Methylenation Wittig reagents

The reaction of a selenoester with Ae methylene Wittig reagent (77) readily produces the vinyl ether (78 equation 27). ... 

Methylenation of ol-(N-Boc-amino) aldehydes. Methylenation of these chiral aldehydes with the Wittig reagent or with CH2Ir-Zn-TiCl4 (13, 114) is accompanied by extensive racemization. However, the neutral reagent 1 obtained from CH2I2, Zn, and A1(CH3), converts these aldehydes to the protected allylamines in 40-75% yield and in >99% ee. 

The Wittig reaction consists in the replacement of carbonyl oxygen of aldehydes and ketones by a methylene group with the aid of phosphine-methylenes resulting in the formation of cis or trans olefines. The reaction proceeds through the nucleophilic addition of Wittig reagent (phosphine methylene) across the > C = O bond and formation of an intermediate cyclic. 

As shown in equation 21, the methylenation of polyketone is performed with bis(iod-ozincio)methane (3) and /S-TiCl339. With these substrates, the Wittig reagent and the... 

Can serve as alternative to Wittig reagent for the methylenation of hindered ketones. 

The corresponding Wittig reagent, CHj PPhj, reacts smoothly with both aldehydes and ketones to give methylenated products In high yield but with one subtle limitation. The problem cannot be detected with aldehydes because they react rapidly even at temperatures as low as -78°C, but ketones react more slowly, and an adjacent enolizable chiral center can be epimerized as a result of competitive reversible enolization. This limitation of the Wittig... 

The rest of the synthesis (Scheme 13) is completely stereospecific and most of the steps are known (20). The bicyclic acid was oxidatively decarboxylated with lead tetraacetate and copper acetate (21). The resulting enone was alkylated with methyllithium giving a single crystalline allylic tertiary alcohol. This compound was cleaved with osmium tetroxide and sodium periodate. Inverse addition of the Wittig reagent effected methylenation in 85% yield. Finally, the acid was reduced with lithium aluminum hydride to grandisol. 

Note The reduction of C-acyl- to C-alkylpyrazines has been used occasionally 1022,1567 in addition, pyrazinecarbaldehydes react with methylene reagents to afford alkenylpyrazines, providing one or other reactant is preconverted into a Wittig reagent, as here illustrated. 

The Wittig olefination of 1,5-oxazocine 416 with [(methoxy)methylene]triphenylphosphorane led to the formation of the enol ether 431a (88% yield) as an inseparable mixture of E and Z isomers (2.5 1 ratio). Instead, when the reaction was carried out using methyltriphenylphosphorane as Wittig reagent, the as 3,5-disubstituted diastereoisomer 431b was exclusively formed in 85% yield (Scheme 84) <1998JOC3492>. 

Wittig reagent Me3P=CH2 gave the methylene-methyl complex 37 [Eq. (53)]. This complex decomposed thermally to TaCp2(CT2H4)CH3 and... 

Phenylthiomethyllithium was also used for ketone methylenation, - mainly in the case of hindered ketones which do not react with the usual Wittig reagent. This is a three-step sequence the reagent (2a) is added, then the resulting alcohol is acylated, and finally the exocyclic methylene is formed by reduction with lithium in ammonia (Scheme 17). 

Methylenation of aldehydes and ketones. A reagent prepared in CH2CI2 from CH2I2, Zn, and TiCh is considerably more reactive than one prepared from CH2Br2, Zn, and TiCh (8, 339,11, 337,12, 322). Moreover, it affords less of the coupled products. This new reagent does not react with esters. It is particularly useful for methylenation of easily enolizable ketones, for which the Wittig reagent is not useful. The isolated yields of some methylenated products are shown. 

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