Oxidation enals

Acetylene is also protected as propargyl alcohol (300)[2H], which is depro-tected by hydrolysis with a base, or oxidation with MnOi and alkaline hydrolysis. Sometimes, propargyl alcohols are isomerized to enals. Propargyl alcohol (300) reacts with 3-chloropyridazine (301) and EtiNH to give 3-diethylami-noindolizine (303) in one step via the enal 302[2I2]. Similarly, propargyl alcohol reacts with 2-halopyridines and secondary amines. 2-Methyl-3-butyn-2-ol (304) is another masked acetylene, and is unmasked by treatment with KOH or NaOH in butanol[205,206,213-2l5] or in situ with a phase-transfer cata-lyst[2l6]. 

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). 

Work at Rhc ne-Poulenc has involved a different approach to retinal and is based on the paHadium-cataly2ed rearrangement of the mixed carbonate (41) to the aHenyl enal (42). Isomerization of the aHene (42) to the polyene (43) completes the constmction of the carbon framework. Acid-catalyzed isomerization yields retinal (5). A decided advantage of this route is that no by-products such as triphenylphosphine oxide or sodium phenylsulfinate are formed. However, significant yield improvements would be necessary for this process to compete with the current commercial syntheses (25—27) (Fig. 9). 

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, ... 

Williams and Rastetter also accomplished an elegant synthesis of ( )-hyalodendrin (83) in 1980 [39]. Beginning with the sarcosine anhydride-derived enolic aldehyde 78, silyl protection of the enal enabled alkylation of the glycine center with benzyl bromide and thiolation using LDA and monoclinic sulfur a la Schmidt. After protection of the thiol with methylsulfenyl chloride and deprotection of the silyl ether, the enol was sulfenylated with triphenylmethyl chlorodisulfide to afford bis(disulfide) 82 as a 2 1 mixture of diastereomers favoring the anti isomer. Reduction of the disulfides with sodium borohydride and oxidation with KI3 in pyridine afforded ( )-hyalodendrin (83) in 29 % yield (Scheme 9.4). 

In relation to the above mechanisms, direct observation of oxidative cyclizations of nickel-enal complexes such as 191 with Ni(COD)2/R3P (1 equiv.) (R = Cy or Ph) to nickelacycles 192 was reported (Scheme 89).432... 

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. 

Hetero Pauson-Khand reactions with an aldehyde or ketone component have been shown to afford synthetically versatile y-butyrolactones. Buchwald [50] and Crowe [51] independently showed that aliphatic enones and enals react with CO under Cp2Ti(PMe3)2 mediation (Scheme 11). CO insertion and thermal (or oxidative) decomposition gave diastereomerically pure bicyclic y-butyrolactones and stable Cp2Ti(CO)2. Imines did not react under the reaction conditions. 

The same rhodium precursor, (S Rh,/ c)-[(Tl -C5Me5)Rh (l )-Prophos (H20)] (SbFg)2, promotes the reaction between the nitrones A-benzylideneaniline A-oxide or 3,4-dihydroisoquinoline A-oxide with other enals different from methacrolein (Scheme 10). The cycloadducts were prepared with excellent regioselec-tivity, perfect endo selectivity, and enantiomeric excesses up to 94% [35]. 

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... 

A2-Butenolides. A simple route to A2-butenolides from a,/5-enals involves conversion to the O-trimethylsilylcyanohydrin (cyanotrimethylsilane, 4, 542 -543 5, 720 722 6, 632 633), which is then oxidized by PDC (3 equivalents) in DMF. The sequence from geraniol is typical (equation I). 

The reaction provides access to a number of quinoxaline-1,4-dioxide derivatives, by reaction of the benzofurazan oxide with 1,3-diketones, 3-ketoesters, enals, enamines, phenols and a, 3-unsaturated ketones. 

Bassette and Keeney (1960) ascribed the cereal-type flavor in dry skim milk to a homologous series of saturated aldehydes resulting from lipid oxidation in conjunction with products of the browning reaction. The results of Parks and Patton (1961) suggest that saturated and unsaturated aldehydes at levels near threshold may impart an off-flavor suggestive of staleness in dry whole milk. Wishner and Keeney (1963) concluded from studies on milk exposed to sunlight that C6 to Cn alk-2-enals are important contributors to the oxidized flavor in this product. Parks et al. (1963) concluded, as a result of quantitative carbonyl analysis and flavor studies, that alk-2-4-dienals, especially... 

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... 

Rather than a direct oxidation to dienone, the secondary alcohol suffers an oxidative transposition to give a mixture of enone and enal. 

PCC reacts with tertiary allylic alcohols, forming an intermediate chromate ester that evolves giving a conjugated enone or enal. Sometimes, the isomeric chromate ester produces the epoxidation of the alkene, giving an epoxy alcohol that can be further oxidized to an epoxy ketone. 

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