Aldehydes enol acetates

Cationic olefin cyclization of aldehyde enol acetates.1 The enol acetate (2) of citronellal (1) undergoes cyclization to dihydrocyclocitral (3) in the presence of... 

Allylic halogenation of aldehyde enol acetates, e.g. 23, derived from norbornadiene provided an elegant and efficient construction of the tricyclic structure 24 found in many sesquiterpenes such as cyclosativene, cyclocopacamphene, longicyclene, a-santalene and its derivatives. This rearrangement in fact arises from an electrophilic addition to a multiple bond with participation of the homoallylic bond. The tricyclic skeleton was also obtained successfully by treatment of 5-methylenenorborn-2-ene with A-bromosuccinimide in aqueous dimethyl sulfoxide which gave 5-bromo-2-hydroxymethyltricyclo[2.2.1.0 ]heptane (25) in high yield. 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

Owing to the instability of a-halogenoaldehydes it is occasionally preferable to use more stable derivatives, such as enol acetate prepared according to Bedoukian s method (204) and a-bromoacetals (4, 8, 10, 16, 22, 67, 101, 426). An advantage is said to be in the yield however, this appears to be slight. The derivatives react in the same sense as the aldehydes themselves, that is, the acetal group as the more polarized reacts first and enters the C-4 position. It is likely that the condensation and cyclization occur by direct displacement of alkoxide ions. Ethyl-a,/3-dihalogeno ethers (159, 164, 177, 248) have also been used in place of the free aldehydes in condensation with thioamides. 

Acetic anhydride can be used to synthesize methyl ketones in Friedel-Crafts reactions. For example, benzene [71-43-2] can be acetylated to furnish acetophenone [98-86-2]. Ketones can be converted to their enol acetates and aldehydes to their alkyUdene diacetates. Acetaldehyde reacts with acetic anhydride to yield ethyhdene diacetate [542-10-9] (18) ... 

Finally, the importance of quinolinium salts to dye chemistry accounts for the long, productive history of their synthesis. The reaction of A/-methylformanihde with ketones, aldehydes, ketone enamines, or enol acetates in phosphoryl chloride leads to high yields of /V-methylquinolinium salts (60). 

Other methods of protecting the aldehyde group include formation of an enol acetate, an enamine, or an imine (174,175). In the enamine route, regeneration of the aldehyde is accompHshed simply by the addition of water. 

The dimethyl acetal (94) is readily prepared from the 22-aldehyde (93) by direct reaction with methanol in the presence of hydrogen chloride. Ena-mines (95) are formed without a catalyst even with the poorly reactive piperidine and morpholine.Enol acetates (96) are prepared by refluxing with acetic anhydride-sodium acetate or by exchange with isopropenyl acetate in pyridine.Reaction with acetic anhydride catalyzed by boron trifluoride-etherate or perchloric acid gives the aldehyde diacetate. 

Both alcohols and phenols add to ketenes to give carboxylic esters (R2C=C= O+ROH —> R2CHC02R). This has been done intramolecularly (with the ketene end of the molecule generated and used in situ) to form medium- and large-ring lactones. In the presence of a strong acid, ketene reacts with aldehydes or ketones (in their enol forms) to give enol acetates. 

Mukaiyama aldol reactions have been reported, usually using chiral additives although chiral auxiliaries have also been used. This reaction can also be run with the aldehyde or ketone in the form of its acetal R R C(OR )2> in which case the product is the ether R COCHR2CR R OR instead of 27. Enol acetates and enol ethers also give this product when treated with acetals and TiCLi or a similar catalyst. When the catalyst is dibutyltin bis(triflate), Bu2Sn(OTf)2, aldehydes react, but not their acetals, while acetals of ketones react, but not the ketones themselves. 

Trialkylstannyl enolates can be prepared from enol acetates by reaction with trialkyltin alkoxides and are sufficiently reactive to add to aldehydes. Uncatalyzed addition of trialkylstannyl enolates to benzaldehyde shows anti stereoselectivity.31... 

K. Naemura, K. Kittaka, M. Murata, H. Ida, K. Hirose, Y. Tobe, Lipase-Catalyzed Enantioselective Alcoholysis of Enol Acetates Optical Resolution of Ketones and Aldehydes Using Lipases in Organic Solvents , Enantiomer 1996, 1, 219-222. 

The approach to polyketide synthesis described in Scheme 5.2 requires the relatively nontrivial synthesis of acid-sensitive enol acetals 1. An alternative can be envisioned wherein hemiacetals derived from homoallylic alcohols and aldehydes undergo dia-stereoselective oxymercuration. Transmetallation to rhodium could then intercept the hydroformylation pathway and lead to formylation to produce aldehydes 2. This proposal has been reduced to practice as shown in Scheme 5.6. For example, Yb(OTf)3-cata-lyzed oxymercuration of the illustrated homoallyhc alcohol provided organomercurial 14 [6]. Rhodium(l)-catalyzed hydroformylation of 14 proved successful, giving aldehyde 15, but was highly dependent on the use of exactly 0.5 equiv of DABCO as an additive [7]. Several other amines and diamines were examined with variation of the stoichiometry and none proved nearly as effective in promoting the reaction. This remarkable effect has been ascribed to the facilitation of transmetallation by formation of a 2 1 R-HgCl DABCO complex and the unique properties of DABCO when both amines are complexed/protonated. 

From enol acetates 2-3 Treatment of aldehydes or ketones with base... 

An extremely useful alternative method, employing catalytic amounts of Pd° complexes, rather than stoichiometric (or near stoichiometric) quantities of Pd11 salts has been developed. The oxa-tr-allyl complex is accessed via allyl p-ketocarboxylates360-363 or allyl alkenylcarbonates360,361,363,364 in the intramolecular cases and via enol acetates,361,363,365 enol silyl ethers361,366 or ketene silyl acetals367 with allyl carbonates in the intermolecular cases. The products of these reactions are the corresponding a,p-un-saturated ketones, aldehydes and esters (equations 138-142). 

Yamamoto has recently described a novel catalytic, asymmetric aldol addition reaction of enol stannanes 19 and 21 with aldehydes (Eqs. 8B2.6 and 8B2.7) [14]. The stannyl ketones are prepared solvent-free by treatment of the corresponding enol acetates with tributyltin methoxide. Although, in general, these enolates are known to exist as mixtures of C- and 0-bound tautomers, it is reported that the mixture may be utilized in the catalytic process. The complexes Yamamoto utilized in this unprecedented process are noteworthy in their novelty as catalysts for catalytic C-C bond-forming reactions. The active complex is generated upon treatment of Ag(OTf) with (R)-BINAP in THF. Under optimal conditions, 10 mol % catalyst 20 effects the addition of enol stannanes with benzaldehyde, hydrocinnamaldehyde, or cinnamaldehyde to give the adducts of acetone, rerf-butyl methyl ketone (pinacolone), and acetophenone in good yields and 41-95% ee (Table 8B2.3). 

The mechanism of the Perkin condensation involving benzal acetate has been revised.17 It has been demonstrated that the enolate of the gem-diacetate derived from the aromatic aldehyde and acetic anhydride-rather than the enolate of acetic anhydride itself-adds to the aldehyde in the key step. The deprotonation of the diacetate to the enolate appeared to be assisted electrophilically by the neighbouring acetate group. 

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