Wittig rearrangement chirality transfer

Of these reactions, the [2,3] Wittig rearrangement in particular has often been used as a means of transferring chirality. The product of this reaction has potential chiral centers at C-3 and C-4 (if R ), and if the starting... 

In order to establish the correct absolute stereochemistry in cyclopentanoid 123 (Scheme 10.11), a chirality transfer strategy was employed with aldehyde 117, obtained from (S)-(-)-limonene (Scheme 10.11). A modified procedure for the conversion of (S)-(-)-limonene to cyclopentene 117 (58 % from limonene) was used [58], and aldehyde 117 was reduced with diisobutylaluminium hydride (DIBAL) (quant.) and alkylated to provide tributylstannane ether 118. This compound underwent a Still-Wittig rearrangement upon treatment with n-butyl lithium (n-BuLi) to yield 119 (75 %, two steps) [59]. The extent to which the chirality transfer was successful was deemed quantitative on the basis of conversion of alcohol 119 to its (+)-(9-methyI mande I ic acid ester and subsequent analysis of optical purity. The ozonolysis (70 %) of 119, protection of the free alcohol as the silyl ether (85 %), and reduction of the ketone with DIBAL (quant.) gave alcohol 120. Elimination of the alcohol in 120 with phosphorus oxychloride-pyridine... 

Stereospecific Wittig rearrangement.1 Wittig rearrangement of the optically active (Z)-allylic ether 1 (9, 475 for a related reaction) gives (R,E)-2 with complete chirality transfer. Rearrangement of (E)-l results in two products, again with complete chirality transfer.1... 

An asymmetric [2,3]-Wittig rearrangement triggered by a non-racemic carban-ion generated by chirality transfer from epoxide via Brook rearrangement has been... 

Treatment of the (.V)-( A )-[(.svr-allylo y )dimcsitylsilyl]stannanc with -BuLi provides a (R)-(.E)-allylsilane with high enantioselectivity, in which 1,3-chirality transfer occurs during the [2,3]-sila-Wittig rearrangement (Equation (118)).290... 

Of these reactions, the [2,3]-Wittig rearrangement in particular has often been used as a means of transferring chirality. The product of this reaction has potential stereogenic centers at C-3 and C-4 (if R ), and if the starting ether is optically active because of a stereogenic center at C-1, the product may be optically active as well. Many examples are known in which an optically active ether was converted to a product that was optically active because of chirality at C-3, C-4, or both. If a... 

With a phenylsulfonyl group as X (Scheme 41) the intermediate, after rearrangement, will decompose directly to an aldehyde function, which reacts wiA excess alkyllithium to form an unsaturated alcohol. The often efficient transfer of chirality from C-1 of an optically active allylic alcohol to the newly created stereogenic centers at C-3 and/or C-4 is another valuable aspect of the 2,3-Wittig rearrangement which has already found extensive use in natural product synthesis. ... 

Complete chirality transfer from cw-ethers (96 equation 24) to homoallylic alcohols (97) was the cornerstone for numerous applications of the Wittig rearrangement in naturd product synthesis (Table 9). The predictability of the absolute configuration of the rearranged product on the basis of a suprafacial bond shift and the ready availability of optically active starting materials make these reactions attractive. 

Allylic alcohols with a trans double bond give product mixtures in the Still-Wittig rearrangement cf. equation 7 ). Advantageously, such substrates e.g. 98) can be converted to homoallylic alcohols with 100% chirality transfer by the Biichi rearrangement (equation 25). ... 

Chirality transfer through a Still-Wittig reaction provided the C-glycoside (113) from the enol ether (equation 29). The low yield (25%) was mainly due to protonation of the intervening oxyanion to the methyl ether (114) prior to rearrangement. Presumably, this side reaction could have been suppressed with HMPA as cosolvent. ... 

In connection with studies on chirality transfer in 2,3-Wittig rearrangements, Tsai and Midland examined the ( )- and (Z)-( )-l-isopropyl-2-butenyl benzyl ethers (131 equation 32) and (135 equation 33). Both ethers rearranged with essentially complete suprafaciality, but the (Z)-isomer (135) showed considerably higher ( )/(Z) and synlanti selectivity in accord with transition state considerations previously discussed for the analogous propargylic ethers (Scheme 7). 

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 . 

Self-irnmolative chirality transfer for rr-sLabilized [2,3] Wittig systems derived from nonracemic secondary alcohols follows a stereochemical course consistent with rearrangement through the conformation (vide supra). For bisallylic ethers 46, the fidelity of chiral transmission is larger than 90%34. 

Benzyl ethers were among the first [2,3] Wittig substrates for which self-immolalive chirality transfer was documented46. Thus, rearrangement of benzyl ether 50 proceeds with excellent 1,3 chirality transfer, but essentially no simple diastereoselection. 

Scheme 6.11. Asymmetric induction and chirality transfer in [2,3]-Wittig rearrangements of allylic benzyl [78], ally [78], and trimethylsilylpropargyl [79] ethers.

Chirality transfer in the rearrangement of allyloxymethyl stannanes is complete, even in cases where the rearrangement itself is not selective for one product, as shown by the examples in Scheme 6.17 [85]. Recall from Scheme 6.7b and c that in the Still-Wittig rearrangement, one product double bond configuration is formed selectively only when the educt has the Z configuration. This is due to severe strain in one of the two transition structures (e.g., between the isopropyl and the methyl in Scheme 6.17a). In 1985, Midland reported that rearrangement of the Z-... 

Methyl ketone 398, which is available from 379 according to procedures previously discussed, has been used as a chiral precursor for rearrangement studies. The requisite substrate 399 is prepared by addition of vinylmagnesium bromide to 398, which produces a tertiary alcohol with > 95% optical purity. Deprotonation of oxazoline ether 399 with Ai-butyllithium results in a [2,3] Wittig rearrangement and furnishes 400 as the sole product [125]. This remote transfer of chirality is of potential use in constructing fragments associated with a variety of macrolides. 

The synthesis of (5 S)-thiolactomycin (792), an enantiomer of an antibacterial agent, makes use of a Wittig olefination early in the sequence as a way of preparing a,jS-unsaturated ester 786 (Scheme 106). The key step in the synthesis is an allyl xanthate-dithiocarbonate rearrangement of 788 to 789. This process occurs upon distillation of 788 at 145 °C (0.4 mm Hg) and gives the desired product 789 in nearly quantitative yield. Chirality transfer is equally efficient, with an enantiomeric excess of at least 98% [222]. 

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