Allylation relative diastereoselection

Enantiomerically pure allyl(triethoxy)silanes (82) react readily with aldehydes to provide homoallylic alcohols (Scheme 10-35) [62]. The y-carbon of the allylsiliconate attacks the aldehyde on the same side of the allyl group syn Sg). The observation of high syn-relative diastereoselectivity and high syn S (internal diastereoselec-tivity) is readily explained by a cyclic six-membered transition structure. 

The relative diastereoselectivity in the indium trichloride-mediated allylation with allylic stannanes in water is for the anti homoallylic alcohol [204]. The reactions are anti selective regardless of the geometry of the starting 2-butenylbro-mide. The in-situ-generated allylic indium species undergoes reaction with the... 

We have seen in Section 1.1.3 that reactions of many allyl organometallics and chiral C=X electrophiles proceed with only modest levels of relative diastereoselection. Significant improvement in dia-stereoselectivity is possible, however, by using double asymmetric synthesis, that is, by using the highly enantioselective allyl metal reagents described in Section 1.1.4 rather than the less diastereoface-selec-tive achiral allyl metal compounds discussed in Section 1.1.3. Double asymmetric synthesis is also... 

Several factors must be considered in selecting a crotyl metal or allyl metal reagent for use in an acyclic stereoselective synthesis. First, it is necessary that the new stereocenters generated in concert with the new C—C bond (Scheme 1) be formed with a high degree of stereoselectivity. This is the problem of simple diastereoselectivity. Two diastereomeric products may be produced, and in this chapter Masa-mune s synlanti nomenclature system will be used to describe them. Second, the issue of diastereofacial selectivity is encountered if the aldehyde (or other C=X reaction partner) is chiral. This is a problem of relative diastereoselectivity, and four products may be produced in the reactions of the crotyl oiganome-tallics (Scheme 2). The diastereofacial selectivity issue is also critical in the reactions of allyl metal reagents and chiral C=X electrophiles. 

Sulfonic peracids (66) have also been applied recently to the preparation of acid sensitive oxiranes and for the epoxidation of allylic and homoallylic alcohols, as well as relatively unreactive a, p - unsaturated ketones. These reagents, prepared in situ from the corresponding sulfonyl imidazolides 65, promote the same sense of diastereoselectivity as the conventional peracids, but often to a higher degree. In particular, the epoxidation of certain A -3-ketosteroids (e.g., 67) with sulfonic peracids 66 resulted in the formation of oxirane products (e.g., 68) in remarkably high diastereomeric excess. This increased selectivity is most likely the result of the considerable steric requirements about the sulfur atom, which enhances non-bonded interactions believed to be operative in the diastereoselection mechanism <96TET2957>. 

Good diastereoselectivity was obtained with BQ as the oxidant in acidic media but the reaction times were relatively long (1-2 days at 40 °C). Using the copper(II)-oxy-gen system in slightly basic media permits a much faster reaction (0.5-1 h at 20 °C) with better isolated yields but with poor or even reversed diastereoselectivity. The slower reaction with BQ as oxidant is due to the fact that this oxidant requires an acidic medium, which lowers the nucleophilicity of the acid moiety. It is also likely that BQ or copper(II) has to coordinate to palladium(II) before the second nucleophile can attack to make the Jt-allyl complex more electrophilic. Coordination of cop-per(II) would make a more electrophilic intermediate than coordination of BQ. The relation between reaction time and diastereoselectivity supports a mechanism analogous to that in Scheme 17.7. 

Kinetic resolution (enantiomer differentiation) of cycloalkenyl diazoacetates has been achieved (for example, according to Eq. 3) [34]. In these cases one enantiomer of the racemic reactant matches with the catalyst configuration to produce the intramolecular cyclopropanation product in high enantiomeric excess, whereas the mismatched enantiomer preferentially undergoes hydride abstraction from the allylic position [35] to yield the corresponding cycloalkenone. With acyclic secondary allylic diazoacetates the hydride abstraction pathway is relatively unimportant, and diastereoselection becomes the means for enantiomer differentiation [31]. 

The factors that influence the diastereoselectivity for the class of monocyclic hydrocarbons, from which monoterpenes are the most studied group, are mainly steric and conformational. Monoterpenes, in general, show relatively low overall syn/anti selectivity, usually attributed to the availability of allylic hydrogen atoms in the right alignment for abstraction. 

For alkenylmetals bearing two stereocenters at both the allylic and homoallylic positions, two situations have to be distinguished depending on their relative influence (matched or mismatched) with respect to the stereochemical outcome of the allylzincation. Not surprisingly, in the matched case, as illustrated for substrate 232, the diastereoselectivity was excellent and 233 was obtained as a single diastereomer. The allyl moiety was delivered anti to both the allylic and homoallylic substituents in the chelated allyl alkenylzinc species (equation 113). 

Several allylic and homoallylic alcohols prepared from (+)-camphor and (-)-fenchone were ozonolyzed in EtzO at -78 °C and then treated with Et3N or LiAlH4 furnishing chiral hydroxyl carbonyl compounds and diols (the latter with high diastereoselectivity). Several relatively stable 1,2,4-trioxolanes were isolated and characterized by H, 13C, and 170 NMR spectra and by ESI-MS <1999HCA1385>. All stereoisomers of products 159 and 160 were isolated and characterized. 

The control of diastereoselectivity in the allylation reaction of carbonyl compounds with allylic indium reagents has been an important issue since the discovery of the indium-mediated carbonyl allylation. As earlier discussions have been summarized in the precedent reviews,6-24 only relatively recent references are cited below. 

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