Wittig-Horner cyclization

Another route to thioglycosides from hemiacetals involving a cyclization of an open-chain sulfide has been described recently. A Wittig-Horner reaction afforded the Q ,/3-unsatu-rated thiophenyl derivative, which then was treated with iodonium reagents to induce cyclization to afford 2-iodo-l-thioglycosides, which are good precursors for 2-deoxy-sugars (O Scheme 13) [167]. 

In a novel synthesis of pyridazinones, a Wittig-Horner reaction is used to prepare an intermediate hydrazone of an a,)S-unsaturated y-keto ester, which undergoes geometrical isomerization and cyclization when heated under reflux in DMF (Scheme 91). The starting a-formylhydrazone is prepared from ascorbic acid <87H(26)2loi>. 

Chromans. - 2,4-Diethoxychromans (78) (mainly cis) represent a new type of chroman and have been prepared in high yield from a phenol (but not a deactivated phenol) and malonaldehyde bis(diethyl acetal) in the presence of SnCU they are converted into the benzopyrylium salts (79), in excellent yield, by treatment with perchloric acid. A Wittig-Horner reaction of the chiral phosphoryl ( S)-sulphoxide (81) and the ketone (80) gave the chiral sulphoxide (82), which was cyclized by aqueous alkali to a mixture which contained 22% diastereoisomeric excess of (25 )-chroman (i )-sulphoxide. This was converted, in three steps, into the aldehyde (83), which is a useful synthon for a-tocopherol. ... 

Cyclopentenones. Heathcock et al have developed a cyclopentenone synthesis that involves an intramolecular Wittig-Horner reaction of 3,e-diketo-phosphonates. For example, the reaction of 2 eq. of (1) with the ester(2)inTHF gives the diketone (3), after hydrolysis of the protective group. When treated with sodium hydride in DME at 20°, (3) cyclizes to the cyclopentenone (4) in 80% yield. 

The Wittig-Horner olefination of the aldehyde 28 provided alkenes 29 which were subjected to radical cyclization leading to benzofused tricyclic j6-lactams 30, obtained as single diastereomers (Scheme 8) [36]. A convenient, direct regio- and stereoselective route to optically pure unusually fused or bridged tricyclic /3-lactams has been developed by the use of intramolecular nitrone-alkene cycloaddition reactions. For example, the aldehyde 21 can be transformed into nitrone 31 which subsequently was used for a variety... 

Danishefsky has reported a modified route to /ra 5-fused butyrolactones (53) involving attack on a c/j-epoxide (51) by the acetylenic alane (52), followed by acid catalysed hydrolysis and lactonization other anions were found to be unsuitable. Similar fused lactones are available from a -epoxycyclohexanones by sequential Wittig-Horner reaction and acid-catalysed cyclization. 

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... 

Cyclocondensation of pipecolinic acid and malic acid anhydride in pyridine afforded 3-hydroxy-2,3-dimethylperhydropyrido[l,2-a]pyrazine-l, 4-dione (74CB2804). Cyclocondensation of bis(2,4,6-trichlorophenyl) mal-onates with 2-methyl-, 2-benzyl- and 2-ethoxycarbonylmethylquinoxalines and -3-ones at 250°C afforded 8-hydroxy-10//-pyrido[l,2-a]quinoxalin-10-ones and their 5,6-dihydro-6,10-dione derivatives (77M103). Under Horner-Wittig reaction conditions, the reactions of 2-formylquinoxaline and dialkyl phosphonosuccinates (314) also involved cyclization to give alkyl 10-oxo-10//-pyrido[l,2-a]quinoxahne-8-carboxylate (80LA542). 

The Horner-Wittig reaction of 1-substituted imidazole-2-aldehydes (304) gave intermediates (305) that cyclized to imidazo[l,2-a]pyridin-5-ones (306) (80LA542). 

Subsequently, however, we have prepared a series of diazocompounds 21a.b closely ressembling 21, via the Wittig and Horner-Emmons-Wittig (HEW) olefination vide infra, and observed that none of them cyclized even upon heating. It... 

In the first synthetic key step, the -ketophosphonate 2 was alkylated with 1-bromo-2-methoxyprop-2-ene. Then, the product of monoalkylation was hydrolyzed under acidic conditions to the corresponding phosphorylated 1,4-diketone 4 that was cyclized to the precursor of methylenomycin B, the 5-phospho-rylcyclopentenone 5. The Horner-Wittig reaction of the latter with formaldehyde under very mild conditions completed the synthesis of 1 in 39% overall yield (Scheme 2). 

Thus, 28 was treated with dimethyl lithiomethanephosphonate to give the corresponding bis-jS-ketophosphonate 29. Base-catalyzed cyclization of 29 afforded the cyclopentenone 30 which was next reacted with acetaldehyde to give the Horner-Wittig olefination product 31. Deprotection of the diol moiety in 31 gave (-)-isoterrein (22). Its optical purity was, however, very low (11%). 

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