Zimmerman-Traxler model stereoselectivity

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. 

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... 

A.iv. The Evans Model. It is known that (Z) enolates are more stereoselective than ( ) enolates even when r1 is not large. The Zimmerman-Traxler model transition states 352-355 do not account for this observation. It has been suggested that the transition states are not chair-like, but skewed, as in 381-384.221 In this representation (Z) enolate 381 leads to the syn aldol. Similarly, (Z) enolate 382 gives the anti aldol, ( ) enolate 383 give the anti aldol and E) enolate 384 is the precursor to the syn aldol. The major steric interactions in this model are those for r1 r3 and r2 - r3. For both (Z) and E) enolates, the r1 r3 interaction favors 381 and 383, respectively. The r2 r3 interaction is more important for the E) enolate and... 

Scheme 1. Zimmerman-Traxler models for aldol stereoselectivity with boron enolates.

The condensation step a gave a 3 1 mixture of isomers 2. Assuming that the stereoselectivity of the reaction can be rationalised by a Zimmerman-Traxler transition state model, what should be the structure of the predominant isomer ... 

The observed stereoselectivity in the Evans aldol reaction can be explained by the ZImmerman-Traxler transition state model. There are eight possible transition states, four of which would lead to the anti aldol product. These, however, are disfavored due to the presence of unfavorable 1,3-diaxial interactions (not depicted below). The possible transition states leading to the syn aldol product are shown below. The preferred transition state leading to the product is transition state A, where the dipoles of the enolate oxygen and the carbonyl group are opposed, and there is the least number of unfavored steric interactions. 

Remarkably, the induced stereoselectivity of enolates 303 and 306 is opposite despite the homochiral diazaborolidine skeleton cis-enolate 303 attacks predominantly from the Re-face to the aldehyde, whereas traws-enolate 306 approaches from the Si-face. The opposite stereochemical outcome was explained by Zimmerman—Traxler-like transition state models 308 and 309, respectively. It was assumed that transition state 308 is favored because it avoids repulsion between the phenylthio and the arylsulfonyl group, whereas 309 prevents steric hindrance between the arylsulfonyl moiety and the aldehyde (Scheme 4.68) [151d]. The chiral controller group 300 was also applied to acetates and thioacetates, but the reactions were found to be plagued by distinctly lower enantioselectivity of 52-80% ee with benzaldehyde - another example of the problematic asymmetric acetate aldol addition. 

The additions of allyl-, crotyl-, and prenylborane or -boronate reagents to aldehydes are among the most widely studied, well developed, and powerful reactions in stereoselective synthesis. The additions not only display excellent levels of absolute induction in enantioselective synthesis, but also exhibit superb levels of reagent control in diastereoselective additions. The additions of ( )- or (Z)-crotyl pinacol boronates to aldehydes have been observed to give predominantly 1,2-anti- and 1,2-syn-substituted products, respectively (Scheme 5.3) [31, 50]. The inherent stereospecificity of the reaction is consistent with a closed, cyclic Zimmerman-Traxler transition state structure [51], In the accepted model, coordination of the aldehyde to the allylation reagent results in synergistic activation of both the electrophile and the nucleophile... 

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