2,3-Wittig-oxy-Cope rearrangement

S ily 1) ally lie ethers 234 readily undergo 2,3-Wittig rearrangement upon treatment with an amide base to give, after methylation, 235 (equation 192)37,343. Tandem Claisen-2,3-Wittig-oxy-Cope rearrangement has been observed when 236 is treated under similar... 

Ethyl lactate was used for diastereocontrol and asymmetric transmission in a sequential 2,3-Wittig-oxy-Cope rearrangement, affording product in 91% ee (eq 9). - 4 Excellent asymmetric induction has also been noted in the Lewis acid-mediated ene reaction of (5)-ethyl lactate-derived intermediates (eq 10). ... 

Mercury(n) triiluoroacetate has been shown to induce the oxy-Cope rearrangement of tertiary hexa-l,5-dien-3-ols at room temperature. Further details of the stereochemical consequences of sequential tandem Cope-Claisen rearrangements have been disclosed, and the use of the tandem [2,3]-Wittig-oxy-Cope rearrangement has been demonstrated in the synthesis of (E S-octenal, a precursor of exo-brevicomin [equation (36)]. Investigation of the trans-... 

Scheme 2.193. Domino [2,3]-Wittig/anionic-oxy-Cope rearrangement process...

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. 

Lastly it should be mentioned that a 2,3-Wittig rearrangement can be coupled with other sigmatropic processes in synthetically valuable tandem sequences. An illustrative example is a tandem 2,3-Wit-tig-oxy-Cope rearrangement, which provides a versatile route to 8,e-unsaturated carbonyl compounds (Scheme 46). ... 

It is remaikable that the ( )/(Z)-stereochemistry of the oxy-Cope product is not dependent on the erythrolthreo ratio of the 2,3-Wittig rearrangement but on the specific rearrangement procedures used thermal rearrangement exhibits higher ( )-selectivity (92-95%) than the anionic oxy-Cope and siloxy-Cope variants. 

Allylation of the 2,3-Wittig products (167) leads to diallylic ethers (171) in which one of the allylic double bonds is part of a 1,5-diene system. These ethers undergo 3,3-oxy-Cope rearrangement to afford vinyl allyl ethers (170), which rearrange in situ by a 3,3-Claisen process to yield the ( )-dienals (169). Some typical results are summarized in Table 14. The cyclopentanols (175) were shown to arise from aldehydes (169) by an intramolecular thermal ene reaction. ... 

For instance, the one-pot tandem reaction [2,3]-Wittig-anionic oxy-Cope rearrangement affords the unsaturated aldehydes 571 starting from the bis-allylic ethers 570 at a high level of stereocontrol (equation 224). It was shown that the efficiency of chirality transfer in anionic oxy-Cope rearrangements is determined only by the orientational preference of the oxyanionic bond in the precursors having a single carbinol carbon chiral center . 

As an example, the anionic oxy-Cope rearrangement of the two geometrically isomeric. sww-sub-strates 12 (E.E. 96% stereopurity E.Z. 92% stereopurity), which are prepared via [2,3] Wittig rearrangement of 10 followed by trans or cis reduction of 11 (97% anti. 99% ), respectively, affords the. ytt-aldehyde 13 with 95 % de and 99 % E and the an -aldehyde 13 with 88 % de and 97 % E, respectively. The diastereomeric excesses are determined by capillary GC analysis after conversion of the mixtures to cis- and /ranj-3,4-dimethyl-5-pentanolides (14)968,969... 

The [2,3] Wittig rearrangement can be followed by an oxy-Cope rearrangement. In most cases, these reactions are performed in a sequential mode, e.g., 1 -> 2 —> 3 -> 4117S. 

Asymmetric oxy-Cope rearrangement. The anionic rearrangement of l,5-dicn-3-ols (3) can proceed with high diastcrcosclectivity. The trans- and as-isomers of 3 are prepared by [2,3]-Wittig rearrangement of 1, followed by (E)- and (Z)-reduction of the... 

Another natural product, (+ )-faranal (27), a trail pheromone of the Pharaoh s ant, has also been synthesized starting with 2 (see Scheme 3) [11].The crucial transformation in the sequence is a [2,3] Wittig rearrangement of 24 which, after cw-hydrogenation, gives diene 25 in > 96% ee. This intermediate, when treated with potassium hydride, undergoes an anionic oxy-Cope rearrangement to afford the erythro aldehyde 26 in 91% ee. 

Hiersemann has reported the synthesis of 2-hydroxy-y-lactones 77 by the [2,3]-Wittig rearrangement of ester dienolate substrates 75 and 76. The products of the rearrangements were required as substrates for 3-oxy-Cope rearrangements, ultimately leading to the stereoselective synthesis of nonnatural amino acids. ... 

Wittig and anionic oxy-Cope rearrangements using potassium hydride. The anionic oxy-Cope rearrangement went through a chair-like transition state to yield the iyn-substituted aldehydes 257, which were oxidized to acid 258. Treatment of 8,e-unsaturated carboxylic acids 258 with either iodine or phenylselenium chloride afforded the cyclized iodo-/phenylselenolactones 259-261 as a mixture of diaste-reomers. In most cases, lactone 259 was obtained as the major or sole product. 

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