoUum species can be generated from the Breslow intermediate in the presence of a mild oxidant such as Mn02 [112], TEMPO [113], or a quinone 

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The oxidation of enals 144 using sodium chlorite and hydrogen peroxide under mild conditions gave the corresponding acids 145. When acids 145 were treated with polyphosphoric acid at high temperatures, the desired chromones 130 were obtained in predominantly very high yields [66] (Scheme 45). 

Scheme 18.28 Dihydropyranones formed via oxidation of enals, according to You and coworkers.

Citral is prepared starting from isobutene and formaldehyde to yield the important C intermediate 3-methylbut-3-enol (29). Pd-cataly2ed isomeri2ation affords 3-methylbut-2-enol (30). The second C unit of citral is derived from oxidation of (30) to yield 3-methylbut-2-enal (31). Coupling of these two fragments produces the dienol ether (32) and this is followed by an elegant double Cope rearrangement (21) (Fig. 6). 

Oxidation Processes Scheidt and co-workers have employed cascade oxidation pathways from aUyhc or propargylic alcohols to afford unsaturated ester products 25. In situ oxidation of an unsaturated alcohol 21 to the enal 22 using MnO, ... 

Selective oxidation of allylic alcohols.1 This zircononcene complex when used in catalytic amount can effect an Oppenauer-type oxidation of alcohols, including allylic ones, in the presence of a hydrogen acceptor, usually benzaldehyde or cyclohexanone. This system oxidizes primary alcohols selectively in the presence of secondary ones. Thus primary allylic alcohols are oxidized to the enals with retention of the configuration of the double bond in 75-95% yield. The method is not useful for oxidation of propargylic alcohols. 

RuCl/TMP), as RuCl2(TMP)/(Cl2pyNO)/CDCl3, oxidised alkenes RCHj=CH to the aldehydes RCH CHO. Oxidation of 1,3-dienes gave the unsaturated aldehyde -thus 1-phenyl-l,3-butadiene gave the p, y-unsaturated aldehyde 4-phenylbut-3-enal (styrylacetaldehyde) RuClj(TDCPP) also effected these reactions [584],... 

It is noteworthy that allylic alcohols are oxidized to products with retained configuration of the olefinic bond. Geraniol and nerol were oxidized to the corresponding ( )-and (Z)-a-enals, respectively. As expected, primary alcohols were oxidized faster than secondary ones with the RuCl2(PPh3)3/BTSP system with relative rates from 20-40 1. The new system was applicable for the selective oxidation of primary-secondary diols... 

Oxidation of a p,y-ena/.2 The gradual addition of CIQH4CO3H (2 equiv.) to the p, y-enal 1 in refluxing CHC13 (17 hours) results in formation of the phytotoxin dihydroactinidiolide (2) in 83% yield. However, if the reaction is conducted in... 

To avoid the C4a-C5 epoxide issue, a new route to the keto enal "73-a" was pursued [Scheme 15]. Triol 71 could be attained via LAH reduction of epoxy diol 49, and acylation of 71 would lead to the acetate 72 whose stereochemistry was assigned by X-ray analysis. The subsequent TPAP oxidation of 72 followed by deacylation and PCC oxidation led to the keto-enal "73-a" in 73% overall yield. 

Oxidation of ailylic CH3 groups.1 "This reaction is possible with minimal side reactions with SeC>2 supported on silica g l and r-butyl hydroperoxide (70%) in hexane or CH2C12. The main products are primary alcohols, sometimes accompanied by the corresponding a,/ -enals. The ailylic alcotiol formed has the more stable configuration of the double bond (second example). 

Alkaline silver oxide is the most satisfactory reagent for oxidation of the aldehyde 3 to the acid 4.2 This reagent has been recommended for oxidation of aryl aldehydes (1,1012-1013), but only moderate yields have been reported for oxidation of a,/ -enals with Ag20.3 Apparently, the successful results in the oxidation of 3 are the result of the activating effect of the keto group. 

