Steric discrimination

These examples illustrate the issues that must be considered in analyzing the stereoselectivity of enolate alkylation. The major factors are the conformation of the enolate, the stereoelectronic requirement for an approximately perpendicular trajectory, the steric preference for the least hindered path of approach, and minimization of torsional strain. In cyclic systems the ring geometry and positioning of substituents are often the dominant factors. For acyclic enolates, the conformation and the degree of steric discrimination govern the stereoselectivity. 

A survey of several of alkylborohydrides found that LiBu3BH in ether-pentane gave the best ratio of chelation-controlled reduction products from a- and (3-alkoxy ketones.134 In this case, the Li+ cation acts as the Lewis acid. The alkylborohydrides provide an added increment of steric discrimination. 

Eq. 59), and even surprisingly high for aliphatic ketones such as 2-butanone, a substrate that offers very little steric discrimination (Eq. 60). Reagent 74 is less effective than 70 in allylations of aldehydes (e.g., 90% ee vs. >98% ee for 70 in the allylation of benzaldehyde). The superior reactivity and selectivity of 74 with ketones is ascribed in part to the lesser steric bulk of the phenyl substituent compared to the trimethylsilyl unit of reagent 70. The smaller phenyl substituent of 74 would provide a better fit for ketones in the chiral pocket of the reagent. 

A more clear-cut demonstration of electronic deactivation was provided55 by the cyclization of ethyl 5-(2-diazo-l-oxoethyl)octanoate. In this case, there should not be any steric discrimination, vet very substantial selectivity was observed. In subsequent work, ethers and tosylates were shown to induce similar remote deactivation50. 

MAD is a bulky Lewis acid used to complex with functional groups to provide a steric discrimination to a number of organic transformations. 

A good mediator for the hetero Diels-Alder reaction of aldehydes is the bulky, oxygenophilic aluminium tris(2,6-diphenylphenoxide) (ATP) 2-19 developed by Yamamoto [78] which allows the differentiation between two sterically discriminated aldehydes. Thus, reaction of a mixture of 2-10,2-16 and 2-17 in the presence of 2-19 gave nearly exclusively 2-15, whereas in the presence of BF3-OEt2 a 1.3 1 mixture of 2-15 and 2-18 was formed (Fig. 2-5). 

A clear correlation between the stabilisation of the endo-transition structure and the size of substituent at the 2-position of an 1-oxa-1,3-butadiene is again seen in the cycloaddition of the N-acetyl-enaminoketone 8-20 to 8-12. As expected, the reaction of 8-20 a to give 8-21 a and 8-22 a shows only a very small AAV, whereas with growing bulkiness of R as in 8-20 b and 8-20 c an increase of AAV is observed with the formation of the trans-cycloadduct 8-22 as the major product under high pressure. Because of the pressure effect it can clearly be deduced that 8-22 is formed via an endo-Z-anti-transition structure, presumably due to a strong hydrogen bond in the (Z)-diastereomer and a steric discrimination of the ( )-diastereomer of 8-20. However, an exo-E-anti-transition structure would give the same product (Fig. 8-7) [548]. 

Synthetic complexes modeling a-keto carboxylate-dependent enzymes have played a key role in furthering our understanding of these enzymes. Several [Fe (L)(a -keto acid)] complexes have been reported as functional models using tetradentate and tridentate ligands. All of the model complexes that react with O2 afford quantitative yields of the decarboxylated a-keto acid, but in only two cases was the active oxidant trapped. Intermolecular olefin epoxidation has been observed in the case of [Fe (Tp )(BF)j complex. This complex reacts with O2 to form a species capable of stereospecific oxidation of cA-stilbene to its oxide as the product. However trans -stilbene is not epoxidized, suggesting that the active oxidant is capable of steric discrimination. 

The bi- or tricyclic systems were designed to create a three-dimensional void about the metal ion, thus allowing for steric discrimination between small and large ligands. These sterically hindered ligands also protect end-on dioxygen adducts from oxidative decomposition via formation of peroxo- or oxo-bridged dimers ... 

Either non-covalent or covalent templates need to be absent in the original substrate as well as in the product or, at least, should be removable after having accomplished their task. Tethers should be effective in the transition states of reactions and, by acting as a mold, control the rate and the regio- and stereochemistry. Thus the monograph focuses on reactivity rather than on static structural chemistry. It is intended to promote the use of intermolecular non-covalent interactions, besides steric discrimination, to control reactivity and selectivity. Its content was selected to provide useful template- or tether-based methodology to both expert and novice practitioners in both the molecular and supramolecular sciences. 

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