Grignard reagents ester transformation into

Compared with aldehydes, ketones and esters are less reactive electrophiles in the addition of dialkylzincs. This makes it possible to perform a unique reaction that cannot be done with alkyllithium or Grignard reagents, which are too reactive nucleophiles. For example, Watanabe and Soai reported enantio- and chemoselective addition of dialkylzincs to ketoaldehydes and formylesters using chiral catalysts, affording enantiomerically enriched hydroxyketones 30 (equation 12)43 and hydroxyesters 31 in 91-96% , respectively (equation 13). The latter are readily transformed into chiral lactones 3244. 

A variety of functional transformations occurring far from the SMA framework have been described. Acylation of a silyl ether, sodium borohydride or LAH reduction of an ester into a carbinol, oxidation of a carbinol into an aldehyde or a ketone, and the addition of Grignard reagents to a carbonyl are some examples.95,168,255... 

Imino aldol reaction of ketene silyl acetals with the chiral imine derived from tartaric acid 83 in the presence of a cation-exchange resin provided the corresponding /i-amino esters 84 in a good yield and high diastereose-lectivity [68]. The esters 84, thus obtained, were subjected to the Grignard reagent which promoted S-lactam formation. After a sequence of reactions compound 84 was transformed into the ester 85 [68] which in the past was... 

This reaction was first reported by Behai and Sommelet in 1904. It is the transformation of methyl -hydroxylalkyl ethers into aldehydes in the presence of acids, preferably oxalic acid. The methyl j -hydroxylalkyl ethers can be prepared via the Grignard Reaction between the Grignard reagents and esters of a-methoxy acetic acids. 

Alkyl substituents can be introduced into heterocyclic rings also via direct ONSH reaction with the Grignard reagents [72] or via the VNS reaction with carbanions of a-chloroalkyl carboxylic esters [17], followed by hydrolysis and decarboxylation [95-97]. For example, treatment of 5-nitroisoquinoline with the carbanion of ethyl chloroacetate under the standard VNS condition in DMF in the presence of t-BuOK gave the expected (5-nitroisoquinol-6-yl)acetate, which was transformed into 6-methyl-5-nitroisoquinoline via hydrolysis and decarboxylation (Scheme 23) [95]. 

The S-ifl type compounds 72, prepared from the reaction of MBH acetates and Grignard reagents, have been treated with 3 equiv. of H2SO4 at 60-70 °C, giving 3,4-dihydronaphthalenes 74 in moderate yields via an acid-catalyzed Friedel-Crafts-type reaction and subsequent acid hydrolysis of the ester moiety (Scheme 4.24). However, when the reactions were conducted at reduced temperature (0-10 °Q, 5,5-dimethyllactone derivatives 73 were obtained in 70-76% yields via acid-catalyzed lactonization. Such lactones could also be transformed into 3,4-dihydronaphthalenes 74 by treatment with H2SO4 in benzene at elevated temperature (60-70 °Q. 

Grignard reagents transform esters into alcohols... 

Esters can be converted into alcohols by using two equivalents of a Grignard reagent. In this way, ordinary esters are transformed into tertiary alcohols, whereas formate esters furnish secondary alcohols. 

To our knowledge no possibility exists to cleave ester linkers with carbon nucleophiles to give ketones. In contrast, thioester linkers can be ap-pUed for these purposes as shown by Bradley et al. [89]. The thioester 55 in Scheme 8 was prepared easily by addition of an arylthioamide and sodiiun iodide to Merrifield resin in aqueous DMF. It was shown that thioesters without the need of special Hnker demands can be transformed into ketones 57 as well as into primary (60) and tertiary alcohols (59). The addition of Grignard reagents to thioesters gives tertiary alcohols whereas the addition of C-nucleophUes via organocuprates provides ketones in 53% yield. These results differ from those found by Vlattas et al. in 1997 who observed the... 

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