Zimmerman—Traxler model

TS, which is usually based on the chair (Zimmerman-Traxler) model. This pattern is particularly prevalent for the allylic borane reagents, where the Lewis acidity of boron promotes a tight cyclic TS, but at the same time limits the possibility of additional chelation. The dominant factors in these cases are the E- or Z-configuration of the allylic reagent and the conformational preferences of the reacting aldehyde (e.g., a Felkin-type preference.)... 

Excellent (3-facial selectivity on the enolate was observed, but there was a lower facial selectivity on the aldehyde partner. The cation was of tremendous importance, as seen from the reversal of selectivity when going from lithium to zinc or magnesium enolates [12] (Scheme 40). This is explained by a Zimmerman-Traxler model in which a... 

The stereoelectronic requirements for carbonyl addition are that electron donation occurs by interaction of die donor with the it orbital of the carbonyl group. To meet the stereoelectronic requirements and explain the diastereoselectivity, the Zimmerman-Traxler model is used. Interaction of the lithium cation with the oxygen of die enolate and of die carbonyl electrophile leads to a six-membered... 

The stereoselectivity can be explained with the Zimmerman-Traxler Model, which predicts a six-membered cyclic transition state leading to excellent stereoselectivity for ont/ -substituted products. 

The key idea of the Zimmerman-Traxler model is that aldol additions proceed via six-membered ring transition state structures. In these transition states, the metal (a magnesium... 

The application of the Zimmerman-Traxler model to the specific case of the Ivanov reaction of Figure 13.45 is illustrated in Figure 13.46. The reaction proceeds preferentially through... 

Fig. 13.46. Explanation of the anti-selectivity of the Ivanov reaction of Figure 13.45 by means of the Zimmerman-Traxler model. The stereodescriptors Re and Si are defined as follows. Suppose you are looking down on the plane of an alkene, in which an sp2-hybridized C atom is connected to three different substituents. You are on the Re side of the double bond if the Cahn-Ingold-Prelog priorities of these substituents decrease going clockwise, and on the Si side otherwise.

The key idea of the Zimmerman-Traxler model is that aldol additions proceed via six-membered ring transition state structures. In these transition states, the metal (a magnesium cation in the case of the Ivanov reaction) coordinates both to the enolate oxygen and to the O atom of the carbonyl compound. By way of this coordination, the metal ion guides the approach of the electrophilic carbonyl carbon to the nucleophilic enolate carbon. The approach of the carbonyl and enolate carbons occurs in a transition state structure with chair conformation. C—C bond formation is fastest in the transition state with the maximum number of quasi-equatorially oriented and therefore sterically unhindered substituents. 

Fig. 10.41. Explanation of the anh-selectivity of the Ivanov reaction of Figure 10.40 by means of the Zimmerman-Traxler model. The...

When an aldehyde is reacted with a ketone-derived enolate under equilibrating conditions, the thermodynamically more stable 2,3-anti product predominates regardless of the geometry of the enolate. If, however, the reaction is kinetically controlled, the (Z)- and ( )-enolates furnish 2,3-syn and anti aldol products, respectively. This behavior has been interpreted in terms of a chair-type transition state known as the Zimmerman-Traxler model. ... 

The formation of syn-64 and anti-64 diastereomer aldol products emerges from the transition states 69 and 70, respectively. Thus, the Zimmerman-Traxler model [80] involving a six-membered like assembly of the reactants provide a reasonable explanation of the (Z)-syn, (E)-anti correlation. 

The most intensely studied aldol addition mechanisms are those beUeved to proceed through closed transition structures, which are best understood within the Zimmerman-Traxler paradigm (Fig. 5) [Id]. Superposition of this construct on the Felkin-Ahn model for carbonyl addition reactions allows for the construction of transition-state models impressive in their abiUty to account for many of the stereochemical features of aldol additions [50a, 50b, 50c, 51]. Moreover, consideration of dipole effects along with remote non-bonding interactions in the transition-state have imparted additional sophistication to the analysis of this reaction and provide a bedrock of information that may be integrated into the further development and refinement of the corresponding catalytic processes [52a, 52b]. One of the most powerful features of the Zimmerman-Traxler model in its application to diastereoselective additions of chiral enolates to aldehydes is the correlation of enolate geometry (Z- versus E-) with simple di-astereoselectivity in the products syn versus anti). Consequently, the analyses of catalytic, enantioselective variants that display such stereospecificity often invoke closed, cyclic structures. Further studies of these systems are warranted, since it is not clear to what extent such models, which have evolved in the context of diastereoselective aldol additions via chiral auxiliary control, are applicable in the Lewis acid-catalyzed addition of enol silanes and aldehydes. 

Possible transition states for the reactions of type I and III crotyl organometallics with aldehydes are depicted in Scheme 7. Most of the available stereochemical evidence suggests that these reactions proceed preferentially through transition state (12) in which the metal is coordinated to the carbonyl oxygen syn to the smallest carbonyl substituent, H. This necessitates that R of RCHO adopt an equatorial position if the transition state is chair-like, an arrangement that is structurally similar to the Zimmerman-Traxler model commonly invoked for many aldol reactions. Transition states (13) and (14), however, may potentially intervene and are frequently cited to rationalize the production of minor diastereomers (17). 

Kinetic control. The Zimmerman-Traxler model, as applied to propionate and ethyl ketone aldol additions, is shown in Scheme 5.7 (note the similarity to the boron-mediated allyl additions in Scheme 5.3). Based on this model, we would expect a significant dependence of stereoselectivity on the enolate geometry, which is in turn dependent on the nature of X and the deprotonating agent (see section... 

If both the Z(0)- and the (0)-enolates can be made, and if both follow the Zimmerman-Traxler models (i.e., chair transition structures), then both syn and anti adducts should be available (Scheme 5.11, path a vs. b or c V5. d). Since both enantiomers of the auxiliary are available, any desired combination of relative and absolute configurations in the products would be available. 

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