Wittig-methylenation

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

A similar procedure was applied to the synthesis of quinazolidine 189 from precursor 188 in the total synthesis of the natural product known as ( )-quinolizidine 2071 190, an alkaloid isolated from the skin of the Madagascar mantelline frog Mantella baroni, that shows an exceptional axial stereochemistry for the ethyl group at C-l. Quinolizidine 189 was transformed into 190 by oxidation and two consecutive Wittig methylenations (Scheme 34) <1999CC2281>. 

In one example of application of the RCM strategy, summarized in Scheme 107, the key intermediate 454 was obtained from 451 by sequential Wittig methylenation to 452, reductive iV-deprotection to 453, and introduction of an alkenyl chain onto the secondary amine. The RCM reaction of 454 to 455 proceeded in quantitative yield in the presence of the second-generation Grubbs catalyst <20040L965>. 

The late stages of the synthesis (Scheme 1.17) proceeded with Wittig methylenation of ketone 144 with Ph3P=CH2 at 70 °C to furnish exocyclic alkene 145 in 77 % yield. Finally, the alcohol was installed via a Se02-mediated allylic hydroxylation [57] of the exocyclic alkene 145 to afford ( )-nominine (1) in 66 % and 7 1 dr. The structure of nominine (1) was verified via an X-ray crystal structure determination, thereby completing the racemic total synthesis of ( )-nominine (1). 

The obtained telluroacroleins have been submitted to a Wittig methylenation giving the expected tellurodienes. ... 

The stereochemistry at C-4 and C-6 is then established. The cuprate addition in step C, occurs anti to the substituent at C-2 of the pyran ring. After a Wittig methylenation, the catalytic hydrogenation in step D, establishes the stereochemistry at C-6. 

The 2-vinyl derivatives 256-258 were obtained by standard Wittig methylenation of the corresponding aldehydes <1996GCC888, 1997CCC1468> (Equation 5) with methylene(triphenyl)phosphorane in 54-78% yield after chromatographic purification. 

The Wittig methylenation of geranial to (E)-4,8-dimethyl-l,3,7-nonatriene is best carried out with phenyl 1ithium 1n tetrahydrofuran as described in Part... 

Application of this two-step sequence to phosphines is a useful alternative to Wittig methylenation (equation I).1... 

Rotane was first synthesized by Rippol and Conia29. The key steps included the synthesis of dispirononanone 13 (equation 11). Condensation of 13 with formaldehyde provided the tetrahydroxymethyl derivative 32, which was converted into the tetraspiro compound 33 by tosylation-bromination followed by reductive cyclization. Subsequent Wittig methylenation and cyclopropanation of the ketone 33 completed the synthesis (equation 30). 

The Peterson silyl-Wittig methylenation of carbonyl compounds has been significantly improved by performing the elimination of the trimethylsilanol form of the intermediate /3-hydroxysilanes with Nafion-H under mild conditions1001 [Eq. (5.362)]. 

Wittig methylenations similar to those described in Scheme 65 were also used by Zurfliih et al. 215), Kosugi et al. 216) and Stork and Cohen 217) in the synthesis of racemic grandisol (Scheme 66). In the first two cases (refs. 215,216)) the cyclobutane... 

Hydrocarbons with methyl branching at C-ll to C-13 were isolated from Heliothis virescens (Noctuidae, Lepidoptera) 229). These compounds release a host-seeking behavior in the braconid Cardiochiles nigriceps, a Heliothis parasit. These kairomones were prepared in 1975 by Vinson et al. 229) by Wittig methylenation of the corresponding methyl ketones and subsequent catalytic hydrogenation 229). 

White peach scale. Several scale sex pheromones have now been elucidated each of them possesses an asymmetric center and usually a trisubstituted alkene link within an isoprenoid framework (43). The structure of the white peach scale pheromone, R,Zb-II (Figure 8), lent itself to synthesis with another chiral starting material, namely limonene (44). Selective ozonlysis followed by workup with dimethyl sulfide-methanol provided a ketoacetal, III. Wittig methylenation followed by hydrolytic cleavage of the acetal gave a dienaldehyde, IV. Conversion of the aldehyde via the acid to an amide (45) with enantiomerically pure ot-methylbenzylamine permitted chromatographic assessment of the purity of the diene aldehyde (and the limonene). The required R-isomer of the diene aldehyde was >48% ee. 

Combined uses of epoxide opening and the above-mentioned sequence involving ketone formation, Wittig methylenation and reduction was exploited by Lukacs to produce all possible stereoisomers of methyl 2,4-dideoxy-2,4-dimethyl hexopyranosides (key compounds of macrolide antibiotics syntheses). The sequence, illustrated in Scheme 11.25, utilized the altro derivative 7, which was transformed into a 3 1 mixture of 104 and 105 via olefin 103. 

Application of the preceding strategy to multistriatin synthesis (Scheme 11.26) started with compound 7, which was deoxygenated at C3 and further elaborated to ketone 106 [49]. Wittig methylenation provided 107, and subsequent double bond reduction using Wilkinson s catalyst afforded the dimethylated compound 34 [93]. Further manipulation yielded a-multistriatin 108, the pheromone of Scolytus multistriatus. Other syntheses of this pheromon from sugars have been reported [48,94,95]. 

Aldol reaction of (5)-2-benzyloxypropanal with the lithium enolate of methyl 2-methoxy-propanoate gives a 7 2 1 mixture of (3-hydroxyesters (Scheme 13.70). After protection of the alcohol moiety, the isomeric mixture is reduced with LiAlH4 and the resulting primary alcohols separated by chromatography on silica gel. Oxidation of the major alcohol 223 (isolated in 40% yield) into an aldehyde is followed by Wittig methylenation. This provides 224. Hydroboration of 224 gives a primary alcohol that is oxidized (Swem) into aldehyde 225. Hydrogenation yields L-cladinose, a saccharide moiety of erythromycin A [127]. 

Then, the resulting dicarbonyl compound is subjected to a Wittig methylenation. 

In the second step of this reaction sequence, the two carbonyl moieties of 38 are converted to methylene moieties using standard Wittig methylenation conditions. 

Of particular note in comparison with the Wittig procedure is Boeckman s total synthesis of gascardic acid (equation 11). It was found that direct Wittig methylenation was low yielding in the reaction with (36). It was hypothesized that this was because of interference with the two-carbon side chain. The problem was solved by hydrolyzing the esters, followed by addition and elimination of the sulfoximine and reesterification to obtain the desired adduct (37) in 70% overall yield. The Johnson method was also utilized to selectively methylenate the less-hindered ketone (38) in the synthesis of (-)-picrotoxinin (equation 12). ... 

For a recent discussion comparing the Wittig methylenation to the methods discussed below see L. Fitjer and U. Quabeck, Synth. Commun., 198S, 15, 855. 

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