Trajectory of nucleophile

Good Cram selectivity is observed for Lewis acid induced reactions between allylstannanes and aldehydes with alkyl-substituted a-chiral centers66,87. This enhanced Cram selectivity may be due to the effect of the Lewis acid on the trajectory of nucleophilic attack on the aldehyde66. 

Figure 7.6 Calculated conformations of aldehydes 28, 29, 32, and 33. Dot lines on 29 and 33 indicate hydrogen bondings and arrows show the approach trajectory of nucleophile.

Figure 2 Possible trajectories of nucleophilic attack on 1,3-dioxin-4-ones.

Figure 3.23. Trajectory of nucleophilic attack on a carbonyl group deduced from orbital interaction...

Baldwin and coworkers have developed a set of rules that describe the trajectory of nucleophiles when they attack jt systems48-51 (Scheme 7) ... 

Scheme 4.5 Understanding the direction of bond polarity allows identification of reaction site, trajectory of nucleophile, and identification of the leaving group.

Figure 4 Postulated effect of Lewis acids (LA) on the trajectory of nucleophilic attack...

Such simplified analysis, based on the dominant two-electron stabilizing interaction between FMOs, is commonly used for understanding stereoelectronic preferences in intermolecular interactions. In particnlar, the preferred trajectories of nucleophilic additions or substitutions optimize the overlap of incoming nucleophile HOMO with the a and it LUMO of the target (vide infra. Figure 2.38). On the other hand, in electrophilic reactions, the favorable 2e-interaction involves the electrophile LUMO and the target HOMO. 

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). 

The stereoelectronic basis for these trajectories is illustrated below. Trajectories of nucleophilic attack avoid the node in the antibonding orbitals because the unfavorable symmetry of orbital overlap involved in the attack at the node leads to the cancelation of bond-forming 2e-interactions. Attacks of electrophiles have no such restrictions because both o- and x-orbitals are bonding and, thus, do not have a node between the atoms. The lack of a symmetry restriction in electrophilic reactions opens stereoelectronic routes not available to nucleophiles. For o-bonds, this is the frontside attack with retention of configuration (Figure 2.38). For x-bonds, this is the acute (or perpendicular) attack leading to the so-called endo-cyclizations (vide infra). 

FIGURE 2.20. Trajectories of nucleophilic approaches to ( )- and (Z)-iminium ions. 

The trajectory of nucleophilic attack upon the double bond of VIII is quite close to that of the addition of nucleophiles to the carbonyl bond. For the addition reaction of the hydride-ion (Y = H) to ethylene (R = Z = H), and propene (R = CH3) the angle d is 123° (according to the ab initio 3-21G calculations in Ref. [23]. The driving force of the reaction is the charge transfer from the electron lone pair orbital of the nucleophile Y to the 7i -orbital of olefine. The latter has, unlike the orbital n Q (see Fig. 4.1), no loop on the a-atom of carbon and is delocalized, which diminishes the overlap integral and thereby the energy of interaction AE from Eq. (4.10) of the nucleophile with alkene as compared to the energy of interaction with the carbonyl... 

These observations led us to test the idea that an N-tritylamino group of an aminoketone could be used as a 1,3-allylic stereocontrol element for the electrophilic fluorination of silyl enol ethers. This was deemed feasible since the approach trajectory of nucleophiles to the carbonyl group of N-tritylated aminoketones along the Dunitz angle is not all that different from the perpendicular approach trajectory of electrophiles to the n-bond of the enol ether and therefore might be subject to the same type of stereochemical control (Figure 2). 

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