Wittig reactions stereoselectivity

Vedejs, E., Peterson, M. J. The Wittig reaction stereoselectivity and a history of mechanistic ideas (1953-1995). Advances in Carbanion... 

Whereas the effects of Li salts on Wittig reaction stereoselectivity are well known, effects of sodium salts have received less attention. As in the case of the Li salts, the presence of Na salts tends to increase the TJE ratio in alkene formation. However, this effect is observed only in those cases where the sodium salts are soluble and available for complexation with the reactants (Nal and NaB(C6H5)4). In cases where the metal ion is sequestered by an additive such as 15-crown-5 or DMSO or when the metal salt is not soluble in the reaction media (NaCl, NaBr), lower Z/E ratios in alkene formation are observed. 

The hindered reducing agent (28) converts acids (27) into aldehydes (26) whilst L1AIH4gives the alcohols. The Wittig reaction stereoselectively gives cis alkenes (24) (Chapter 15), which Lambert chose to hydroxylate cis. 

Vedejs, E. Peterson, M. J. The Wittig Reaction Stereoselectivity and a History of Mechanistic Ideas (1953-1995) Advances in Carbanion Chemistry, 1996, 2, 1-85. Vedejs, E. Peterson, M. J. Stereochemistry and Mechanism in the Wittig Reaction Topics in Stereochemistry 1994,21,1-157. Maryanoff, B. E. Reitz, A. B. The Wittig Olefmation Reaction and Modifications Involving Phosphoryl-Stabilized Carbanions. Stereochemistry, Mechanism, and Selected Synthetic Aspects Chemical Reviews 1989, 89, 863-927. 

The Peterson reaction has two more advantages over the Wittig reaction 1. it is sometimes less vulnerable to sterical hindrance, and 2. groups, which are susceptible to nucleophilic substitution, are not attacked by silylated carbanions. The introduction of a methylene group into a sterically hindered ketone (R.K. Boeckman, Jr., 1973) and the syntheses of olefins with sulfur, selenium, silicon, or tin substituents (D. Seebach, 1973 B.T. Grdbel, 1974, 1977) illustrate useful applications. The reaction is, however, more limited and time consuming than the Wittig reaction, since metallated silicon derivatives are difficult to synthesize and their reactions are rarely stereoselective (T.H. Chan, 1974 ... 

Several structures of the transition state have been proposed (I. D. Williams, 1984 K. A. Jorgensen, 1987 E.J. Corey, 1990 C S. Takano, 1991). They are compatible with most data, such as the observed stereoselectivity, NMR measuiements (M.O. Finn, 1983), and X-ray structures of titanium complexes with tartaric acid derivatives (I.D. Williams, 1984). The models, e. g., Jorgensen s and Corey s, are, however, not compatible with each other. One may predict that there is no single dominant Sharpless transition state (as has been found in the similar case of the Wittig reaction see p. 29f.). 

Compound 16, the projected precursor of 15, could conceivably be assembled from bishomoallylic alcohol 17 via a pathway that features the oxidative functionalization of the A20,21 double bond with participation by the C-17 secondary hydroxyl. Compound 17 is an attractive retrosynthetic precursor for compound 16 because the A20-21 double bond, which could permit the introduction of the adjacent C-20 and C-21 stereocenters in 16, provides a convenient opportunity for significant molecular simplification. Thus, retrosynthetic cleavage of the A20 21 double bond in 17 furnishes compounds 18 and 19 as potential building blocks. The convergent union of the latter two compounds through a Wittig reaction would be expected to afford 17 stereoselectively. 

The path to the complex heptacycle 87 (Scheme 17 a) commences with a stereoselective Wittig reaction between 2-deoxy-D-ribose (110) and (ethoxycarbonylethylidene)triphenylphosphorane (see Scheme 21). This reaction takes advantage of a ring-chain tauto-... 

Some Wittig reactions give the (Z) alkene some the ( ), and others give mixtures, and the question of which factors determine the stereoselectivity has been much... 

Ketone (18) is a familiar starting material (Chanter T 1). The first Wittig reaction gave mostly B-(17) but the second, to give (14), is not very stereoselective so that a mixture of isomers was obtained. 

The Horner-Wittig reaction of a-phosphoryl sulphoxides 442, which are chemically stable, results in the formation of a, -unsaturated sulphoxides 443 in high yields (equation 264). The reaction has been found to be non-stereoselective, mixtures of E and Z isomers being formed from aldehydes and unsymmetrical ketones . In the case of aromatic aldehydes this reaction can also be advantageously performed in a two-phase catalytic system even without the usual PTC catalysts (Table 24). Intramolecular Horner-Wittig reaction of a-phosphoryl-5-oxosulphoxides 444 leads to a, -unsaturated cyclic sulphoxides 445 (equation 265). Starting from optically active 0,0-... 

The stereoselectivity of the Wittig reaction is believed to be the result of steric effects that develop as the ylide and carbonyl compound approach one another. The three phenyl substituents on phosphorus impose large steric demands that govern the formation of the diastereomeric adducts.240 Reactions of unstabilized phosphoranes are believed to proceed through an early TS, and steric factors usually make these reactions selective for the d.v-alkcnc.241 Ultimately, however, the precise stereoselectivity is dependent on a number of variables, including reactant structure, the base used for ylide formation, the presence of other ions, solvent, and temperature.242... 

The carbonyl group of l-oxo-2-alkenylphosphonates (57) undergoes stereoselective Wittig reaction with acylidenephosphoranes... 

A useful application of the silver-mediated additions is 1,3 -diene synthesis by three-carbon elongation of aldehydes [48,51,53]. The bimetallic reagent 3-trimethylsilyl-l-propenylzirco-nocene chloride (A Scheme 8.23) reacts with aldehydes under the influence of a catalytic amount of Ag+ to give the intermediate zirconocene-alkoxide B, which then undergoes a Peterson-type 1,4-elimination of TMS alkoxide to stereoselectively afford ( )-dienes (fc/Z > 96 4) (Scheme 8.23). A Wittig reaction yields the same products without stereoselectivity (ca. 1 1 mixtures of E- and Z-isomers). 

Russo and co-workers98 have reported a high stereoselective method for the preparation of 1,2-czls-C-glycosyl compounds based on the iodocyclization of some hept- and hexenitols obtained by Wittig reaction of sugar... 

The condensation of the cinnamaldehyde derivative (18) with ethoxycarbonyl-pentyltriphenylphosphorane in DMF gave a mixture of tram-trans- and trans-cis-products.22 A general method to prepare l-substituted-m-9-alkenes (19), using a stereoselective Wittig reaction, has been described.23 2,2-Dimethyl-3-butenal (20)... 

The Wittig reaction was employed to fuse diene 49 and aldehyde 50, in the final stages of the stereoselective synthesis of epothilone B, a macrocyclic compound with potential antifungal properties (equation 31)49. 

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