Wittig rearrangement examples

The aza-[2,3]-Wittig rearrangement [47] and the related aza-[3,3]-Claisen rearrangement [48] of vinylaziridines are elegant examples of expansion of the aziridine ring in a stereocontrolled fashion (Scheme 38). 

An earlier example of this type of domino reaction was reported by Greeves and coworkers (Scheme 2.194) [443]. Treatment of either the ( )- or (Z)- allyl vinyl ether 2-870 with NaH initiates the [2,3]-Wittig rearrangement to afford 2-872 via 2-871. The subsequent oxy-Cope rearrangement led to the aldehyde 2-873, which was reduced with NaBH4 to give the alcohols 2-874. Both isomers of 2-870 predominantly generated the (/ )-xyu-product 2-874 in comparable ratios as the main product. 

A few isomerizations cover the Wittig rearrangement [501, 502]. Usually, anion-stabilizing groups, for example an imidate such as 149, are used [503] (Scheme 1.67). 

Another recent example is the formation of 152 [504] (Scheme 1.68). However, the allene unit was formed by a base-catalyzed isomerization after the [2,3]-Wittig rearrangement of 151. Only one diastereomer was detected the configuration of the allenic unit in 152 was not determined. 

An interesting problem of the periselectivity arises in the rearrangement involving an a-oxyallylic carbanion as the terminus. In this particular case, the [l,4]-shift may compete with the [1,2]-Wittig rearrangement (see Section n.C). For example, the rearrangement of 5 affords a mixture of the [l,4]-product 6 and the [l,2]-product 7 (equation 5) °. 

The acetal [1,2]-Wittig rearrangement protocol is also applicable to the synthesis of medium-sized cyclic ethers. For example, a reaction of the 9-membered cyclic acetal 37 with lithium piperidide provides the 8-membered ring ether 38 in good yield along with high diastereoselectivity (equation 20) . 

The first example of a retro-Brook rearrangement 158 159 was discovered by West and colleagues tor the [l,3]-variant (equation 91) °. Subsequently, the [l,2]-variant 160 —> 161 was reported by the same group (equation 92) °. The rearrangement is much faster than the corresponding Wittig rearrangement. 

The [2,3] Wittig rearrangement of, for example, (7 )-2-(tributylstannylmethoxy)-3-octyne (93% ee) to give (M)-2-(l-propenyiidene)-l-hexanol has been reported20. 

Diastereoselective [2,3] Wittig rearrangement of propynyloxyacetic acids and esters has recently been reported95 and leads to allenic esters with d.r. in excess of 90 10 [(S,M)/(7t,Af)] for the examples shown. 

It is notable that allyloxylation can also be performed in relatively good yields (Table 6) although allyl alcohols are easily oxidized anodically12. The allyloxylated sulfides thus obtained are easily converted into the corresponding ft, /-unsaturated ketones by a [2,3] Wittig rearrangement using bases as shown in equation 21. Anodic desilylation/carboxylation of a-thiomethylsilanes also takes place similarly as shown in an example in Table 6. 

Properly designed strategies based on the [2,3]-Wittig Rearrangement are powerful tools for asymmetric synthesis as exemplified by the many examples presented. 

Wittig rearrangements proceed with predominant inversion, with radicals intervening in the mechanism.27 For example, stannane (/ )-30 of 88% ee rearranges, on transmetallation with alkyllithiums, to the alcohol (/ )-31 of 42% ee, a reaction demonstrating 74% invertive stereospecificity. 

In a general sense, [1,2]-Wittig rearrangements have only a limited application in synthesis because yields and selectivities are frequently moderate at best. For example, the valuable stereoselective conversion of 117 to 118 (which also works with higher homologues) proceeds in only 14% yield.85 86... 

We also observed similar phenomena in the reaction of silyl enol ethers with cation radicals derived from allylic sulfides. For example, oxidation of allyl phenyl sulfide (3) with ammonium hexanitratocerate (CAN) in the presence of silyl enol ether 4 gave a-phenylthio-Y,5-un-saturated ketone 5. In this reaction, silyl enol ether 4 reacts with cation radical of allyl phenyl sulfide CR3 to give sulfonium intermediate C3, and successive deprotonation and [2,3]-Wittig rearrangement affords a-phenylthio-Y,6-unsaturated ketone 5 (Scheme 2). Direct carbon-carbon bond formation is so difficult that nucleophiles attack the heteroatom of the cation radicals. 

Allyloxysilyl)lithiums undergo a [2,3]Wittig-type rearrangement smoothly to form allylsilanolate anions in an intramolecular fashion (Scheme 11). This is the first example of the sila-Wittig rearrangement (54g). 

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