Acetone Wittig reaction

Out first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and pentylmagnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

The Wittig reaction, for which George Wittig received the 1979 Nobel Prize in Chemistry, is an important synthetic procedure for converting aldehydes and ketones into alkenes. The active reagent is a phosphorous ylide which undergoes nucleophilic addition to the carbonyl carbon, e.g., for addition of triphenylphosphinemethylidene to acetone. 

Z)-Trisubstituted aRylic alcohols. The conditions used by Bestmann et al. (7, 329) for preparation of (Z)-disubstitutcd alkcncs via the Wittig reaction also can provide a stereoselective route to (Z)-trisubstiluted allylic alcohols. An example is the reaction of ethylidenetriphenylphosphorane with the THP ether of hydroxy-acetone (equation 1). The stereoselectivity is decreased with other protecting... 

Citranaxanthene 543 is found in citrus fruits and is used as a food dye like P-carotene. The same phosphonium salt synthon 505 as used for the vitamin A synthesis is monoolefinated with the polyene dialdehyde 539. The Wittig reaction of the resulting 540 with phosphorane 541 followed by aldol condensation of the obtained 542 with acetone gives citranaxanthene 54 3 255,263) (Scheme 92). In the preparation of the polyenedial 539 l,4-dibromo-2-butene 544 is reacted with trimethyl... 

Methyl 4,6-0-benzylidene-3-deoxy-a-D-ribo-hexopyranoside (56) was benzoylated, debenzylidenated, and partially p-toluenesulfon-ylated to 57 this was converted into 58 by reaction with sodium iodide, followed by catalytic reduction. The methanesulfonate of 58 was converted into 59 by reaction with sodium azide in N,N-dimethylformamide, and 59 was converted into 4-azido-3,4,6-trideoxy-a-D-xylo-hexose (60) by acetolysis followed by alkaline hydrolysis. Reduction of 60 with borohydride in methanol afforded 61, which was converted into 62 by successive condensation with acetone, meth-anesulfonylation, and azide exchange. The 4,5-diazido-3,4,5,6-tetra-deoxy-l,2-0-isopropylidene-L-ara/uno-hexitol (62) was reduced with hydrogen in the presence of Raney nickel, the resultant diamine was treated with phosgene in the presence of sodium carbonate, and the product was hydrolyzed under acidic conditions to give 63. The overall yield of 63 from 56 was 4%. The next three reactions (with sodium periodate, the Wittig reaction, and catalytic reduction) were performed without characterization of the intermediate products, and gave (+)-dethiobiotin methyl ester indistinguishable from an authentic sample thereof prepared from (+)-biotin methyl ester. 

Z)-condenses with aldehydes in a (Z)-stereoselective Wittig reaction to afford diethyl acetals of (Z)-a,jS-unsaturated aldehydes in 57-86% yield. Hydrolysis of the acetals with p-TsOH as catalyst in acetone-water or with moist silica gel (2 days at 23°) affords the corresponding (Z)-unsaturated aldehydes in 47-98% yield. The product usually contains 4-14% of the (E)-isomer. These results contrast with those of Wittig reactions of formylmethylenetriphenylphosphorane and l,3-dioxolan-2-ylmethylenetriphenyl-phosphorane (5, 269), which afford (E)-unsaturated aldehydes. 

Anion (51) protonates and methylates at the a-position but reacts with TMS-Cl and acetone (equation 49) specifically at the -Y-position. No product derived from a boron-Wittig reaction was noted in the reaction with acetone, which upon work-up with propionic acid gave the corresponding alkene (52). ... 

Other methods for the synthesis of indole involve an intramolecular Wittig reaction or an aromatic nucleophilic substitution by the carbanion derived from acetone. 

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/ ... 

In another approach to the technical synthesis of the apocarotenoids 286, 287 and 292 [118] the C25-aldehyde 12 -apo-p-caroten-12 -al (293) is the key intermediate. Several ways to synthesize this compound have been developed, applying the Wittig reaction to couple the building blocks. By the reaction of the Cas-aldehyde 293 with the protected Cs-phosphonium salt 294 the Cao-aldehyde is obtained [119,120], and this can be transformed by a base-catalysed aldol condensation with acetone (295) to give the Css-ketone citranaxanthin (292) [121]. Alternatively the C2s-aldehyde 293 can be reacted in a Horner-Emmons reaction with the Cs-phosphonate 296 to give 292 [122] Scheme 61). 

Butenolides may be prepared by the cyclisation of 4,5-epoxyalk-2-enoates, one of the simplest cases being the formation of (.160) (15%). by treatment of (159) with HC104 in aqueous dioxane or aqueous acetone. These simple a,e-butenolides have proved to be convenient synthons for mere complex molecules. The starting material for these cyclisations is obtained via a Wittig reaction of an epoxy-ketone thus (l6l X=0), when condensed with (EtO)2P(0)CH O Et yields a mixture of E and Z (l6lj X=CHC02Et)llt8. The Z isomer forms (162) stereospecifically on hydrolysis. 

An intramolecular Wittig reaction of the phosphonium salt PhsP—CH2-CH2CH20C0Ph Br yields the dihydrofuran (15). Compound (16) is formed from styrene and acetone in the presence of lead dioxide by a free-radical mechanism. The A -dihydrofuran (17) is produced by the action of silver fluoroborate on the allenic alcohol HOCH2CH=C=CMeBu another compound of this type, namely (18), is the product of the reaction of the sulphurane H2C=SMe2 with salicylideneacetone. ... 

Apo-jS-carotenal, ethyl 8 -apo- -carotenoate and citranaxanthin are readily accessible by this modular synthesis. The central building block is ll -apo- -carotenal, which itself may be synthesised in diverse ways by Wittig reactions from the intermediates mentioned above. Of particular appeal is a synthesis, wh ich starts from retinol. First, the retinol is oxidised to retinal by an Oppenau-er or TEMPO oxidation. Successive reactions of retinal with Cs-phosphonium salts or phosphonate esters, followed by isomerisation, lead to 8 - po-)8-carotenal and ethyl 8 -apo-yS-carotenoate. Citranaxanthin is obtained by an aldol condensation of 8 -flpo-yS-carotenal with acetone. [55]... 

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