Esters, carboxylic acid with Grignard reagents

With organolithium reagents, stable intermediates are produced by addition to a carboxylic acid. On workup, these intermediates produce ketones. As with Grignard reagents, the reaction of organolithium reagents with esters produces tertiary alcohols because the intermediates decompose to ketones under the reaction conditions. The mechanisms for these processes are illustrated in the examples that follow. 

Titanocene dichloride catalyzes the reduction of alkyl, aryl, and vinyl bromides, aryl chlorides, alkoxy- and halosilanes ketones, esters, and carboxylic acids with alkyl Grignard reagents. This Cp2TiCl2/RMgX system can also be used for the hydromagnesation of alkynes, dienes, and alkenes (Section 3.2.5). Kambe et al. have reported a new type of titanocene-catalyzed transformation with vinyl Grignard reagents and chlorosilanes to furnish l,4-disilyl-2-butenes, as shown in Scheme 3.43 [31]. 

An alternate route to fluoroolefins relies upon the ease of reduction of difluoroolefins(18). Reduction of 114 with sodium bis(2-methoxyethoxy)aluminum hydride (Scheme 35) afforded the fluoroolefins 115 and 116 considerably enriched with the (E)-isomer 116. In a complementary reaction, reduction of the allylic alcohol 117 with LiAlH4 afforded selectively the (Z)-isomer 118. The difluoromethacrylic acid (121) was prepared in similar manner from 120 (Scheme 36) (53 for related examples see references 75 and 76). Under more forcing conditions, further reduction afforded 3-fluoromethacrylic acid 122. Of more general use is the reaction of 120 with Grignard reagents whereupon the 1,4-addition elimination mechanism offers an entry into a-difluoromethylene substituted aliphatic and aromatic carboxylic acids 123. Ester enolates (125) have been shown to add to trifluoropropene (124) forming the difluoroolefins (126) (Scheme 37) (54). 

Section 19.8 Esters give amides on reaction with ammonia and amines and are cleaved to a carboxylic acid and an alcohol on hydrolysis (Table 19.4). Esters react with Grignard reagents and are reduced by lithium aluminum hydride (Table 19.5). 

In Chapter 12, we saw how Grignard reagents readily attack the carbonyl carbon of ketones and aldehydes. Should the same process occur with Grignards and carboxylic acids With esters ... 

As we have seen, most reactions of carboxylic acids, esters, and related compounds involve, as the first step, nucleophilic attack on the carbonyl carbon atom. Examples are Fischer esterification, saponification and ammonolysis of esters, and the first stage of the reaction of esters with Grignard reagents or lithium aluminum hydride. All of these reactions can be summarized by a single mechanistic equation ... 

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