Acid chlorides with organometallic reagents

Reaction of Acid Chlorides with Organometallic Reagents Grignard reagents react with acid chlorides to yield tertiary alcohols in which two of the substituents are the same. 

Reaction of Acid Chlorides with Organometallic Reagents... 

Acid chlorides and esters can be converted to ketones or 3° alcohols with organometallic reagents. The identity of the product depends on the identity of R —M and the leaving group Z. 

Asymmetric synthesis of dihydropyridones. 8-Phenylmenthol has been used frequently as a chiral auxiliary, but this derivative (1) is more effective as the chiral auxiliary for enantioselective reactions of N-acylpyridinium salts with organometallic reagents. Thus 2, prepared by reaction of 4-methoxy-3-(triisopropylsilyl)pyridine with the chloroformate of 1 reacts with the Grignard reagent 3 to give an adduct that on acidic deprotection provides the dihydropyridone 4 in 94% de. Conversion of the alcohol to a chloride [P(C6H5)3 and NCS] followed by treatment with sodium methoxide in methanol cleaves the chiral auxiliary as the methyl carbonate (94% yield) and at the same time effects cyclization to form the chiral bicyclic dihydropyridone 5 in 84% yield. 

Pd-catalyzed coupling of acyl halides with organometallic reagents is a useful synthetic method of ketones. The alkylzinc reagent 127, prepared from the corresponding alkyl iodide with Zn/Cu couple, was coupled with the acid chloride 128 to give the ketone 129 in 50 % yield and used for the total synthesis of amphidinolide T14 [55]. 

Similarly, reaction of an acid chloride with an organometallic reagent, R—M, initially gives a ketone that usually reacts with a second equivalent of R-—M to give the tertiary alcohol (Fig. 18.24). Note that this reaction must give a tertiary alcohol in which at least two R groups are the same. 

FIGURE 18.24 The reaction of an acid chloride with an organometallic reagent proceeds all the way to the tertiary alcohol. The organometallic reagent adds twice. 

The reaction of acid chlorides with 2 equiv of a trimethylsi-lylmethyl organometallic reagent, where the metal can be chloro-magnesium, lithium, or, best, dichlorocerium, proved to be an excellent direct synthesis of allylsilanes via the intermediacy of an a-trimethylsilyl ketone (eq 3). By reaction of a-trimethylsilyl ketones with vinylmagnesium bromide, one can prepare 2-substituted 1,3-butadienes (eq4). ... 

REACTION OF ACYL DERIVATIVES WITH ORGANOMETALLIC REAGENTS Acid Chlorides... 

Protection of Alcohols. Trimethylsilyl ethers, readily prepared from alcohols by treatment with a variety of silylating agents have found considerable use for the protection of alcohols. They are thermally stable and reasonably stable to many organometallic reagents and they are easily cleaved by hydrolysis in acid or base or by treatment with fluoride ion. t, Butyl dimethylsilyl ethers have considerably greater hydrolytic stability and are easier to work with than trimethylsilyl ethers. They are prepared from alcohols by treatment with t. butyl dimethylsilyl chloride. 

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