Amides organomagnesium compound

Detailed reviews on the structures of organomagnesium compounds and the constitution of their solutions have been published [D, 1, 2]. These references, especially the first two, also cover alkylmagnesium hydrides, amides, alkoxides and thiolates. However, while all of these compounds are of intrinsic interest, they are little used in synthesis. 

Similar considerations apply to reactions of organomagnesium compounds with formate esters (leading to aldehydes), chloroformates or carbonates (leading to esters) or carbamoyl chlorides (leading to amides) ... 

Reactions of organomagnesium compounds with /V,/V-disubstituted amides differ from those of other acyl derivatives (Section 6.2) in that the initial adducts are much more stable. However, although examples are known where a carbinolamine may be isolated following careful hydrolysis, acid hydrolysis without special precautions usually gives the... 

The synthesis of ketones from organomagnesium compounds and N,N-dialkylamides has been comparatively little exploited, but a few examples are included in Table 6.5. A significant limitation has been the low reactivity of the amides, but this has been overcome by the use of 7V-(2-pyridyl)amides (see penultimate entry in Table 6.5) and especially A-methoxyamides (hydroxamates). Examples of the use of the latter are listed in Table 6.6. 

The usual reactions of organomagnesium compounds with esters, amides and nitriles are those described in Sections 5.3, 6.2 and 6.3. However, factors such as steric hindrance and stability of leaving group may lead to reactions resulting in overall nucleophilic displacement. Most of them are of limited applicability (see Ref. [39] for examples involving carbamate), but two warrant coverage. 

Addition of an organomagnesium bond to an alkene, alkyne, or a benzenoid ring generates a new organomagnesium compound. With simple alkenes, addition occurs only under strenuous conditions. This reaction will be discussed later, with appropriate examples, as a reaction of organomagnesium compounds in the Section on Amides and Lactans.. 

Chloroformates, chlorocarbamates, and phosgene are similarly reactive toward organomagnesium compounds. The first two provide useful syntheses of esters and amides, respectively, but phosgene usually leads to the tertiary alcohol. 

Amides and Lactams. The amide carbonyl group is less reactive than that of aldehydes or ketones, but the intermediate formed on addition of one equivalent of organomagnesium compound is relatively stable to elimination of a magnesium dialkylamide, and so protects... 

Addition to the C=N of an imine forms the magnesium amide, which is hydrolyzed to an amine. Isolated C=N double bonds of simple imines are relatively unreactive toward organomagnesium compounds, and may instead be depro-tonated at the a-position. Oximes and other N-substituted imines may react better, although an alternative sequence can produce aziridines. Imminium ions, because of their positive charge, are more reactive, and are useful in making tertiary amines. A-Silylimines yield primary amines after hydrolysis. Grignard reagents also add to one C=N of carbodiimides to produce amidines, and to nitrones to produce hydroxylamines. Some varied examples are shown in Scheme 6. 

Organozinc reagents are less nucleophilic than organomagnesium compounds and can be easily prepared with a variety of functional groups (see Chapter 7), several of them were tested for the reductive cyclopropanation of amides. Therefore, a new protocol was devised for the efficient preparation of various tert-butoxycar-bonyl and chloroalkylsubstituted cydopropylamine derivatives (Scheme 12.50) [70]. 

Organomagnesium amides and related compounds with group 15-bonded ligands 106... 

---