Still— Wittig rearrangement ethers

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... 

Transformation of allyl ethers into homoallylic alcohols by treatment with base. Also known as Still-Wittig rearrangement. Cf. Sommelet-Hauser rearrangement... 

The Still-Wittig rearrangement of stannylated cis-ethers (11) gives trans homoallylic alcohols (12) selectively (equation 5). If the underlying alcohols (R = Me) are rearranged under Biichi s conditions (DMF acetal, xylene, reflux), trans selectivity is achieved, too, but yields are lower (41-49%). ... 

Still-Wittig rearrangement of the ( )- and (Z)-17-ethylidene-16a ethers (93) and (94) afforded the 20a- and 20p-methyl steroids (95) and (96) with complete stereochemical control (equation 23). As in other examples, sp stereochemistry depends upon double bond geometry in the starting allylic ether. 

Still-Wittig rearrangement of the nonracemic (/ )-propargylic ethers (100a) and (100b) has been found to give the (/ )-allenes (100c) and (lOOd) with complete asymmetric transfer (equation 25a). The stereochemistry is consistent with a five-membered cyclic transition state. 

Scheme 6.17. I2,3]-Still-Wittig rearrangements of allyl ethers [85],...

The preparation of a synthetically useful 4-C-hydroxymethyl>hex-2-enopyranoside by use of a Still-Wittig rearrangement of a stannyl ether has been described (Scheme n). ... 

Z)-Trisubstitutedalkenes. Still and Mitra have described an efficient synthesis of alkenes of this type from allylic alcohols by a [2.3] sigmatropic Wittig rearrangement. The alcohol 2 is converted into the allyl stannylmethyl ether (3), which can be isolated if desired. Treatment with n-butyllithium results in tin-lithium exchange and rearrangement to the homoallylic alcohol 4 in 95% overall yield. When 3 is transmetalated and immediately quenched with cyclohexanone, 5 is obtained in 73% yield. 

Axial ViS. equatorial selectivities of Wittig rearrangements were studied with the f-butylcyclohexane derivatives (89 equation 22) (Table 8). The lithio dianion of acid (89a) prefers equatorial attack. The Bu 02C (89b) and MesSiCsC substituted ethers (89c) undergo nonstereoselective rearrangements. The Still-Wittig reaction of (89d) is the only one among all known 2,3-sigmatropic shifts on this skeleton that prefers axial attack (67 33). 

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. ... 

The first asymmetric total synthesis of (+)-astrophylline was accomplished in the laboratory of S. Blechert. The Still variant of the [2,3]-Wittig rearrangement was used to generate the 1,2-trans relationship between the substituents of the key cyclopentene intermediate. The tributylstannylmethyl ether substrate was transmetalated with n-BuLi, which initiated the desired [2,3]-sigmatropic shift to afford the expected homoallylic alcohol as a single enantiomer. 

Transmetallation can be employed in order to avoid the use of strongly basic conditions. One such variant is the [2,3]-Wittig-Still rearrangement wherein stannyl ethers can be converted to homoallylic alcohols. Several examples of this tranformation in the synthesis of amino acid components of bioactive polyoxins have been reported by Ghosh. In their synthesis of 5-0-carbomylpolyoxamic acid, a bioactive amino acid nucleoside, E and Z-allylic stannyl ethers, such as 45, derived from an isopropylidene L-threitol derivative, were subjected to the [2,3]-Wittig-Still rearrangement. 

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