Attack trajectories

We postulate that the attack on both sides is accelerated by positive SOI (89a), but an unfavorable orbital interaction along the syn attack trajectory (89b) cancels the acceleration at the syn face [151] as the diene approaches the anhydride moiety (preferentially in endo fashion), unfavorable out-of-phase interaction (SOI) of the n lobes at Cj and of the diene with the tt lobes of the aromatic moiety of the dienophile occurs (89). The unexpected anti-selectivity stems from nnfavorable SOI on the syn side. 

The broken lines in the diagrams show the trace of the plane of the n orbitals. A reaction will occur readily if X lies on this plane and makes an obtuse angle with the C=Y bond. Molecular models show that the carbon backbone is long and flexible enough to satisfy both of these criteria for the exo reactions. The 6-endo reaction poses problems. If X lies in the n plane, the carbon skeleton has to adopt a boat conformation, leading to a perpendicular attack. However, if X moves slightly out of the n plane, an acceptable compromise can be achieved the attack trajectory becomes non-perpendicular, with a fair nucleophile-n overlap. However, neither condition can be satisfied for a 5-endo reaction. Note that a direct application of Baldwin s empirical rules would have masked these subtleties. 

Figure 7 Dihydrogen attack trajectories for the major and minor diastereo-mers of [(diphosphine)Rh(enamide)] studied by Bosnich and coworkers (30). In this figure the enamide is represented by coordinated O and olefin and the diphosphine by the coordinated phosphorus atoms. (Redrawn from Ref. 30.)...

Since enantioselectivity in this reaction is a result of the energy difference between the diastereomeric transition states after H2 is added, Landis modeled the addition of Hj to the diastereomers of the CHIRAPHOS and DIPAMP complexes with MAC as the substrate. Landis posed a simple question Is there a significant barrier to hydrogen attack at the Rh center that can be modeled by molecular mechanics In the first study Landis found that all possible attack trajectories allowed almost strain-free attack of dihydrogen (molecular mechanics barriers were less than 3 kcal/mol) (32). In a subsequent study, a better picture of the reaction coordinate was generated using DFT and quantum mechanical models, which are outside the scope of this chapter. 

Figure 4.9. (a) Deviation of the attack trajectory from the normal plane in the reaction of hydride with pivaldehyde. Reprinted with permission from ref. [25], copyright 1987, American Chemical Society, (b) Newman projection of a ketone, with an approaching nucleophile, and the Flippin-Lodge angle of deviation from the normal plane, away from the larger substituent, R (after ref. [27]). 

Fig. 6.39. a Attack of hydride on pivalaldehyde [(CH3)3CC(=0)H], deviation of the attack trajectory from the plane normal to the carbonyl plane and passing through C=0 b definition of the Flippin-Lodge angle [Pg.272]

Attack trajectories for electrophilic reagents are quite different from the above nucleophilic trajectories. For example, electrophiles can attack a single bond with retention of configuration. In another example, cationic 1,2-shifts are ubiquitous in contrast to the topologically analogous, but unfavorable, anionic 1,2-shifts. 

For several experimental and computational investigatioiis on similar reactions, see (a) M. N. Paddon-Row, N. G. Rondan, K. N. Houk, J. Am. Chem. Soc. 1982, 104, 7162—7166. Staggered models for asymmetric induction attack trajectories and conformations of allylic bonds from ab initio transition structures of addition reactions, (b) S. E. Denmark, E. J. Weber, Helv. Chim. Acta 1983, 159, 1655-1660. On the stereochemistry of aUyl-metal-aldehyde condensations, (c) S. E. Denmark, E. J. Weber,... 

As a consequence of this observation, the essential dynamics of the molecular process could as well be modelled by probabilities describing mean durations of stay within different conformations of the system. This idea is not new, cf. [10]. Even the phrase essential dynamics has already been coined in [2] it has been chosen for the reformulation of molecular motion in terms of its almost invariant degrees of freedom. But unlike the former approaches, which aim in the same direction, we herein advocate a different line of method we suggest to directly attack the computation of the conformations and their stability time spans, which means some global approach clearly differing from any kind of statistical analysis based on long term trajectories. 

Let us focus attention on the unfavorable ring closures. Why, for example, should formation of a five-membered ring by an endo-trig process be difficult The answer is provided by a consideration of the trajectory of approach of the nucleophile." If Z is an electron-attracting conjugating group of the type necessary to activate the double bond to nucleophilic attack, the reaction would involve the LUMO of the conjugated system, a 7t ... 

Backside attack may be favored for electrostatic reasons. Examine electrostatic potential maps fox bromide + methyl bromide frontside attack and bromide + methyl bromide backside attack, transition states involving frontside and backside attack of Br (the nucleophile) onto CHsBr, respectively. Which atoms in the transition states are most electron-rich Which trajectory better minimizes electrostatic repulsion ... 

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. 

Thus, the predictions seem to be in conflict with the observed syn biases. However, along the trajectory of attack of the nucleophile to the carbonyl group of the bicyclo[2.2.2]octane structures (indicated in 23 and 24), out-of-phase interactions between the reagent and the substrate are involved, and this is different from the situation in the bicyclo[2.2.1]heptane structures (15a) [83-87]. Thus, attack on the side opposite to the unsaturated moiety will be favored. This is a kind of SOI (Fig. 3a) which unsymmetrizes the n face. 

The iyn-preference of 105b and 105c is similar to those observed in the reduction of the related ketones, 34 and in the epoxidation and dihydroxylation of the related olefins 71 [104]. Although the trajectories of the attacking reagents are considered to be different in these reactions [83-87, 170, 171], all three types of reactions favor iyn-addition, which excludes a predominant role of divergent trajectories in these dibenzobicyclic systems. 

Associated with the propensity to intramolecular delivery of the organocopper reagent is the benefit of high regioselectivity, since an intramolecular trajectory prohibits the alternative a-attack. This is best exemplified by the reaction behavior of the cyclic system 161 (Scheme 6.33). For this substrate, y-attack is sterically hindered. Hence, treatment of the acetate of 161 with a higher order methyl cuprate... 

Ground-state and excited-state reactions of chiral Meldrum s acid derivatives 39 with the enone function have been reviewed with an emphasis on the facial selectivity in the C=C bond (Figure 2) <1996H(42)861>. Top-face preference, even when it is sterically more hindered than bottom-face attack, is supported by hyperconjugation no —r c=c 39a, whereas bottom-face preference is dominated by steric effects in the sofa conformation of the molecule 39. The trajectory of the attacking reagent plays a balancing role. 

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

A and B differ in the angle which the trajectory of the nucleophile forms with the plane of the olefin. For obtuse angles, the Felkin-Anh model is preferred, as the steric crowding outside the olefin has to be minimized (attack from the side of S). In contrast, B (Houk model)41 is superior for acute angles (minimal steric crowding inside the olefin). 

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