Unsaturated Ethers and Acetals

The hydroformylation of ethers has been known for a long time, but only recently has it been investigated systematically. 

In vinyl ether, the formyl group goes on the a-carbon atom, under standard hydroformylation conditions (125 °C/200-300 atm). Butyl vinyl ether gives a-n-butoxypropionaldehyde in 31% yield [24]. 

It is not yet clear whether the electron withdrawing influence of the ether oxygen is noticeable even across a methylene group. Ethyl allyl ether [24] e.g. was reported to give 30% p-ethoxyisobutyraldehyde with only 4 % y-ethoxy-n-butyraldehyde. The methacrolein isolated (6 %) was probably formed by loss of alcohol from the formed p-ethoxy-n-butyraldehyde. 

On the other hand allyl phenyl ether was found to give only phenoxy-butyraldehyde with a selectivity up to 84% [971]. 

In analogy with the results of unsaturated esters, unbranched aldehydes can also be obtained from vinyl ethers at higher temperatures. Thus, 

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TABLE VI. HYDROFORMYLATION OF UNSATURATED ETHERS AND ACETALS Continued)... 

The lower members of the homologous series of 1. Alcohols 2. Aldehydes 3. Ketones 4. Acids 5. Esters 6. Phenols 7. Anhydrides 8. Amines 9. Nitriles 10. Polyhydroxy phenols 1. Polybasic acids and hydro-oxy acids. 2. Glycols, poly-hydric alcohols, polyhydroxy aldehydes and ketones (sugars) 3. Some amides, ammo acids, di-and polyamino compounds, amino alcohols 4. Sulphonic acids 5. Sulphinic acids 6. Salts 1. Acids 2. Phenols 3. Imides 4. Some primary and secondary nitro compounds oximes 5. Mercaptans and thiophenols 6. Sulphonic acids, sulphinic acids, sulphuric acids, and sul-phonamides 7. Some diketones and (3-keto esters 1. Primary amines 2. Secondary aliphatic and aryl-alkyl amines 3. Aliphatic and some aryl-alkyl tertiary amines 4. Hydrazines 1. Unsaturated hydrocarbons 2. Some poly-alkylated aromatic hydrocarbons 3. Alcohols 4. Aldehydes 5. Ketones 6. Esters 7. Anhydrides 8. Ethers and acetals 9. Lactones 10. Acyl halides 1. Saturated aliphatic hydrocarbons Cyclic paraffin hydrocarbons 3. Aromatic hydrocarbons 4. Halogen derivatives of 1, 2 and 3 5. Diaryl ethers 1. Nitro compounds (tertiary) 2. Amides and derivatives of aldehydes and ketones 3. Nitriles 4. Negatively substituted amines 5. Nitroso, azo, hy-drazo, and other intermediate reduction products of nitro com-pounds 6. Sulphones, sul-phonamides of secondary amines, sulphides, sulphates and other Sulphur compounds... 

N. Moufid, Y. Chapleur, and P. Mayon, Radical cyclisation of some unsaturated carbohydrate-derived propargyl ethers and acetals, J. Chem. Soc. Perkin Trans, p. 999 (1992). 

Palladium was about half as active as rhodium, and platinum and ruthenium were almost inactive for the hydrogenation of isopropenyl methyl ether. Since these metals showed the same order of activity for the hydrogenolysis of acetone diisopropyl acetal, it has been suggested that the dissociation of the acetal to unsaturated ether and alcohol to form an equilibrium mixture (eq. 13.2) constitutes the first step in the hydrogenolysis of acetals. Hydrogenation then removes the unsaturated ether and allows further conversion of the acetal to the unsaturated ether. 

