Houk model

The stereochemical outcome of these reactions can be explained by considering the transition-state geometry. For example, applying the Houk model (495) to akyhc alcohols and their derivatives, the smallest substituent at the preexisting chiral center is oriented "inside" over the face of the transition-state ring and the oxygen atom "outside" (483). 

The stereochemical outcomes of the above reactions can be explained by the proposed transition states A and B (Fig. 2.25). Model A, derived from the Houk model for nucleophilic addition to olefins, explains the formation of, v y -adducts. Model B, involving a different nitrone conformation, due to the chelation of diethylaluminum chloride, accounts for the formation of anti -adducts (581). 

The transition-state model for these cyclizations (Scheme 34) differs fundamentally from the well-established Beckwith-Houk transition model for radical cyclizations [130,146-148]. Thus, while both models invoke chairlike transition states, without excluding the possibility of twist boatlike systems in some instances, the Beckwith-Houk model involves full conformational... 

Free-radical cyclizations using ethyl radicals generated by EtsB/air system or stannyl radicals systems provide a range of carbocyclic and heterocyclic hydroxylamines (equation 77). Stereoselectivity in these reactions is variable but can be semiquaUtatively predicted by Beckwith-Houk models . Depending on the substitution pattern of the emerging cyclic system, stereoselectivity can be very high, especially in fused polycyclic systems (equation... 

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). 

Normally, additions depicted by model C lead to the highest asymmetric induction. The antiperiplanar effect of OR substituents can be very efficient in the Houk model B ( , , , , ) however it plays no role in model C. Furthermore, the Houk model B must be considered in all cycloaddition-like reactions. The Felkin-Anh model A is operative for nucleophilic additions other than cuprate additions ( ). The epoxidation reactions are unique as they demonstrate the activation of one diastereoface by a hydroxy group which forms a hydrogen bridge to the reagent ( Henbest phenomenon ). The stereochemical outcome may thus be interpreted in terms of the reactive conformations 1 and 2 where the hydroxy function is perpendicular to the olefinic plane and has an optimal activating effect. 

The two computational models differ on this point. The Beckwith model (ref. 6) indicates increased bending and torsional strain in the 6-endo TS. The Houk model (ref. 7) indicates increased bending strain only, and states this strain is due in part to the bending of the allylic carbon out of the alkene plane to accommodate a better angle of attack. 

Representing R by one orbital was another approximation of the Rondan-Houk model. This model may fail if R can be approximated by an allyl fragment. The reason is that the HOMO of NOz or C02 has a coefficient of zero at its central atom the overlap between R and C4 is then nil. Consequently, four of the five interactions shown in Figures 6.2 and 6.3 disappear and prediction is no longer possible. 

Hint. Two AOs belonging to the same atom are orthogonal. In other words, the overlaps between the nitrogen lone pair and the oCN and oCN orbitals are negligible. A modification of the Rondan-Houk model is therefore required. 

The addition of (219) to ,j8-dialkoxynitrones (220) can be rationalized by assuming a transition state model A (Figure 2) similar to that involved in nucleophilic addition to C= (Houk model) <82JA7162>. The reversal of stereoselectivity induced by diethyl aluminum chloride is consistent with a j8-chelation model B. The scope and the synthetic utility of these reactions have been amply demonstrated <95MI 306-01 >. 

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