Lactones, reaction with Grignard reagents

S -Dialkylbutenolides, The reagent is converted by reaction with Grignard reagents into the lactone 2, which loses furane when heated to 150° to form 5,5-dialkylbutenolides (3). 

The formation of the endocyclic double bonds of unsaturated lactones has been accomplished via the rDA reaction. The preparation of 2-alkyl-2-butenolactones, such as (179), by a method that incorporates the rDA reaction as a key step has been a q>lied to the synthesis of butyrolactone lignans such as ( >-hinokinin (180) as shown in equation (80). An extensive study of the preparation of substituted 2-bute-nolides (183) has been reported. The mono-, di- and tri-alkyl bicyclobutenolides are prepared by reacting adducts (181) with Grignard reagents or with LDA followed by alkyl halides. Alkylated adducts (182) were then either directly distilled under vacuum or heated in a sealed tube to give the alkylated 2-bute-nolides (183) (equation 81). " ... 

Reaction of Esters with Grignard Reagents Esters and lactone react with 2 equivalents of a Grignard reagent to yield a tertiary alcohol in which two of the substituents are identical (Section 17.6). The reactioo occurs by the usual nucleophilic substitution mechanism to give an intermediate ketone, which reacts further with the Grignard reagent to yield a tertiary alcohol. ... 

The Diels-Alder adduct of furan and maleic anhydride reacts with Grignard reagents to form lactones, which are converted to butenolides in a thermal cycloreversion reaction. Work continues on the synthesis of 4-ylidenebutenolides using the Wittig reaction on substituted maleic anhydrides the products have been converted into cyclopentene-l,3-diones. ... 

The reaction involves nucleophilic substitution of for OR and addition of R MgX to the carbonyl group. With 1,4-dimagnesium compounds, esters are converted to cyclopentanols (40). Lactones react with Grignard reagents and give diols as products. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Chiral butenolides are valuable synthons towards y-butyrolactone natural products [37] and have also been successfully applied to the synthesis of paraconic acids. The lactone 91, readily available from the hydroxyamide (rac)-90 by enzymatic resolution [38] followed by iodolactonization, proved to be an especially versatile key intermediate. Copper(I)-catalyzed cross coupling reactions with Grignard reagents allowed the direct introduction of alkyl side chains, as depicted in 92a and 92b (Scheme 13) [39, 40]. Further... 

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. 

The reaction of a chiral Grignard reagent derived from ephedrine with the oxathiane 2 was used to prepare the 8-hydroxy acid 5 in 34% overall yield. On standing, 5 lactonizes to (— )-malyngolide (6). ... 

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