Wittig conditions Subject

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... 

Moreover, vinyl-bridged Pc adducts with ferrocene derivatives have been described [78,79], Upon reaction of 3,4-dicyanobenzylphosphonate with formylfer-rocene under Wittig-Horner conditions with the corresponding ferrocene-containing mono- or bisphthalonitriles have been obtained, which were then subjected to statistical cyclotetramerization with 4-tert-butylphthalonitrile in the presence of the appropriate metal salt. Furthermore, a double bond has also been employed as spacer between the Pc and ruthenium(trisbipyridine) [47],... 

Another variation of the Wittig reaction is the Wittig-Horner reaction, in which the anion generated ot- to phosphine oxide is used as a nucleophile to react with carbonyl compounds. The intermediate formed in this reaction, -hydroxyphosphine oxide, is isolable particularly when bases with lithium counterion are used for deprotonation. Since the j6-hydroxyphosphine oxides are diastereomers, they can be separated and subjected to elimination to form the corresponding alkenes. Since the elimination of phosphonate moiety is syn, stereospecific alkenes are obtained from the elimination step. As expected, the generation of erythro and threo isomers is dependent on the solvent and the reaction conditions. 

S.F. Martin and co-workers utilized a double Swern oxidation in their synthesis of ircinal A and related manzamine alkaloids. The advanced tricyclic did intermediate was first subjected to the Swern oxidation conditions at -78 °C to afford the corresponding dialdehyde in excellent yield. In the next step, the dialdehyde was exposed to excess Wittig reagent under salt-free conditions to form the two terminal alkenes. 

On the other hand, attempted synthesis of 3-cp/-australine (10) from 144 has failed (Scheme 14). The lactol 144 was subjected to a Wittig reaction to produce the alkene 158, which was triflated followed by azidolysis to give the alkene 159. Ozonolysis of 159 followed by oletination of the resulting aldehyde 160 with the allylic borane reagent produced the diene 161 in 50% overall yield from the alkene 159. Heating of 161 in chloroform produced the two cyclized products 162 and 163 in equal amounts. Subjection of 163 to different conditions has failed to produce the ketone 164 required for the synthesis of 10, where decomposition had taken place. 

Notwithstanding us having side-stepped the internal hemiacetalisation problem, difficulties were once again encountered when we attempted to methylenate 66 under Wittig or Tebbe conditions. In both cases, starting aldehyde was always recovered untouched from either reaction. Fortunately, when 66 was subjected to Kocienski/Julia olefmation with 5-methanesulfonyl-1-phenyl-1//-tetrazole and potassium hexamethyl-disilazide at low temperature, diene 67 was formed in 77% yield. 

An improved synthesis of glutinosone (1) was also accomplished by Masamune and coworkers6 and this was based on procedure developed by Dastur7,8 for the synthesis of sesquiterpenes nootkatone. (Scheme 2) Diels-Alder reaction of 3,6-dihydro-3,5-dimethyl anisole with methyl acrylate in absence of Lewis acids afforded a 1 3 mixture of esters (17) and (18) which were converted to a,(3-unsaturated aldehydes (19) in 77% yield by oxidation with selenium (IV) oxide in dioxane. Wittig reaction of aldehydes under the usual condition yielded the dienes (20) in 63% yield which on being subjected to Grignard reaction with an excess of methyllithium produced tettiary alcohols (21) in quantitative yield. This on treatment with formic acid at room temperature gave bicyclic enone (22) and its formate (23) in 45% and 41% yield respectively. Formates (23) were hydrolyzed to enone (22) in 88% yield. 

---