Wittig condensation intramolecular

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. 

To date, reverse cyclative cleavage with C-C bond formation has relied on ylid chemistry. A single example was reported54 of the intramolecular Wittig condensation of an immobilized amide to give a two-substituted indole (Fig. 18). Macrocyclization through an immobilized... 

The basic nature of methylenetriphenylphosphorane caused D-homoannulation of 17a-acetyloestr-4-en-17/3-ol (294) before effecting a Wittig condensation the mixed 17-methylene-D-homoandrostanes (295) were formed. When the 17/3-OH group was protected by acetylation, an intramolecular Claisen condensation occurred in polar solvents under Wittig conditions, giving the spiro-lactone (296) and a... 

Scheme 1.21). Transformation of ester 103 into acid chloride 104 then set the stage for the novel macrocyclization step. Deprotonation of 104 induced an intramolecular Wittig condensation followed by immediate loss of HCl to produce allenic lactone 105 in 42% yield. Subsequent [4 + 2] cycloaddition of diene 100 with 105 gave cyclohexene 106 in 55% yield. Aromatization of 106 under basic conditions then afforded a 50% yield of lasiodiplodin (90). 

Fried s group at Syntex has described a similar synthesis of zearalenone employing a Wittig condensation and ring closure by intramolecular lactonization (Scheme 1.27). The aromatic residue 131 was constructed from the known ethyl o-orsellinate diacetate (130) by acid hydrolysis and methylation of the phenolic hydroxy groups. 

Aromatic aldehydes condense with azidoacetates to produce species which by treatment with trivalent phophorus compounds give aza-ylids which undergo intramolecular aza-Wittig condensations giving aromatic isoquinolines. ... 

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

Phenylcyclopent[c]azcpine (33a) and 6,7-fused cyclopentazepines 33b-d are formed in moderate yields in a one-pot, two-stage process involving initial condensation of triphenyl-[(l-phenylvinyl)imino]phosphoranes 32 with 6-(dimethylamino)fulvene-2-carbaldehyde (30), followed by an intramolecular aza-Wittig reaction of the iminophosphorane with the pendant aldehyde function.5 The method fails with the unsubstituted vinylphosphorane 32 (R1 = R2 = H). 

A tandem enzymatic aldol-intramolecular Homer-Wadsworth-Emmons reaction has been used in the synthesis of a cyclitol.310 The key steps are illustrated in Scheme 8.33. The phosphonate aldehyde was condensed with dihydroxyacetone phosphate (DHAP) in water with FDP aldolase to give the aldol adduct, which cyclizes with an intramolecular Horner-Wadsworth-Emmons reaction to give the cyclo-pentene product. The one-pot reaction takes place in aqueous solution at slightly acidic (pH 6.1-6.8) conditions. The aqueous Wittig-type reaction has also been investigated in DNA-templated synthesis.311... 

The Wittig reaction efficiently olefinates aldehydes and ketones, but not esters or amides. Several early-transition-metal approaches have been taken to this problem. Recently, Takeshi Takeda of the Tokyo University of Agriculture and Technology reported (Tetrahedron Lett. 44 5571,2003) that the titanocene reagent can effect the condensation of an amide 10 with a thioacetal 11 to give the enamine 12. On hydrolysis, 12 is converted into the ketone 13. When the reaction is intramolecular, reduction proceeds all the way, to give the pyrrolidine IS. 

Intramolecular Wittig-Horner reaction of the compounds 399, which are prepared by the condensation of 2-mercapto-2-arylethanols with a vinyl phosphonate followed by oxidation, gives dihydrothiophenes 400 <1996JHC687>. 

The Wittig-like reactions are well known for C=C bond formation. An intramolecular process can serve as a ring closure and has been generally employed in the synthesis of numerous macrocyclic natural products [150]. Oishi and coworkers [151] applied this strategy to the synthesis of the aglycone (252) of the antibiotics venturicidins A and B. Thus, as shown in Scheme 84, the aldehyde phosphate 250 was subjected to the modified intramolecular Wittig-Homer condensation with a mild base, yielding the macrocycle 251 in 48% yield. 

Cyclopentenone annelation. Enolates condense with 1 in an alkylation-intramolecular Wittig reaction sequence to afford cyclopentenones (yields, 14-39%). 

Quinazolines have also been prepared by the reaction of a polystyrene-bound phosphoranimine and isocyanates, followed by an intramolecular cyclization of the carbodiimide intermediate 4-Ferrocenylidene-l-aminoimidazolone derivatives have been obtained from p-ferrocenyl-a-azidoacrylates and isocyanates followed by condensation of the resulting carbodiimidoester with hydrazines " In a Staudinger/ aza-Wittig process and in the presence of PPh3, bimetallic ferrocenyl oxazole derivatives (23) - (26) have been formed by the reaction of a-... 

---