Stereospecific -Wittig rearrangement

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... 

However, stereochemically well-defined acyclic ethers are in demand too, for instance, for the stereospecific Wittig rearrangement. 

There are two aspects to the stereospecificity of the [1,2]-Wittig rearrangement the steric course (inversion vs. retention) at the migrating carbon atom and at the Li-bearing carbanion center (equation 6). 

The Wittig-Still Rearrangement is also a suitable starting point for performing mechanistic studies about the stereospecificity of this process, and Maleczka and Feng have reported on the stereochemical outcome of the [1,2]-Wittig Rearrangement. 

Maleczka, R. E. Geng, F. Stereospecificity of the 1,2-Wittig rearrangement how chelation effects influence stereochemical outcome. 

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 cyclic system, the stereochemistry of the product of a [2,3]-Wittig rearrangement may be ensured by the rearrangement s suprafacial nature. [2,3]-Wittig rearrangement of lithiomethyl ethers derived from stannanes provides a valuable method for stereospecific... 

Kodama, M., Yoshio, S., Yamaguchi, S., Fukuyama, Y., Takayanagi, H., Morinaka, Y., Usui, S., Fukazawa, Y. Total syntheses of both enantiomers of sarcophytols A and T based on stereospecific [2,3]Wittig rearrangement. Tetrahedron Lett. 1993, 34, 8453-8456. 

Along with the Claisen rearrangement, other related reactions are applicable for the preparation of natural products. For instance a [2,3]-Wittig rearrangement is one step in the stereospecific synthesis of HMG-CoA reductase inhibitor pravastatin and in the total synthesis of the HMG-CoA synthase inhibitor 1233A according to the general scheme (equation 253). 

A stereocontrolled entry into congugated silylalkynes has been based on a combination of the highly diastereoselective (2,3)-Wittig rearrangement followed by the stereospecific fragmentation of the... 

The [2,3]Wittig rearrangement of bisallyl ethers and allyl ethers of glycollic acid offers a versatile method of preparing non-conjugated unsaturated aldehydes in a highly stereospecific fashion (Scheme 30). ... 

A [2,3]- Wittig rearrangement carried out on a carbohydrate template has been used in a route to 3-alkyl malic acids, as indicated in Scheme 24. The product of opposite chirality at C-3 could be obtained from the cis-alkene, and transition-state models were proposed to rationalize the results.93 Somewhat similar intermediates were used in a synthesis of the stereospecifically-deuteriated ester (llO), required as a standard in a study of enzyme stereospeciflcity in this case C-3 of D-glucose became C-1 of the carbojqrlic acid by oxidative cleavage.94... 

On a number of occasions, the Wittig rearrangement has proven instrumental for the stereoselective preparation of homoallylic alcohols. One of the earliest examples was demonstrated by Felkin and showased the ability of optically active ethers to participate in stereospecific rearrangements (Equation 21) [100], Treatment of optically active allyl ether 177 (> 90% ee) with n-BuLi leads to stereospecific formation of a benzylic alcohol 179 (>90% ee) as a side product after a series of manipulations. 

Potassium Amides. The strong, extremely soluble, stable, and nonnucleophilic potassium amide base (42), potassium hexamethyldisilazane [40949-94-8] (KHMDS), KN [Si(CH2]2, pX = 28, has been developed and commercialized. KHMDS, ideal for regio/stereospecific deprotonation and enolization reactions for less acidic compounds, is available in both THF and toluene solutions. It has demonstrated benefits for reactions involving kinetic enolates (43), alkylation and acylation (44), Wittig reaction (45), epoxidation (46), Ireland-Claison rearrangement (47,48), isomerization (49,50), Darzen reaction (51), Dieckmann condensation (52), cyclization (53), chain and ring expansion (54,55), and elimination (56). 

The readily available aldehyde (118) has served as a suitable precursor for a number of 6-endo-( al-kenyl)bicyclo[3.1,0]hex-2-enes. For example, treatment of (118) with PhsP —CHC02Me gives a mixture of die bicyclic diene esters (121)-(123) (Scheme 18). In view of the stereospecific nature of the Cope rearrangement process (vide supra), it is highly likely that (121) and (122) are derived by bond reorganization of the initially formed Wittig products (119) and (120), respectively. The ratio of (121) (122) is, therefore, a reflection of the (expected) fact that the Wittig reaction produces primarily the rrans-a,P-un-saturated ester (119). The diene ester (123) is, presumably, formed by partial isomerization of (121) and (or) (122). 

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