As with other intramolecular ene reactions, this reaction is best suited to the preparation of cyclopentanes, but can also be used for the preparation of cyclohexanes. The reaction cannot be used for the formation of cyclopropanes or cyclobutanes since the unsaturated carbonyl compound is more stable than the ene adduct. 8,e-Unsaturated ketones (167) do not give cyclobutanes (171) by enolization to give (170) followed by a type I reaction but instead give cyclohexanones (169) by enolization to give (168) followed by a type II reaction. Alkynes can replace alkenes as the enophile. Enols can be prepared from pyrolysis of enol esters, enol ethers and acetals and from -keto esters and 1,3-dicaibonyl compounds. Tlie reaction is well suited to the preparation of fused or bridged bicyclic and spirocyclic compounds. Tandem ene reactions in which two rings are formed in one pot from dienones have also been described. The examples discussed below 2-i63 restricted to those published since Conia and Le Perchec s 1975... 

There is now general agreement that Vilsmeier reactions with acetals, ketals, and the corresponding thio derivatives proceed by loss of a molecule of alcohol or thiol to give the reactive unsaturated ether or thioether with cyclic ketals the alcohol remains tethered, and may be chlorinated. The acetals and ketals are often more readily available than the unsaturated ethers, and yields of products are similar. A wide range of aliphatic and alicyclic acetals and ketals has been formylated the reaction can tolerate bulky groups at either end of the double bond, as is shown for compound 64 (Eq. 51). Products are isolated as iminium sails... 

Two reports of Simmons-Smith methylene addition (iodomethylzinc iodide) on to A -olefinic steroids contain several points of disagreement. The earlier paper states that cholest-5-en-3a-ol (epicholesterol) reacts readily to give the 5a,6a-methano-derivative (165). A stereospecific reaction in this sense would accord with earlier indications that a suitably placed hydroxy-group directs the approach of the reagent towards the same side of the olefinic bond. The 3/ -alcohol (cholesterol), as well as the methyl ethers and acetates of both alcohols, apparently failed to react. The later paper, by different authors, states that both unsaturated alcohols react, each giving a similar mixture of the 5a,6a- and 5) ,6/ -methano-adducts. with no evidence for control by the oxygen function. 

Preparation of o,/3-Unsaturated Carbonyl Compounds by the Reactions of Silyl Enol Ethers and Enol Acetates with Ally Carbonates... 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

The reaction of butyllithium with 1-naphthaldehyde cyclohexylimine in the presence of (/C )-l,2-diphenylethane-1,2-diol dimethyl ether in toluene at —78 °C, followed by treatment with acetate buffer, gave 2-butyl-1,2-dihydronaphthalene-l-carbaldehyde, which was then reduced with sodium borohydride in methanol to afford (1 R,2.S)-2-butyl-1 -hydroxymcthyl-1,2-dihydronaphthalene in 80% overall yield with 91 % ee83. Similarly, the enantioselective conjugate addition of organolithium reagents to several a,/J-unsaturated aldimines took place in the presence of C2-symmetric chiral diethers, such as (/, / )-1,2-butanediol dimethyl ether and (/, / )- ,2-diphenylethane-1,2-diol dimethyl ether. 

Silyl enol ethers and ketene acetals derived from ketones, aldehydes, esters and lactones are converted into the corresponding o/i-unsaturated derivatives on treatment with allyl carbonates in high yields in the catalytic presence of the palladium-bis(diphenylphosphino)ethane complex (32). A phosphinc-free catalyst gives higher selectivity in certain cases, such as those involving ketene acetals. Nitrile solvents, such as acetonitrile, are essential for success. 

Using the above procedures, allyl a-azido alkyl ethers of type 281 were prepared by employing an unsaturated alcohol such as allyl alcohol [76] (Scheme 32). The reaction of an aldehyde with allyl alcohol and HN3 in a ratio of 1 3 9 carried out in the presence of TiCl4 as catalyst provided azido ethers 281, 283, and 285 in 70-90% yield. The ratio of reagents is critical to ensure a high yield of azido ether and to prevent formation of acetal and diazide side products [75]. Thermolysis of azido alkenes 281, 283, and 285 in benzene (the solvent of choice) for 6-20 h led to 2,5-dihydrooxazoles 282,284, and 286, respectively, in 66-90% yield. 

Dialkyl(trimethylsilyl)phosphines undergo 1,4-addition to a,/3-unsaturated ketones and esters to give phosphine-substituted silyl enol ethers and silyl ketene acetals, respectively. A three-component coupling reaction of a silylphosphine, activated alkenes, and aldehydes in the presence of a catalytic amount of GsF affords an aldol product (Scheme 76).290 291... 

