Wittig condensations

A variation of the Madelung cyclization involves installing a functional group at the o-methyl group which can facilitate cyclization. For example, a triphenylphosphonio substituent converts the reaction into an intramolecular Wittig condensation. The required phosphonium salts can be prepared by starting with o-nitrobenzyl chloride or bromide[9]. The method has been applied to preparation of 2-alkyl and 2-arylindoles as well as to several 2-alkenylindoles. Tabic 3.2 provides examples. 

Wittig condensation of the ylide from the phosphonium salt, 19, with the hydroxymethylene ketone, 20, affords the product,... 

Wilkinson s catalyst 117,345,777 Wittig condensation 73 Wittig homologation 503 Wittig methylenation 649 Wittig reaction 17, 68 f., 86 f.,... 

Another modification of the Hantzsch thiazole synthesis afforded C-4 thiazolylmethyl phosphonium salts (49). These ylids could then undergo Wittig condensations to furnish a wide variety of 2,4-disubstituted thiazoles <96TL983>. 

The synthesis of quadrupolar chromophores has also been achieved from 2,6-DTT-dicarboxaldehyde 117. Push-push (i.e., bis-donor) compound 118 was prepared via a double Wittig reaction carried out under solid-liquid phase transfer conditions. Pull-pull (i.e., bis-acceptor) compounds 119 were obtained from a symmetrical bis-aldehydes via a double Horner-Emmons-Wittig condensation (Scheme 9) <2002SM17, 1999CC2055>. 

SCHEME 2.19 Synthesis of dicyanophenylene vinylene copolymers by Wittig condensation. 

Water lipid partition, 3, 21 Wittig condensation, 148, 339 Wohler, Friedrich, 5... 

Whipworm, 303 Willgerodt reaction, 68 Wittig condensation, 3, 6 Wittig reaction, 420 Woodward hydroxylation,... 

Wittig condensation of a thietan-2-one with stabilized phos-phoranes. ... 

The other stereoselective synthesis/281 shown in Scheme 8, foresees conversion of Boc-L-Asp-OtBu 20 into the related (3-aldehyde 22 via the Weinreb amide 21 and its reduction with diisobutylaluminum hydride (DIBAL-H). Wittig condensation of 22 with the ylide derived from (3-carboxypropyl)triphenylphosphonium bromide using lithium hexamethyldisilaza-nide at —78 to 0°C, produces the unsaturated compound 23 which is catalytically hydrogenated to the protected L-a-aminosuberic acid derivative 24. Conversion of the co-carboxy group into the 9-fluorenylmethyl ester, followed by TFA treatment and reprotection of the M -amino group affords Boc-L-Asu(OFm)-OH (25). 

Aminomethylation of cyclododecanone (79) gave 86a which was converted to 1,2-dimethylenecyclododecane (87) via the Wittig condensation, quaternization, and Hofmann elimination. Bromination of 87 to the ( )-dibromide 88 (98 % yield) was the key step in this approach. The routine synthetic sequence modified the side chains of 88 to provide the ( )-dialdehyde 88b whose McMurry ring closure, followed by removal of the newly formed unsaturated center, completed the synthesis. 

Bromocyclododecanone (93a) was converted into the spiroketone 94a via 93b, and the Wittig condensation transformed the resulting 94a to the unsaturated 94b. 

Activity is largely retained in a compound in which one of the terminal double bonds in the side chain of tretinoin is replaced by an aromatic ring. The key reaction in the constmction of this compound consists in Wittig condensation of the ylide from... 

Benzoxepin (27) has been synthesized from phthalaldehyde and a bis-phosphonium salt by a double Wittig condensation reaction as shown in equation (50) (66CB634). 

As shown in Scheme 1, isotretinoin (1) was first synthesized by Garbers et al. in 1968 utilizing a key Wittig condensation. Phosphonium salt 8 was prepared from direct treatment of vinyl p-ionol 7 with triphenylphosphonium bromide (PhsPaHBr) in ethanol. Subsequent addition of an excess of sodium ethoxide to 8 was followed by an ethanol solution of cij-3-formyl crotonic acid (9) to produce isotretinoin (1,2-cjs-vitamin A acid. 

In a 1985 patent by Hoffmann-La Roche, the Wittig condensation was also the crucial step in assembling isotretinoin (1, Scheme 2). Under the optimized conditions, 1.03 equivalents of phosphonium salt 8 was condensed with 1 equivalent of hydroxybutenolide 9 in the presence of 1.25 equivalents of 2 N KOH in isopropanol at -30°C for 1 to 1.5 h. The product (91.5% total yield) consisted of 75.9% of 2-cis-4-cis-vitamin A acid (10) and 16.7% of isotretinoin (1). Without separation, the mixture of 10 and 1 was subjected to palladium-catalyzed isomerization conditions the mixture was heated at 50°C for 1 h in acetonitrile in the presence of 0.10 mol% of palladium(n) nitrate, four equivalents (based on palladium nitrate) of triphenylphosphine and 2... 

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