Magnesium enolates, formation

On the other hand, the predominant formation of the diastereomeric aldols 3 b results from the titanium enolate 1 b of (S )-5,5-dimethyl-4-tert-butyldimethylsilyloxy-3-hexanone. For this purpose, the ketone is first deprotonated with A-(bromomagnesio)-2,2,6,6-tetramethylpiperidine and the magnesium enolate, presumably (E) configurated, formed is thereby treated with hexamethylphosphoric triamide and triisopropyloxytitanium chloride. After sonification, the aldehyde is added to give predominantly aldol adducts 3b the diastereomeric ratio of 3b/2b surpasses 95 5 and the chemical yields range from 85 to 88%53b. 

Acyl imidazolides are more reactive than esters but not as reactive as acyl halides. Entry 7 is an example of formation of a (3-ketoesters by reaction of magnesium enolate monoalkyl malonate ester by an imidazolide. Acyl imidazolides also are used for acylation of ester enolates and nitromethane anion, as illustrated by Entries 8, 9, and 10. (V-Methoxy-lV-methylamides are also useful for acylation of ester enolates. 

Different protocols have been tested to prepare enolates from /1-aryl-a-iodoketones. Reactions nsing EtsB/PhsSnH in benzene, EtsB in benzene or ether and w-BuLi in ether failed to provide the corresponding enolates. Alternatively, the use of EtMgBr succeeds in generating reactive magnesium enolates from a-iodo ketones. In most cases, the formation of the enolate in THF is cleaner than that in EtiO (equation 8). 

A study of the enolisation mechanism with Kohler s ketone has shown the formation of an ( )-magnesium enolate (equation 47). 

The metallation should proceed via the formation of a chelated tetrahedral magnesium enolate complex, with a (Z)-geometry. The conformational rigidity would be enforced by chelation of both the imide enolate and bis(sulfonamide) ligand to the tetrahedral magnesium ion. 

Conseqnently, the magnesinm chelate 71 can also react as a nucleophilic donor in aldol reactions. In the chemistry involving magnesium chelates, these two aspects model their mode of action as nucleophilic partners in aldol condensations. This is exemplified in aldol condensations of y-diketones . Thus, sodium hydroxyde catalyzed cyclization of diketone 73 to give a mixtnre of 3,5,5-trimethyl-cyclopent-2-enone 74 and 3,4,4-trimethyl-cyclopent-2-enone 75 in a 2.2/1 isomeric ratio (equation 100). When treated with magnesinm methanolate, the insertion of a a-methoxy carbonyl group as control element, as in 76, allows the formation of a chelated magnesium enolate 77, and the major prodnct is now mainly the aldol 78. This latter treated with aqueous NaOH provides the trimethylcyclopent-2-enones 74 and 75 in a 1/49 ratio. 

Thus, a-sulfinyl lithium carbanion of 1-chloroethyl p-tolyl sulfoxide was reacted with 1,4-cyclohexanedione mono ethylene ketal (195) to afford the adduct (196) in quantitative yield. The adduct was treated with ferf-butylmagnesium chloride (magnesium alkoxide was initially formed) followed by isopropylmagnesium chloride to result in the formation of magnesium /3-oxido carbenoid 197. The /3-oxido carbenoid rearrangement then takes place to give one-carbon expanded magnesium enolate 198. Finally, an electrophile was... 

Silyl enol ethers react with aldehydes in the presence of chiral boranes or other additives " to give aldols with good asymmetric induction (see the Mukaiyama aldol reaction in 16-35). Chiral boron enolates have been used. Since both new stereogenic centers are formed enantioselectively, this kind of process is called double asymmetric synthesis Where both the enolate derivative and substrate were achiral, carrying out the reaction in the presence of an optically active boron compound ° or a diamine coordinated with a tin compound ° gives the aldol product with excellent enantioselectivity for one stereoisomer. Formation of the magnesium enolate anion of a chiral amide, adds to aldehydes to give the alcohol enantioselectively. 

The 1,4-addition of Grignard reagents under copper catalysis, followed by a trap of the resulting (magnesium) enolates with an appropriate electrophile, is a versatile method for double functionalization or double carbon-carbon bond formation at the a- and / -positions of an olefinic bond that bears a carbonyl group [Eq. (89)]. Recently, this topic has been extensively reviewed [155]. Examples [170,173,174] of this notion are presented in Eqs. (77), (90) [170], and (91) [174]. 

C-Alkylation of ketones. Fauvarque and Fauvarque1 found that the reaction of alkyl Grignard reagents with ketones in HMPT results in formation of magnesium enolates with elimination of the alkane. The enolates thus formed are readily... 

Magnesium enolates are similar to alkali metal enolates. For example, often the same stereoselectivity is observed in their formation and in the aldol reactions of these enolates. 

Traditionally, aldol reactions were carried out under protic conditions, such that the enolate was formed reversibly (see Volume 2, Chapter 1.5). An added measure of control is possible if one uses a sufficiently strong base that the enolate may be quantitatively formed prior to addition of the electrophile. The renaissance that has occurred in the aldol reaction in the last two decades has been mainly due to the development of methods for the formation and use of preformed enolates. The simplest enolates to prepare are those associated with lithium and magnesium, and there now exists a considerable literature documenting certain aspects of lithium and magnesium enolate aldol chemistry. This chapter summarizes the aldol chemistry of preformed enolates of these Group I and Group II metals. Other chapters in this volume deal with boron enolates, zinc enolates, transition metal enolates and the related chemistry of silyl and stannyl enol ethers. 

Use of a Grignard Reagent as a Base (Formation of Magnesium Enolates)... 

As bases. Formation of magnesium enolates from a-chloro-a-arenesulfinylcar-boxylic acid derivatives involves desulfinylation with a Grignard reagent. f-Butyl Grignard reagents are preferred in certain circumstances for the deprotonation of carbon acids. This method has been applied to a synthesis of chiral jS-hydroxy esters from arenesulfinylacetic esters. ... 

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