Dienol ether

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). 

Another route to 5a compounds (57) proceeds from the dienol ether (58) by selective catalytic hydrogenation of the A -double bond with concomitant shift of the 3,4-double bond to the 2,3-position. If the hydrogenation is carried out in the presence of traces of base, double bond migration is suppressed and the difficultly accessible A -enol ethers of 5a-series (59) are thus obtained. 

Small groups on silicon favor the formation of the corresponding silyl dienol ether, formed by a Brook rearrangement of 81, and this reaction pathway is minimized by employment of P(OPh)3. 

Iododesilylation, 41 of aryltrimethylsilanes, 42 Iodomethyltrimethylsilane, 27 4-Iodophenylalanine, 42 Ionic hydrogenation, 136 Ireland-Claisen rearrangement, 112-14 ftwtf-2 Isocyanocyclohexanol, 137 Isophorone, 52 Isophorone dienol ether, 135 (Isopropoxydimethylsilyl)methyl magnesium chloride, 58... 

Oxidation with mepba — -hydroxyketones, using the reaction of isophorone dienol ether (detailed preparation given), and Et3N.HF cleavage of the intermediate silyl ether. 

From the beginning of the 1970s unhl the mid 1980s, several examples of the telomerization of dienes with water [76, 77] or methanol [78, 79] to isomeric mixtures of dienols or dienol ethers catalyzed by palladium-phosphine complexes in the presence of carbon dioxide have been reported. Neither the yield nor the selectivity were very high. However, when allene was employed as a diene , 3-methyl-2-meth-ylene-3-buten-l-ol was obtained with fairly good selectivity (up to 98%) (Eq. 6.43) [78]. 

Another Japanese group developed the Baccatin III synthesis shown in Scheme 13.58. The eight-membered B-ring was closed early in the synthesis using a Lewis acid-induced Mukaiyama reaction (Step B-l), in which a trimethylsilyl dienol ether served as the nucleophile. 

Sensitive dienol ether functionality in the diene carboxylate was shown to be compatible with the conditions of the aqueous Diels-Alder reaction (Eq. 12.26).84 The dienes in the Diels-Alder reactions can also bear other water-solubilizing groups such as the sodium salt of phosphoric acid and dienyl ammonium chloride (Eq. 12.27).85 The hydrophilic acid functionality can also be located at the dienophile.86... 

TITANIUM-MEDIATED ADDITION OF SILYL DIENOL ETHERS TO ELECTROPHILIC GLYCINE A SHORT SYNTHESIS OF 4-KETOPIPECOLIC ACID HYDROCHLORIDE (Pipecolic acid, 4-oxo-, hydrochloride)... 

Acetylenic ethers 7 can be hydrozirconated, and subsequent iododezirconation leads to (fc)-iodo enol ethers 8 (Scheme 4.4) [18], These species undergo efficient Sonogashira couplings to give (E)-enynes, which are ultimately converted to stereodefined dienol ethers. These dienes have proven useful in studies of diastereoselective cycloaddition reactions with singlet oxygen, where R in 8 is a nonracemic auxiliary (e. g., menthyl) (Procedure 3, p. 140). 

Refluxing in acid protonates the end ether to give a nice stable carbocation. Loss of CO2 from this carbocation gives a new dienol ether. Acidic hydrolysis of this dienol ether gives the product enone in the usual fashion. 

Having used their catalytic systems with dienolates derived from unsaturated esters, Denmark performed aldol reactions with the dioxanone-derived dienol ether described above in the context of Carreira s and Campagne s vinylogous aldol reactions (Scheme 21). Here, exclusively, the y product was formed with the nucleophile attacking from the Re face. For all three aldehydes, very good yields (83-92%) and selectivities (74-89% ee) were observed with only 0.01-0.05 mol% of the catalyst. 

The Birch reduction has been used by several generations of synthetic organic chemists for the conversion of readily available aromatic compounds to alicyclic synthetic intermediates. Birch reductions are carried out with an alkali metal in liquid NH3 solution usually with a co-solvent such as THF and always with an alcohol or related acid to protonate intermediate radical anions or related species. One of the most important applications of the Birch reduction is the conversion of aryl alkyl ethers to l-alkoxycyclohexa-l,4-dienes. These extremely valuable dienol ethers provide cyclohex-3-en-l-ones by mild acid hydrolysis or cyclohex-2-en-l-ones when stronger acids are used (Scheme 1). 

Bismuth-Catalyzed Mukaiyama Aldol Reaction of Dioxinone-Derived Silyl Dienol Ethers... 

Hydroperoxylation of silyl dienol ethers was effected by the in t7/ -generated reagent triphenyl phosphite ozonide (Equation 26). The yields are moderate and the products are always accompanied by the hydroxylated equivalents. The mechanism was studied and it was found that the oxygen attached to the carbon came from the central O of the ozonide <2001JOC3548>. 

The regioselectivity of alkylations of silyl dienol ethers has been studied87,88. These reactions favor y-alkylation products. In contrast, alkylations of the corresponding lithium enolates mainly occur in the a-position. Substituents on the silyl diene unit, as well as the substituents at the silicon, strongly influence the regioselectivity of the reaction87 91,... 

It is important to note that, under the same conditions, isophorone or other /3-alkyl cyclic enones predominantly afford the exocyclic conjugated silyl dienol ether (Scheme 3). 

On the contrary, the endocyclic conjugated silyl dienol ether is almost exclusively formed under the Kharasch conditions (Scheme 4). 

The endocyclic silyl dienol ether is also obtained as the major product when the conjugated cyclic enone is successively treated with the Fe complex prepared according to Scheme 2, then with one equivalent of methylmagnesium bromide (Table 2). This is interesting since these products are difficult to obtain otherwise. The mechanism of this unusual reaction remains obscure. 

Recently, Filrstner and coworkers have prepared a super-ate complex of iron(II) as shown in Scheme 5. The structure was fully characterized by X-ray crystallography. They have shown that methylmagnesium bromide reacts with pulegone in the presence of this complex to give the corresponding endocyclic silyl dienol ether. Consequently, they have proposed that a similar ate-complex is probably involved when the reaction is performed under the Kharasch conditions. 

TABLE 2. Regioselective preparation of trimethylsilyl dienol ethers... 

Another work of Duhamel and Ancel [59] related this synthesis of retinal via (3-ionylideneacetaldehyde. Condensation of methallyl-magnesium chloride with diethyl phenyl orthoformate (EtC CHOPh) led after bromination of the ene-acetal, deshydrohalogenation (NaOH 50%), ethanol elimination with hexamethyldisilazane (HMDS) and ISiMes, to the bromo-dienol ether. This latter was submitted to bromine lithium exchange and the lithio enol ether was then condensed with p ionylideneacetaldehyde to give retinal, Fig. (28). 

Cleavage of acetals. Ethylene acetals of /J,y-unsaturatcd carbonyl compounds arc cleaved to dienol ethers by NaH in DMSO. 

A3 5-Dienol ethers are also formed by acid-catalyzed reaction of the steroid directly with benzyl alcohol with azeotropic removal of water.17 Use of isooctane as azeotropic carrier may improve yields.55... 

Simple pyrans are unstable compounds as is to be expected of a dienolic ether system. Thus, 2H-pyran (1) has not yet been synthesized, whilst the preparation of 4/Z-pyran (2) was only achieved in 1962. Introduction of unsaturated groups lends some stability, but a... 

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