Magnesium amide bases

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... 

Scheme 3.9 A selection of magnesium amide-based inverse crown complexes ...

Novel chiral bases introduced recently include the magnesium amide base 7 and analogs reported by Henderson [48] and Knochel s urea base 8 (mono and di-anions) [49]. 

Initial attempts at this important reaction were done using lithium and magnesium amide bases. The reaction condition typically employed is at low temperatures with an excess of the base as well as the electrophile needed to capture the metallated ring. 

These reagents are appropriate even for very sensitive molecules. Their efficacy is presumably due to the Lewis acid effect of the aluminum and magnesium ions. The hindered nature of the amide bases also minimizes competition from nucleophilic ring opening. 

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 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. 

Hammerschmidt, F. Hanninger, A. Enantioselective deproto nation of benzyl phosphates by homochiral lithium amide bases. Configurational stability of benzyl carbanions with a dialkoxyphosphoryloxy substituent and their rearrangement to optically active a-hydroxy phosphonates. Chem. Ber. 1995, 328, 823-830. Avolio, S. Malan, C. Marek, I. Knochel, P. Preparation and reactions of functionalized magnesium carbenoids. Synlett 1999, 1820-1822. 

Novel and readily accessible polymer-supported chiral magnesium amide reagents have been prepared and shown to be effective in the asymmetric deprotonation of a series of prochiral cyclohexanones, affording good to excellent conversion and enantiomeric ratio (up to 93 7) the Merrifield-based chiral amine species has been shown to be readily recyclable (Scheme 3.39) [29]. 

Two independent studies rapidly followed considering the alternative pathway to mixed imides in the Li-Mg-N-H system, namely combining magnesium amide with lithium hydride [84, 85]. The two studies differed in the ratios of starting materials considered. The former took the 1 2 ratio of amide hydride and by analogy to Eq. (16.22) sought to liberate hydrogen as a by-product of mixed imide formation, viz. Eq. (16.23) (hereafter referred to as the 1 2 reaction based on the Mg(NH2)2 LiH ratio) ... 

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