Nucleophilic carbonyl addition trajectory

Additionally, one may be tempted to allow 5c to react with nucleophiles along the trajectory shown by the arrow. This trajectory is not only anti to the largest substituent, cyclohexyl, on the asymmetric carbon but it also fulfills the requirement of near tetrahedral angle for such an attack. Additionally, the product is formed directly in the staggered conformation as one allows for a gradual rotation (clockwise in the present instance) during the event that the carbonyl carbon changes its hybridization from sp2 to sp3. The product 6c is the same product as 6b. 

B3LYP/6-31+G level calculations on the reaction between a-bromoacetophenones and hydroxide ion in the gas phase suggest that two products (from substitution of the or-bromine and addition to the carbonyl carbon) form from a single transition state where the OH nucleophile is associated with both the C and the carbonyl carbon. Trajectory calculations have shown that substrates with a more electron-withdrawing substituent than meta-C on the benzene ring react at the carbonyl group, while those with more electron-donating substituents react at bromine. 

Like Cram s Rule, the Felkin-Cherest-Anh model, developed by Felkin and coworkers6, is an attempt to understand and predict the stereochemistry of addition to a carbonyl group. This model requires a "small 0" interpretation in which the largest group is oriented anti to the attacking nucleophile s trajectory. One should note that the Felkin-Cherest-Anh model neglects the interaction of the carbonyl oxygen. In this approach, the R/S or RJM interactions dominate. 

Chiral a-methyl aldehydes (43) show exceptional diastereofacial preferences in their Lewis acid mediated reactions with enol silanes (equation i6) 2i 25c-26-64 selected data are reported in Table 8. The reason for this selectivity may be due to an approach trajectory of the nucleophile closer to the stereocenter when the carbonyl group is bound to the Lewis acid. Additions to chiral a-alkoxy aldehyde (48) were studied with both nonstereogenic (equation 17 Table 9) and stereogenic enol silanes (equation 18 Table 10). (Stereogenic and nonstereogenic are defined according to Mislow and Siegel.) ... 

Trajectories of nucleophilic attack at the jt-bond are incorporated in the Felkin-Anh model of stereoselection in nucleophilic addition to carbonyls (Figure 2.37). 

---