Grignard reagents, addition reactions esters

Alkenyl sulfoxides (42 and 43) were first prepared in optically active form by Mulvaney and Ottaviani , described in an article overlooked by most workers in the field, and a year later by Stirling and coworkers through the reaction of the appropriate vinyl Grignard reagent with sulfinate ester 19. Both groups studied the addition of nucleophiles to the carbon-carbon double bond . More recently, Posner and coworkers reported a similar synthesis of ( )-l-alkenyl sulfoxides, e.g. 44 and In the synthesis of 45,... 

Introduction. Ti-TADDOLates are a,a,a, a -tetraaryl-2,2-disubstituted l,3-dioxolane-4,5-dimethanolatotitanium derivatives. The most common substituents are R, R = Me/Me and Ph/Me, Ar=Ph and 2-naphthyl, X, Y = C1/C1, t-PrO/Cl, Cp/Cl, and i-PrO/i-PtO. The corresponding TADDOLs (2) are available in both enantiomeric forms from tartrate esters which are acetalized (R R CO) and allowed to react with aryl Grignard reagents. The reactions performed in the presence of Ti-TADDOLates or with Ti-TADDOLate derivatives include nucleophilic additions to aldehydes - - and nitroalkenes of alkyl, aryl, and allylic - groups aldol additions hydrophosphonylations and cyanohydrin reactions of aldehydes inter- and intramolecular Diels-Alder additions ... 

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. 

A different type of reaction is the addition of two equivalents of vinyl Grignard reagent to an ester. This involves a conjugate addition to a sterically hindered ketone in the second step (Scheme 23). ... 

The mechanism of the reaction of a Grignard reagent with an ester first involves nucleophilic addition to the carbonyl carbon of the ester, forming a tetrahedral intermediate, illustrated in step 1 in Mechanism 19.5. The tetrahedral intermediate is unstable and breaks down to form a ketone (step 2), which rapidly undergoes addition of a second equivalent of the Grignard reagent (step 3). Subsequent hydrolysis gives the tertiary alcohol (step 4). 

Propose a synthesis of 3-phenyl-3-pentanol using the addition reaction of a Grignard reagent to an ester. 

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 conversion of a nitrile R —CN into a ketone R —CO—R demonstrates that polarized multiple bonds other than C=0 also react with Grignard reagents, and that such reactions are synthetically useful. Esters 22 and acid chlorides can react subsequently with two equivalents of RMgX the initially formed tetravalent product from the first addition reaction can decompose to a ketone that is still reactive, and reacts with a second RMgX. The final product 23 then contains two substituents R, coming from the Grignard reagent ... 

Acid halides are among the most reactive of carboxylic acid derivatives and can be converted into many other kinds of compounds by nucleophilic acyl substitution mechanisms. The halogen can be replaced by -OH to yield an acid, by —OCOR to yield an anhydride, by -OR to yield an ester, or by -NH2 to yield an amide. In addition, the reduction of an acid halide yields a primary alcohol, and reaction with a Grignard reagent yields a tertiary alcohol. Although the reactions we ll be discussing in this section are illustrated only for acid chlorides, similar processes take place with other acid halides. 

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