Diastereoselectivity allylic strain

Additional studies, concerning the influence of 1,2-allylic strain caused by a geminal substituent near the stereogenic centre of allylic alcohols , showed that it does not effectively compete with 1,3-allylic strain in differentiating the diastereoselectivity of the... 

This reversal of diastereoselectivity i.e., high selectivity in favor of the. mt-alkylation product 19b has been explained by the authors by an allylic strain effect65. If R3 is bulky, then in A and B the preferred entry is syn to R1. In these conformations the C—H bond in the exn allylic position is coplanar with the enolate n-system and R2 is antiperiplanar to R1 to minimize steric interaction. 

While reaction of the acetate 40 as well as the acetyl- and phthalimide derivatives of chiral amine (41b and 41c) proceeded with erythro diastereoselectivity (in accordance with the classical cis effect, minimization of 1,3-allylic strain) (Table 6, entries 8, 10, 11), for the allylic alcohols 39, primary allylic amine 41a, silyl enol ethers 42 and enol ether 43 threo selectivity was observed (Table 6, entries 1-7, 9, 12-14) (see also Scheme 24). For allylic alcohols with an alkyl group R4 cis to the substituent carrying the hydroxyl group, diastereoselectivity was high (Table 6, entries 1-7) in contrast, stereoselection was low for allylic alcohols which lack such an R4 (cis) substituent (substrates 39h and 39i, see Figure 4). 

The diastereoselectivity dropped drastically in presence of protic methanol and totally disappeared for the corresponding silyl ethers. These data are in agreement with the presence of a hydroxy directing effect in the Patemo-Bilchi reaction. Threo stereoisomer can be favored through the formation of an hydrogen bond between triplet excited benzophenone and the substrate in the exciplex, while the formation of the erythro stereoisomer would be less favored due to allylic strain (Scheme 3.41). 

Due to the absence of appreciable allylic strain, the diastereoselectivity might be primarily determined by stereoelectronic effects with a preference for one of the conformations. The moderate control may be accounted for by a reduced sensitivity of singlet oxygen towards stereoelectronic factors. 

The substrate-induced diastereoselectivity can be understood in terms of nonbonded steric interactions in the two likely diastereomeric transition states allylic strain between the thio-phenyl or vinyl group (depending on the geometry) and the allylic ether is apparent in only one transition state. 

Chirahty transmission can also be induced in thio-Claisen reactions by a chiral center adjacent to the allyl vinyl sulfide core. The group of Metz-ner examined the diastereoselectivity of the rearrangement of acyclic S-allyl ketene dithioacetals bearing a chiral center adjacent to carbon 6. hi these substrates, the sigmatropic shift proceeded smoothly and with modest syn anti diastereoselectivity [74]. In contrast, higher selectivities are foimd for thio-Claisen precursors bearing a chiral center adjacent to carbon 1 mainly due to steric effects and allylic strain [75]. In 1991, the group of Beslin examined the effect of a hydroxyl substituted chiral center attached to C-1 of Z and E S-allyl ketene dithioacetals [76,77] (Scheme 7). Under the reaction conditions, these... 

Another explanation takes into account that boat- and twist-shaped six-membered, closed transition states can successfully compete with the chair model. " Evans et al. pointed out that in a-unsubstituted enolate reactions, missing allyl strain interactions lead to lower selectivity in diastereoselective aldol reactions.Calculations indicate that a twist-boat can easily be formed from the U-configuration of a-unsubstituted enolates. The possible transition state in this case has a geometry like 34 and is favored by the chelating character of the complexation mode for the zinc cation and the outward-pointing substituents of the oxazolidinone moiety. This twist-boat transition state correctly predicts the stereochemical outcome of the reaction. 

Crotyl silanes offer the possibility of diastereoselectivity in reactions with aldehydes in the same way as the corresponding boranes. The mechanism is completely different because crotyl trialkylsilanes react via an open transition state as the silicon is not Lewis acidic enough to bind the carbonyl oxygen of the electrophile. Instead, the aldehyde has to be activated by an additional Lewis acid or by conversion into a reactive oxonium ion by one of the methods described above. The stereoelectronic demands of the allylic silane system contribute to the success of this transformation. Addition takes place in an Se2 sense so that the electrophile is attached to the remote carbon on the opposite side of the n system to that originally occupied by silicon and the newly formed double bond is trans to minimize allylic strain. 

In 1978, Larcheveque and coworkers reported modest yields and diastereoselectivities in alkylations of enolates of (-)-ephedrine amides. However, two years later, Evans and Takacs and Sonnet and Heath reported simultaneously that amides derived from (S)-prolinol were much more suitable substrates for such reactions. Deprotonations of these amides with LDA in the THF gave (Z)-enolates (due to allylic strain that would be associated with ( )-enolate formation) and the stereochemical outcome of the alkylation step was rationalized by assuming that the reagent approached preferentially from the less-hindered Jt-face of a chelated species such as (133 Scheme 62). When the hydroxy group of the starting prolinol amide was protected by conversion into various ether derivatives, alkylations of the corresponding lithium enolates were re-face selective. Apparently, in these cases steric factors rather than chelation effects controlled the stereoselectivity of the alkylation. It is of interest to note that enolates such as (133) are attached primarily from the 5/-face by terminal epoxides. ... 

W. Adam, T. Wirth, Hydroxy group directivity in the epoxidation of chiral allylic alcohols Control of diastereoselectivity through allylic strain and hydrogen bonding, Acc. Chem. Res. 32 (1999) 703. 

The stereochemical outcome of Q [WZnM2(ZnW9034)2] [M = Zn(II), Mn(II), Ru(III), Fe(III)]-cafalyzed H2O2 epoxidation of various allylic alcohols with the OH group attached to a chiral center is controlled by allylic strain effects [23,24]. Thus, allylic alcohols with only 1,2-allylic strain were foimd to afford erythro-epoxides with excellent diastereoselectivity (Fig. 16.4, alkene A). In contrast, threo-epoxides predominate strongly in case of 1,3-allylic strain (alkene B). Diastereoselectivity drops to very low values in the absence of allylic strain (alkene C) or when both 1,2- and 1,3-allylic strain are present in the substrate (alkene D). 

FIGURE 16.4 Effect of 1,2- and/or 1,3-allylic strain on the diastereoselectivity observed with sandwich polyoxometalate (POM)-catalyzed epoxidations of chiral allylic alcohols. 

---