Stereoselectivity ester-substituted radicals

The low temperature ( —78 C) radical allylation of 3-alkoxy-substituted ethyl 2-iodo-3-phenylbutanoates proceeds via an ester-substituted radical that undergoes stereoselective addition across the double bond of tributyl(2-propenyl)stannanc8. The diastereomeric excess of the products is influenced only to a small extent by the steric bulk of the alkoxy substituent in the 3-position. 

Asymmetric induction is used in the stereoselective synthesis of silanes via the hvdrosilyla-tion of a,/l-unsaturated esters30. The addition of the tris(trimethylsilyl)silyl radical to the double bond is highly regioselective. yielding an ester-substituted radical that abstracts hydrogen diastereoselectively. 

Hart [4] and Giese [5] have recognized that the concept of A-strain can be applied to ester-substituted radicals. Thus, radical 2 reacts stereoselectively because the upper side of the semioccupied / -orbital in 2 is shielded to a larger extent (L large substituent) than the lower side (M medium-sized substituent). 

The stereoselectivities of ester-substituted radicals 9a-f show that with tertiary radicals 9a-c the anti products 10 are always formed predominantly. In secondary radicals 9d-f the selectivity is lower and can even lead to a loss of selectivity with the substituent L=Ph (Scheme 4) [6, 7],... 

Also, it was demonstrated that acyclic radicals can react with high stereoselectivity [45]. In order for the reactions to be stereoselective, the radicals have to adopt preferred conformations where the two faces of the prochiral radical centers are shielded to different extents by the stereogenic centers. Giese and coworkers [49] demonstrated with the help of Electron Spin Resonance studies that ester-substituted radicals with stereogenic centers in (3-positions adopt preferred conformations that minimize allylic strain [49] (shown below). In these conformations, large (L) and medium sized substituents (M) shield the two faces. The attacks come preferentially from the less shielded sides of the radicals. Stereoselectivity, because of A-strain conformation, is not limited to ester-substituted radicals [50]. The strains and steric control in reactions of radicals with alkenes can be illustrated as follows [50] ... 

Scheme 11.16 Diastereocontrol via chelate effect stereoselective 5-exo-trig cyclization on to a cumulated Jt-bond of a chelated ester-substituted ketyl radical anion 50 [74]. a 94 6 mixture of diastereomers.

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

These normally occur in a regio- and stereoselective manner and provide a useful alternative to the well-known AIBN-catalyzed radical addition. Cochran et al. [194] demonstrated this clearly in the case of the addition of MejSnH to diphenylacetylene, the radical addition proceeding in a trans manner and the Pd-catalyzed reaction cis. Rossi et al. carried out additions of BugSnH to 1,3-diynes to give 2-stannyl-l-en-3-ynes [195] and to esters of substituted propynoic acids [196]. A basically similar reaction was reported by Sai et al. [197]. Paley et al. [198] obtained enantiomerically pure dienyl sulfoxides by first... 

Phenylmenthyl esters are also suitable chiral groups for inducing stereoselectivity in radical addition reactions, as shown in the allylation of phenylmenthyloxycarbonyl-substituted xanthates. The photoinitiated reaction of the radical precursor with tributyl(2-propenyl)stannane at — 78 =C affords only one diastereomer4. The absolute configuration of (— )-8-phenylmenthyl 2-methyl-2-phenyl-4-pentenoate (5) is not known. 

Togo, H., Aoki, M., and Yokoyama, M., Facile radical decarboxylative alkylation of heteroaromatic bases using carboxylic acids and trivalent iodine compounds, Tetrahedron Lett., 32, 6559, 1991. Togo, H., Aoki, M., and Yokoyama, M., Alkylation of aromatic heterocycles with oxalic acid monoalkyl esters in the presence of trivalent iodine compounds, Chem. Lett., 1691,1991. Vismara, E., Torri, G., Pastori, N., and Marchiandi, M., A new approach to the stereoselective synthesis of C-nucleosides via homolytic heteroaromatic substitution. Tetrahedron Lett., 33, 7575, 1992. 

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