Grignard reagents, reaction with amides

The amide and lactam groups in 136 and 137 are inactive when boiled with concentrated HC1 on reaction with Grignard reagents they yield trialkylgermyl derivatives (equation 35). According to the IR spectra, there is no intramolecular O — Ge interaction in compounds of type 141480. 

Methoxyamine solid supports 7x can be used to anchor carboxylic acids in the presence of BOP/DIEA as Weinreb amides [338,339]. The resultant anchor is compatible with peptide assembly using Boc or Fmoc strategies, and treatment of the final sequence with LiAlH4 in THF led to release of peptide aldehydes. A related support with RAM as the base resin has also been used to prepare resin-bound Weinreb amides, which afforded ketones on cleavage induced by reaction with Grignard reagents [340]. 

Good chemoselectivity has been observed in the reactions of substrates containing both nitrile and Weinreb amide functionalities with Grignard reagents Even in the presence of excess Grignard reagent, in most cases only the Weinreb amide group reacted at room temperature. 

Nitriles are similar in some respects to carboxylic acids and are prepared either by 5 2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with Grignard reagents to yield ketones. 

Other Rea.ctlons, The anhydride of neopentanoic acid, neopentanoyl anhydride [1538-75-6] can be made by the reaction of neopentanoic acid with acetic anhydride (25). The reaction of neopentanoic acid with acetone using various catalysts, such as titanium dioxide (26) or 2irconium oxide (27), gives 3,3-dimethyl-2-butanone [75-97-8] commonly referred to as pinacolone. Other routes to pinacolone include the reaction of pivaloyl chloride [3282-30-2] with Grignard reagents (28) and the condensation of neopentanoic acid with acetic acid using a rare-earth oxide catalyst (29). Amides of neopentanoic acid can be prepared direcdy from the acid, from the acid chloride, or from esters, using primary or secondary amines. 

Preparation Of Thiol Acids, Thiol Esters And Amides By Reactions Of Carbonyl Sulfides With Grignard Reagents," Katritzky. A.R. Moutou, J.-L. Yang, Z. Org. Prep. Proceed. Int., 1995, 27, 361... 

Amidation-the Bodroux reaction Finally, amidahon of methyl ester 33 was required to complete the process. To accomplish this transformation, we turned to a reaction first reported in 1904 by Bodroux [12]. The reaction involves activation of an amine by conversion to the magnesium amide using a Grignard reagent. Subsequent reaction of the magnesium amide with the ester produces the carboxamide. 

TABLE 2. Structurally characterized organomagnesium amides synthesized from the reaction of metal amides with Grignard reagents... 

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