Oxidation of a,p-enals. Sodium chlorite is superior to other reagents for oxidation of oc,/l-unsaturated aldehydes to the corresponding carboxylic acid, particularly of aldehydes containing an ct-methylene group. In addition, the oxidation is stereospecific. 2-Methyl-2-butene2 was used as the chlorine scavenger. 

Chiral asymmetric epoxidations have been intensively investigated due to the fundamental importance of epoxides in organic chemistry [69, 70], Nevertheless, catalytic asymmetric Lewis acid epoxidation of a,/i-unsaturated aldehydes remains a challenge to chemists. Recently, Jorgensen and co-workers developed the first asymmetric approach to epoxides of enals, in which chiral pyrrolidine 11 was used as catalyst and H2O2 as oxidant, thus following the concept of iminium catalysis (Scheme 3.9) [71-73]. Importantly, reaction conditions are tolerant to a variety of functionalities and this chemical transformation proceeds in different solvents, with no loss of enantioselectivity. (For experimental details see Chapter 14.13.1). 

Desilylation of 135 afforded alcohol 136, which was oxidized to enal 137 by Parikh-Doering oxidation in 62% yield. Removal of the p-nitrobenzoyl group and the menthyl group resulted in completion of the total synthesis of mniopetal F (6). 

Two short syntheses of P-lapachone from readily available naphthols and 3-methylbut-2-enal via a mild phenyl-boronic acid mediated cyclization to 2//-chromenes have been reported. Catalytic hydrogenation of 2H-chromenes with H /Pd-C in ethyl acetate afforded the corresponding naturally occurring chromanes (72) and (73). Oxidation of the adequate chromane with an excess of cerium ammonium nitrate (CAN) furnished P-lapachone in 62% yield [153]. 

The same proline derivative 77 was found to catalyze a highly enantioselective synthesis of 5-hydroxyisoxazolidines 79 hy tandem reaction of -protected hydroxylamines and enals. In situ oxidation of 79 by NaC102 afforded directly /V-protected 5-isoxazolidinones 80 in high yield and ee... 

Oxidation of allylsUanes to a, -enals. 2-Substituted allylsilanes are oxidized to a,p-enals by reaction with QH5l=0 (2 equiv.) activated with BF, etherate (1 equiv.) in dioxanc. 

In a short known reaction sequence, enal 250 was obtained from commercially available material 184). With methylamine and magnesium sulfate imine 251 was formed and combined with acyl chloride 252 185) (>4 steps). The use of low temperatures for this acylation led exclusively to the less substituted dienamide 253. The desired basic skeleton of dendrobine 254 was obtained by cyclizing 253 at 180°C in an acceptable 50% yield, Adduct 254 was accompanied by small amounts of the exo-adduct. Epoxidation led exclusively to exo-epoxide 255, which by means of trimethylsilyltriflate was converted into the allylic silyl ether. Acid treatment liberated the hydroxy group and subsequent oxidation of alcohol 256 led to enone 163, an intermediate of Inubushi s dendrobine synthesis and thus concluded this formal synthesis. The intermediate 163 was obtained from commercially not available materials in seven steps in 22.5% overall yield. To reach ( )-dendrobine according to Inubushi et al. would afford six additional steps, reducing the overall yield to 0.4% without including the preparation of the starting materials from commercially available compounds. 

Treatment of 1,1-disubstituted epoxides of the gibberellin family with sulfuiyl chloride results in the formation of the corresponding a,3-enal in good yield, as shown in equation (31). Four examples were reported in which alcohols, esters, lactones and sdkenes survive. The postulated mechanism involves an electrophilic opening of the epoxide with elimination, followed by oxidation of the primary chlorosulfate ester. A steroidal 3-spirooxirane also undergoes this reaction, but the yield is poor and several products are obtained, suggesting that the overall scope of this reaction may be limited. 

OL-PhenylseUno aldehydes. Oxidation of allylic f-butyldimethylsilyl ethers remits in a-phenylseleno aldehydes, which on desilylation give a-phenylseleno-a,/9-unsaturated enals. A typical example is formulated in equation (I). 

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