Ivanov reaction Zimmerman-Traxler transition states

The Ivanov reaction is the preparation of a 3-hydroxy acid by reaction of the magnesium dianion of a carboxylic acid with an aldehyde or ketone." In a seminal paper, Zimmerman and Traxler investigated the Ivanov reaction of phenylacetic acid and benzaldehyde and obtained anti and syn 3-hydroxy acids (127) and (128) in 69% and 22% yields, respectively (equation 85). The observed stereochemistry was rationalized with a cyclic, chair-like transition state in which a magnesium cation is chelated by one oxygen each of the carboxylate enolate and the aldehyde (the Zimmerman-Traxler transition state ). 

Scheme 5.1. The Zimmerman-Traxler transition state model for the Ivanov reaction [1],...

In this reaction, the onfr-product is preferentially formed.The Ivanov reaction is known to proceed through the Zimmerman-Traxler transition state model. 

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... 

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 simple diastereoselectivity of aldol reactions was first studied in detail for the Ivanov reaction (Figure 13.45). The Ivanov reaction consists of the addition of a carboxylate enolate to an aldehyde. In the example of Figure 13.45, the diastereomer of the /1-hydroxycarboxylic acid product that is referred to as the and-diastereomer is formed in a threefold excess in comparison to the. vy/j-diastereoisomer. Zimmerman and Traxler suggested a transition state model to explain this selectivity, and their transition state model now is referred to as the Zimmer-man-Traxler model (Figure 13.46). This model has been applied ever since with good success to explain the simple diastereoselectivities of a great variety of aldol reactions. 

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. 

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