Alcohols chlorides with organometallic

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. 

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. 

A similar transposition can be applied to saturated ketones. For example, a ketone is treated with a vinyl organometallic reagent to generate a derivative of an aUylic alcohol. Reaction with benzenesulfenyl chloride then gives an aUylic sulfoxide by means of a [2,3] sigmatropic rearrangement. The remain-... 

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. 

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. 

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. 

Acid chlorides are easily converted to 1° alcohols and aldehydes (see Section 5.7.21) and 3° alcohols and ketones through the choice of appropriate metal hydride and organometallic reagents (see Section 5.5.5). Acid chloride reacts with benzene in the presence of Lewis acid (AICI3) in Friedel-Crafts acylation (see Section 5.5.6). 

Isomerization of allylic alcoholsAllylic alcohols can be isomerized to carbonyl compounds by several organometallic reagents at elevated temperatures. The reaction can be conducted at 25-30° overnight with [Rh(CO)2Cll2 under phase-transfer conditions. Cleaner reactions obtain if benzyltriethylammonium chloride is used as catalyst. 

An organometallic reagent has also been used to ring-open an aziridinium ion (181), formed in situ by the treatment of the amino alcohol derivative 180 with lithium chloride. Subsequent addition of the aryl magnesium bromide 182 led to the formation of amine 183 in 95% overall yield <02TL6121>. 

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