Wittig Reaction modifications

A sequence for the regiospecific production of the allylic alcohols (37) from terminal isopropylidene groups (Scheme 17), involving phenylsulphenyl chloride addition, was reported last year (3,140). More recently, extension of this work (also Scheme 17)" has provided a route to the internal alcohol isomer (38), and a new alternative scheme" leads either to (37) or to the cw-terminal isomer (39) this latter depends on a stereoselective Wittig reaction modification. 

Treatment of dimethylsulfoxide (DMSO) with sodium hydride generates methylsulfinyl carbanion (dimsyl ion), which acts as an efficient base in the production of ylides. The Wittig reaction appears to proceed more readily in the DMSO solvent, and yields are generally improved over the reaction with -butyl lithium (i). Examples of this modification are given. 

Retrosynthetic cleavage of the trans A8,9 disubstituted double bond in intermediate 11, the projected precursor of diketone 10, provides phosphorus ylide 12 and aldehyde 13 as potential precursors. In the forward sense, a Wittig reaction could conceivably achieve a convergent coupling of intermediates 12 and 13 with concomitant formation of the requisite trans C8-C9 olefin. Ordinarily, the union of a nonstabilized ylide, such as 12, with an aldehyde would be expected to afford an alkene with a cis geometry.8 Fortunately, however, the Schlosser modification of the Wittig reaction permits the construction of trans olefins from aldehydes and nonstabilized phosphorus ylides.9... 

Olefin cross metathesis starts to compete with traditional C=C bondforming reactions such as the Wittig reaction and its modifications, as illustrated by the increasing use of electron-deficient conjugated alkenes for the ( )-selective construction of enals and enoates. 

An important modification to the Wittig reaction is the use of stabilized phosphonate carbanions in olefin synthesis. This reaction, originally discovered by Homer but developed by Wadsworth and Emmons, is used extensively for transformation of a carbonyl... 

The Wittig reaction, or its phosphonate modification, can be a very useful reaction in the synthesis of anomerically functionalized precursors to C-nucleosides, particularly when the ring-closure reaction leads to five-membered, anhydro derivatives, and occurs with a high degree of stereocontrol. Zhdanov and coworkers,130 showed that the following five-membered, Wittig products (179-182) were formed from various free sugars and (p-methoxybenzoyl)- and (acetyl-methylene)-triphenylphosphoranes. 

The normal Wittig reaction of nonstabilized ylides with aldehydes gives Z-olefms. The Schlosser modification of the Wittig reaction of nonstabilized ylides furnishes f-olefins instead. 

By elaboration of benzofurans, dibenzofurans can be obtained. The annelation of 4-isopropyl-7-methylbenzofuran-2-carbaldehyde (393) by Wittig reaction with 2-carboxy-l-methoxycarbonylethyltriphenylphosphorane gave the itaconic half ester (394), which on treatment with hot acetic acid cyclized to the dibenzofuran (395). Functional group modification furnished cannabifuran (396) (82JCS(P1)1605). 

By adding a strong base to the cold solution of the oxaphosphetane before it eliminates, die oxaphosphetane equilibrates to die more stable anti isomer and die E olefin is produced upon elimination. This so-called Schlosser modification in conjunction with the normal Wittig reaction enables either the Z or E isomer of the olefin to be prepared selectively. 

THE HORNER-EMMONS OR WADSWORTH-EMMONS MODIFICATION OF THE WITTIG REACTION... 

The Schlosser Modification of the Wittig Reaction allows the selective formation of -alkenes through the use of excess lithium salts during the addition step of the ylide and subsequent deprotonation/protonation steps. 

Addition of the ylide to the carbonyl is postulated to lead first to the zwitterionic intermediate betaine, which would then close to form a four-membered cyclic intermediate, an oxaphosphetane. The existence of the betaine hasn t been fully established, although its intermediacy plays an important role in the Schlosser Modification. Betaines may be stabilized by lithium salts leading to side products therefore, suitable bases in the Wittig Reaction are for example NaH, NaOMe, NEt3). 

Step 1 (3-keto phosphonates often are used for olefmation of ketones (Horner-Wadsworth-Emmons modification of the Wittig reaction). Steps 2 + 3 The cuprate-mediated 1,4-addition and subsequent Lemieux-Johnson oxidation of a vinyl group are excellent procedures for the introduction of the p-formyl group. 

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