Chelation control also group effects

The effect of the steric bulk of the hydride reducing agent has been examined in the case of 3-benzyloxy-2-butanone.135 The ratio of chelation-controlled product increased with the steric bulk of the reductant. This is presumably due to amplification of the steric effect of the methyl group in the chelated TS as the reductant becomes more sterically demanding. In these reactions, the degree of chelation control was also enhanced by use of CH2C12 as a cosolvent. 

Chelation control has also been implicated in conjugate addition reactions. For example, during a synthesis of the macrolide antibiotic 6-ep/-erythromycin, Mul-zer and co-workers86 found that the stereochemistry at the anomeric centre (l position) of the tetrahydropyranyl protecting group had a profound effect on the stereochemistry of conjugate addition of lithium dimethylcuprate to the ynone 49.1 [Scheme 1.49]. 

The mechanism of olefination can be deduced by consideration of orbital interactions to proceed via torquoselective olefination, rather than chelation control, for the following reasons (1) the sterically hindered siloxy and phenoxy groups are also effective for high -induction (2) in the presence of a crown ether, the selectivity still remains high and (3) an axially oriented siloxy group induces a high Z-selectivity. Theoretical calculations indicate that the transition state of inward rotation is stabilized by an orbital interaction between a(C-O) and ct (C-OR) (157) . 

Stereochemical results were similar to previous studies, with a predominance of anti products observed for the allylation of aromatic and alkyl aldehydes using y-substituted allylic bromides. In the same paper, the system was also used for the allylation of unprotected carbohydrates, a use that is particularly advantageous for such water-soluble substrates. As with aldehydes that possess functional groups at the a-position that is Lewis basic, a five-membered chelation transition state was proposed to account for the proportion of syn products. The group extended this work to the synthesis of P-trifluoromethylated allylic alcohols [32], and the effects of chelation control was again demonstrated in dramatic stereochemical reversal from minor structural changes in the aldehyde (Figure 8.13). 

The effect of /rfive-coordinate aluminum alkyls have been discussed.94 Studies have also focused on the equilibrium between four-coordinate and five-coordinate isomers in compounds of the type [R2Al /i-0(GH2) ER1x ]2 (n = Z, 3 ER1x = OR1, SR1, NRX2) (shown in Figure 7(h) for n = Z). Factors that control this equilibrium and hence the coordination around the aluminum include the steric bulk of the substitutent at the aluminum (R), and the Lewis base donor R1, the basicity of the neutral donor group ER1, and the chelate ring size (as determined by n).95... 

The stereoselectivity of reduction of carbonyl groups can also be controlled by chelation effects when there is a nearby donor substituent. In the presence of such a group, specific complexation between the substituent, the carbonyl oxygen, and the Lewis acid can establish a preferred conformation for the reactant which then controls reduction. Usually, hydride is then delivered from the less sterically hindered face of the chelate. 

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