Traxler state

Zimmerman-Traxler Transition State Ivanov condensation JACS 1957, 7.9, 1920. 

The Zimmerman-Traxler like transition state model can involve either a chair or boat geometry. 

The diastereoselectivity observed on carbonyl addition of ( )-alkenyltitanium derivatives is in accordance with the reaction proceeding via a chair-like six-membered Zimmerman Traxler transition state. The following facts are diagnostic ... 

The most widely accepted transition state hypothesis for aldol reactions is the Zimmerman Traxler model29 which involves a six-membered chair-like assembly of the rcaetants. This... 

A Zimmerman-Traxler transition state model is postulated in order to rationalize the ul topicity of this aldol addition [i.e., the (S)-enolate preferentially attacks the 7 e-face of the aldehyde]33. In the two alternative transition states 3a [ul topicity (S)jRe] and 3b [Ik topicity (S)/Si, the substituents at the stereogenic center of the enolatc are oriented in such a way that... 

Although the chiral propanoates I and 5 are similar and the reaction conditions are almost identical, the stereochemical outcomes arc explained by completely different transition state models. Predominant attack of the ketene acetal 2 to the Ai-face of 2-methylpropanal is interpreted by assuming a Zimmerman-Traxler like model, which minimizes steric hindrance in a plausible way65. 

The preference of the (5, .S )-boron cnolatc to attack almost exclusively the Si-face of an aldehyde is rationalized by assuming the Zimmerman-Traxler transition state model. It is postulated that the methyl group of the propyl residue directs the 3-elhylpenlane-3-thiol group towards the borolane moiety, the chirality of which is thus effectively transferred34. 

The major aldol product 4 is consistent with the intermediacy of a Zimmerman-Traxler cyclic transition state such as A. Diastereoselectivities are moderate for aldehydes which are less sterically demanding than 2,2-dimethylpropanal. 

The configurational course depends on the enolatc configuration and the metal ion which determines whether a cyclic (e.g., Zimmerman-Traxler type) or an acyclic transition state is traversed. At present the following transition state models have been proposed. 

The selectivity of the aldol addition can be rationalized in terms of a Zimmer -man-Traxler transition-state model with TS-2-50 having the lowest energy and leading to dr-values of >95 5 for 2-51 and 2-52 [18]. The chiral copper complex, responsible for the enantioselective 1,4-addition of the dialkyl zinc derivative in the first anionic transformation, seems to have no influence on the aldol addition. To facilitate the ee-determination of the domino Michael/aldol products and to show that 2-51 and 2-52 are l -epimers, the mixture of the two compounds was oxidized to the corresponding diketones 2-53. 

A proposed simplified mechanism for the conjugate addition/aldol cyclization, as depicted in Scheme 2.25, is based on detailed mechanistic studies performed on related Rh-catalyzed enone conjugate additions [45]. A model accounting for the observed relative stereochemistry invokes the intermediacy of a (Z)-enolate and a Zimmerman-Traxler-type transition state as shown in 2-110 to give 2-111. 

One of the key features of such stereocontrolled aldol reactions is the predictability of the absolute stereochemistry of the enantiomers (or diastereo-mers) that will be formed as the major products. The preferred intermediate for an archetypal aldol reaction, proceeding by way of a metal enolate, can be tracked using the Zimmerman Traxler transition state and the results from the different variations of the aldol reaction can be interpreted from similar reasoning, and hence predictions made for analogous reactions1129]. 

From a historical standpoint, the Zimmerman-Traxler study on the stereochemical aspects of the Ivanov reaction is of considerable significance (22). Their investigation revealed that the magnesium enediolate 19a, upon condensation with benzaldehyde (Et2 O, reflux 5 hr), afforded the erythro and threo acids 20E and 20T, respectively, in a 24 76 ratio (eq. [13]). In the analysis of plausible transition states, both chair A and boat B geometries were considered. Zimmerman and Traxler concluded that the major diastereomer 20T could... 

As was worked out with the racemic reagents, titanated ( )-2-alkenyl carbamates rac-334 and rac-335 undergo a highly diastereoselective addition to aldehydes via a Zimmerman-Traxler transition state (equation q-jjg yields are high and the... 

Figure 6.8 Proposed modes of action of hydrogen-bonding catalyst 16 Bidentate hydrogen bonding coordination of the zwitterion derived from Michael-type DABCO attack to methyl acrylate (1) and Zimmerman-Traxler transition state for the reaction of methyl acrylate with benzaldehyde (2).

The following examples show how open and closed transition states may be invoked by the choice of the reaction type. For instance, aldol-type addition normally proceeds via a closed transition state because the metal ion is shifted from the enolate oxygen to the carbonyl oxygen in an ene-like mechanism ( Zimmerman-Traxler transition state 9). The crucial interactions in the Zimmerman-Traxler transition state 16 are those between the 1,3-diaxially oriented substituents around the chair-like structure. R2 adopts the location shown, thus R3 avoids the 1,3-interaction and assumes an equatorial position. Therefore, the diastereomeric ratio depends mainly on the ( )/(Z) configuration of the enolate. Whereas (Z)-enolates 13 afford syn-config-urated enantiomers, 17 and 18, the corresponding ( )-enolates 14 lead to anti-configurated adducts 19 and 20 10. 

Aldol reactions of magnesium enolates are frequently more diastereoselective than the corresponding reactions of lithium enolates. The aldol condensation proceeds via a cyclic transition state in agreement with the Zimmerman-Traxler chelated model . 

A few years ago, Blagonev and Ivanov described the bis-deprotonation of aryl acetic acids by Grignard reagents. These magnesinm dianions, known as Ivanov reagents, react with aldehydes and ketones. Reaction between dianions of phenylacetic acid and benzaldehyde yields the anti S-hydroxy acid as the major diastereomer anti/syn 69/22) (equation 113). This result is in agreement with the formation of a cyclic chair-like transition state according to the model of Zimmerman-Traxler . 

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. 

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