Magnesium amide

Magnesium amides are now the most numerous among the group 2 metals and they have been treated, either fully or in part, in a number of reviews. The crystal structure of 

Magnesium diorganoamides can be synthesized by a number of routes. The oldest involves the displacement of an alkane from a diorganomagnesium upon reaction with an amine as shown in Equation (3.2). 

Grignard reagents also react with amines in a similar fashion. Equation (3.3). 

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Application of magnesium amide instead of alkyl lithium for the cyclopropanation formation from 5-chloropentyne was reported in the patent application ... 

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. 

From our experience with the Bodroux reaction, we knew that the magnesium amide of t-BuNH2 reacts with 33. Recall that, in order to avoid solubility problems in preparation of the magnesium amide reagent, EtMgBr was added to a mixture... 

E. Reactions of Magnesium Amide and Lactam Enoiates with Electrophiles. 499... 

The same type of reaction has been applied to the preparation of 1,2-dihydroquinoline-3- and 277-l-benzothiopyran-3-carboxylic acid derivatives (equation 38) via a magnesium amide-induced sequential conjugate addition-aldol condensation reaction between 2-(alkylamino)phenylketones or 2-mercaptobenzophenones . 

Dihydroquinoline-3-carbonitriles can also be prepared by the tandem reaction between 2-(mediylamino)-benzophenone and a,/3-unsaturated carbonitriles in the presence of magnesium amide under the same conditions as for the reaction with a,-unsaturated carboxylates (equation 39). 

The propensity of magnesium amide to undergo Michael additions with a,/S-unsaturated esters has been developed into a general protocol using homochiral amide to give magnesium /3-aminoenolate intermediates (equation 40). 

In recent years, a variety of hindered magnesium amides have been used to produce magnesium enolates. The versatility of these bases is now well recognized. Some typical examples are presented below. 

The magnesium amides may be prepared either by reaction of lithium amide and magnesium bromide, by reaction of DIBAL-H with RiMg, or by reaction of the corresponding amine with a Grignard reagent " . ... 

The magnesium amides and diamides are more thermally stable and less reactive than their lithium analogues, leading to different selectivities. 

Examples for the preparation of magnesium enolates (or further subsequent reactions of the enolates) by magnesium amides are listed in Table 7. 

The magnesium amides of choice for the preparation of magnesium enolates via met-allation are the Hauser bases, such as 39 and 40, or (bis)amidomagnesium reagents, such as 46 and 47. The reaction has been successfully applied to the preparation of enolates derived from cyclic, acyclic and a-siloxyketones, benzyUc ketones, aldehydes, carboxylic esters and amides, even with the less hindered Hauser bases. 

Substrate Magnesium amide Magnesium enolate or reaction product after trapping procedure of enolates Ref- erence... 

The increasing interest in enolization reactions mediated by magnesium amides led to new investigations for structural features of these reagents . 

Magnesium amides have also found good utility in enantioselective deprotonation processes. A range of chiral amines has been prepared by Henderson and coworkers and it was found after conversion to their Mg-bisamide derivatives that it react with 4- and 2,6-substituted cyclohexanones with good to excellent selectivities (see Section m). Structures of some chiral magnesium amides are given in Chart 1. 

The concept of chiral magnesium amides for the preparation of magnesium enolates has been extended to chiral magnesium bis(sulfonamide) complexes as catalysts for the enolization of A-acyloxazolidines ° (equation 63). 

Recently, Henderson has investigated the effect of Lewis base additives such as HMPA in enantioselective deprotonation of ketones mediated by chiral magnesium amide bases. In almost all reactions investigated, the additive HMPA could be replaced by DMPU without any undue effect on either selectivity or conversion (equation 69) ... 

C. Metalation Reactions with Magnesium Amide Bases. 537... 

Reaction of aLkyknagnesium reagents with sterically hindered amines leads to the formation of magnesium amides 110-112 °, reacting much faster than the parent alkyl-magnesium derivatives with C—H acidic substrates (Scheme 9). 

The chemistry of magnesium bisamides has been reviewed" . They can be used for the regio- and stereoselective formation of enolates", while chiral magnesium amides are applied in asymmetric synthesis for enantioselective enolisations ". 

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