Enol ethers from aldehyde

I. From Aldehydes and Ketones with 1-Alkoxy-l-lithiocyclopropanes and from Enol Ethers by Cyclopropanation... 

Tetrasubstituted pyrroles could be obtained by skeletal rearrangement of 1,3-oxazolidines, a reaction that is substantially accelerated by microwave irradiation. Dielectric heating of a 1,3-oxazolidine 7, absorbed on silica gel (1 g silica gel/mmol) for 5 min in a household MW oven (900 W power) cleanly afforded the 1,2,3,4-tetrasubstituted pyrrole 8 in 78% yield, thus reducing the reaction time from hours to minutes (Scheme 5) [24], 1,3-Oxazolidines are accessible in one-pot, two-step, solvent-free domino processes (see also Sect. 2.6). The first domino process, a multi-component reaction (MCR) between 2 equivalents of alkyl propiolate and 1 equivalent of aldehyde furnished enol ethers 9 (Scheme 5). Subsequent microwave-accelerated solvent-free reactions of enol ethers 9 with primary amines on silica support afforded intermediate 1,3-oxazolidines, which in situ rearranged to the tetrasubstituted pyrroles (2nd domino process). Performed in a one-pot format, these... 

Modem variants of the Mukaiyama aldol addition start from silyl enol ethers, not from enol ethers, and use an aldehyde instead of the acetal as the electrophile. Mukaiyama aldol additions of this kind have been included in the C,C coupling reactions that build the basic repertoire of modem synthetic chemistry and can even be performed in a catalytic enantioselective fashion. 

As can be expected, use of ethyl diazoacetate procides y-oxoesters15) ory-oxocarboxylic acids 16) from enol ethers. Emploging the Julia method with 25 leads to the p,y-unsaturated aldehyde 26. Thus, this sequence establishes an overall a-vinylation of a given aldehyde n 17 18). 

Catalytic asymmetric aldol addition of tributylstannyl enol ethers to aldehydes is achieved in the presence of (R)-BINAP AgOTf catalyst.The catalyst is considered to enhance the electrophilic reactivity of aldehydes to give diastereomeric adducts with high selectivities from -enol ethers, awft -aldol products are produced, whereas yn-aldol products result from Z-enol ethers. The stereochemical outcome is understood in terms of 6-membered cyclic transition states (Scheme 3-195). 

A useful catalyst for asymmetric aldol additions is prepared in situ from mono-0> 2,6-diisopropoxybenzoyl)tartaric acid and BH3 -THF complex in propionitrile solution at 0 C. Aldol reactions of ketone enol silyl ethers with aldehydes were promoted by 20 mol % of this catalyst solution. The relative stereochemistry of the major adducts was assigned as Fischer- /ir o, and predominant /i -face attack of enol ethers at the aldehyde carbonyl carbon atom was found with the (/ ,/ ) nantiomer of the tartaric acid catalyst (K. Furuta, 1991). 

The methyl enol ether 37 is oxidized to the a,/3-unsaturated aldehyde 39 via hemiacetal 38. Unsaturated aldehyde 39, elongated one carbon from the aldehyde 36, is prepared by the Wittig reaction of 36 to give 37, and application of this reaction[ 88]. 

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]... 

Two techniques have been described for producing trimethylsilyl enol ethers from aldehydes or ketones (10) reaction of (CH2)2SiCl and (C2H3)2N in DMF and reaction of LiN(C2H3)2, which generates enolate ions in the presence of... 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

The procedure described illustrates a general method for the preparation of o ,j3-unsaturated aldehydes and ketones from the enol ethers of 3-dicarbonyl compounds. 

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. 

The preference for chairlike TSs has been confirmed by using deuterium-labeled enolates prepared from the corresponding silyl enol ethers. The ratio of the location of the deuterium corresponds closely to the ratio of the stereoisomeric enolates for several aldehydes.4... 

When there is also a stereogenic center in the silyl enol ether, it can enhance or detract from the underlying stereochemical preferences. The two reactions shown below possess reinforcing structures with regard to the aldehyde a-methyl and the enolate TBDMSO groups and lead to high stereoselectivity. The stereochemistry of the (3-TBDMSO group in the aldehyde has little effect on the stereoselectivity. 

This regiochemistry is consistent with the electrophilic character of Pd(II) in the addition step. Solvent and catalyst composition can affect the regiochemistry of the Wacker reaction. Use of /-butanol as the solvent was found to increase the amount of aldehyde formed from terminal alkenes, and is attributed to the greater steric requirement of /-butanol. Hydrolysis of the enol ether then leads to the aldehyde. 

Reaction of the enatiopure aldehyde 2-800, obtained from the corresponding imine by enantioselective hydrogenation, with Meldrum s acid (2-801) and the enol ether 2-802a (E/Z= 1 1) in the presence of a catalytic amount of ethylene diammonium diacetate for 4h gave 2-805 in 90 % yield with a 1,3 induction of >24 1. As intermediates, the Knoevenagel product 2-803 and the primarily produced cycloadduct 2-804 can be supposed the latter loses C02 and acetone by reaction with water formed during the condensation step (Scheme 2.178). 

The method can be further improved using trimethylsilyl (TMS) enol ethers, which can be prepared in situ from aldehydes and ketones [49]. TMS enol ethers of cyclic ketones are also suitable, and diversity can be enhanced by making either the kinetic or thermodynamic enol ether, as shown for benzyl methyl ketone. Thus, reaction of the kinetic TMS enol ether 10-133 with the amino aldehyde 10-134 and dimethylbarbituric acid 10-135 yielded 10-136, whereas the thermodynamic TMS enol ether 10-137 led to 10-138, again in excellent purity, simply by adding diethyl ether to the reaction mixture (Scheme 10.33). 

In aldol reactions, especially Mukaiyama aldol reactions, TiIV compounds are widely employed as efficient promoters. The reactions of aldehydes or ketones with reactive enolates, such as silyl enol ethers derived from ketones, proceed smoothly to afford /3-hydroxycarbonyl compounds in the presence of a stoichiometric amount of TiCl4 (Scheme 17).6, 66 Many examples have been reported in addition to silyl enol ethers derived from ketones, ketene silyl acetals derived from ester derivatives and vinyl ethers can also serve as enolate components.67-69... 

The 1,4-reduction of a,/3-unsaturated aldehydes is best carried out with diphenylsilane in the presence of zinc chloride and tetrakis(triphenylphosphine) palladium436 or a combination of triethylsilane and tris(triphenylphosphine) chlororhodium 437 Other practical approaches use phenylsilane with nickel (0) and triphenylphosphine438 and diphenylsilane with cesium fluoride.83 It is possible to isolate the initial silyl enol ether intermediate from the 1,4-hydrosilylation of o, /3-unsaturated aldehydes (Eq. 264).73,411 The silyl enol ethers are produced as a mixture of E and Z isomers. 

The intermediate enolate or enol ether from the initial reduction of an enone may be alkylated in situ (Eq. 281).455 / -Substituted cyclopentenones may be asymmetrically reduced and alkylated459 (see section on asymmetric reductions of enones). Enolates may also be trapped with an aldehyde in a reductive aldol condensation of an enone with an aldehyde,455 permitting a regioselective aldol condensation to be carried out as shown in Eq. 282.455 This class of reductive aldol condensation reactions can also occur in a cyclic manner (Eq. 283).460... 

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