Hirst and Woolvin169 preferentially methylated positions 3, 4 and 6 by the use of glucal, an unsaturated sugar derivative having a 1,2-olefinic bond, introduced by the reduction of triacetyl-a-D-glucopyranosyl bromide with zinc dust and acetic acid. By the action of an ethereal solution of perbenzoic acid on an aqueous solution of 3,4,6-trimethyl-glucal a sirupy product was obtained. This was shown to contain... 

In contrast to the other large cats, the urine of the cheetah, A. jubatus, is practically odorless to the human nose. An analysis of the organic material from cheetah urine showed that diglycerides, triglycerides, and free sterols are possibly present in the urine and that it contains some of the C2-C8 fatty acids [95], while aldehydes and ketones that are prominent in tiger and leopard urine [96] are absent from cheetah urine. A recent study [97] of the chemical composition of the urine of cheetah in their natural habitat and in captivity has shown that volatile hydrocarbons, aldehydes, saturated and unsaturated cyclic and acyclic ketones, carboxylic acids and short-chain ethers are compound classes represented in minute quantities by more than one member in the urine of this animal. Traces of 2-acetylfuran, acetaldehyde diethyl acetal, ethyl acetate, dimethyl sulfone, formanilide, and larger quantities of urea and elemental sulfur were also present in the urine of this animal. Sulfur was found in all the urine samples collected from male cheetah in captivity in South Africa and from wild cheetah in Namibia. Only one organosulfur compound, dimethyl disulfide, is present in the urine at such a low concentration that it is not detectable by humans [97]. 

On the other hand, the method of Mukaiyama can be succesfully applied to silyl enol ethers of acetic and propionic acid derivatives. For example, perfect stereochemical control is attained in the reaction of silyl enol ether of 5-ethyl propanethioate with several aldehydes including aromatic, aliphatic and a,j5-unsaturated aldehydes, with syir.anti ratios of 100 0 and an ee >98%, provided that a polar solvent, such as propionitrile, and the "slow addition procedure " are used. Thus, a typical experimental procedure is as follows [32e] to a solution of tin(II) triflate (0.08 mmol, 20 mol%) in propionitrile (1 ml) was added (5)-l-methyl-2-[(iV-l-naphthylamino)methyl]pyrrolidine (97b. 0.088 mmol) in propionitrile (1 ml). The mixture was cooled at -78 °C, then a mixture of silyl enol ether of 5-ethyl propanethioate (99, 0.44 mmol) and an aldehyde (0.4 mmol) was slowly added to this solution over a period of 3 h, and the mixture stirred for a further 2 h. After work-up the aldol adduct was isolated as the corresponding trimethylsilyl ether. Most probably the catalytic cycle is that shown in Scheme 9.30. 

Miscible with acetamide solutions, acetone, carbon tetrachloride, chloroform, 1,2-dichloroethane, ether, ethyl acetate, methanol, methyl acetate, and many unsaturated hydrocarbons (Windholz et al., 1983). Immiscible with many saturated hydrocarbons (quoted, Keith and Walters, 1992). 

A mammal may emit many volatile compounds. Humans, for instance, give off hundreds of volatiles, many of them chemically identified (Ellin etal., 1974). The volatiles include many classes of compound such as acids (gerbil), ketones, lactones, sulfides (golden hamster), phenolics (beaver, elephant), acetates (mouse), terpenes (elephant), butyrate esters (tamarins), among others. The human samples mentioned before contained hydrocarbons, unsaturated hydrocarbons, alcohols, acids, ketones, aldehydes, esters, nitriles, aromatics, heterocyclics, sulfur compounds, ethers, and halogenated hydrocarbons. Sulfur compounds are found in carnivores, such as foxes, coyotes, or mustelids. The major volatile compound in urine of female coyotes, Canis latrans, is methyl 3-methylhut-3-enyl sulfide, which accounts for at least 50% of all urinary volatiles (Schultz etal, 1988). 

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