Wittig procedure

The (Horner-)Wadsworth-Emmons reaction generally is superior to the Wittig reaction, and has found application in many cases for the synthesis of a ,/3-unsaturated esters, a ,/3-unsaturated ketones and other conjugated systems. Yields are often better then with the original Wittig procedure. However the Wadsworth-Emmons method is not suitable for the preparation of alkenes with simple, non-stabilizing alkyl substituents. 

Recently, several one-pot oxidation-Wittig procedures that circumvent the need to isolate the intermediate aldehydes have been developed. Various oxidants, including Swern [52], Dess-Martin periodinane [53], IBX [54], Mn02 [55], and BaMnCU [56], can be used in the presence of stabilized ylides to generate a,(3-unsaturated esters. 

In Aldrich, the widest collection belongs to PPV derivatives, which includes dialkoxy-PPVs (e.g., MEH-PPV 13,14), phenyl-substituted PPV 43, meta-para-linked PPV copolymer 159, etc. Many monomer precursors for PPV synthesis by Gilch and Wittig procedure as well as the Wessling Zimmerman precursor 2 for unsubstituted PPV are also available. 

When artemisinin 9a was treated with 2-lithiothiazole followed by in situ O-acetylation, the thiazole carbonyl adduct 161 was formed chemoselectively in good yield (Scheme 22) the same reaction with PhLi produced a mixture of uncharacterized products. When this acetyl adduct 161 was exposed to TMSOTf, the corresponding elimination product 162 was formed, which was converted in three steps without purification of intermediates into aldehyde 163. This was reacted with high chemoselectivity in reactions with organometallics ( -BuLi, PhMgBr) and with phosphonium ylides in a Wittig procedure <1999T3625>. 

Halofluoroalkenes may be prepared by using fluorodihalomethanes or fluoro-halomethanes in olefination procedures similar to those described above. Fluoro-trichloromethane treated with tris(dimethylamino)phosphine forms the corresponding phosphomum salt, which can then be used in the Wittig procedure. The reaction depends on the nature of the solvent in tetrahydrofuran, little olefination if any occurs however, when benzomtrile is added to the mixture, ylide formation is promoted [50] (equation 48) (Table 19). 

In this case the Zs/Z-selectivity does not matter because a terminal double bond is generated. In principle the Zs/Z-selectivity depends on the stability of the ylide employed (see chapter 9). The most valuable feature of the Wittig procedure is that, in contrast to elimination and pyrolytic reactions, it gives rise to alkenes with unambiguous position of the double bond. 

The Staudinger/aza-Wittig procedure has recently also been used by Mellet and Fernandez for the synthesis of calystegine B2, B3, and B4 analogues, emphasizing the growing importance of this methodology [12]. 

Trichlorofluoromethane treated with tris(dimethylainino)phosphane forms the phosphonium salt 12 which can then be used in the Wittig procedure. ... 

Examides of the Johnson Metkylenation Procedure 3.1.43 Comparison with the Wittig Procedure... 

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). ... 

Homoconjugated or skipped trienes are vital components of natural products such as fatty acids, leucotrienes and insect pheromones. Pohnert and Boland have reported a detailed discussion of the synthesis of these molecules using a one-pot Wittig approach which employs bis(ylides) (77), (78) and (79) as key building blocks.New one-pot Wittig procedures have also been developed for the synthesis of alkynes and bromoalkynes (Scheme 13) and iodoalkynes (Scheme 14). The latter process utilises diiodomethyltriphenyl-phosphorane (80), which is generated in situ from triphenylphosphine, iodoform and potassium butoxide. 

When chiral amino aldehydes were coupled to phosphorus ylides on a support, the salt-free Wittig procedure caused minimal epimerization [500]. 

As an example, the synthesis of oct-2-ene by the normal Wittig procedure gives an 80 20 Z E mixture. By the Schlosser modification, set out in detail below, virtually pure (99 1) E-oct-2-ene is formed in good yield in a one-pot process. Notice the low temperature used when the aldehyde is added. This is necessary to avoid completion of the Wittig. After epimerisation with a second molecule of PhLi, the oxido ylid 107 is acidified to give the alcohol syn-109 that eliminates quickly with a potassium base.19... 

Cyclization by way of the aldehyde (22, R = CHO) provides the appropriate ester of the bicyclic nucleus (23), which on deprotection gives an unstable sodium salt. Formation of the [2,3] double bond by this intramolecular Wittig procedure has been widely used for both analogue and natural product synthesis (35). Cyclization is achievable even using a thiol ester such as (24) which leads to the protected olivanic acid MM 22383 [74819-56-0] (25), C28H26N4OiiS (36). Addition of thiols to the double bond of phosphorane-derived derivatives lacking a C-2 substituent (26) has been used for the... 

The same heptadienyl phosphonium phosphonium salt (B) has been used for a synthesis of the germination stimulant occurring in Sorghum bicolor, for the seeds of the parasitic Striga asiatica, namely (Fig (4)-66) 5-methoxy-3-[(Z,Z)-pentadeca-8,11,14-trienyl]-1,2,4-trihydroxybenzene [208] by a Wittig procedure. 

A variation of the Wittig procedure with reversed building blocks served to prepare the chiral 2-aminobutadiene 17 in good yield from diacetyl 15 and (5)-2-(methoxymethyl)-... 

Reaction conditions play a critical role in many of the above options for loss of stereochemistry, and factors such as the presence of Lewis acids (i.e., lithium ion), elevated temperatures, and hydroxylic solvents or impurities may well induce partial equilibration. However, the most commonly employed Wittig procedures rely upon inert solvents (ethers, hydrocarbons, DMSO, etc.) and temperatures no higher than 25°C. Under these conditions, significant equilibration is seldom encountered, especially with the simple nonstabilized ylides. 

Wittig procedure was used in a synthesis of methyl garosaminide (11)... 

Olefins have been obtained in a stereoselective manner via the Wittig procedure. The ylid-carbonyl adduct is treated with a strong base and an electrophile (Mel, PhCHO) to form olefins of predictable stereochemistry. The Wittig reaction has also been reported to occur with phosphonium fluorides in the absence of base. ... 

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