Acetaldehyde Wittig reaction

Restrepo-Cossio, A. A., Cano, H., Mari, F., Gonzalez, C. A. Molecular modeling of the Wittig reaction. 6. Theoretical study of the mechanism of the Wittig reaction ab initio and MNDO-PM3 treatment of the reaction of unstabilized, semistabilized and stabilized ylides with acetaldehyde. Heteroatom Chem. 1997, 8, 557-569. 

Nagata, W., Wakabayashi, T., and Hayase, Y., Preparation of a,P-unsaturated aldehydes via the Wittig reaction. Cyclohexylideneacetaldehyde (Acetaldehyde, cyclohexyl idene-), Org. Synth., Si, 104, 1973 Synth. Coll. Vol. VI, iS, 1988. 

Indoles and Carbazoles. - Formation. 2-Arylindoles (132) are formed by intramolecular Wittig reaction of the phosphonium salts (131). The hydroxamic acids PhN(OH)COCH2COR (R = alkyl or aryl) cyclize in boiling toluene to mixtures of indoles (133) and 3-isoxazolones (134). Irradiation of a solution of o-iodoaniline and the potassium enolate of acetone affords 2-methylindole. The enamino-ketone (135) cyclizes photochemically to 1,2-dimethylindole (136) with elimination of acetaldehyde/ The styrene derivative (137), obtained by the action of Meerwein s acetal, Me2NCH(OMe)2, on o-nitrotoluene, yields 1-hydroxyindole on treatment with zinc/ Azidobenzocyclobutanes (138 R = Me, Ph, or CH2Ph) are converted into indoles (133) by the action of concentrated sulphuric acid/ ... 

A related methodology (ref. 112) was employed in which rather than a C.,5 farnesyl component a compound was reacted with a chroman-2-acetaldehyde derivative. In this scheme the C.,4 aldehyde simultaneously formed at the ozonolysis stage in the previosly described synthesis was used. Thus, 2-carboxymethyl-6-hydroxy-2,5,7,8-tetramethylchroman, [(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)acetic acid] served as a source by resolution with (S)-a-methylbenzylamine of the two enantiomeric acids. The 2(S)-enantiomer was converted by way of the acid chloride to the aldehyde, a homologue of that employed by the Swiss workers in the foregoing method. The aldehyde was reacted with the triphenylphosphonium salt from the C bromide by the Wittig reaction to afford 2R,4 R,8 R-a-tocopherol. A novel aspect of this approach was that it enabled a synthesis of 2R,3 E,7 E-a-tocotrienol to be achieved from the same carboxymethyl intermediate. 

A general synthesis for all diastereomeric L-hexoses, as an example for monosaccharides that often do not occur in the chiral pool, has been worked out. The epoxidation of allylic alcohols with tertiary butyl hydroperoxide in presence of titanyl tartaric ester catalysts converts the carbon-carbon double bond stereose-lectively to a diol and is thus ideally suited for the preparation of carbohydrates. The procedure is particularly useful as a repetitive two-carbon homologiza-tion in total syntheses of higher monosaccharides and other poly hydroxy compounds. It starts with a Wittig reaction of a benzylated a-hydroxy aldehyde with (triphenylphosphoran-ylidene)acetaldehyde to produce the olefinic double bond needed for epoxidation. Reduction with sodium-borohydride... 

The ketophosphonate chemistry briefly discussed above indicates that the cycloalkenones 23 can be easily functionalized and, therefore, can serve as synthetic intermediates in the synthesis of bioactive products. Having this in mind, Altenbach and Holzapfel [35] devised an elegant and short synthesis of natural (+)-terrein (21) from the protected ethyl ester of (+)-(l)-tartaric acid 24. Upon reaction of 24 with diethyl lithiomethanephosphonate in the presence of acetic acid under strictly controlled reaction conditions a mixture of two cyclic products 25 and 26 was formed. The first of them, readily separated chromatograph-ically, was the desired product of an intramolecular Horner-Wittig reaction of the transiently formed bis-jS-ketophosphonate. Introduction of the unsaturated side chain was achieved via Horner-Wittig reaction with acetaldehyde. Subsequent deprotection of the chiral diol moiety with fluoride ion gave (+)-terrein (21) in 26% overall yield (Scheme 12). 

