Alcohols with organometallic reagents

Coupling of allylic alcohols 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. 

The behavior of unsaturated azlactones with organometallic reagents has been studied in detail. Arylmagnesium halides and phenyllithium attack 4-arylidene-5-oxazolones at the carbonyl carbon to give ring-opened amido tertiary alcohols (26) and oxazolines (27) (by ring closure), usually as mixtures [Eq. (17)]. The nature of the... 

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. 

Especially in the early steps of the synthesis of a complex molecule, there are plenty of examples in which epoxides are allowed to react with organometallic reagents. In particular, treatment of enantiomerically pure terminal epoxides with alkyl-, alkenyl-, or aryl-Grignard reagents in the presence of catalytic amounts of a copper salt, corresponding cuprates, or metal acetylides via alanate chemistry, provides a general route to optically active substituted alcohols useful as valuable building blocks in complex syntheses. 

The formation of chiral alcohols from carbonyl compounds has been fairly widely studied by reactions of aldehydes or ketones with organometallic reagents in the presence of chiral ligands. Mukaiyama et al. 1081 obtained excellent results (up to 94% e.e.) in at least stoichiometric addition of the chiral auxiliary to the carbonyl substrate and the organometallic reagent. 

Acetylide (RC=CNa) and alkynide (RC=CMgX and RC=CLi) are good nucleophiles. They react with carhonyl group to from alkoxide, which under acidic work-up gives alcohol. The addition of acelylides and alkynides produces similar alcohols to organometallic reagents. 

Reduction of unsaturated halides 0-78 Reduction of allylic alcohols 0-82 Reductive cleavage of enamines 0-86 Coupling of vinylic halides 0-87 Coupling of unsaturated halides with organometallic reagents 0-88 Coupling of allylic halides, tosylates, or acetates... 

As already mentioned, unsaturated sugars, particularly glycals, are readily available compounds. Perrier rearrangement of glycals in the presence of Lewis acids and alcohols easily takes place to provide 2,3-unsaturated carbohydrates. The allylic esters obtained this way can be engaged in different reactions with organometallic reagents. 

Reaction cf epoxies with organometallic reagents 1.1.2.32 23-Epoxy alcohols... 

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. 

Aldehydes and ketones react with organometallic reagents to form secondary and tertiary alcohols, respectively, and some examples are shown with the general schemes here. 

FIGURE 16.63 The reaction of ketones with organometallic reagents, followed by hydrolysis, yields tertiary alcohols. 

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. 

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