Carboxylation Ivanov reaction

A completely different dipolar cycloaddition model has been proposed39 in order to rationalize the stereochemical outcome of the addition of doubly deprotonated carboxylic acids to aldehydes, which is known as the Ivanov reaction. In the irreversible reaction of phenylacetic acid with 2,2-dimethylpropanal, metal chelation is completely unfavorable. Thus simple diastereoselectivity in favor of u f/-adducts is extremely low when chelating cations, e.g., Zn2 + or Mg- +, are used. Amazingly, the most naked dianions provide the highest anti/syn ratios as indicated by the results obtained with the potassium salt in the presence of a crown ether. 

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. 

Fig. 10.40. The Ivanov reaction. For the generation of the carboxylate enolate, see Figure 10.8.

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 ). 

The reactions of aldehydes with carboxylate enolates are stereochemical-ly related to the Ivanov reaction (dianions of arylacetic acids -t carbonyl compounds), named after the Bulgarian chemist Dimitar Ivanov Popov (1894-1975). 

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