In the second case, more options are available. Our solution su ests using a Wittig reaction for the first as we need the enolate of acetaldehyde (p. 628 in the textbook), and malonic acid for the second (p. 630 in the textbook). There are many alternatives such as using an aldol reaction for the first step, but with an excess of acetaldehyde, to compensate for selfcondensation. 

The B3P86/6-31G mechanistic results for the Wittig reaction of acetaldehyde in vacuo and in tetrahydrofuran (THF) solution with an unsubstituted trimethylphospho-nium or triphenylphosphonium ylide have been compared to those obtained at the same levels for the reaction of triphenylphosphonium ylide with a bulky chiral aldehyde, (2S, 3/ )-2,4-dimethyl-3-pyrrol-l-yl-pentanal. ° Betaine-type intermediates were found not located in vacuo when trimethylphosphonium yUde was used, while only a gauche betaine is obtained using triphenylphosphonium ylide. Conversely, in THF, the concerted and stepwise mechanisms are both represented and show TSl/TSb barriers, which are negligibly small for unsubstituted triphenylphosphonium yUde. 

Carotene, a yellow food-coloring agent and dietary source of vitamin A can be prepared by a douWe Wittig reaction between 2 equivalents of 8-ionylidene-acetaldehyde and a diylide. Show the structure of the 8-carotene product. 

The lithium etiolate of acetaldehyde DMH has recently been utilized in the opening reaction of the ot-epoxide obtained by DM DO oxidation ofenol ether 142, to provide hemiacetal 143 after mild oxidative acid hydrolysis. The protected carbonyl functionality was subsequently used for the introduction of the trans enyne chain through a Wittig olefmation reaction to provide alcohol 144, which was then transformed into (+)-laurenyne (Scheme 8.37) [71]. 

In the other approach, again harmalane (150) was treated with methyl 2-(di-ethylphosphono)acrylate (174), resulting in iminophosphonate 175. By its sodium borohydride reduction and subsequent lactonization, the amidophospho-nate 176 has been obtained, Wittig-Homer reaction of 176 with acetaldehyde followed by selective reduction of the carbonyl group of the enamide function supplied ( )-deplancheine in good yield (116). 

Two six-membered necic acid lactones 46 (integerrinedc acid lactone) and 47 (senedc acid lactone) having an exo-a-methylene moiety were synthesized by Wiemer et al. [45] in the stereocontrolled Horner-Wittig condensation of the a-phosphonolactone 48 with acetaldehyde (Scheme 20). When KHMDS in acetonitrile was used as a base in this reaction, a 9 1 mixture of E and Z products was obtained from which the -isomer of integerrinecic acid lactone 46 was isolated in 77% yield. When K2C03/18-crown-6/toluene was employed in a parallel... 

A catalytic triple domino Michael-aldol-oxa-Michael reaction of acetaldehyde with ( -2-(2-nitrovinyl)phenols catalyzed by (R)-2- diphenyl [(trimethylsilyl)oxy] methyl pyrrolidine followed by a sequential one-pot Wittig, Michael/Wittig-Horner reactions with PPh3=CHC02Et was applied to the asymmetric synthesis of polyfunctionalized chromans (14EJO3076). 

The problem of directing Wittig and Horner reactions to both the ( )- and the (Z)-olefins has found a variety of solutions. One is the use of phosphine oxides as the donor component (Scheme 3.85) [137]. Thus, 445 was deprotonated and then treated with acetaldehyde to give the erythro-adduct 446 with d.r. 3 1. After separation, base-catalyzed syn-elimination of phosphinate gave (Z)-olefin 449. On the other hand, 445 was deprotonated and acylated to give ketone 447, which was then reduced with sodium borohydride to give the threo-isomer 448 with d.r. 3.5 1. Separation/syn-elimination generated the ( )-olefin 450 selectively. 

The reduction of ethyl bromo[ " C]acetate can be stopped at the aldehyde level when the reaction is performed with DIBAL-H at low temperature. This has been demonstrated for doubly carbon-13-labeled material. The resulting bromo[ C2]acetaldehyde (1021 was not isolated but trapped with Ph3P to give the corresponding Wittig reagent 103. which was used for two sequential C2 extensions of the aldehyde 104 in the synthesis of... 

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